January 2015 Volume 38, Supplement 1

Standards of Medical Care in —2015

S1 Introduction S49 8. Cardiovascular Disease and Risk Management S3 Professional Practice Committee Hypertension/Blood Pressure Control S4 Standards of Medical Care in Diabetes—2015: Dyslipidemia/Lipid Management Summary of Revisions Antiplatelet Agents Coronary Heart Disease S5 1. Strategies for Improving Care S58 9. Microvascular Complications and Foot Care Diabetes Care Concepts Care Delivery Systems Nephropathy When Treatment Goals Are Not Met Retinopathy Neuropathy S8 2. Classification and Diagnosis of Diabetes Foot Care Classification S67 10. Older Adults Diagnostic Tests for Diabetes Categories of Increased Risk for Diabetes Treatment Goals () Pharmacological Therapy S70 11. Children and Adolescents Mellitus Monogenic Diabetes Syndromes Type 1 Diabetes Cystic Fibrosis–Related Diabetes Type 2 Diabetes S17 3. Initial Evaluation and Psychosocial Issues Planning S77 12. Management of Diabetes in Pregnancy Medical Evaluation Diabetes in Pregnancy Management Plan Preconception Counseling Common Comorbid Conditions Glycemic Targets in Pregnancy S20 4. Foundations of Care: Education, Nutrition, Pregnancy and Antihypertensive Drugs Physical Activity, Smoking Cessation, Management of Gestational Diabetes Mellitus Psychosocial Care, and Immunization Management of Pregestational Type 1 Diabetes and Type 2 Diabetes in Pregnancy Diabetes Self-management Education and Support Postpartum Care Medical Nutrition Therapy Physical Activity S80 13. Diabetes Care in the Hospital, Nursing Home, Smoking Cessation and Skilled Nursing Facility Psychosocial Assessment and Care in the Hospital Immunization Glycemic Targets in Hospitalized Patients S31 5. Prevention or Delay of Type 2 Diabetes Antihyperglycemic Agents in Hospitalized Patients Preventing Hypoglycemia Lifestyle Modifications Diabetes Care Providers in the Hospital Pharmacological Interventions Self-management in the Hospital Diabetes Self-management Education and Support Medical Nutrition Therapy in the Hospital S33 6. Glycemic Targets Bedside Blood Glucose Monitoring Discharge Planning Assessment of Glycemic Control Diabetes Self-management Education A1C Goals Hypoglycemia S86 14. Diabetes Advocacy Intercurrent Illness Advocacy Position Statements S41 7. Approaches to Glycemic Treatment S88 Professional Practice Committee for the Standards Pharmacological Therapy for Type 1 Diabetes of Medical Care in Diabetes—2015 Pharmacological Therapy for Type 2 Diabetes Bariatric Surgery S90 Index

This issue is freely accessible online at care.diabetesjournals.org.

Keep up with the latest information for Diabetes Care and other ADA titles via Facebook (/ADAJournals) and Twitter (@ADA_Journals). Diabetes Care Volume 38, Supplement 1, January 2015 S1 INTRODUCTION

Introduction Diabetes Care 2015;38(Suppl. 1):S1–S2 | DOI: 10.2337/dc15-S001

Diabetes is a complex, chronic illness re- ADA STANDARDS, STATEMENTS, ADA Scientific Statement quiring continuous medical care with AND REPORTS A scientific statement is an official multifactorial risk-reduction strategies The ADA has been actively involved in ADA point of view or belief that may or beyond glycemic control. Ongoing pa- the development and dissemination of may not contain clinical or research rec- tient self-management education and diabetes care standards, guidelines, and ommendations. Scientificstatements support are critical to preventing acute related documents for over 20 years. contain scholarly synopsis of a topic re- complications and reducing the risk of ADA’s clinical practice recommenda- lated to diabetes. Workgroup reports long-term complications. Significant tions are viewed as important resources fall into this category. Scientific state- evidence exists that supports a range for health care professionals who care ments are published in the ADA journals of interventions to improve diabetes for people with diabetes. ADA’s “Stan- and other scientific/medical publications, outcomes. dards of Medical Care in Diabetes,” as appropriate. Scientific statements also The American Diabetes Association’s position statements, and scientific undergo a formal review process. (ADA’s) “Standards of Medical Care in statements undergo a formal review Diabetes” is intended to provide cli- process by ADA’s Professional Practice Consensus Report nicians, patients, researchers, payers, Committee (PPC) and the Executive A consensus report contains a compre- and other interested individuals with Committee of the Board of Directors. hensive examination by an expert panel the components of diabetes care, gen- The Standards and all ADA position state- (i.e., consensus panel) of a scientificor eral treatment goals, and tools to eval- ments, scientific statements, and consensus medical issue related to diabetes. A con- uate the quality of care. The Standards reports are available on the Association’s sensus report is not an ADA position and of Care recommendations are not in- Web site at http://professional.diabetes.org/ represents expert opinion only. The cat- tended to preclude clinical judgment adastatements. egory may also include task force and and must be applied in the context of expert committee reports. The need excellent clinical care, with adjustments “Standards of Medical Care in Diabetes” for a consensus report arises when clini- for individual preferences, comorbid- Standards of Care: ADA position state- cians or scientists desire guidance on ities, and other patient factors. For ment that provides key clinical practice a subject for which the evidence is con- more detailed information about man- recommendations. The PPC performs an tradictory or incomplete. A consensus agement of diabetes, please refer to extensive literature search and updates report is typically developed immedi- Medical Management of Type 1 Diabetes the Standards annually based on the ately following a consensus conference (1) and Medical Management of Type 2 quality of new evidence. where the controversial issue is exten- Diabetes (2). sively discussed. The report represents The recommendations include screen- ADA Position Statement the panel’s collective analysis, evalua- ing, diagnostic, and therapeutic actions A position statement is an official ADA tion, and opinion at that point in time that are known or believed to favor- point of view or belief that contains clinical based in part on the conference pro- ably affect health outcomes of patients or research recommendations. Position ceedings. A consensus report does not with diabetes. Many of these interven- statements are issued on scientificormed- undergo a formal ADA review process. tionshavealsobeenshowntobecost- ical issues related to diabetes. They are effective (3). published in ADA journals and other scien- GRADING OF SCIENTIFIC EVIDENCE The ADA strives to improve and update tific/medical publications. ADA position Since the ADA first began publishing the Standards of Care to ensure that clini- statements are typically based on a sys- practice guidelines, there has been con- cians, health plans, and policy makers can tematic review or other review of pub- siderable evolution in the evaluation of continue to rely on them as the most au- lished literature. Position statements scientific evidence and in the develop- thoritative and current guidelines for di- undergo a formal review process. They ment of evidence-based guidelines. abetes care. are updated annually or as needed. In 2002, we developed a classification

“Standards of Medical Care in Diabetes” was originally approved in 1988. Most recent review/revision: October 2014. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. S2 Introduction Diabetes Care Volume 38, Supplement 1, January 2015

Table 1—ADA evidence-grading system for “Standards of Medical Care in Diabetes” recommendations have the best chance Level of of improving outcomes when applied to evidence Description the population to which they are appro- priate. Recommendations with lower A Clear evidence from well-conducted, generalizable randomized controlled trials that are adequately powered, including levels of evidence may be equally impor- c Evidence from a well-conducted multicenter trial tant but are not as well supported. c Evidence from a meta-analysis that incorporated quality ratings in the Of course, evidence is only one com- analysis ponent of clinical decision making. Clini- Compelling nonexperimental evidence; i.e., “all or none” rule developed by cians care for patients, not populations; the Centre for Evidence-Based Medicine at the University of Oxford guidelines must always be interpreted Supportive evidence from well-conducted randomized controlled trials that with the individual patient in mind. are adequately powered, including c Evidence from a well-conducted trial at one or more institutions Individual circumstances, such as co- c Evidence from a meta-analysis that incorporated quality ratings in the morbid and coexisting diseases, age, ed- analysis ucation, disability, and, above all, B Supportive evidence from well-conducted cohort studies patients’ values and preferences, must c Evidence from a well-conducted prospective cohort study or registry be considered and may lead to different c Evidence from a well-conducted meta-analysis of cohort studies treatment targets and strategies. Also, Supportive evidence from a well-conducted case-control study conventional evidence hierarchies, such C Supportive evidence from poorly controlled or uncontrolled studies as the one adapted by the ADA, may c Evidence from randomized clinical trials with one or more major or three miss nuances important in diabetes or more minor methodological flaws that could invalidate the results c Evidence from observational studies with high potential for bias (such as care. For example, although there is ex- case series with comparison with historical controls) cellent evidence from clinical trials sup- c Evidence from case series or case reports porting the importance of achieving Conflicting evidence with the weight of evidence supporting the multiple risk factor control, the optimal recommendation way to achieve this result is less clear. It E Expert consensus or clinical experience is difficult to assess each component of such a complex intervention.

system to grade the quality of scienti- and codify the evidence that forms the References fi c evidence supporting ADA recommen- basis for the recommendations. 1. Kaufman FR (Ed.). Medical Management of dations for all new and revised ADA ADA recommendations are assigned Type 1 Diabetes, 6th ed. Alexandria, VA, Amer- position statements. A recent analysis ratings of A, B,orC, depending on the ican Diabetes Association, 2012 of the evidence cited in the Standards quality of evidence. Expert opinion E is a 2. Burant CF (Ed.). Medical Management of Type 2 Diabetes of Care found steady improvement in separate category for recommendations , 7th ed. Alexandria, VA, Amer- ican Diabetes Association, 2012 quality over the past 10 years, with last in which there is no evidence from clin- 3. Li R, Zhang P, Barker LE, Chowdhury FM, year’s Standards for the first time having ical trials, in which clinical trials may Zhang X. Cost-effectiveness of interventions to the majority of bulleted recommenda- be impractical, or in which there is con- prevent and control diabetes mellitus: a system- tions supported by A-orB-level evi- flicting evidence. Recommendations atic review. Diabetes Care 2010;33:1872–1894 Table 1 A 4. Grant RW, Kirkman MS. Trends in the evi- dence (4). A grading system ( ) with an rating are based on large dence level for the American Diabetes Associa- developed by ADA and modeled after well-designed clinical trials or well- tion’s “Standards of Medical Care in Diabetes” existing methods was used to clarify done meta-analyses. Generally, these from 2005 to 2014. Diabetes Care 2015;38:6–8 RFSINLPATC COMMITTEE PRACTICE PROFESSIONAL Diabetes Care Volume 38, Supplement 1, January 2015 S3

Professional Practice Committee Diabetes Care 2015;38(Suppl. 1):S3 | DOI: 10.2337/dc15-S002

The Professional Practice Committee for human studies related to each sec- Edward W. Gregg, PhD; Silvio E. Inzucchi, (PPC) of the American Diabetes Associa- tion and published since 1 January 2014. MD; Mark E. Molitch, MD; John M. tion (ADA) is responsible for the “Stan- Recommendations were revised based Morton, MD; Robert E. Ratner, MD; dards of Medical Care in Diabetes” on new evidence or, in some cases, to Linda M. Siminerio, RN, PhD, CDE; and position statement, referred to as the clarify the prior recommendation or Katherine R. Tuttle, MD. “Standards of Care.” The PPC is a multidis- match the strength of the wording to ciplinary expert committee comprised of the strength of the evidence. A table link- Members of the PPC physicians, diabetes educators, registered ing the changes in recommendations to dietitians, and others who have expertise new evidence can be reviewed at http:// Richard W. Grant, MD, MPH (Chair)* in a range of areas, including adult and professional.diabetes.org/SOC. As for Thomas W. Donner, MD pediatric endocrinology, epidemiology, all position statements, the Standards Judith E. Fradkin, MD public health, lipid research, hypertension, of Care position statement was reviewed and preconception and pregnancy care. andapprovedbytheExecutiveCommittee Charlotte Hayes, MMSc, MS, RD, CDE, Appointment to the PPC is based on excel- of ADA’s Board of Directors, which in- ACSM CES lence in clinical practice and/or research. cludes health care professionals, scientists, William H. Herman, MD, MPH While the primary role of the PPC is to and lay people. William C. Hsu, MD review and update the Standards of Feedback from the larger clinical Eileen Kim, MD Care, it is also responsible for overseeing community was valuable for the 2015 the review and revisions of ADA’sposition revision of the Standards of Care. Read- Lori Laffel, MD, MPH statements and scientificstatements. ers who wish to comment on the Stan- Rodica Pop-Busui, MD, PhD All members of the PPC are required dards of Medical Care in Diabetesd2015 Neda Rasouli, MD* to disclose potential conflicts of interest are invited to do so at http://professional with industry and/or other relevant or- .diabetes.org/SOC. Desmond Schatz, MD ganizations. These disclosures are dis- The ADA funds development of the Joseph A. Stankaitis, MD, MPH* cussed at the onset of each Standards Standards of Care and all ADA position Tracey H. Taveira, PharmD, CDOE, of Care revision meeting. Members of statements out of its general revenues CVDOE the committee, their employer, and and does not use industry support for their disclosed conflicts of interest are these purposes. Deborah J. Wexler, MD* listed in the “Professional Practice Com- The PPC would like to thank the fol- *Subgroup leaders mittee for the Standards of Medical lowing individuals who provided their ex- Care in Diabetesd2015” table (see pertise in reviewing and/or consulting with ADA Staff p. S88). the committee: Donald R. Coustan, MD; For the current revision, PPC mem- Stephanie Dunbar, MPH, RD; Robert H. Jane L. Chiang, MD bers systematically searched MEDLINE Eckel, MD; Henry N. Ginsberg, MD; Erika Gebel Berg, PhD

© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. S4 Diabetes Care Volume 38, Supplement 1, January 2015

Standards of Medical Care in Diabetesd2015: SUMMARY OF REVISIONS Summary of Revisions Diabetes Care 2015;38(Suppl. 1):S4 | DOI: 10.2337/dc15-S003

GENERAL CHANGES Section 4. Foundations of Care: reflect evidence from randomized clinical Diabetes Care Supplement 1 was previ- Education, Nutrition, Physical Activity, trials. Lower diastolic targets may still be ously called Clinical Practice Recommen- Smoking Cessation, Psychosocial Care, appropriate for certain individuals. dations and included the “Standards of and Immunization Recommendations for statin treat- Medical Care in Diabetes” and key The physical activity section was revised ment and lipid monitoring were revised American Diabetes Association (ADA) to reflect evidence that all individuals, after consideration of 2013 American position statements. The supplement including those with diabetes, should College of Cardiology/American Heart has been renamed Standards of Medical be encouraged to limit the amount of Association guidelines on the treatment Care in Diabetes (“Standards”)and time they spend being sedentary by of blood cholesterol. Treatment initia- contains a single ADA position state- breaking up extended amounts of time tion (and initial statin dose) is now ment that provides evidence-based clin- (.90 min) spent sitting. driven primarily by risk status rather ical practice recommendations for Due to the increasing use of e-cigarettes, than LDL cholesterol level. diabetes care. the Standards were updated to make clear With consideration for the new Whereas the “Standards of Medical that e-cigarettes are not supported as an statin treatment recommendations, the Care in Diabetesd2015” should still alternative to smoking or to facilitate Standards now provide the following be viewed as a single document, it has smoking cessation. lipid monitoring guidance: a screening been divided into 14 sections, each in- Immunization recommendations were lipid profile is reasonable at diabetes di- dividually referenced, to highlight im- revisedtoreflect recent Centers for Disease agnosis, at an initial medical evaluation portant topic areas and to facilitate Control and Prevention guidelines re- and/or at age 40 years, and periodically navigation. garding PCV13 and PPSV23 vaccinations thereafter. The supplement now includes an in- in older adults. fi Section 9. Microvascular dex to help readers nd information on Section 6. Glycemic Targets particular topics. Complications and Foot Care The ADA now recommends a premeal To better target those at high risk for – SECTION CHANGES blood glucose target of 80 130 mg/dL, foot complications, the Standards em- – rather than 70 130 mg/dL, to better re- phasize that all patients with insensate Although the levels of evidence for sev- fl ect new data comparing actual average feet, foot deformities, or a history of eral recommendations have been up- glucose levels with A1C targets. dated, these changes are not included foot ulcers have their feet examined at To provide additional guidance on the every visit. below as the clinical recommendations successful implementation of continuous have remained the same. Changes in ev- glucose monitoring (CGM), the Standards C E Section 11. Children and Adolescents idence level from, for example, to are include new recommendations on assessing “ To reflect new evidence regarding the not noted below. The Standards of apatient’s readiness for CGM and on d ” risks and benefits of tight glycemic con- Medical Care in Diabetes 2015 con- providing ongoing CGM support. tains, in addition to many minor changes trol in children and adolescents with di- that clarify recommendations or reflect Section 7. Approaches to Glycemic abetes, the Standards now recommend , new evidence, the following more sub- Treatment a target A1C of 7.5% for all pediatric stantive revisions. The type 2 diabetes management algo- age-groups; however, individualization is rithm was updated to reflect all of the still encouraged. Section 2. Classification and currently available therapies for diabe- Diagnosis of Diabetes Section 12. Management of Diabetes tes management. The BMI cut point for screening over- in Pregnancy weight or obese Asian Americans for pre- Section 8. Cardiovascular Disease and This new section was added to the diabetes and type 2 diabetes was changed Risk Management Standards to provide recommendations to 23 kg/m2 (vs. 25 kg/m2)toreflect The recommended goal for diastolic related to pregnancy and diabetes, in- the evidence that this population is at an blood pressure was changed from 80 cluding recommendations regarding increased risk for diabetes at lower BMI mmHg to 90 mmHg for most people preconception counseling, , levels relative to the general population. with diabetes and hypertension to better blood glucose targets, and monitoring.

© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. Diabetes Care Volume 38, Supplement 1, January 2015 S5

1. Strategies for Improving Care American Diabetes Association

Diabetes Care 2015;38(Suppl. 1):S5–S7 | DOI: 10.2337/dc15-S004

Recommendations c A patient-centered communication style that incorporates patient prefer- ences, assesses literacy and numeracy, and addresses cultural barriers to care should be used. B c Treatment decisions should be timely and founded on evidence-based guide- lines that are tailored to individual patient preferences, prognoses, and comorbidities. B c Care should be aligned with components of the Chronic Care Model (CCM) to ensure productive interactions between a prepared proactive practice team and an informed activated patient. A OIINSTATEMENT POSITION c When feasible, care systems should support team-based care, community involvement, patient registries, and decision support tools to meet patient needs. B

DIABETES CARE CONCEPTS In the following sections, different components of the clinical management of patients with (or at risk for) diabetes are reviewed. We highlight the following three themes that are woven throughout these sections that clinicians, policymakers, and advocates should keep in mind:

1. Patient-Centeredness: Practice recommendations, whether based on evidence or expert opinion, are intended to guide an overall approach to care. The science and art of medicine come together when the clinician is faced with making treatment recom- mendations for a patient who would not have met eligibility criteria for the studies on which guidelines were based. Recognizing that one size does not fit all, these Standards provide guidance for when and how to adapt recommendations (e.g., see Section 10. Older Adults and Fig. 6.1. Approach to the Management of Hyperglycemia). Because patients with diabetes are also at greatly increased risk of cardiovascular disease, a patient-centered approach should include a comprehensive plan to reduce cardiovas- cular risk by addressing blood pressure and lipid control, smoking cessation, weight management, and healthy lifestyle changes that include adequate physical activity. 2. Diabetes Across the Life Span: An increasing proportion of patients with type 1 diabetes are adults. Conversely, and for less salutary reasons, the incidence of type 2 diabetes is increasing in children and young adults. Finally, patients both with type 1 diabetes and with type 2 diabetes are living well into older age, a stage of life for which there is little evidence from clinical trials to guide therapy. All these de- mographic changes highlight another challenge to high-quality diabetes care, which is the need to improve coordination between clinical teams as patients pass through different stages of the life span or the stages of pregnancy (preconception, preg- nancy, and postpartum). 3. Advocacy for Patients With Diabetes: Advocacy can be defined as active support and engagement to advance a cause or policy. Advocacy in the cause of improving the lives of patients with (or at risk for) diabetes is an ongoing need. Given the tremendous Suggested citation: American Diabetes Associa- toll that lifestyle factors such as obesity, physical inactivity, and smoking have on the tion. Strategies for improving care. Sec. 1. In Standards of Medical Care in Diabetesd2015. health of patients with diabetes, ongoing and energetic efforts are needed to address Diabetes Care 2015;38(Suppl. 1):S5–S7 and change the societal determinants at the root of these problems. Within the more © 2015 by the American Diabetes Association. narrow domain of clinical practice guidelines, the application of evidence level grading Readers may use this article as long as the work to practice recommendations can help identify areas that require more research is properly cited, the use is educational and not investment (1). This topic is explored in more depth in Section 14. Diabetes Advocacy. for profit, and the work is not altered. S6 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

CARE DELIVERY SYSTEMS to the care team), 5) community resources diabetes self-management education There has been steady improvement in the and policies (identifying or developing (DSME) has been shown to improve pa- proportion of diabetic patients achieving resources to support healthy lifestyles), tient self-management, satisfaction, and recommended levels of A1C, blood pres- and 6)healthsystems(tocreateaquality- glucose control (25,26), as has delivery of sure, and LDL cholesterol in the last 10 oriented culture). Redefining the roles ongoing diabetes self-management sup- years (2). The mean A1C nationally has of the clinic staff and promoting self- port (DSMS), so that gains achieved during declined from 7.6% in 1999–2002 to management on the part of the patient DSME are sustained (27–29). National 7.2% in 2007–2010 based on the National are fundamental to the successful imple- DSME standards call for an integrated ap- Health and Nutrition Examination Survey mentation of the CCM (8). Collaborative, proach that includes clinical content and (NHANES) data (E.W. Gregg, Centers for multidisciplinary teams are best suited to skills, behavioral strategies (goal setting, Disease Control and Prevention, personal provide care for people with chronic con- problem solving), and engagement with communication). This has been accompa- ditions such as diabetes and to facilitate emotional concerns in each needed curric- nied by improvements in lipids and blood patients’ self-management (9–12). ulum content area. pressure control and has led to substantial Key Objectives Objective 3: Change the Care System reductions in end-stage microvascular The National Diabetes Education Pro- An institutional priority in most successful complications in patients with diabetes. gram (NDEP) maintains an online resource care systems is providing a high quality of Nevertheless, between 33 and 49% of pa- (www.betterdiabetescare.nih.gov) to help care (30). Changes that have been shown tients still do not meet targets for glyce- health care professionals design and im- to increase quality of diabetes care in- mic, blood pressure, or cholesterol control, plement more effective health care de- clude basing care on evidence-based and only 14% meet targets for all three livery systems for those with diabetes. guidelines (19); expanding the role of measures and nonsmoking status (2). Evi- Three specific objectives, with refer- teams and staff and implementing more dence also suggests that progress in car- ences to literature that outlines practical intensive disease management strategies diovascular risk factor control (particularly strategies to achieve each, are delin- (6,22,31); redesigning the care process tobacco use) may be slowing (2,3). Certain eated below. (32); implementing electronic health re- patient groups, such as young adults and cord tools (33,34); activating and educat- Objective 1: Optimize Provider and Team patients with complex comorbidities, fi- ing patients (35,36); removing financial Behavior nancial or other social hardships, and/or barriers and reducing patient out-of- The care team should prioritize timely and limitedEnglishproficiency, may present pocket costs for diabetes education, eye appropriate intensification of lifestyle and/ particular challenges to goal-based care exams, self-monitoring of blood glucose, or pharmaceutical therapy for patients who (4–6). Persistent variation in quality of di- and necessary medications (6); and iden- have not achieved beneficial levels of blood abetes care across providers and across tifying/developing/engaging community pressure, lipid, or glucose control (13). practice settings even after adjusting for resources and public policy that support Strategies such as explicit goal setting patient factors indicates that there re- healthy lifestyles (37). Recent initiatives with patients (14); identifying and address- mains potential for substantial system- such as the Patient-Centered Medical ing language, numeracy, or cultural barriers levelimprovementsindiabetescare. Home show promise for improving out- to care (15–18); integrating evidence-based comes through coordinated primary care guidelines and clinical information tools Chronic Care Model and offer new opportunities for team- into the process of care (19–21); and incor- Although numerous interventions to im- based chronic disease care (38). Addi- porating care management teams including prove adherence to the recommended tional strategies to improve diabetes nurses, pharmacists, and other providers standards have been implemented, a ma- care include reimbursement structures (22–24) have each been shown to optimize jor barrier to optimal care is a delivery that, in contrast to visit-based billing, re- provider and team behavior and thereby system that too often is fragmented, lacks ward the provision of appropriate and catalyze reductions in A1C, blood pressure, clinical information capabilities, dupli- high-quality care (39), and incentives and LDL cholesterol. cates services, and is poorly designed that accommodate personalized care for the coordinated delivery of chronic Objective 2: Support Patient Behavior goals (6,40). care. The CCM has been shown to be an Change It is clear that optimal diabetes man- effective framework for improving the Successful diabetes care requires a sys- agement requires an organized, system- ’ quality of diabetes care (7). The CCM in- tematic approach to supporting patients atic approach and the involvement of a 1 cludes six core elements for the provision behavior change efforts, including ) coordinated team of dedicated health of optimal care of patients with chronic healthy lifestyle changes (physical activity, care professionals workinginanenvi- 1 disease: ) delivery system design (mov- healthy eating, tobacco cessation, weight ronment where patient-centered high- reactive proactive 2 ing from a to a care management, and effective coping), ) quality care is a priority (6). delivery system where planned visits disease self-management (taking and are coordinated through a team-based managing and, when clinically approach, 2) self-management support, appropriate, self-monitoring of glucose WHEN TREATMENT GOALS ARE 3) decision support (basing care on and blood pressure), and 3) prevention NOT MET evidence-based, effective care guide- of diabetes complications (self-monitoring Some patients and their health care pro- lines), 4) clinical information systems of foot health; active participation in viders may not achieve the desired (using registries that can provide patient- screening for eye, foot, and renal compli- treatment goals. Reassessing the treat- specific and population-based support cations; and immunizations). High-quality ment regimen may require evaluation of care.diabetesjournals.org Position Statement S7

barriers such as income, health literacy, a systematic review. Diabetes Care 2001;24: 26. Berikai P, Meyer PM, Kazlauskaite R, Savoy diabetes-related distress, depression, 1821–1833 B, Kozik K, Fogelfeld L. Gain in patients’ knowl- poverty, and competing demands, in- 11. Katon WJ, Lin EHB, Von Korff M, et al. Col- edge of diabetes management targets is associ- laborative care for patients with depression and ated with better glycemic control. Diabetes cluding those related to family respon- chronic illnesses. N Engl J Med 2010;363:2611– Care 2007;30:1587–1589 sibilities and dynamics. Other strategies 2620 27. Funnell MM, Brown TL, Childs BP, et al. Na- may include culturally appropriate and 12. Parchman ML, Zeber JE, Romero RR, Pugh tional standards for diabetes self-management enhanced DSME and DSMS, comanage- JA. Risk of coronary artery disease in type 2 di- education. Diabetes Care 2007;30:1630–1637 abetes and the delivery of care consistent with ment with a diabetes team, referral to a 28. Klein S, Sheard NF, Pi-Sunyer X, et al. the chronic care model in primary care settings: Weight management through lifestyle modifica- medical social worker for assistance a STARNet study. Med Care 2007;45:1129– tion for the prevention and management of with insurance coverage, medication- 1134 type 2 diabetes: rationale and strategies: a state- 13. Davidson MB. How our current medical taking behavior assessment, or change ment of the American Diabetes Association, the in pharmacological therapy. Initiation of care system fails people with diabetes: lack of timely, appropriate clinical decisions. Diabetes North American Association for the Study of or increase in self-monitoring of blood Care 2009;32:370–372 Obesity, and the American Society for Clinical glucose, continuous glucose monitoring, 14. Grant RW, Pabon-Nau L, Ross KM, Youatt EJ, Nutrition. Diabetes Care 2004;27:2067–2073 frequent patient contact, or referral to a Pandiscio JC, Park ER. Diabetes oral medication 29. Norris SL, Zhang X, Avenell A, et al. Efficacy mental health professional or physician initiation and intensification: patient views of pharmacotherapy for weight loss in adults with type 2 diabetes mellitus: a meta-analysis. with special expertise in diabetes may compared with current treatment guidelines. Diabetes Educ 2011;37:78–84 Arch Intern Med 2004;164:1395–1404 be useful. 15. Schillinger D, Piette J, Grumbach K, et al. 30. Tricco AC, Ivers NM, Grimshaw JM, et al. Closing the loop: physician communication Effectiveness of quality improvement strategies References with diabetic patients who have low health lit- on the management of diabetes: a systematic 1. Grant RW, Kirkman MS. Trends in the evi- eracy. Arch Intern Med 2003;163:83–90 review and meta-analysis. Lancet 2012;379: dence level for the American Diabetes Associ- 16. 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Long-term of top-performing practice sites. Ann Fam Med 18. Rothman R, Malone R, Bryant B, Horlen C, and recent progress in blood pressure levels 2007;5:233–241 DeWalt D, Pignone M. The relationship between among U.S. adults with diagnosed diabetes, 33. Reed M, Huang J, Graetz I, et al. Outpatient – literacy and glycemic control in a diabetes 1988-2008. Diabetes Care 2011;34:1579 1581 electronic health records and the clinical care 4. Kerr EA, Heisler M, Krein SL, et al. Beyond disease-management program. Diabetes Educ – and outcomes of patients with diabetes melli- comorbidity counts: how do comorbidity type 2004;30:263 273 ’ tus. Ann Intern Med 2012;157:482–489 and severity influence diabetes patients’ treat- 19. O Connor PJ, Bodkin NL, Fradkin J, et al. Di- abetes performance measures: current status 34. Cebul RD, Love TE, Jain AK, Hebert CJ. Elec- ment priorities and self-management? J Gen In- tronic health records and quality of diabetes tern Med 2007;22:1635–1640 and future directions. Diabetes Care 2011;34: – care. N Engl J Med 2011;365:825–833 5. Fernandez A, Schillinger D, Warton EM, et al. 1651 1659 20. Garg AX, Adhikari NK, McDonald H, et al. 35. Battersby M, Von Korff M, Schaefer J, et al. Language barriers, physician-patient language Effects of computerized clinical decision sup- Twelve evidence-based principles for implement- concordance, and glycemic control among in- port systems on practitioner performance and ing self-management support in primary care. Jt sured Latinos with diabetes: the Diabetes Study patient outcomes: a systematic review. JAMA Comm J Qual Patient Saf 2010;36:561–570 of Northern California (DISTANCE). J Gen Intern 2005;293:1223–1238 36. Grant RW, Wald JS, Schnipper JL, et al. Med 2011;26:170–176 21. Smith SA, Shah ND, Bryant SC, et al.; Evi- Practice-linked online personal health records 6. TRIAD Study Group. Health systems, pa- dens Research Group. Chronic care model and for type 2 diabetes mellitus: a randomized con- tients factors, and quality of care for diabetes: shared care in diabetes: randomized trial of an fi trolledtrial.ArchInternMed2008;168:1776– asynthesisof ndings from the TRIAD study. electronic decision support system. Mayo Clin Diabetes Care 2010;33:940–947 1782 Proc 2008;83:747–757 37. Pullen-Smith B, Carter-Edwards L, Leathers 7. Stellefson M, Dipnarine K, Stopka C. The 22. Jaffe MG, Lee GA, Young JD, Sidney S, Go chronic care model and diabetes management KH. Community health ambassadors: a mod- AS. Improved blood pressure control associated el for engaging community leaders to pro- in US primary care settings: a systematic review. with a large-scale hypertension program. JAMA mote better health in North Carolina. J Prev Chronic Dis 2013;10:E26 2013;310:699–705 Public Health Manag Pract 2008;14(Suppl.): 8. Coleman K, Austin BT, Brach C, Wagner EH. 23. Davidson MB, Ansari A, Karlan VJ. Effect of a S73–S81 Evidence on the Chronic Care Model in the new nurse-directed diabetes disease management 38. Bojadzievski T, Gabbay RA. Patient-centered millennium. Health Aff (Millwood) 2009;28:75– program on urgent care/emergency room visits 85 and hospitalizations in a minority population. medical home and diabetes. Diabetes Care 2011; – 9. Piatt GA, Anderson RM, Brooks MM, et al. 3- Diabetes Care 2007;30:224–227 34:1047 1053 year follow-up of clinical and behavioral im- 24. Stone RA, Rao RH, Sevick MA, et al. Active 39. Rosenthal MB, Cutler DM, Feder J. The ACO d provements following a multifaceted diabetes care management supported by home telemon- rules striking the balance between participa- care intervention: results of a randomized con- itoring in veterans with type 2 diabetes: the tion and transformative potential. N Engl J Med trolled trial. Diabetes Educ 2010;36:301–309 DiaTel randomized controlled trial. Diabetes 2011;365:e6 10. Renders CM, Valk GD, Griffin SJ, Wagner EH, Care 2010;33:478–484 40. Washington AE, Lipstein SH. The Patient- Eijk Van JT, Assendelft WJ. Interventions to im- 25. Duncan I, Birkmeyer C, Coughlin S, Li QE, Centered Outcomes Research Instituted prove the management of diabetes in primary Sherr D, Boren S. Assessing the value of diabetes promoting better information, decisions, and care, outpatient, and community settings: education. Diabetes Educ 2009;35:752–760 health. N Engl J Med 2011;365:e31 S8 Diabetes Care Volume 38, Supplement 1, January 2015

2. Classification and Diagnosis of American Diabetes Association Diabetes Diabetes Care 2015;38(Suppl. 1):S8–S16 | DOI: 10.2337/dc15-S005

CLASSIFICATION Diabetes can be classified into the following general categories:

1. Type 1 diabetes (due to b-cell destruction, usually leading to absolute deficiency) 2. Type 2 diabetes (due to a progressive insulin secretory defect on the background of ) 3. Gestational diabetes mellitus (GDM) (diabetes diagnosed in the second or third trimester of pregnancy that is not clearly overt diabetes) 4. Specific types of diabetes due to other causes, e.g., monogenic diabetes syndromes (such as and maturity-onset diabetes of the young [MODY]), dis- eases of the exocrine pancreas (such as cystic fibrosis), and drug- or chemical-induced diabetes (such as in the treatment of HIV/AIDS or after organ transplantation)

This section reviews most common forms of diabetes but is not comprehensive.

POSITION STATEMENT For additional information, see the American Diabetes Association (ADA) position statement “Diagnosis and Classification of Diabetes Mellitus” (1). Assigning a type of diabetes to an individual often depends on the circumstances present at the time of diagnosis, with individuals not necessarily fitting clearly into a single category. For example, some patients cannot be clearly classified as having type 1 or type 2 diabetes. Clinical presentation and disease progression may vary considerably in both types of diabetes. The traditional paradigms of type 2 diabetes occurring only in adults and type 1 diabetes only in children are no longer accurate, as both diseases occur in both cohorts. Occasionally, patients with type 2 diabetes may present with (DKA). Children with type 1 diabetes typically present with the hallmark symptoms of polyuria/polydipsia and occasionally with DKA. The onset of type 1 diabetes may be variable in adults and may not present with the classic symptoms seen in children. However, difficulties in diagnosis may occur in children, adolescents, and adults, with the true diagnosis becoming more obvious over time. DIAGNOSTIC TESTS FOR DIABETES Diabetes may be diagnosed based on A1C criteria or plasma glucose criteria, either the fasting plasma glucose (FPG) or the 2-h plasma glucose (2-h PG) value after a 75-g oral (OGTT) (1,2) (Table 2.1). The same tests are used to both screen for and diagnose diabetes. Diabetes may be identified anywhere along the spectrum of clinical scenarios: in seemingly low- risk individuals who happen to have glucose testing, in symptomatic patients, and in higher-risk individuals whom the provider tests because of a suspicion of diabetes. The same tests will also detect individuals with prediabetes. A1C The A1C test should be performed using a method that is certified by the NGSP and standardized or traceable to the Diabetes Control and Complications Trial (DCCT) Suggested citation: American Diabetes Association. reference assay. Although point-of-care (POC) A1C assays may be NGSP certified, Classification and diagnosis of diabetes. Sec. 2. fi In Standards of Medical Care in Diabetesd2015. pro ciency testing is not mandated for performing the test, so use of POC assays for Diabetes Care 2015;38(Suppl. 1):S8–S16 diagnostic purposes may be problematic and is not recommended. © 2015 by the American Diabetes Association. The A1C has several advantages to the FPG and OGTT, including greater conve- Readers may use this article as long as the work nience (fasting not required), greater preanalytical stability, and less day-to-day is properly cited, the use is educational and not perturbations during stress and illness. These advantages must be balanced by for profit, and the work is not altered. care.diabetesjournals.org Position Statement S9

Table 2.1—Criteria for the diagnosis Hemoglobinopathies/Anemias FPG (,126 mg/dL [7.0 mmol/L]), that of diabetes Interpreting A1C levels in the presence of person should nevertheless be consid- A1C $6.5%. The test should be performed certain hemoglobinopathies and anemia ered to have diabetes. in a laboratory using a method that is may be problematic. For patients with an Since all the tests have preanalytic and NGSP certified and standardized to the abnormal hemoglobin but normal red cell analytic variability, it is possible that an ab- DCCT assay.* turnover, such as those with the sickle cell normal result (i.e., above the diagnostic OR trait, an A1C assay without interference threshold), when repeated, will produce FPG $126 mg/dL (7.0 mmol/L). Fasting is from abnormal hemoglobins should be a value below the diagnostic cut point. fi de ned as no caloric intake for at least used. An updated list of interferences is This scenario is least likely for A1C, more 8h.* available at www.ngsp.org/interf.asp. In likely for FPG, and most likely for the 2-h OR conditions associated with increased red PG, especially if the glucose samples are $ 2-h PG 200 mg/dL (11.1 mmol/L) during cell turnover, such as pregnancy (second collected at room temperature and not an OGTT. The test should be performed and third trimesters), recent blood loss as described by the WHO, using centrifuged promptly. Barring labora- a glucose load containing the or transfusion, erythropoietin therapy, tory error, such patients will likely equivalent of 75 g anhydrous glucose or hemolysis, only blood glucose criteria have test results near the margins of dissolved in water.* should be used to diagnose diabetes. the diagnostic threshold. The health OR care professional should follow the In a patient with classic symptoms of Fasting and 2-Hour Plasma Glucose patient closely and repeat the test in hyperglycemia or hyperglycemic crisis, In addition to the A1C test, the FPG and 3–6months. a random plasma glucose $200 mg/dL 2-h PG may also be used to diagnose diabe- (11.1 mmol/L). tes (Table 2.1). The concordance between CATEGORIES OF INCREASED RISK *In the absence of unequivocal the FPG and 2-h PG tests is imperfect, as FOR DIABETES (PREDIABETES) fi hyperglycemia, results should be con rmed is the concordance between A1C and ei- by repeat testing. ther glucose-based test. National Health Recommendations and Nutrition Examination Survey c Testing to assess risk for future di- (NHANES) data indicate that an A1C cut abetes in asymptomatic people point of $6.5% identifies one-third greater cost, the limited availability of should be considered in adults of fewer cases of undiagnosed diabetes A1C testing in certain regions of the any age who are overweight or than a fasting glucose cut point of developing world, and the incomplete obese (BMI $25 kg/m2 or $23 $126 mg/dL (7.0 mmol/L) (9). Numer- correlation between A1C and average kg/m2 in Asian Americans) and ous studies have confirmed that, com- glucose in certain individuals. who have one or more additional pared with these A1C and FPG cut It is important to take age, race/ risk factors for diabetes. For all points, the 2-h PG value diagnoses ethnicity, and anemia/hemoglobinopathies patients, particularly those who more people with diabetes. Of note, into consideration when using the A1C to are overweight or obese, testing the lower sensitivity of A1C at the desig- diagnose diabetes. should begin at age 45 years. B nated cut point may be offset by the c If tests are normal, repeat testing Age test’s ease of use and facilitation of carried out at a minimum of 3- The epidemiological studies that formed more widespread testing. year intervals is reasonable. C the framework for recommending A1C Unless there is a clear clinical diagno- c To test for prediabetes, the A1C, to diagnose diabetes only included adult sis (e.g., a patient in a hyperglycemic FPG, and 2-h PG after 75-g OGTT populations. Therefore, it remains un- crisis or with classic symptoms of hyper- are appropriate. B clear if A1C and the same A1C cut point glycemia and a random plasma glucose c In patients with prediabetes, iden- should be used to diagnose diabetes in $200 mg/dL), it is recommended that – tify and, if appropriate, treat other children and adolescents (3 5). the same test be repeated immediately cardiovascular disease (CVD) risk Race/Ethnicity using a new blood sample for confirma- factors. B A1C levels may vary with patients’ race/ tion because there will be a greater like- c Testing to detect prediabetes ethnicity (6,7). For example, African lihood of concurrence. For example, if should be considered in children Americans may have higher A1C levels the A1C is 7.0% and a repeat result is and adolescents who are over- than non-Hispanic whites despite simi- 6.8%, the diagnosis of diabetes is con- weight or obese and who have lar fasting and postglucose load glucose firmed. If two different tests (such as two or more additional risk factors levels. A recent epidemiological study A1C and FPG) are both above the diagnos- for diabetes. E found that, when matched for FPG, tic threshold, this also confirms the diag- African Americans (with and without di- nosis. On the other hand, if a patient has abetes) had higher A1C levels than non- discordant results from two different Description Hispanic whites, but also had higher levels tests, then the test result that is above In 1997 and 2003, the Expert Commit- of and glycated albumin the diagnostic cut point should be re- teeonDiagnosisandClassification of and lower levels of 1,5-anhydroglucitol, peated. The diagnosis is made on the ba- Diabetes Mellitus (10,11) recognized a suggesting that their glycemic burden sis of the confirmed test. For example, if a group of individuals whose glucose lev- (particularly postprandially) may be patient meets the diabetes criterion of els did not meet the criteria for diabetes higher (8). the A1C (two results $6.5%), but not but were too high to be considered S10 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

Table 2.2—Criteria for testing for diabetes or prediabetes in asymptomatic adults TYPE 1 DIABETES 1. Testing should be considered in all adults who are overweight (BMI $25 kg/m2 or $23 kg/m2 in Asian Americans) and have additional risk factors: Recommendation c physical inactivity c Inform the relatives of patients with c first-degree relative with diabetes type 1 diabetes of the opportunity c high-risk race/ethnicity (e.g., African American, Latino, Native American, Asian to be tested for type 1 diabetes risk, American, Pacific Islander) but only in the setting of a clinical c . women who delivered a baby weighing 9 lb or were diagnosed with GDM research study. E c hypertension ($140/90 mmHg or on therapy for hypertension) c , . HDL cholesterol level 35 mg/dL (0.90 mmol/L) and/or a triglyceride level 250 mg/dL Immune-Mediated Diabetes (2.82 mmol/L) “ c women with polycystic ovary syndrome This form, previously called insulin- c A1C $5.7%, IGT, or IFG on previous testing dependent diabetes” or “juvenile-onset c other clinical conditions associated with insulin resistance (e.g., severe obesity, diabetes,” accounts for 5–10% of diabetes acanthosis nigricans) and is due to cellular-mediated autoimmune c history of CVD destruction of the pancreatic b-cells. 2. For all patients, particularly those who are overweight or obese, testing should Autoimmune markers include islet cell begin at age 45 years. autoantibodies, autoantibodies to insu- 3. If results are normal, testing should be repeated at a minimum of 3-year intervals, with lin, autoantibodies to GAD (GAD65), consideration of more frequent testing depending on initial results (e.g., those with autoantibodies to the tyrosine phospha- prediabetes should be tested yearly) and risk status. tases IA-2 and IA-2b, and autoantibodies to zinc transporter 8 (ZnT8). Type 1 di- abetes is defined by the presence of one normal. “Prediabetes” is the term used 9to25%).AnA1Crangeof6.0–6.5% or more of these autoimmune markers. for individuals with impaired fasting had a 5-year risk of developing diabe- The disease has strong HLA associations, glucose (IFG) and/or impaired glucose tes between 25–50% and a relative risk with linkage to the DQA and DQB genes. tolerance (IGT) and indicates an in- 20 times higher compared with an A1C These HLA-DR/DQ alleles can be either creased risk for the future develop- of 5.0% (12). In a community-based predisposing or protective. ment of diabetes. IFG and IGT should study of African American and non- Therateofb-cell destruction is quite not be viewed as clinical entities in Hispanic white adults without diabetes, variable, being rapid in some individuals their own right but rather risk factors baseline A1C was a stronger predictor (mainly infants and children) and slow in for diabetes (Table 2.2)andCVD.IFG of subsequent diabetes and cardiovas- others (mainly adults). Children and and IGT are associated with obesity cular events than fasting glucose (13). adolescents may present with ketoaci- (especially abdominal or visceral obe- Other analyses suggest that an A1C of dosis as the first manifestation of the sity), dyslipidemia with high triglycer- 5.7% is associated with a diabetes risk disease. Others have modest fasting hy- ides and/or low HDL cholesterol, and similar to that of the high-risk partici- perglycemia that can rapidly change to hypertension. pants in the Diabetes Prevention Pro- severe hyperglycemia and/or ketoacido- gram (DPP) (14). sis with or other stress. Adults Diagnosis Hence, it is reasonable to consider an may retain sufficient b-cell function to In 1997 and 2003, the Expert Commit- A1C range of 5.7–6.4% as identifying in- prevent ketoacidosis for many years; tee on Diagnosis and Classification of dividuals with prediabetes. As with those such individuals eventually become de- Diabetes Mellitus (10,11) defined IFG with IFG and/or IGT, individuals with an pendent on insulin for survival and are as FPG levels 100–125 mg/dL (5.6–6.9 A1C of 5.7–6.4% should be informed of at risk for ketoacidosis. At this latter mmol/L) and IGT as 2-h PG after 75-g their increased risk for diabetes and CVD stage of the disease, there is little or OGTT levels 140–199 mg/dL (7.8–11.0 and counseled about effective strategies no insulin secretion, as manifested by mmol/L). It should be noted that the to lower their risks (see Section 5. Preven- low or undetectable levels of plasma WorldHealthOrganization(WHO)and tion or Delay of Type 2 Diabetes). Similar C-peptide. Immune-mediated diabetes numerous diabetes organizations de- to glucose measurements, the continuum fine the IFG cutoff at 110 mg/dL (6.1 of risk is curvilinear, so as A1C rises, the mmol/L). diabetes risk rises disproportionately Table 2.3—Categories of increased risk As with the glucose measures, sev- (12). Aggressive interventions and vigilant for diabetes (prediabetes)* eral prospective studies that used A1C follow-up should be pursued for those FPG 100 mg/dL (5.6 mmol/L) to 125 mg/dL to predict the progression to diabetes considered at very high risk (e.g., those (6.9 mmol/L) (IFG) demonstrated a strong, continuous with A1C .6.0%). OR association between A1C and sub- Table 2.3 summarizes the categories 2-h PG in the 75-g OGTT 140 mg/dL (7.8 sequent diabetes. In a systematic re- of prediabetes. For recommendations mmol/L) to 199 mg/dL (11.0 mmol/L) (IGT) view of 44,203 individuals from 16 regarding risk factors and screening for OR cohort studies with a follow-up interval prediabetes, see p. S12 (“Testing for A1C 5.7–6.4% averaging 5.6 years (range 2.8–12 Type 2 Diabetes and Prediabetes in *For all three tests, risk is continuous, years), those with an A1C between Asymptomatic Adults” and “Testing for extending below the lower limit of the range 5.5–6.0% had a substantially increased Type 2 Diabetes and Prediabetes in Chil- and becoming disproportionately greater at higher ends of the range. risk of diabetes (5-year incidence from dren and Adolescents”). care.diabetesjournals.org Position Statement S11

commonly occurs in childhood and ado- children who developed more than two c Testing to detect type 2 diabetes lescence, but it can occur at any age, autoantibodies, nearly 70% developed should be considered in children even in the 8th and 9th decades of life. type 1 diabetes within 10 years and 84% andadolescentswhoareover- b fi Autoimmune destruction of -cells has within 15 years (16,18). These ndings are weight or obese and who have fi multiple genetic predispositions and is highly signi cant because, while the Ger- two or more additional risk factors also related to environmental factors man group was recruited from offspring for diabetes. E that are still poorly defined. Although pa- of parents with type 1 diabetes, the Finn- tients are not typically obese when they ish and American groups were recruited present with type 1 diabetes, obesity from the general population. Remark- Description should not preclude the diagnosis. These ably, the findings in all three groups This form, previously referred to as “non- patients are also prone to other autoim- were the same, suggesting that the insulin-dependent diabetes” or “adult- mune disorders such as Graves’ disease, same sequence of events led to clinical onset diabetes,” accounts for ;90–95% Hashimoto’s thyroiditis, Addison’sdis- disease in both “sporadic” and genetic of all diabetes. Type 2 diabetes encom- ease, vitiligo, celiac disease, autoimmune cases of type 1 diabetes. passes individuals who have insulin resis- hepatitis, myasthenia gravis, and perni- While there is currently a lack of tance and usually relative (rather than cious anemia. accepted screening programs, one absolute) insulin deficiency. At least ini- should consider referring relatives of tially, and often throughout their lifetime, Idiopathic Diabetes those with type 1 diabetes for antibody these individuals may not need insulin Some forms of type 1 diabetes have no testing for risk assessment in the treatment to survive. known etiologies. These patients have per- setting of a clinical research study There are various causes of type 2 di- manent insulinopenia and are prone to (http://www2.diabetestrialnet.org). abetes. Although the specificetiologies ketoacidosis, but have no evidence of au- Widespread clinical testing of asymptom- are not known, autoimmune destruc- toimmunity. Although only a minority of atic low-risk individuals is not currently tion of b-cells does not occur, and pa- patients with type 1 diabetes fall into this recommended due to lack of approved tients do not have any of the other category, of those who do, most are of therapeutic interventions. Higher-risk in- known causes of diabetes. Most, but African or Asian ancestry. Individuals dividuals may be tested, but only in the not all, patients with type 2 diabetes with this form of diabetes suffer from ep- context of a clinical research setting. In- are obese. Obesity itself causes some isodic ketoacidosis and exhibit varying dividuals who test positive will be coun- degree of insulin resistance. Patients fi degrees of insulin de ciency between epi- seled about the risk of developing who are not obese by traditional weight sodes. This form of diabetes is strongly diabetes, diabetes symptoms, and DKA criteria may have an increased percent- inherited, lacks immunological evidence prevention. Numerous clinical studies age of body fat distributed predomi- b for -cell autoimmunity, and is not HLA are being conducted to test various meth- nantly in the abdominal region. associated. An absolute requirement for ods of preventing type 1 diabetes in Ketoacidosis seldom occurs sponta- insulin replacement therapy in affected those with evidence of autoimmunity neously in type 2 diabetes; when seen, patients may come and go. (www.clinicaltrials.gov). it usually arises in association with Testing for Type 1 Diabetes the stress of another illness such as in- The incidence and prevalence of type 1 TYPE 2 DIABETES fection. Type 2 diabetes frequently goes diabetes is increasing (15). Type 1 dia- undiagnosed for many years because hy- betic patients often present with acute Recommendations perglycemia develops gradually and at symptoms of diabetes and markedly ele- c Testing to detect type 2 diabetes earlier stages is often not severe enough vated blood glucose levels, and some are in asymptomatic people should for the patient to notice the classic di- diagnosedwithlife-threateningketo- be considered in adults of any abetes symptoms. Nevertheless, such acidosis. Several studies suggest that mea- age who are overweight or patients are at an increased risk of obese (BMI $25 kg/m2 or $23 suring islet autoantibodies in relatives of 2 developing macrovascular and micro- those with type 1 diabetes may identify kg/m in Asian Americans) and vascular complications. individuals who are at risk for developing who have one or more addi- Whereaspatientswithtype2diabetes type 1 diabetes. Such testing, coupled tional risk factors for diabetes. may have insulin levels that appear nor- with education about diabetes symptoms For all patients, particularly mal or elevated, the higher blood glucose and close follow-up in an observational those who are overweight or levels in these patients would be expected clinical study, may enable earlier identifi- obese, testing should begin at to result in even higher insulin values had B cation of type 1 diabetes onset. There is age 45 years. their b-cell function been normal. Thus, evidence to suggest that early diagnosis c If tests are normal, repeat testing insulin secretion is defective in these pa- may limit acute complications (16) and carried out at a minimum of 3-year tients and insufficient to compensate for C extend long-term endogenous insulin intervals is reasonable. insulin resistance. Insulin resistance may production (17). c To test for diabetes, the A1C, FPG, improve with weight reduction and/or A recent study reported the risk of pro- and 2-h PG after 75-g OGTT are pharmacological treatment of hyper- B gression to type 1 diabetes from the time appropriate. glycemia but is seldom restored to normal. of seroconversion to autoantibody posi- c In patients with diabetes, identify The risk of developing type 2 diabetes tivity in three pediatric cohorts from Fin- and, if appropriate, treat other increases with age, obesity, and lack of B land, Germany, and the U.S. Of the 585 CVD risk factors. physical activity. It occurs more frequently S12 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

in women with prior GDM, in those with beginning at age 30 or 45 years and Diagnostic Tests hypertension or dyslipidemia, and in cer- independent of risk factors, may be The A1C, FPG, and 2-h PG after 75-g OGTT tain racial/ethnic subgroups (African cost-effective (,$11,000 per quality- are appropriate for testing. It should be American, American Indian, Hispanic/ adjusted life-year gained) (20). noted that the tests do not necessarily Latino, and Asian American). It is often Additional considerations regarding detect diabetes in the same individuals. associated with a strong genetic predis- testing for type 2 diabetes and predia- The efficacy of interventions for primary position, more so than type 1 diabetes. betes in asymptomatic patients include prevention of type 2 diabetes (26–32) has However, the genetics of type 2 diabetes the following: primarily been demonstrated among in- dividuals with IGT, not for individuals with is poorly understood. Age isolated IFG or for those with prediabetes Testing recommendations for diabetes in defined by A1C criteria. Testing for Type 2 Diabetes and asymptomatic adults are listed in Table Prediabetes in Asymptomatic Adults 2.2. Age is a major risk factor for diabetes. Testing Interval Prediabetes and diabetes meet criteria for Testing should begin at age 45 years for all The appropriate interval between tests is conditions in which early detection is ap- patients, particularly those who are over- not known (33). The rationale for the propriate. Both conditions are common weight or obese. 3-year interval is that with this interval, and impose significant clinical and public the number of false-positive tests that re- BMI and Ethnicity health burdens. There is often a long pre- quire confirmatory testing will be reduced Testingshouldbeconsideredinadults symptomatic phase before the diagnosis and individuals with false-negative tests of any age with BMI $25 kg/m2 and one of type 2 diabetes. Simple tests to detect will be retested before substantial time or more additional risk factors for dia- preclinical disease are readily available. elapses and complications develop (33). The duration of glycemic burden is a strong betes. However, recent data (21) and predictor of adverse outcomes. There are evidence from the ADA position state- Community Screening “ effective interventions that prevent pro- ment BMI Cut Points to Identify At-Risk Ideally, testing should be carried out gression from prediabetes to diabetes Asian Americans for Type 2 Diabetes within a health care setting because of ” (see Section 5. Prevention or Delay of Screening (22)suggestthattheBMI the need for follow-up and treatment. Type 2 Diabetes) and reduce the risk cut point should be lower for the Asian Community testing outside a health care of diabetes complications (see Section American population. For diabetes setting is not recommended because peo- 8. Cardiovascular Disease and Risk screening purposes, the BMI cut points ple with positive tests may not seek, or – 2 Management and Section 9. Microvas- fall consistently between 23 24 kg/m have access to, appropriate follow-up test- cular Complications and Foot Care). (sensitivity of 80%) for nearly all Asian ing and care. Community testing may also Approximately one-quarter of people American subgroups (with levels slightly be poorly targeted; i.e., it may fail to reach with diabetes in the U.S. are undiag- lower for Japanese Americans). This the groups most at risk and inappropri- 2 nosed. Although screening of asymptom- makes a rounded cut point of 23 kg/m ately test those at very low risk or even atic individuals to identify those with practical. In determining a single BMI those who have already been diagnosed. prediabetes or diabetes might seem rea- cut point, it is important to balance sen- fi sonable, rigorous clinical trials to prove sitivity and speci city so as to provide a Testing for Type 2 Diabetes and the effectiveness of such screening have valuable screening tool without numer- Prediabetes in Children and not been conducted and are unlikely to ous false positives. An argument can be Adolescents occur. A large European randomized con- made to push the BMI cut point to lower 2 In the last decade, the incidence and prev- trolled trial compared the impact of than 23 kg/m in favor of increased alence of type 2 diabetes in adolescents has screening for diabetes and intensive sensitivity; however, this would lead increased dramatically, especially in ethnic fi multifactorial intervention with that of to an unacceptably low speci city populations (15). Recent studies question screening and routine care (19). General (13.1%). Data from the WHO also sug- the validity of A1C in the pediatric popula- $ 2 practice patients between the ages of gest that a BMI 23 kg/m should be tion, especially among certain ethnicities, fi 40–69 years were screened for diabetes used to de ne increased risk in Asian and suggest OGTT or FPG as more suitable and randomized by practice to intensive Americans (23). diagnostic tests (34). However, many of treatment of multiple risk factors or rou- Evidence also suggests that other these studies do not recognize that diabe- fi tine diabetes care. After 5.3 years of populations may bene tfromlower tes diagnostic criteria are based on long- follow-up, CVD risk factors were modestly BMI cut points. For example, in a large term health outcomes, and validations are but significantly improved with intensive multiethnic cohort study, for an equiv- not currently available in the pediatric pop- treatment compared with routine care, alent incidence rate of diabetes, a BMI 2 ulation (35). The ADA acknowledges the but the incidence of first CVD events or of 30 kg/m in non-Hispanic whites was limited data supporting A1C for diagnosing 2 mortality was not significantly different equivalent to a BMI of 26 kg/m in Afri- diabetes in children and adolescents. How- between the groups (19). The excellent can Americans (24). ever, aside from rare instances, such as cys- care provided to patients in the routine Medications tic fibrosis and hemoglobinopathies, the care group and the lack of an unscreened Certain medications, such as glucocorti- ADA continues to recommend A1C in this control arm limit our ability to prove coids, thiazide diuretics, and atypical anti- cohort (36,37). The modified recommenda- that screening and early intensive treat- psychotics (25), are known to increase the tions of the ADA consensus report “Type 2 ment impact outcomes. Mathematical risk of diabetes and should be considered Diabetes in Children and Adolescents” are modeling studies suggest that screening, when ascertaining a diagnosis. summarized in Table 2.4. care.diabetesjournals.org Position Statement S13

Table 2.4—Testing for type 2 diabetes or The ongoing epidemic of obesity and points for GDM as the average glucose prediabetes in asymptomatic children* diabetes has led to more type 2 diabetes values (fasting, 1-h, and 2-h PG) in the Criteria in women of childbearing age, resulting in HAPO study at which odds for adverse c Overweight (BMI .85th percentile an increase in the number of pregnant outcomes reached 1.75 times the esti- for age and sex, weight for height women with undiagnosed type 2 diabetes mated odds of these outcomes at the . . 85th percentile, or weight 120% (38). Because of the number of pregnant mean glucose levels of the study popu- of ideal for height) women with undiagnosed type 2 diabe- lation. This one-step strategy was an- Plus any two of the following risk factors: fi c tes, it is reasonable to test women with ticipated to signi cantly increase the Family history of type 2 diabetes in Table 2.2 – ; – first- or second-degree relative risk factors for type 2 diabetes ( ) incidence of GDM (from 5 6% to 15 c Race/ethnicity (Native American, at their initial prenatal visit, using stan- 20%), primarily because only one abnormal African American, Latino, Asian dard diagnostic criteria (Table 2.1). value, not two, became sufficient to make American, Pacific Islander) Women with diabetes in the first trimes- the diagnosis. The ADA recognized that the c Signs of insulin resistance or ter would be classified as having type 2 anticipated increase in the incidence of conditions associated with insulin diabetes. GDM is diabetes diagnosed in GDM would have significant impact on resistance (acanthosis nigricans, the second or third trimester of preg- the costs, medical infrastructure capacity, hypertension, dyslipidemia, “ polycystic ovary syndrome, or small- nancy that is not clearly overt diabetes. and potential for increased medicaliza- for-gestational-age birth weight) tion” of pregnancies previously catego- c Maternal or GDM Diagnosis rized as normal, but recommended these during the child’s gestation GDM carries risks for the mother and diagnostic criteria changes in the context Age of initiation: age 10 years or at onset neonate. Not all adverse outcomes are of worrisome worldwide increases in obe- of puberty, if puberty occurs at a of equal clinical importance. The Hyper- sity and diabetes rates with the intent of younger age glycemia and Adverse Pregnancy Out- optimizing gestational outcomes for Frequency: every 3 years come (HAPO) study (39), a large-scale women and their offspring. *Persons aged #18 years. (;25,000 pregnant women) multina- The expected benefits to these preg- tional cohort study, demonstrated that nancies and offspring are inferred from risk of adverse maternal, fetal, and neo- intervention trials that focused on GESTATIONAL DIABETES MELLITUS natal outcomes continuously increased women with lower levels of hyperglyce- as a function of maternal glycemia at mia than identified using older GDM di- Recommendations 24–28 weeks, even within ranges previ- agnostic criteria and that found modest c Test for undiagnosed type 2 diabe- ously considered normal for pregnancy. benefits including reduced rates of large- tes at the first prenatal visit in For most complications, there was no for-gestational-age births and preeclamp- those with risk factors, using stan- threshold for risk. These results have sia (42,43). It is important to note that dard diagnostic criteria. B led to careful reconsideration of the di- 80–90% of women being treated for c Test for GDM at 24–28 weeks of ges- agnostic criteria for GDM. GDM diagno- mild GDM in two randomized controlled tation in pregnant women not pre- sis (Table 2.5) can be accomplished with trials (whose glucose values overlapped viously known to have diabetes. A either of two strategies: with the thresholds recommended by c Screen women with GDM for per- the IADPSG) could be managed with life- sistent diabetes at 6–12 weeks 1. “One-step” 75-g OGTT or style therapy alone. Data are lacking on postpartum, using the OGTT and 2. “Two-step” approach with a 50-g how the treatment of lower levels of hy- clinically appropriate nonpreg- (nonfasting) screen followed by a perglycemia affects a mother’s risk for nancy diagnostic criteria. E 100-g OGTT for those who screen the development of type 2 diabetes in c WomenwithahistoryofGDM positive the future and her offspring’sriskfor should have lifelong screening for obesity, diabetes, and other metabolic the development of diabetes or Different diagnostic criteria will identify dysfunction. Additional well-designed prediabetes at least every 3 years. B different degrees of maternal hypergly- clinical studies are needed to determine c WomenwithahistoryofGDM cemia and maternal/fetal risk, leading the optimal intensity of monitoring and found to have prediabetes should some experts to debate, and disagree treatment of women with GDM diag- receive lifestyle interventions or on, optimal strategies for the diagnosis nosed by the one-step strategy. metformin to prevent diabetes. A of GDM. Two-Step Strategy Definition One-Step Strategy In 2013, the National Institutes of Health For many years, GDM was defined as In the 2011 Standards of Care (40), the (NIH) convened a consensus develop- any degree of glucose intolerance that ADA for the first time recommended ment conference on diagnosing GDM. was first recognized during pregnancy that all pregnant women not known to The 15-member panel had representatives (10), regardless of whether the condi- have prior diabetes undergo a 75-g from obstetrics/gynecology, maternal- tion may have predated the pregnancy OGTT at 24–28 weeks of gestation, fetal medicine, pediatrics, diabetes re- or persisted after the pregnancy. This basedonarecommendationoftheIn- search, biostatistics, and other related definition facilitated a uniform strategy ternational Association of the Diabetes fields to consider diagnostic criteria (44). for detection and classification of GDM, and Pregnancy Study Groups (IADPSG) The panel recommended the two-step but it was limited by imprecision. (41). The IADPSG defined diagnostic cut approach of screening with a 1-h 50-g S14 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

Table 2.5—Screening for and diagnosis of GDM of diabetes are frequently characterized One-step strategy by onset of hyperglycemia at an early age Perform a 75-g OGTT, with plasma glucose measurement when patient is fasting and at 1 and (generally before age 25 years). 2h,at24–28 weeks of gestation in women not previously diagnosed with overt diabetes. Neonatal Diabetes The OGTT should be performed in the morning after an overnight fast of at least 8 h. Diabetes diagnosed in the first 6 months of The diagnosis of GDM is made when any of the following plasma glucose values are met or exceeded: life has been shown not to be typical au- c Fasting: 92 mg/dL (5.1 mmol/L) toimmune type 1 diabetes. This so-called c 1 h: 180 mg/dL (10.0 mmol/L) neonatal diabetes can either be transient c 2 h: 153 mg/dL (8.5 mmol/L) or permanent. The most common genetic Two-step strategy defect causing transient disease is a defect Step 1: Perform a 50-g GLT (nonfasting), with plasma glucose measurement at 1 h, at 24–28 on ZAC/HYAMI imprinting, whereas weeks of gestation in women not previously diagnosed with overt diabetes. permanent neonatal diabetes is most If the plasma glucose level measured 1 h after the load is $140 mg/dL* (7.8 mmol/L), proceed commonly a defect in the gene encoding to a 100-g OGTT. the Kir6.2 subunit of the b-cell KATP chan- Step 2: The 100-g OGTT should be performed when the patient is fasting. nel. Diagnosing the latter has implications, The diagnosis of GDM is made if at least two of the following four plasma glucose levels since such children can be well managed (measured fasting and 1 h, 2 h, 3 h after the OGTT) are met or exceeded: with sulfonylureas. Carpenter/Coustan (56) or NDDG (57) Maturity-Onset Diabetes of the Young c Fasting 95 mg/dL (5.3 mmol/L) 105 mg/dL (5.8 mmol/L) c 1 h 180 mg/dL (10.0 mmol/L) 190 mg/dL (10.6 mmol/L) MODY is characterized by impaired insulin c 2 h 155 mg/dL (8.6 mmol/L) 165 mg/dL (9.2 mmol/L) secretion with minimal or no defects in in- c 3 h 140 mg/dL (7.8 mmol/L) 145 mg/dL (8.0 mmol/L) sulin action. It is inherited in an autosomal dominant pattern. Abnormalities at six ge- NDDG, National Diabetes Data Group. *The ACOG recommends a lower threshold of 135 mg/dL (7.5 mmol/L) in high-risk ethnic netic loci on different chromosomes have populations with higher prevalence of GDM; some experts also recommend 130 mg/dL been identified to date. The most common (7.2 mmol/L). form is associated with mutations on chro- mosome 12 in a hepatic transcription factor referred to as hepatocyte nuclear factor glucose load test (GLT) followed by a 3-h implement must therefore be made based (HNF)-1a. A second form is associated 100-g OGTT for those who screen on the relative values placed on factors with mutations in the glucokinase gene positive, a strategy commonly used in thathaveyettobemeasured(e.g.,cost- on chromosome 7p and results in a defec- fi the U.S. bene t estimation, willingness to change tive glucokinase molecule. Glucokinase ’ Key factors reported in the NIH panel s practice based on correlation studies converts glucose to glucose-6-phosphate, decision-making process were the lack of rather than clinical intervention trial the metabolism of which, in turn, stimu- clinical trial interventions demonstrating results, relative role of cost consid- lates insulin secretion by the b-cell. The fi the bene ts of the one-step strategy erations, and available infrastructure lo- less common forms of MODY result from and the potential negative consequences cally, nationally, and internationally). mutations in other transcription factors, in- of identifying a large new group of As the IADPSG criteria have been cluding HNF-4a,HNF-1b, insulin promoter women with GDM, including medicaliza- adopted internationally, further evi- factor (IPF)-1, and NeuroD1. tion of pregnancy with increased inter- dence has emerged to support im- ventions and costs. Moreover, screening proved pregnancy outcomes with cost Diagnosis with a 50-g GLT does not require fast- savings (47) and may be the preferred Readily available commercial genetic ing and is therefore easier to accomplish approach. In addition, pregnancies testing now enables a true genetic diag- for many women. Treatment of higher complicated by GDM per IADPSG crite- nosis. It is important to correctly diag- threshold maternal hyperglycemia, as ria, but not recognized as such, have nose one of the monogenic forms of identified by the two-step approach, re- comparable outcomes to pregnancies di- diabetes because these children may duces rates of neonatal macrosomia, agnosed as GDM by the more stringent be incorrectly diagnosed with type 1 or large-for-gestational-age births, and two-step criteria (48). There remains type 2 diabetes, leading to suboptimal shoulder dystocia, without increasing strong consensus that establishing a uni- treatment regimens and delays in diag- small-for-gestational-age births (45). form approach to diagnosing GDM will nosing other family members (49). The American College of Obstetricians benefit patients, caregivers, and policy- The diagnosis of monogenic diabetes and Gynecologists (ACOG) updated its makers. Longer-term outcome studies are should be considered in children with guidelines in 2013 and supported the currently underway. the following findings: two-step approach (46). MONOGENIC DIABETES ○ Diabetes diagnosed within the first 6 SYNDROMES Future Considerations months of life The conflicting recommendations from Monogenic defects that cause b-cell dys- ○ Strong family history of diabetes but expert groups underscore the fact that function, such as neonatal diabetes and without typical features of type 2 di- there are data to support each strategy. MODY, represent a small fraction of pa- abetes (nonobese, low-risk ethnic The decision of which strategy to tients with diabetes (,5%). These forms group) care.diabetesjournals.org Position Statement S15

○ Mild fasting hyperglycemia (100–150 with and without diabetes and have elim- Hemoglobin A1c versus oral glucose tolerance mg/dL [5.5–8.5 mmol/L]), especially if inatedthesexdifferenceinmortality(52). test in postpartum diabetes screening. Diabetes – young and nonobese Recent trials comparing insulin with oral Care 2012;35:1648 1653 10. The Expert Committee on the Diagnosis and ○ fi Diabetes with negative autoantibod- repaglinide showed no signi cant differ- Classification of Diabetes Mellitus. Report of the ies and without signs of obesity or in- ence between the groups. However, an- Expert Committee on the Diagnosis and Classi- sulin resistance other study compared three different fication of Diabetes Mellitus. Diabetes Care groups: premeal insulin aspart, repagli- 1997;20:1183–1197 CYSTIC FIBROSIS–RELATED nide, or oral placebo in cystic fibrosis pa- 11. Genuth S, Alberti KG, Bennett P, et al.; Ex- pert Committee on the Diagnosis and Classifica- DIABETES tients with abnormal glucose tolerance. tion of Diabetes Mellitus. Follow-up report on Patients all had weight loss; however, in the diagnosis of diabetes mellitus. Diabetes Recommendations the insulin-treated group, this pattern was Care 2003;26:3160–3167 c Annual screening for cystic fibrosis– reversed, and they gained 0.39 (6 0.21) 12. Zhang X, Gregg EW, Williamson DF, et al. A1C related diabetes (CFRD) with OGTT BMI units (P 5 0.02). Patients in the level and future risk of diabetes: a systematic re- – should begin by age 10 years in all repaglinide-treated group had initial weight view. Diabetes Care 2010;33:1665 1673 13.SelvinE,SteffesMW,ZhuH,etal.Glycated patients with cystic fibrosis who gain, but this was not sustained by 6 B hemoglobin, diabetes, and cardiovascular risk in do not have CFRD. A1C as a months. The placebo group continued to nondiabetic adults. N Engl J Med 2010;362:800–811 screening test for CFRD is not rec- lose weight (53). Insulin remains the most 14. Ackermann RT, Cheng YJ, Williamson DF, ommended. B widely used therapy for CFRD (54). Gregg EW. Identifying adults at high risk for di- c Patients with CFRD should be Recommendations for the clinical man- abetes and cardiovascular disease using hemo- treated with insulin to attain in- globin A1c National Health and Nutrition agement of CFRD can be found in the ADA Examination Survey 2005-2006. Am J Prev dividualized glycemic goals. A position statement “Clinical Care Guide- Med 2011;40:11–17 c In patients with cystic fibrosis and lines for Cystic Fibrosis–Related Diabetes: 15. Dabelea D, Mayer-Davis EJ, Saydah S, et al.; IGT without confirmed diabetes, A Position Statement of the American SEARCH for Diabetes in Youth Study. Prevalence prandial insulin therapy should be Diabetes Association and a Clinical Prac- of type 1 and type 2 diabetes among children and adolescents from 2001 to 2009. JAMA 2014; considered to maintain weight. B tice Guideline of the Cystic Fibrosis 311:1778–1786 c Annual monitoring for complica- Foundation, Endorsed by the Pediatric 16. Ziegler AG, Rewers M, Simell O, et al. Sero- tions of diabetes is recommended, Endocrine Society” (55). conversion to multiple islet autoantibodies and beginning 5 years after the diagno- risk of progression to diabetes in children. JAMA E – sis of CFRD. References 2013;309:2473 2479 17. Sorensen JS, Johannesen J, Pociot F, et al. 1. American Diabetes Association. Diagnosis Residual b-cell function 3-6 years after onset of fi and classi cation of diabetes mellitus. Diabetes type 1 diabetes reduces risk of severe hypogly- CFRD is the most common comorbidity – Care 2014;37(Suppl. 1):S81 S90 cemia in children and adolescents. Diabetes fi in people with cystic brosis, occurring in 2. The International Expert Committee. Inter- Care 2013;36:3454–3459 about 20% of adolescents and 40–50% of national Expert Committee report on the role 18. Sosenko JM, Skyler JS, Palmer JP, et al.; Type of the A1C assay in the diagnosis of diabetes. 1 Diabetes TrialNet Study Group; Diabetes Pre- adults. Diabetes in this population is as- – Diabetes Care 2009;32:1327 1334 vention Trial-Type 1 Study Group. The prediction sociated with worse nutritional status, 3. Nowicka P, Santoro N, Liu H, et al. Utility of of type 1 diabetes by multiple autoantibody levels more severe inflammatory lung disease, hemoglobin A for diagnosing prediabetes and 1c and their incorporation into an autoantibody risk diabetes in obese children and adolescents. Di- and greater mortality from respiratory score in relatives of type 1 diabetic patients. Di- abetes Care 2011;34:1306–1311 failure. Insulin insufficiency related to abetes Care 2013;36:2615–2620 4. Garc´ıa de Guadiana Romualdo L, Gonzalez´ fi 19. Griffin SJ, Borch-Johnsen K, Davies MJ, et al. partial brotic destruction of the islet Morales M, Albaladejo Oton´ MD, et al. [The Effect of early intensive multifactorial therapy mass is the primary defect in CFRD. Ge- value of hemoglobin A1c for diagnosis of diabe- on 5-year cardiovascular outcomes in individu- netically determined function of the re- tes mellitus and other changes in carbohydrate als with type 2 diabetes detected by screening maining b-cells and insulin resistance metabolism in women with recent gestational diabetes mellitus] Endocrinol Nutr 2012;59: (ADDITION-Europe): a cluster-randomised trial. associated with infection and inflamma- – 362–366 [in Spanish] Lancet 2011;378:156 167 tion may also play a role. While screening 5. Cowie CC, Rust KF, Byrd-Holt DD, et al. Prev- 20. Kahn R, Alperin P, Eddy D, et al. Age at ini- for diabetes before the age of 10 years alence of diabetes and high risk for diabetes tiation and frequency of screening to detect using A1C criteria in the U.S. population in type 2 diabetes: a cost-effectiveness analysis. can identify risk for progression to CFRD – 1988-2006. Diabetes Care 2010;33:562–568 Lancet 2010;375:1365 1374 in those with abnormal glucose tolerance, 21. Araneta MR, Gandinetti A, Chang HK. Opti- fi 6.ZiemerDC,KolmP,WeintraubWS,etal. there appears to be no bene twithre- Glucose-independent, black-white differences in mum BMI cut points to screen Asian Americans spect to weight, height, BMI, or lung func- hemoglobin A1c levels: a cross-sectional analysis for type 2 diabetes: the UCSD Filipino Health tion compared with those with normal of 2 studies. Ann Intern Med 2010;152:770–777 Study and the North Kohala Study. Diabetes glucose tolerance ,10 years of age. The 7. Kumar PR, Bhansali A, Ravikiran M, et al. Util- 2014;63(Suppl. 1):A20 22. Hsu WC, Araneta MR, Kanaya AM, Chiang use of continuous glucose monitoring ity of in diagnosing type 2 diabetes mellitus: a community-based study. J JL, Fujimoto W. BMI cut points to identify at-risk may be more sensitive than OGTT to de- Clin Endocrinol Metab 2010;95:2832–2835 Asian Americans for type 2 diabetes screening. tect risk for progression to CFRD, but this 8. Selvin E, Steffes MW, Ballantyne CM, Diabetes Care 2015;38:150–158 likely needs more evidence. Hoogeveen RC, Coresh J, Brancati FL. Racial dif- 23. WHO Expert Consultation. Appropriate Encouraging data suggest that im- ferences in glycemic markers: a cross-sectional body-mass index for Asian populations and its analysis of community-based data. Ann Intern implications for policy and intervention strate- proved screening (50,51) and aggressive Med 2011;154:303–309 gies. Lancet 2004;363:157–163 insulin therapy have narrowed the gap in 9. Picon´ MJ, Murri M, Munoz~ A, Fernandez-´ 24. Chiu M, Austin PC, Manuel DG, Shah BR, Tu mortality between cystic fibrosis patients Garc´ıa JC, Gomez-Huelgas R, Tinahones FJ. JV. Deriving ethnic-specific BMI cutoff points for S16 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

assessing diabetes risk. Diabetes Care 2011;34: 35. Kapadia C, Zeitler P; Drugs and Therapeutics 47. Duran A, Saenz´ S, Torrejon´ MJ, et al. In- 1741–1748 Committee of the Pediatric Endocrine Society. troduction of IADPSG criteria for the screen- 25. Erickson SC, Le L, Zakharyan A, et al. New- Hemoglobin A1c measurement for the diagnosis ing and diagnosis of gestational diabetes onset treatment-dependent diabetes mellitus of type 2 diabetes in children. Int J Pediatr En- mellitus results in improved pregnancy out- and hyperlipidemia associated with atypical an- docrinol 2012;2012:31 comes at a lower cost in a large cohort of tipsychotic use in older adults without schizo- 36. Kester LM, Hey H, Hannon TS. Using hemoglo- pregnant women: the St. Carlos Gestational phrenia or bipolar disorder. J Am Geriatr Soc bin A1c for prediabetes and diabetes diagnosis in Diabetes Study. Diabetes Care 2014;37: 2012;60:474–479 adolescents: can adult recommendations be upheld 2442–2450 26. Knowler WC, Barrett-Connor E, Fowler SE, for pediatric use? J Adolesc Health 2012;50:321–323 48. Ethridge JK Jr, Catalano PM, Waters TP. et al.; Diabetes Prevention Program Research 37. Wu E-L, Kazzi NG, Lee JM. Cost-effectiveness Perinatal outcomes associated with the diagno- Group. Reduction in the incidence of type 2 di- of screening strategies for identifying pediatric sis of gestational diabetes made by the Inter- abetes with lifestyle intervention or metformin. diabetes mellitus and dysglycemia. JAMA Pe- national Association of the Diabetes and N Engl J Med 2002;346:393–403 diatr 2013;167:32–39 Pregnancy Study Groups criteria. Obstet Gyne- 27. Tuomilehto J, Lindstrom¨ J, Eriksson JG, 38. Lawrence JM, Contreras R, Chen W, Sacks col 2014;124:571–578 et al.; Finnish Diabetes Prevention Study Group. DA. Trends in the prevalence of preexisting 49. Hattersley A, Bruining J, Shield J, Njolstad Prevention of type 2 diabetes mellitus by diabetes and gestational diabetes mellitus P, Donaghue KC. The diagnosis and manage- changes in lifestyle among subjects with im- among a racially/ethnically diverse population ment of monogenic diabetes in children and paired glucose tolerance. N Engl J Med 2001; of pregnant women, 1999-2005. Diabetes Care adolescents. Pediatr Diabetes 2009;10(Suppl. 344:1343–1350 2008;31:899–904 12):33–42 28. Pan X-R, Li G-W, Hu Y-H, et al. Effects of diet 39. Metzger BE, Lowe LP, Dyer AR, et al.; HAPO 50. Kern AS, Prestridge AL. Improving screening and exercise in preventing NIDDM in people with Study Cooperative Research Group. Hyperglyce- for cystic fibrosis-related diabetes at a pediatric impaired glucose tolerance: the Da Qing IGT and mia and adverse pregnancy outcomes. N Engl J cystic fibrosis program. Pediatrics 2013;132: Diabetes Study. Diabetes Care 1997;20:537–544 Med 2008;358:1991–2002 e512–e518 29. Buchanan TA, Xiang AH, Peters RK, et al. 40. American Diabetes Association. Standards 51. Waugh N, Royle P, Craigie I, et al. Screen- Preservation of pancreatic b-cell function and of medical care in diabetes–2011. Diabetes ing for cystic fibrosis-related diabetes: a sys- prevention of type 2 diabetes by pharmacolog- Care 2011;34(Suppl. 1):S11–S61 tematic review. Health Technol Assess 2012; ical treatment of insulin resistance in high-risk 41. Metzger BE, Gabbe SG, Persson B, et al.; 16:iii–iv, 1–179 Hispanic women. Diabetes 2002;51:2796–2803 International Association of Diabetes and Preg- 52. Moran A, Dunitz J, Nathan B, Saeed A, 30. Chiasson J-L, Josse RG, Gomis R, Hanefeld nancy Study Groups Consensus Panel. Interna- Holme B, Thomas W. Cystic fibrosis-related di- M, Karasik A, Laakso M; STOP-NIDDM Trial Re- tional Association of abetes: current trends in prevalence, incidence, search Group. Acarbose for prevention of type 2 Study Groups recommendations on the diagno- and mortality. Diabetes Care 2009;32:1626– diabetes mellitus: the STOP-NIDDM randomised sis and classification of hyperglycemia in preg- 1631 trial. Lancet 2002;359:2072–2077 nancy. Diabetes Care 2010;33:676–682 53.MoranA,PekowP,GroverP,etal.;Cystic 31. Gerstein HC, Yusuf S, Bosch J, et al.; DREAM 42. Landon MB, Spong CY, Thom E, et al.; Eu- Fibrosis Related Diabetes Therapy Study Group. (Diabetes REduction Assessment with ramipril nice Kennedy Shriver National Institute of Insulin therapy to improve BMI in cystic fibrosis- and rosiglitazone Medication) Trial Investigators. Child Health and Human Development Ma- related diabetes without fasting hyperglycemia: Effect of rosiglitazone on the frequency of diabe- ternal-Fetal Medicine Units Network. A multi- results of the cystic fibrosis related diabetes tes in patients with impaired glucose tolerance or center, randomized trial of treatment for mild therapy trial. Diabetes Care 2009;32:1783– : a randomised con- gestational diabetes. N Engl J Med 2009;361: 1788 trolled trial. Lancet 2006;368:1096–1105 1339–1348 54. Onady GM, Stolfi A. Insulin and oral 32. Ramachandran A, Snehalatha C, Mary S, 43. Crowther CA, Hiller JE, Moss JR, McPhee agents for managing cystic fibrosis-related dia- Mukesh B, Bhaskar AD, Vijay V; Indian Diabetes AJ, Jeffries WS, Robinson JS; Australian Carbo- betes. Cochrane Database Syst Rev 2013;7: Prevention Programme (IDPP). The Indian Dia- hydrate Intolerance Study in Pregnant CD004730 betes Prevention Programme shows that life- Women (ACHOIS) Trial Group. Effect of treat- 55. Moran A, Brunzell C, Cohen RC, et al.; CFRD style modification and metformin prevent type ment of gestational diabetes mellitus on preg- Guidelines Committee. Clinical care guidelines 2 diabetes in Asian Indian subjects with im- nancy outcomes. N Engl J Med 2005;352: for cystic fibrosis-related diabetes: a position paired glucose tolerance (IDPP-1). Diabetologia 2477–2486 statement of the American Diabetes Associa- 2006;49:289–297 44. Vandorsten JP, Dodson WC, Espeland MA, tion and a clinical practice guideline of the Cystic 33.JohnsonSL,TabaeiBP,HermanWH.The et al. NIH consensus development conference: Fibrosis Foundation, endorsed by the Pediatric efficacy and cost of alternative strategies for diagnosing gestational diabetes mellitus. NIH Endocrine Society. Diabetes Care 2010;33: systematic screening for type 2 diabetes in the Consens State Sci Statements 2013;29:1–31 2697–2708 U.S. population 45-74 years of age. Diabetes 45. Horvath K, Koch K, Jeitler K, et al. Effects of 56. Carpenter MW, Coustan DR. Criteria for Care 2005;28:307–311 treatment in women with gestational diabetes screening tests for gestational diabetes. Am J 34. Buse JB, Kaufman FR, Linder B, Hirst K, El mellitus: systematic review and meta-analysis. Obstet Gynecol 1982;144:768–773 Ghormli L, Willi S; HEALTHY Study Group. Diabe- BMJ 2010;340:c1395 57. National Diabetes Data Group. Classifica- tes screening with hemoglobin A(1c) versus fast- 46. Committee on Practice Bulletins–Obstetrics. tion and diagnosis of diabetes mellitus and ing plasma glucose in a multiethnic middle-school Practice Bulletin No. 137: gestational diabetes other categories of glucose intolerance. Diabe- cohort. Diabetes Care 2013;36:429–435 mellitus. Obstet Gynecol 2013;122:406–416 tes 1979;28:1039–1057 Diabetes Care Volume 38, Supplement 1, January 2015 S17

3. Initial Evaluation and Diabetes American Diabetes Association Management Planning Diabetes Care 2015;38(Suppl. 1):S17–S19 | DOI: 10.2337/dc15-S006

MEDICAL EVALUATION

Recommendation c Consider screening those with type 1 diabetes for autoimmune diseases (e.g., thyroid dysfunction, celiac disease) as appropriate. E

A complete medical evaluation should be performed at the initial visit to

1. Classify diabetes STATEMENT POSITION 2. Detect diabetes complications 3. Review previous treatment and risk factor control in patients with established diabetes 4. Assist in formulating a management plan 5. Provide a basis for continuing care

Laboratory tests appropriate to the evaluation of each patient’s medical condition should be completed. A focus on the components of comprehensive care (Table 3.1) will enable the health care team to optimally manage the patient with diabetes. Adults who develop type 1 diabetes can develop additional autoimmune disorders, although their risk is lower than that in children and adolescents with type 1 diabetes. For ad- ditional details on autoimmune conditions, see Section 11. Children and Adolescents.

MANAGEMENT PLAN People with diabetes should receive medical care from a collaborative, integrated team with expertise in diabetes. This team may include physicians, nurse practitioners, physician’s assistants, nurses, dietitians, pharmacists, and mental health professionals. Individuals with diabetes must also assume an active role in their care. The management plan should be written with input from the patient and family, the physician, and other members of the health care team. Diabetes self-management education (DSME) and ongoing diabetes support should be integral components of the management plan. Various strategies and techniques should be used to enable patients to self-manage diabetes, including providing education on problem-solving skills for all aspects of diabetes management. Treatment goals and plans should be individualized and take patient preferences into account. In developing the plan, consideration should be given to the patient’s age, school/work schedule and con- ditions, physical activity, eating patterns, social situation, cultural factors, presence of diabetes complications, health priorities, and other medical conditions.

COMMON COMORBID CONDITIONS

Recommendation c Consider assessing for and addressing common comorbid conditions Suggested citation: American Diabetes Associa- (e.g., depression, obstructive sleep apnea) that may complicate diabetes tion. Initial evaluation and diabetes manage- management. B ment planning. Sec. 3. In Standards of Medical Care in Diabetesd2015. Diabetes Care 2015;38 (Suppl. 1):S17–S19 Improved disease prevention and treatment efficacy means that patients with © 2015 by the American Diabetes Association. diabetes are living longer, often with multiple comorbidities requiring complicated Readers may use this article as long as the work medical regimens (1). Obesity, hypertension, and dyslipidemia are the most com- is properly cited, the use is educational and not monly appreciated comorbidities. However, concurrent conditions, such as heart for profit, and the work is not altered. S18 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

Fatty Liver Disease Table 3.1—Components of the comprehensive diabetes evaluation Medical history Unexplained elevations of hepatic trans- c Age and characteristics of onset of diabetes (e.g., DKA, asymptomatic laboratory finding) aminase concentrations are signifi- c Eating patterns, physical activity habits, nutritional status, and weight history; growth and cantly associated with higher BMI, development in children and adolescents waist circumference, triglycerides, and c Presence of common comorbidities, psychosocial problems, and dental disease fasting insulin and with lower HDL cho- c Diabetes education history lesterol. In a prospective analysis, diabe- c Review of previous treatment regimens and response to therapy (A1C records) fi c Current treatment of diabetes, including medications, medication adherence and barriers tes was signi cantly associated with thereto, meal plan, physical activity patterns, and readiness for behavior change incident nonalcoholic chronic liver dis- c Results of glucose monitoring and patient’s use of data ease and with hepatocellular carcinoma c DKA frequency, severity, and cause (10). Interventions that improve meta- c Hypoglycemic episodes bolic abnormalities in patients with di- c Hypoglycemia awareness abetes (weight loss, glycemic control, c Any severe hypoglycemia: frequency and cause and treatment with specificdrugsforhy- c History of diabetes-related complications c Microvascular: retinopathy, nephropathy, neuropathy (sensory, including history of foot perglycemia or dyslipidemia) are also lesions; autonomic, including sexual dysfunction and gastroparesis) beneficial for fatty liver disease (11). c Macrovascular: coronary heart disease, cerebrovascular disease, and peripheral arterial disease Cancer Physical examination Diabetes (possibly only type 2 diabetes) c Height, weight, BMI is associated with increased risk of c Blood pressure determination, including orthostatic measurements when indicated cancers of the liver, pancreas, endome- c Fundoscopic examination trium, colon/rectum, breast, and blad- c Thyroid palpation c Skin examination (for acanthosis nigricans and insulin injection sites) der (12). The association may result c Comprehensive foot examination from shared risk factors between type c Inspection 2 diabetes and cancer (obesity, older c Palpation of dorsalis pedis and posterior tibial pulses age, and physical inactivity), but may c Presence/absence of patellar and Achilles reflexes also be due to hyperinsulinemia or c Determination of proprioception, vibration, and monofilament sensation hyperglycemia (13). Patients with diabe- Laboratory evaluation tes should be encouraged to undergo c A1C, if results not available within past 3 months recommended age- and sex-appropriate c If not performed/available within past year c Fasting lipid profile, including total, LDL, and HDL cholesterol and triglycerides, as needed cancer screenings and to reduce their c Liver function tests modifiable cancer risk factors (obesity, c Test for urine albumin excretion with spot urine albumin-to-creatinine ratio smoking, and physical inactivity). c Serum creatinine and calculated glomerular filtration rate c TSH in type 1 diabetes, dyslipidemia, or women over age 50 years Fractures Referrals Age-matched hip fracture risk is signifi- c Eye care professional for annual dilated eye exam cantlyincreasedinbothtype1(sum- c Family planning for women of reproductive age mary relative risk [RR] 6.3) and type 2 c Registered dietitian for medical nutrition therapy c DSME/DSMS diabetes (summary RR 1.7) in both sexes c Dentist for comprehensive periodontal examination (14). Type 1 diabetes is associated with c Mental health professional, if needed osteoporosis, but in type 2 diabetes an DKA, diabetic ketoacidosis; DSMS, diabetes self-management support; TSH, thyroid-stimulating increased risk of hip fracture is seen de- hormone. spite higher bone mineral density (BMD) (15). In three large observational studies of older adults, femoral neck BMD T failure, depression, anxiety, and arthri- Obstructive Sleep Apnea score and the WHO Fracture Risk Algo- tis, are found at higher rates in people Age-adjusted rates of obstructive sleep rithm (FRAX) score were associated with with diabetes than in age-matched people apnea, a risk factor for cardiovascular hip and nonspine fracture, although without diabetes and often complicate disease, are significantly higher (4- to fracture risk was higher in participants diabetes management. These concurrent 10-fold) with obesity, especially with cen- with diabetes compared with those conditions present clinical challenges tral obesity, in men and women (6). The without diabetes for a given T score and relatedtopolypharmacy,prevalent prevalence in general populations with age or for a given FRAX score (16). It is symptoms, and complexity of care (2–5). type 2 diabetes may be up to 23% (7) appropriate to assess fracture history and in obese participants enrolled in and risk factors in older patients with Depression the Look AHEAD trial exceeded 80% diabetes and recommend BMD testing As discussed in Section 4. Foundations (8). Treatment of sleep apnea signif- if appropriate for the patient’s age and sex. of Care, depression, anxiety, and other icantlyimprovesqualityoflifeand Prevention strategies are the same as for mental health symptoms are highly blood pressure control. The evidence the general population. For type 2 diabetic prevalent in people with diabetes and for a treatment effect on glycemic control patients with fracture risk factors, avoid- are associated with worse outcomes. is mixed (9). ing thiazolidinediones is warranted. care.diabetesjournals.org Position Statement S19

Cognitive Impairment disease. In a National Health and Nutri- 12. Suh S, Kim KW. Diabetes and cancer: is Diabetes is associated with a signifi- tion Examination Survey (NHANES) anal- diabetes causally related to cancer? Diabetes – cantly increased risk, and rate, of cogni- ysis, hearing impairment was about Metab J 2011;35:193 198 tive decline and with increased risk of 13. Giovannucci E, Harlan DM, Archer MC, twice as prevalent in people with diabe- et al. Diabetes and cancer: a consensus report. dementia (17,18). In a 15-year prospec- tes compared with those without, after Diabetes Care 2010;33:1674–1685 tive study of community-dwelling peo- adjusting for age and other risk factors 14. Janghorbani M, Van Dam RM, Willett WC, pleovertheageof60years,the for hearing impairment (24). Hu FB. Systematic review of type 1 and type 2 presence of diabetes at baseline sig- diabetes mellitus and risk of fracture. Am J Epi- demiol 2007;166:495–505 nificantly increased the age- and sex- References adjusted incidence of all-cause dementia, 15. Vestergaard P. Discrepancies in bone min- 1. Selvin E, Coresh J, Brancati FL. The burden eral density and fracture risk in patients with Alzheimer disease, and vascular demen- and treatment of diabetes in elderly individuals type 1 and type 2 diabetesda meta-analysis. tiacomparedwithratesinthosewith in the U.S. Diabetes Care 2006;29:2415–2419 Osteoporos Int 2007;18:427–444 normal glucose tolerance (19). In a sub- 2. Grant RW, Ashburner JM, Hong CS, Chang 16. Schwartz AV, Vittinghoff E, Bauer DC, fi study of the Action to Control Cardiovas- Y, Barry MJ, Atlas SJ. De ning patient complex- et al.; Study of Osteoporotic Fractures (SOF) Re- ity from the primary care physician’s perspec- cular Risk in Diabetes (ACCORD) clinical search Group; Osteoporotic Fractures in Men tive: a cohort study. Ann Intern Med 2011;155: (MrOS) Research Group; Health, Aging, and trial, there were no differences in cogni- 797–804 Body Composition (Health ABC) Research 3. Tinetti ME, Fried TR, Boyd CM. Designing tive outcomes between intensive and Group. Association of BMD and FRAX score health care for the most common chronic standard glycemic control, although with risk of fracture in older adults with type 2 conditiondmultimorbidity. JAMA 2012;307: there was significantly less of a decre- – 2493–2494 diabetes. JAMA 2011;305:2184 2192 ment in total brain volume, as measured 4. Sudore RL, Karter AJ, Huang ES, et al. 17. Cukierman T, Gerstein HC, Williamson JD. d by MRI, in participants in the intensive Symptom burden of adults with type 2 diabetes Cognitive decline and dementia in diabetes arm (20). The effects of hyperglycemia across the disease course: Diabetes & Aging systematic overview of prospective observational studies. Diabetologia 2005;48:2460–2469 and insulin on the brain are areas of in- Study. J Gen Intern Med 2012;27:1674–1681 ¨ 18. Biessels GJ, Staekenborg S, Brunner E, tense research interest. 5. Borgnakke WS, Ylostalo PV, Taylor GW, Genco RJ. Effect of periodontal disease on di- Brayne C, Scheltens P. Risk of dementia in di- abetes mellitus: a systematic review. Lancet Low Testosterone in Men abetes: systematic review of epidemiologic observational evidence. J Periodontol 2013; Neurol 2006;5:64–74 Mean levels of testosterone are lower in 84(Suppl.):S135–S152 19. Ohara T, Doi Y, Ninomiya T, et al. Glucose menwithdiabetescomparedwithage- 6. Li C, Ford ES, Zhao G, Croft JB, Balluz LS, tolerance status and risk of dementia in the matched men without diabetes, but Mokdad AH. Prevalence of self-reported clini- community: the Hisayama study. Neurology obesity is a major confounder (21). cally diagnosed sleep apnea according to obe- 2011;77:1126–1134 sity status in men and women: National Health 20. Launer LJ, Miller ME, Williamson JD, et al.; Treatment in asymptomatic men is con- and Nutrition Examination Survey, 2005-2006. ACCORD MIND investigators. Effects of inten- troversial. The evidence that testoster- Prev Med 2010;51:18–23 sive glucose lowering on brain structure one replacement affects outcomes is 7. West SD, Nicoll DJ, Stradling JR. Prevalence and function in people with type 2 diabetes mixed, and recent guidelines suggest of obstructive sleep apnoea in men with type 2 (ACCORD MIND): a randomised open-label sub- – that testing and treating men without diabetes. Thorax 2006;61:945 950 study. Lancet Neurol 2011;10:969–977 8. Foster GD, Sanders MH, Millman R, et al.; symptoms are not recommended (22). 21. Dhindsa S, Miller MG, McWhirter CL, et al. Sleep AHEAD Research Group. Obstructive Testosterone concentrations in diabetic and sleep apnea among obese patients with type 2 Periodontal Disease nondiabetic obese men. Diabetes Care 2010; diabetes. Diabetes Care 2009;32:1017–1019 – Periodontal disease is more severe, but 33:1186 1192 9. Shaw JE, Punjabi NM, Wilding JP, Alberti 22. Bhasin S, Cunningham GR, Hayes FJ, et al. KGMM, Zimmet PZ; International Diabetes Fed- not necessarily more prevalent, in patients Testosterone therapy in men with androgen de- eration Taskforce on Epidemiology and Preven- with diabetes than in those without (23). ficiency syndromes: an Endocrine Society clini- tion. Sleep-disordered breathing and type 2 Current evidence suggests that periodon- cal practice guideline. J Clin Endocrinol Metab diabetes: a report from the International Diabetes – tal disease adversely affects diabetes out- Federation Taskforce on Epidemiology and Pre- 2010;95:2536 2559 comes, although evidence for treatment vention. Diabetes Res Clin Pract 2008;81:2–12 23. Khader YS, Dauod AS, El-Qaderi SS, benefits remains controversial (5). 10. El-Serag HB, Tran T, Everhart JE. Diabetes Alkafajei A, Batayha WQ. Periodontal status increases the risk of chronic liver disease and of diabetics compared with nondiabetics: a meta- Hearing Impairment hepatocellular carcinoma. Gastroenterology analysis. J Diabetes Complications 2006;20: Hearing impairment, both in high fre- 2004;126:460–468 59–68 24. Bainbridge KE, Hoffman HJ, Cowie CC. quency and low/mid frequency ranges, 11. American Gastroenterological Association. American Gastroenterological Association med- Diabetes and hearing impairment in the United is more common in people with dia- ical position statement: nonalcoholic fatty liver States: audiometric evidence from the National betes than in those without, perhaps disease. Gastroenterology 2002;123:1702– Health and Nutrition Examination Survey, 1999 due to neuropathy and/or vascular 1704 to 2004. Ann Intern Med 2008;149:1–10 S20 Diabetes Care Volume 38, Supplement 1, January 2015

4. Foundations of Care: Education, American Diabetes Association Nutrition, Physical Activity, Smoking Cessation, Psychosocial Care, and Immunization Diabetes Care 2015;38(Suppl. 1):S20–S30 | DOI: 10.2337/dc15-S007

DIABETES SELF-MANAGEMENT EDUCATION AND SUPPORT

Recommendations c People with diabetes should receive diabetes self-management education (DSME) and diabetes self-management support (DSMS) according to the na- tional standards for DSME and DSMS when their diabetes is diagnosed and as needed thereafter. B c Effective self-management and quality of life are the key outcomes of DSME and DSMS and should be measured and monitored as part of care. C c DSME and DSMS should address psychosocial issues, as emotional well-being is associated with positive diabetes outcomes. C

POSITION STATEMENT c DSME and DSMS programs are appropriate venues for people with prediabe- tes to receive education and support to develop and maintain behaviors that can prevent or delay the onset of diabetes. C c Because DSME and DSMS can result in cost-savings and improved outcomes B, DSME and DSMS should be adequately reimbursed by third-party payers. E

DSME and DSMS are the ongoing processes of facilitating the knowledge, skill, and ability necessary for diabetes self-care. This process incorporates the needs, goals, and life experiences of the person with diabetes. The overall objectives of DSME and DSMS are to support informed decision making, self-care behaviors, problem solv- ing, and active collaboration with the health care team to improve clinical outcomes, health status, and quality of life in a cost-effective manner (1). DSME and DSMS are essential elements of diabetes care (2,3), and the current national standards for DSME and DSMS (1) are based on evidence of their benefits. Education helps people with diabetes initiate effective self-management and cope with diabetes when they are first diagnosed. Ongoing DSME and DSMS also help people with diabetes maintain effective self-management throughout a lifetime of diabetes as they face new challenges and as treatment advances become avail- able. DSME enables patients (including youth) to optimize metabolic control, pre- vent and manage complications, and maximize quality of life in a cost-effective manner (2,4). Current best practice of DSME is a skill-based approach that focuses on helping those with diabetes make informed self-management choices (1,2). DSME has changed from a didactic approach focusing on providing information to empow- erment models that focus on helping those with diabetes make informed self- management decisions (2). Diabetes care has shifted to an approach that is more patient centered and places the person with diabetes and his or her family at the Suggested citation: American Diabetes Associa- tion. Foundations of care: education, nutrition, center of the care model, working in collaboration with health care professionals. physical activity, smoking cessation, psychoso- Patient-centered care is respectful of and responsive to individual patient pref- cial care, and immunization. Sec. 4. In Standards erences, needs, and values and ensures that patient values guide all decision of Medical Care in Diabetesd2015. Diabetes making (5). Care 2015;38(Suppl. 1):S20–S30 © 2015 by the American Diabetes Association. Evidence for the Benefits Readers may use this article as long as the work Multiple studies have found that DSME is associated with improved diabetes knowl- is properly cited, the use is educational and not edge, improved self-care behavior (1), improved clinical outcomes, such as lower for profit, and the work is not altered. care.diabetesjournals.org Position Statement S21

A1C (3,6–8), lower self-reported weight plan is determining what to eat. It is the programs including nutrition therapy or (9,10), improved quality of life (8,11), position of the ADA that there is not a individualized education sessions have re- healthy coping (12,13), and lower costs one-size-fits-all eating pattern for indi- ported A1C decreases of 0.3–1% for type (14,15). Better outcomes were reported viduals with diabetes. The ADA also rec- 1 diabetes (37–41) and 0.5–2% for type 2 for DSME interventions that were longer ognizes the integral role of nutrition diabetes (42–49). and included follow-up support (DSMS) therapy in overall diabetes manage- (16–18), that were culturally (19,20) and ment and recommends that each per- Carbohydrate Management age appropriate (21,22), that were tai- sonwithdiabetesbeactivelyengaged Individuals with type 1 diabetes should loredtoindividualneedsandprefer- in self-management, education, and be offered intensive insulin therapy ences, and that addressed psychosocial treatment planning with his or her education using the carbohydrate- issues and incorporated behavioral health care provider, which includes counting meal planning approach strategies (2,12,23,24). Both individual the collaborative development of an (37,39,40,43,50), which has been shown and group approaches have been found individualized eating plan (35,36). to improve glycemic control (50,51). effective (10,25). There is growing evi- Therefore, it is important that all mem- Consistent carbohydrate intake with re- dence for the role of community health bers of the health care team be knowl- spect to time and amount can result in workers (26), as well as peer (27–30) and edgeable about diabetes nutrition improved glycemic control for individu- lay leaders (31), in delivering DSME and therapy and support its implementa- als using fixed daily insulin doses (36). A DSMS (32). tion. See Table 4.1 for specific nutrition simple diabetes meal planning approach, Diabetes education is associated with recommendations. such as portion control or healthful food increased use of primary and preventive choices, may be better suited for individ- services (14,33,34) and lower use of Goals of Nutrition Therapy for Adults uals with health literacy and numeracy acute, inpatient hospital services (14). With Diabetes concerns (36–40,42). Patients who participate in diabetes ed- 1. To promote and support healthful ucation are more likely to follow best eating patterns, emphasizing a variety Weight Loss practice treatment recommendations, of nutrient-dense foods in appropriate Intensive lifestyle programs with fre- particularly among the Medicare popu- portion sizes, in order to improve quent follow-up are required to achieve lation, and have lower Medicare and in- overall health and specifically to significant reductions in excess body surance claim costs (15,33). ○ Attain individualized glycemic, weight and improve clinical indicators blood pressure, and lipid goals (52,53). Weight loss of 2–8 kg may pro- National Standards ○ Achieve and maintain body weight vide clinical benefits in those with type 2 The national standards for DSME and goals diabetes, especially early in the disease DSMSaredesignedtodefine quality ○ Delay or prevent complications of process (52,53). Although several studies and to assist diabetes educators in a va- diabetes resulted in improvements in A1C at 1 year riety of settings to provide evidence- 2. To address individual nutrition needs (52,54–56), not all weight-loss interven- based education and self-management based on personal and cultural pref- tions led to 1-year A1C improvements support (1). The standards are reviewed erences, health literacy and numer- (45,57–60). The most consistently identi- and updated every 5 years by a task acy, access to healthful food choices, fied changes in cardiovascular risk factors force representing key organizations in- willingness and ability to make be- were an increase in HDL cholesterol volved in diabetes education and care. havioral changes, and barriers to (52,54,56,59,61), decrease in triglycerides change. (52,61–63), and decrease in blood pres- Reimbursement 3. To maintain the pleasure of eating by sure (52,54,57,59,61). Weight-loss studies have used a vari- DSME, when provided by a program that providing positive messages about ety of energy-restricted eating patterns, meets national standards for DSME and food choices while limiting food with no clear evidence that one eating is recognized by the American Diabetes choices only when indicated by sci- fi pattern or optimal macronutrient dis- Association (ADA) or other approval enti c evidence. tribution was ideal, suggesting that bodies, is reimbursed as part of the 4. To provide the individual with diabe- macronutrient proportions should be Medicare program as overseen by the tes with practical tools for day-to-day individualized (64). Studies show that Centers for Medicare & Medicaid Ser- meal planning rather than focusing people with diabetes eat on average vices. DSME is also covered by most on individual macronutrients, micro- about 45% of their calories from carbo- health insurance plans. Although DSMS nutrients, or single foods. hydrates, ;36–40% of calories from fat, has been shown to be instrumental Nutrition therapy is an integral compo- and ;16–18% from protein (57–59). A for improving outcomes and can be pro- nent of diabetes prevention, manage- variety of eating patterns have been vided via phone calls and telehealth, it ment, and self-management education. showntobeeffectiveinmanagingdi- currently has limited reimbursement as All individuals with diabetes should re- abetes, including Mediterranean-style in-person follow-up to DSME. ceive individualized medical nutrition (53,65), Dietary Approaches to Stop therapy (MNT), preferably provided by a Hypertension (DASH)-style (66), and MEDICAL NUTRITION THERAPY registered dietitian who is knowledgeable plant-based (vegan or vegetarian) (67), For many individuals with diabetes, the and skilled in providing diabetes MNT. lower-fat (68), and lower-carbohydrate most challenging part of the treatment Comprehensive group diabetes education patterns (68). S22 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

Table 4.1—Nutrition therapy recommendations Topic Recommendations Evidence rating Effectiveness of nutrition therapy c Nutrition therapy is recommended for all people with type 1 and type 2 A diabetes as an effective component of the overall treatment plan. c Individuals who have diabetes should receive individualized MNT to A achieve treatment goals, preferably provided by a registered dietitian familiar with the components of diabetes MNT. c For individuals with type 1 diabetes, participation in an intensive, flexible A insulin therapy education program using the carbohydrate-counting meal planning approach can result in improved glycemic control. c For individuals using fixed daily insulin doses, consistent carbohydrate B intake with respect to time and amount can result in improved glycemic control and reduce hypoglycemia risk. c A simple diabetes meal planning approach, such as portion control or C healthful food choices, may be better suited to individuals with type 2 diabetes with health and numeracy literacy concerns. This strategy also may be effective for older adults. c Because diabetes nutrition therapy can result in cost savings B and B, A, E improved outcomes (e.g., A1C reduction) A, MNT should be adequately reimbursed by insurance and other payers. E Energy balance c For overweight or obese adults with type 2 diabetes or at risk for A diabetes, reducing energy intake while maintaining a healthful eating pattern is recommended to promote weight loss. c Modest weight loss may provide clinical benefits in some individuals with A diabetes, especially those early in the disease process. To achieve modest weight loss, intensive lifestyle interventions with ongoing support are recommended. Eating patterns and macronutrient c Evidence suggests that there is not an ideal percentage of calories from B, E distribution carbohydrate, protein, and fat for all people with diabetes B; therefore, macronutrient distribution should be based on individualized assessment of current eating patterns, preferences, and metabolic goals. E c Carbohydrate amount and available insulin may be the most important A factors influencing glycemic response after eating and should be considered when developing the eating plan. c Monitoring carbohydrate intake, whether by carbohydrate counting or B experience-based estimation, remains critical in achieving glycemic control. c Carbohydrate intake from vegetables, fruits, whole grains, legumes, and B dairy products should be advised over intake from other carbohydrate sources, especially those that contain added fats, sugars, or sodium. c Substituting low glycemic2load foods for higher glycemic2load foods C may modestly improve glycemic control. c Individuals at high risk for type 2 diabetes should be encouraged to B achieve the U.S. Department of Agriculture recommendation for dietary fiber (14 g fiber/1,000 kcal) and to consume foods containing whole grains (one-half of grain intake). c While substituting sucrose-containing foods for isocaloric amounts of A other carbohydrates may have similar blood glucose effects, consumption should be minimized to avoid displacing nutrient-dense food choices. c People with diabetes and those at risk should limit or avoid intake of B sugar-sweetened beverages to reduce risk for weight gain and worsening of cardiometabolic risk profile. Protein c In individuals with type 2 diabetes, ingested protein appears to increase B insulin response without increasing plasma glucose concentrations. Therefore, carbohydrate sources high in protein should not be used to treat or prevent hypoglycemia. c Evidence is inconclusive regarding an ideal amount of total fat for people C, B with diabetes; therefore, goals should be individualized. C Fat quality appears to be far more important than quantity. B c A Mediterranean-style eating pattern, rich in monounsaturated fatty B acids, may benefit glycemic control and CVD risk factors and can therefore be recommended as an effective alternative to a lower-fat, higher-carbohydrate eating pattern. Continued on p. S23 care.diabetesjournals.org Position Statement S23

Table 4.1—Continued Topic Recommendations Evidence rating Dietary fat c Increased consumption of foods containing long-chain omega-3 fatty acids B (EPA and DHA), such as fatty fish, and omega-3 linolenic acid (ALA) is recommended. c The consumption of fish (particularly fatty fish) at least two times (two B servings) per week is recommended. c The amount of dietary saturated fat, cholesterol, and trans fat recommended C for people with diabetes is the same as that recommended for the general population. c Evidence does not support recommending omega-3 supplements for people A with diabetes for the prevention or treatment of cardiovascular events. Micronutrients and herbal supplements c There is no clear evidence of benefit from vitamin or mineral C supplementation in people with diabetes who do not have underlying deficiencies. c Routine supplementation with antioxidants, such as vitamins E and C and C carotene, is not advised due to insufficient evidence of efficacy and concerns related to long-term safety. c There is insufficient evidence to support the routine use of C micronutrients such as chromium, magnesium, and vitamin D to improve glycemic control in people with diabetes. c There is insufficient evidence to support the use of cinnamon or other E herbs/supplements for the treatment of diabetes. c It is recommended that individualized meal planning include optimization E of food choices to meet recommended dietary allowance/dietary reference intake for all micronutrients. Alcohol c If adults with diabetes choose to drink alcohol, they should be advised to do so C in moderation (no more than one drink per day for adult women and no more than two drinks per day for adult men). c Alcohol consumption may place people with diabetes at an increased risk for B delayed hypoglycemia, especially if taking insulin or insulin secretagogues. Education and awareness regarding the recognition and management of delayed hypoglycemia are warranted. Sodium c The recommendation for the general population to reduce sodium to less than B 2,300 mg/day is also appropriate for people with diabetes. c For individuals with both diabetes and hypertension, further reduction in sodium B intake should be individualized.

Macronutrients Proteins Protein’s effect on blood glucose levels in Carbohydrates For people with diabetes and no evi- type 1 diabetes is less clear. Studies examining the ideal amount dence of diabetic kidney disease, the of carbohydrate intake for people with evidence is inconclusive about recom- Fats diabetes are inconclusive, although mending an ideal amount of protein Limited research exists concerning the monitoring carbohydrate intake and for optimizing glycemic control or for ideal amount of fat for individuals with considering the available insulin are improving one or more CVD risk mea- diabetes. The Institute of Medicine has key strategies for improving postpran- sures (64). Therefore, these goals should defined an acceptable macronutrient dial glucose control (37,69). The litera- be individualized. For people with dia- distribution range for all adults for total ture concerning glycemic index and betes and diabetic kidney disease (with fat of 20–35%ofenergywithnotolera- glycemic load in individuals with diabe- albuminuria), reducing the amount of ble upper intake level defined (75). The tesiscomplex,althoughreductionsin dietary protein below usual intake is type of fatty acids consumed is more A1C of 20.2% to 20.5% have been dem- not recommended because it does not important than total amount of fat onstrated in some studies (64,70). A sys- alter glycemic measures, cardiovascular when looking at metabolic goals and tematic review (64) found consumption risk measures, or the course of glomer- risk of CVD (53,76,77). Multiple random- of whole grains was not associated with ular filtration rate decline (72,73). In in- ized controlled trials including patients improvements in glycemic control in dividuals with type 2 diabetes, ingested with type 2 diabetes have reported im- people with type 2 diabetes, although protein appears to increase insulin re- proved glycemic control and/or blood lip- it may reduce systemic inflammation. sponse without increasing plasma glucose ids when a Mediterranean-style eating One study did find a potential benefitof concentrations (74). Therefore, carbohy- pattern, rich in monounsaturated fatty whole-grain intake in reducing mortality drate sources high in protein should not acid, was consumed (53,57,78,79). A sys- and cardiovascular disease (CVD) (71). be used to treat or prevent hypoglycemia. tematic review (64) concluded that S24 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

supplementation with omega-3 fatty c Evidence supports that all individ- min/week of vigorous-intensity aerobic acids did not improve glycemic control uals, including those with diabe- physical activity, or an equivalent com- but that higher dose supplementation tes, should be encouraged to bination of the two. In addition, the decreased triglycerides in individuals reduce sedentary time, particu- guidelines suggest that adults also do with type 2 diabetes. Randomized con- larlybybreakingupextended muscle-strengthening activities that in- trolled trials also do not support recom- amounts of time (.90 min) spent volve all major muscle groups 2 or more mending omega-3 supplements for sitting. B days/week. The guidelines suggest that primary or secondary prevention of CVD c In the absence of contraindica- adults over age 65 years, or those with – (80 85). People with diabetes should be tions, adults with type 2 diabetes disabilities, follow the adult guidelines if advised to follow the guidelines for the should be encouraged to perform possible or, if this is not possible, be as general population for the recommended resistance training at least twice physically active as they are able. intakes of saturated fat, dietary choles- per week. A Recent evidence supports that all in- terol, and trans fat (86). dividuals, including those with diabetes, should be encouraged to reduce the Sodium Exercise is an important part of the di- amount of time spent being sedentary A review found that decreasing sodium abetes management plan. Regular exer- (e.g., working at a computer, watching intake reduces blood pressure in those cise has been shown to improve blood TV)particularlybybreakingupex- with diabetes (87). Incrementally lower- glucose control, reduce cardiovascular tended amounts of time (.90 min) ing sodium intake (i.e., to 1,500 mg/day) risk factors, contribute to weight loss, spent sitting (101). has shown beneficial effects on blood and improve well-being. Furthermore, pressure (87–89). The American Heart regular exercise may prevent type 2 di- Exercise and Glycemic Control Association recommends 1,500 mg/day abetes in high-risk individuals (91–93). Based on physical activity studies that in- for African Americans, people diag- Structured exercise interventions of at clude people with diabetes, it seems rea- nosed with hypertension, diabetes, or least 8 weeks’ duration have been sonable to recommend that people with chronic kidney disease, and those over showntolowerA1Cbyanaverageof diabetes follow the physical activity guide- 51 years of age (90). However, other 0.66% in people with type 2 diabetes, lines as for the general population. For studies (88,89) have warranted caution even with no significant change in BMI example, studies included in the meta- for universal sodium restriction to (94). There are considerable data for the analysis of effects of exercise interventions 1,500 mg in this population. For indi- health benefits (e.g., increased cardiovas- on glycemic control (94) had a mean of 3.4 viduals with diabetes and hyperten- cular fitness, muscle strength, improved sessions/week, with a mean of 49 min/ sion, setting a sodium intake goal of insulin sensitivity, etc.) of regular physical session. Also, the Diabetes Prevention Pro- ,2,300 mg/day should be considered activity for those with type 1 diabetes gram (DPP) lifestyle intervention included on an individual basis. Sodium intake (95). Higher levels of exercise intensity 150 min/week of moderate-intensity exer- recommendations should take into ac- are associated with greater improve- cise and showed beneficial effect on gly- count palatability, availability, additional ments in A1C and in fitness (96). Other cemia in those with prediabetes (91). cost of specialty low-sodium products, benefits include slowing the decline in Clinical trials have provided strong evi- and the difficulty of achieving both low- mobility among overweight patients dence for the A1C-lowering value of re- sodium recommendations and a nutri- with diabetes (97). “Exercise and Type 2 sistance training in older adults with type tionally adequate diet (86). Diabetes: The American College of Sports 2 diabetes (98) and for an additive benefit For complete discussion and refer- Medicine and the American Diabetes As- of combined aerobic and resistance exer- ences of all recommendations, see the sociation: Joint Position Statement Exec- cise in adults with type 2 diabetes ADA position statement “Nutrition Ther- utive Summary” reviews the evidence for (102,103). If not contraindicated, patients apy Recommendations for the Manage- the benefits of exercise in people with with type 2 diabetes should be encour- ment of Adults With Diabetes” (36). type 2 diabetes (98). aged to do at least two weekly sessions Exercise and Children of resistance exercise (exercise with free PHYSICAL ACTIVITY As is recommended for all children, chil- weights or weight machines), with each dren with diabetes or prediabetes should session consisting of at least one set of Recommendations be encouraged to engage in at least 60 five or more different resistance exercises c Children with diabetes or predia- min of physical activity each day. Included involving the large muscle groups (98). betes should be encouraged to en- in the 60 min each day, children should Pre-exercise Evaluation gage in at least 60 min of physical engage in vigorous-intensity aerobic As discussed more fully in Section 8. Car- activity each day. B activity, muscle-strengthening activities, diovascular Disease and Risk Manage- c Adults with diabetes should be ad- and bone-strengthening activities at least ment, the best protocol for screening vised to perform at least 150 min/ 3 of those days (99). asymptomatic diabetic patients for coro- week of moderate-intensity aero- Frequency and Type of Exercise nary artery disease (CAD) remains unclear. bic physical activity (50–70% of The U.S. Department of Health and The ADA consensus report “Screening for maximum heart rate), spread Human Services’ physical activity Coronary Artery Disease in Patients With over at least 3 days/week with no guidelines for Americans (100) suggest Diabetes” (104) on this issue concluded more than 2 consecutive days that adults over age 18 years do 150 that routine screening is not recommended. without exercise. A min/week of moderate-intensity or 75 Providers should use clinical judgment in care.diabetesjournals.org Position Statement S25

this area. Certainly, high-risk patients in an increased risk of skin breakdown not separately discuss results on subsets should be encouraged to start with short and infection and of Charcot joint de- of individuals with diabetes, but it does periods of low-intensity exercise and struction with some forms of exercise. suggest that the identified risks are at slowly increase the intensity and dura- However, studies have shown that least equivalent to those found in the tion. Providers should assess patients moderate-intensity walking may not general population. Other studies of in- for conditions that might contraindicate lead to an increased risk of foot ulcers dividuals with diabetes consistently certain types of exercise or predispose to or reulceration in those with peripheral demonstrate that smokers (and people injury, such as uncontrolled hyperten- neuropathy (107). In addition, 150 min/ exposed to secondhand smoke) have a sion, severe autonomic neuropathy, se- week of moderate exercise was re- heightened risk of CVD, premature vere peripheral neuropathy, a history of ported to improve outcomes in patients death, and the microvascular complica- foot lesions, and unstable proliferative with milder forms of neuropathy (106). tions of diabetes. Smoking may have a retinopathy. The patient’s age and pre- All individuals with peripheral neuropa- role in the development of type 2 diabe- vious physical activity level should be thy should wear proper footwear and tes (110). One study in smokers with considered. For type 1 diabetic patients, examine their feet daily to detect le- newly diagnosed type 2 diabetes found the provider should customize the exer- sions early. Anyone with a foot injury that smoking cessation was associated cise regimen to the individual’s needs. or open sore should be restricted to with amelioration of metabolic parame- Those with complications may require a non–weight-bearing activities. ters and reduced blood pressure and al- more thorough evaluation (95). Autonomic Neuropathy buminuria at 1 year (111). Autonomic neuropathy can increase the The routine and thorough assessment Exercise in the Presence of of tobacco use is essential to prevent Nonoptimal Glycemic Control risk of exercise-induced injury or ad- verse event through decreased cardiac smoking or encourage cessation. Nu- Hyperglycemia responsiveness to exercise, postural hy- merous large randomized clinical trials When individuals with type 1 diabetes fi potension, impaired thermoregulation, have demonstrated the ef cacy and are deprived of insulin for 12–48 h and impaired night vision due to impaired cost-effectiveness of brief counseling in are ketotic, exercise can worsen hyper- papillary reaction, and higher suscepti- smoking cessation, including the use of glycemia and ketosis (105); therefore, bility to hypoglycemia (108). Cardiovas- quit lines, in reducing tobacco use. For vigorous activity should be avoided cular autonomic neuropathy is also an the patient motivated to quit, the addi- with ketosis. However, it is not neces- independent risk factor for cardiovascu- tion of pharmacological therapy to coun- sary to postpone exercise based simply lar death and silent myocardial ischemia seling is more effective than either on hyperglycemia, provided the patient (109). Therefore, individuals with dia- treatment alone. Special considerations feels well and urine and/or blood ke- betic autonomic neuropathy should should include assessment of level of tones are negative. undergo cardiac investigation before nicotine dependence, which is associ- fi Hypoglycemia beginning physical activity more intense ated with dif culty in quitting and re- In individuals taking insulin and/or insu- than that to which they are accustomed. lapse (112). Although some patients lin secretagogues, physical activity can may gain weight in the period shortly after cause hypoglycemia if medication dose Albuminuria and Nephropathy smoking cessation, recent research has Physical activity can acutely increase uri- or carbohydrate consumption is not al- demonstrated that this weight gain does nary protein excretion. However, there tered. For individuals on these thera- not diminish the substantial CVD risk ben- is no evidence that vigorous exercise pies, added carbohydrate should be efit realized from smoking cessation (113). increases the rate of progression of ingested if pre-exercise glucose levels There is no evidence that e-cigarettes diabetic kidney disease, and there are ,100 mg/dL (5.6 mmol/L). Hypogly- are a healthier alternative to smoking or appears to be no need for specific exer- cemia is less common in diabetic pa- that e-cigarettes can facilitate smoking cise restrictions for people with diabetic tients who are not treated with insulin cessation. Rigorous study of their short- kidney disease (106). or insulin secretagogues, and no preven- and long-term effects is needed in de- tive measures for hypoglycemia are usu- SMOKING CESSATION termining their safety and efficacy and ally advised in these cases. their cardiopulmonary effects in com- Recommendations parison with smoking and standard ap- Exercise in the Presence of Specific c Advise all patients not to smoke or proaches to smoking cessation (114). Long-Term Complications of Diabetes use tobacco products. A Retinopathy c Include smoking cessation coun- PSYCHOSOCIAL ASSESSMENT AND If proliferative or seling and other forms of treatment CARE severe nonproliferative diabetic reti- as a routine component of diabetes Recommendations nopathy is present, then vigorous aero- care. B bic or resistance exercise may be c Include assessment of the pa- tient’s psychological and social contraindicated because of the risk of Results from epidemiological, case- situation as an ongoing part triggering vitreous hemorrhage or reti- control, and cohort studies provide con- of the medical management of nal detachment (106). vincing evidence to support the causal diabetes. B Peripheral Neuropathy link between cigarette smoking and c Psychosocial screening and follow- Decreased sensation and a higher health risks. Much of the work document- up may include, but are not limited pain threshold in the extremities result ing the effect of smoking on health does S26 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

with diabetes (120) and increases the risk depression (136,137). Interventions to to, attitudes about the illness, for myocardial infarction and postmyo- enhance self-management and address expectations for medical man- cardial infarction (121) and all-cause severe distress have demonstrated effi- agement and outcomes, affect/ mortality (122). There appears to be a cacy in diabetes-related distress (13). mood, general and diabetes- bidirectional relationship between de- related quality of life, resources pression and both diabetes (123) and IMMUNIZATION (financial, social, and emotional), metabolic syndrome (124). and psychiatric history. E Diabetes-related distress is distinct Recommendations c Routinely screen for psychosocial from clinical depression and is very com- c Provide routine vaccinations for problems such as depression, mon (125–127) among people with di- children and adults with diabetes diabetes-related distress, anxi- abetes and their family members (118). as for the general population. C ety, eating disorders, and cogni- Prevalence is reported as 18–45%, with c Annually provide an influenza vac- tive impairment. B an incidence of 38–48% over 18 months. cine to all patients with diabetes c Older adults (aged $65 years) High levels of distress are significantly $6monthsofage.C with diabetes should be consid- linked to A1C, self-efficacy, dietary and c Administer pneumococcal poly- ered a high-priority population exercise behaviors (13,126), and medi- saccharide vaccine 23 (PPSV23) for depression screening and cation adherence (128). Other issues to all patients with diabetes $2 treatment. B known to impact self-management and years of age. C c Patients with comorbid diabetes health outcomes include, but are not lim- c Adults $65 years of age, if not and depression should receive a ited to, attitudes about the illness, ex- previously vaccinated, should re- stepwise collaborative care ap- pectations for medical management and ceive pneumococcal conjugate proach for the management of outcomes, anxiety, general and diabetes- vaccine 13 (PCV13), followed by depression. A related quality of life, resources (finan- PPSV23 6–12 months after initial cial, social, and emotional) (129), and vaccination. C Emotional well-being is an important part psychiatric history (130). Screening tools c Adults $65 years of age, if previ- of diabetes care and self-management. are available for a number of these areas ously vaccinated with PPSV23, Psychological and social problems can should receive a follow-up $12 ’ – (23,131,132). impair the individual s (115 117) or months with PCV13. C family’s (118) ability to carry out Referral to Mental Health Specialist c Administer hepatitis B vaccination diabetes care tasks and therefore Indications for referral to a mental to unvaccinated adults with diabe- compromise health status. There are health specialist familiar with diabetes tes who are aged 19–59 years. C opportunities for the clinician to rou- management may include gross disre- c Consider administering hepatitis B tinely assess psychosocial status in a gard for the medical regimen (by self vaccination to unvaccinated adults timely and efficient manner so that re- or others) (133), depression, overall with diabetes who are aged $60 ferral for appropriate services can be ac- stress related to work-life balance, pos- years. C complished. A systematic review and sibility of self-harm, debilitating anxiety meta-analysis showed that psychosocial (alone or with depression), indications As for the general population, all chil- interventions modestly but significantly of an eating disorder (134), or cognitive dren and adults with diabetes should re- improved A1C (standardized mean dif- functioning that significantly impairs ceive routine vaccinations (138,139). ference 20.29%) and mental health out- judgment. It is preferable to incorporate Influenza and pneumonia are common, comes. However, there was a limited psychological assessment and treatment preventable infectious diseases associ- association between the effects on A1C into routine care rather than waiting for a ated with high mortality and morbidity and mental health, and no intervention specific problem or deterioration in met- in vulnerable populations, such as the characteristics predicted benefitonboth abolic or psychological status (23,125). In young and the elderly, and in people outcomes (119). the Second Diabetes Attitudes, Wishes with chronic diseases. Although there Screening and Needs (DAWN2) study, significant are limited studies reporting the mor- Key opportunities for routine screening diabetes-related distress was reported bidity and mortality of influenza and of psychosocial status occur at diagno- by 44.6% of the participants, but only pneumococcal pneumonia specifically sis, during regularly scheduled manage- 23.7% reported that their health care in people with diabetes, observational ment visits, during hospitalizations, with team asked them how diabetes impacted studies of patients with a variety of new-onset complications, or when prob- their life (125). chronic illnesses, including diabetes, lems with glucose control, quality of life, Although the clinician may not feel show that these conditions are associ- or self-management are identified. Pa- qualified to treat psychological prob- ated with an increase in hospitalizations tients are likely to exhibit psychological lems (135), optimizing the patient- for influenza and its complications. Peo- vulnerability at diagnosis, when their provider relationship as a foundation ple with diabetes may be at an increased medical status changes (e.g., end of the can increase the likelihood that the pa- risk of the bacteremic form of pneumo- honeymoon period), when the need for tient will accept referral for other ser- coccal infection and have been reported intensified treatment is evident, and vices. Collaborative care interventions to have a high risk of nosocomial bacter- when complications are discovered. De- and use of a team approach have dem- emia, with a mortality rate as high as pression affects about 20–25% of people onstrated efficacy in diabetes and 50% (140). In a case-control series, care.diabetesjournals.org Position Statement S27

influenza vaccine was shown to reduce the effect on glycemic control. Diabetes Care 19. Glazier RH, Bajcar J, Kennie NR, Willson K. A diabetes-related hospital admission by 2002;25:1159–1171 systematic review of interventions to improve as much as 79% during fluepidemics 4. Martin D, Lange K, Sima A, et al.; SWEET diabetes care in socially disadvantaged popula- group. Recommendations for age-appropriate tions. Diabetes Care 2006;29:1675–1688 (141). There is sufficient evidence to education of children and adolescents with di- 20. Hawthorne K, Robles Y, Cannings-John R, support that people with diabetes abetes and their parents in the European Union. Edwards AG. Culturally appropriate health edu- have appropriate serologic and clinical Pediatr Diabetes 2012;13(Suppl. 16):20–28 cation for type 2 diabetes mellitus in ethnic mi- responses to these vaccinations. The 5. Committee on Quality of Health Care in Amer- nority groups. Cochrane Database Syst Rev ica. Institute of Medicine. Crossing the Quality 2008;3:CD006424 Centers for Disease Control and Preven- Chasm: A New Health System for the 21st Century 21. Sarkisian CA, Brown AF, Norris KC, Wintz RL, tion (CDC) Advisory Committee on [Internet], Washington, DC: National Academies Mangione CM. A systematic review of diabetes Immunization Practices recommends in- Press, 2001. Available from http://www.iom.edu/ self-care interventions for older, African Amer- fluenza and pneumococcal vaccines for Reports/2001/Crossing-the-Quality-Chasm-A- ican, or Latino adults. Diabetes Educ 2003;29: – all individuals with diabetes (http:// New-Health-System-for-the-21st-Century.aspx. 467 479 Accessed 1 October 2014 22. Chodosh J, Morton SC, Mojica W, et al. Meta- www.cdc.gov/vaccines/recs). 6. Barker JM, Goehrig SH, Barriga K, et al.; analysis: chronic disease self-management pro- DAISY Study. Clinical characteristics of children grams for older adults. Ann Intern Med 2005; Pneumococcal Vaccines in Older diagnosed with type 1 diabetes through inten- 143:427–438 Adults sive screening and follow-up. Diabetes Care 23. Peyrot M, Rubin RR. Behavioral and psycho- – The ADA endorses a recent CDC advisory 2004;27:1399 1404 social interventions in diabetes: a conceptual 7. Frosch DL, Uy V, Ochoa S, Mangione CM. review. Diabetes Care 2007;30:2433–2440 panel that recommends that both Evaluation of a behavior support intervention 24. Naik AD, Palmer N, Petersen NJ, et al. Com- PCV13 and PPSV23 should be adminis- for patients with poorly controlled diabetes. parative effectiveness of goal setting in diabetes tered routinely in series to all adults 65 Arch Intern Med 2011;171:2011–2017 mellitus group clinics: randomized clinical trial. years of age or older (142). 8. Cooke D, Bond R, Lawton J, et al.; U.K. NIHR Arch Intern Med 2011;171:453–459 DAFNE Study Group. Structured type 1 diabetes 25. Duke S-AS, Colagiuri S, Colagiuri R. Individ- Pneumococcal Vaccine-Naïve People education delivered within routine care: impact ual patient education for people with type 2 Adults 65 years of age or older who have on glycemic control and diabetes-specificqual- diabetes mellitus. Cochrane Database Syst Rev not previously received pneumococcal ity of life. Diabetes Care 2013;36:270–272 2009;1:CD005268 vaccine or whose previous vaccination 9. Steinsbekk A, Rygg LØ, Lisulo M, Rise MB, 26. Shah M, Kaselitz E, Heisler M. The role of Fretheim A. Group based diabetes self- community health workers in diabetes: update history is unknown should receive a management education compared to routine on current literature. Curr Diab Rep 2013;13: dose of PCV13 first, followed by PPSV23. treatment for people with type 2 diabetes mel- 163–171 A dose of PPSV23 should be given 6–12 litus. A systematic review with meta-analysis. 27. Heisler M, Vijan S, Makki F, Piette JD. Di- months following a dose of PCV13. If BMC Health Serv Res 2012;12:213 abetes control with reciprocal peer support ver- PPSV23 cannot be given within this time 10. Deakin TA, McShane CE, Cade JE, Williams R. sus nurse care management: a randomized trial. Group based training for self-management strat- Ann Intern Med 2010;153:507–515 period, a dose of PPSV23 should be given egies in people with type 2 diabetes mellitus. 28. Heisler M. Overview of peer support mod- during the next visit. The two vaccines Cochrane Database Syst Rev 2005;2:CD003417 els to improve diabetes self-management and should not be coadministered, and the 11. Cochran J, Conn VS. Meta-analysis of qual- clinical outcomes. Diabetes Spectrum 2007;20: minimum interval between vaccine dos- ity of life outcomes following diabetes self- 214–221 management training. Diabetes Educ 2008;34: 29. Long JA, Jahnle EC, Richardson DM, ing should be 8 weeks. 815–823 Loewenstein G, Volpp KG. Peer mentoring and Previous Vaccination With PPSV23 12. Thorpe CT, Fahey LE, Johnson H, Deshpande financial incentives to improve glucose control Adults 65 years of age or older who pre- M, Thorpe JM, Fisher EB. Facilitating healthy in African American veterans: a randomized tri- coping in patients with diabetes: a systematic al. Ann Intern Med 2012;156:416–424 viously have received one or more doses review. Diabetes Educ 2013;39:33–52 30. Moskowitz D, Thom DH, Hessler D, Ghorob of PPSV23 should also receive PCV13 if 13. Fisher L, Hessler D, Glasgow RE, et al. A, Bodenheimer T. Peer coaching to improve they have not yet received it. PCV13 REDEEM: a pragmatic trial to reduce diabetes diabetes self-management: which patients ben- should be given no sooner than 12 months distress. Diabetes Care 2013;36:2551–2558 efit most? J Gen Intern Med 2013;28:938–942 after receipt of the most recent PPSV23 14. Robbins JM, Thatcher GE, Webb DA, 31. Foster G, Taylor SJC, Eldridge SE, Ramsay J, Valdmanis VG. 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National care intervention: results of a randomized con- 33. Duncan I, Birkmeyer C, Coughlin S, Li QE, standards for diabetes self-management educa- trolled trial. Diabetes Educ 2010;36:301–309 Sherr D, Boren S. Assessing the value of diabetes tion and support. Diabetes Care 2013;37(Suppl. 17. Tang TS, Funnell MM, Brown MB, Kurlander education. Diabetes Educ 2009;35:752–760 1):S144–S153 JE. Self-management support in “real-world” 34. Johnson TM, Murray MR, Huang Y. Associ- 2. Marrero DG, Ard J, Delamater AM, et al. settings: an empowerment-based intervention. ations between self-management education Twenty-first century behavioral medicine: a con- Patient Educ Couns 2010;79:178–184 and comprehensive diabetes clinical care. Dia- text for empowering clinicians and patients with 18. Renders CM, Valk GD, Griffin SJ, Wagner EH, betes Spectrum 2010;23:41–46 diabetes: a consensus report. Diabetes Care Eijk Van JT, Assendelft WJ. Interventions to im- 35. Inzucchi SE, Bergenstal RM, Buse JB, et al.; 2013;36:463–470 prove the management of diabetes in primary American Diabetes Association (ADA); Euro- 3. Norris SL, Lau J, Smith SJ, Schmid CH, care, outpatient, and community settings: a sys- pean Association for the Study of Diabetes Engelgau MM. Self-management education for tematic review. Diabetes Care 2001;24:1821– (EASD). Management of hyperglycemia in type adults with type 2 diabetes: a meta-analysis of 1833 2 diabetes: a patient-centered approach. S28 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

Position statement of the American Diabetes drug treatment–Lifestyle Over and Above Drugs need for antihyperglycemic drug therapy in pa- Association (ADA) and the European Association in Diabetes (LOADD) study: randomised con- tients with newly diagnosed type 2 diabetes: for the Study of Diabetes (EASD). Diabetes Care trolled trial. BMJ 2010;341:c3337 a randomized trial. Ann Intern Med 2009;151: 2012;35:1364–1379 49. Franz MJ, Monk A, Barry B, et al. Effective- 306–314 36. Evert AB, Boucher JL, Cypress M, et al. Nu- ness of medical nutrition therapy provided by 63. Li TY, Brennan AM, Wedick NM, Mantzoros trition therapy recommendations for the man- dietitians in the management of non-insulin- C, Rifai N, Hu FB. Regular consumption of nuts is agement of adults with diabetes. Diabetes Care dependent diabetes mellitus: a randomized, associated with a lower risk of cardiovascular 2014;37(Suppl. 1):S120–S143 controlled clinical trial. 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Diabetes nean diet. N Engl J Med 2013;368:1279–1290 ticipants with type 2 diabetes following a low- Care 2011;34:823–827 54. Metz JA, Stern JS, Kris-Etherton P, et al. A fat vegan diet or a conventional diabetes diet 41. Scavone G, Manto A, Pitocco D, et al. Effect randomized trial of improved weight loss with a for 22 weeks. J Am Diet Assoc 2008;108:1636– of carbohydrate counting and medical nutri- prepared meal plan in overweight and obese 1645 tional therapy on glycaemic control in type 1 patients: impact on cardiovascular risk reduc- 68. Stern L, Iqbal N, Seshadri P, et al. The effects diabetic subjects: a pilot study. Diabet Med tion. Arch Intern Med 2000;160:2150–2158 of low-carbohydrate versus conventional 2010;27:477–479 55. West DS, DiLillo V, Bursac Z, Gore SA, weight loss diets in severely obese adults: 42. UK Prospective Diabetes Study (UKPDS) Greene PG. Motivational interviewing improves one-year follow-up of a randomized trial. Ann Group. 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Ziemer DC, Berkowitz KJ, Panayioto RM, year comparison of a high-monounsaturated fat 70. Thomas D, Elliott EJ. Low glycaemic index, et al. A simple meal plan emphasizing healthy diet with a high-carbohydrate diet in type 2 di- or low glycaemic load, diets for diabetes mellitus. food choices is as effective as an exchange- abetes. Diabetes Care 2009;32:215–220 Cochrane Database Syst Rev 2009;1:CD006296 basedmealplanforurbanAfricanAmericans 58. Davis NJ, Tomuta N, Schechter C, et al. Com- 71. He M, van Dam RM, Rimm E, Hu FB, Qi L. with type 2 diabetes. Diabetes Care 2003;26: parative study of the effects of a 1-year dietary Whole-grain, cereal fiber, bran, and germ intake 1719–1724 intervention of a low-carbohydrate diet versus a and the risks of all-cause and cardiovascular 45. Wolf AM, Conaway MR, Crowther JQ, et al.; low-fat diet on weight and glycemic control in disease-specific mortality among women with Improving Control with Activity and Nutrition type 2 diabetes. 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The chrane Database Syst Rev 2007;4:CD002181 CD004097 Diabetes Excess Weight Loss (DEWL) Trial: 74. Layman DK, Clifton P, Gannon MC, Krauss 47. Davis RM, Hitch AD, Salaam MM, Herman a randomised controlled trial of high-protein RM, Nuttall FQ. Protein in optimal health: heart WH, Zimmer-Galler IE, Mayer-Davis EJ. Tele- versus high-carbohydrate diets over 2 years in disease and type 2 diabetes. Am J Clin Nutr health improves diabetes self-management in type 2 diabetes. Diabetologia 2012;55:905–914 2008;87:1571S–1575S an underserved community: diabetes Telecare. 61. Wing RR, Bolin P, Brancati FL, et al.; Look 75. Institute of Medicine. Dietary Reference In- Diabetes Care 2010;33:1712–1717 AHEAD Research Group. Cardiovascular effects takes for Energy, Carbohydrate, Fiber, Fat, Fatty 48. Coppell KJ, Kataoka M, Williams SM, of intensive lifestyle intervention in type 2 di- Acids, Cholesterol, Protein, and Amino Acids [In- Chisholm AW, Vorgers SM, Mann JI. Nutritional abetes. N Engl J Med 2013;369:145–154 ternet], 2002. Available from http://www.iom. intervention in patients with type 2 diabetes 62. Esposito K, Maiorino MI, Ciotola M, et al. edu/Reports/2002/Dietary-Reference-Intakes- who are hyperglycaemic despite optimised Effects of a Mediterranean-style diet on the for-Energy-Carbohydrate-Fiber-Fat-Fatty-Acids- care.diabetesjournals.org Position Statement S29

Cholesterol-Protein-and-Amino-Acids.aspx. Ac- 88. Thomas MC, Moran J, Forsblom C, et al.; and type 2 diabetes. Diabetes Care 2004;27: cessed 1 October 2014 FinnDiane Study Group. The association be- 2518–2539 76. Office of Disease Prevention and Health tween dietary sodium intake, ESRD, and all- 103. Church TS, Blair SN, Cocreham S, et al. Ef- Promotion, U.S. Department of Health and Hu- cause mortality in patients with type 1 diabetes. fects of aerobic and resistance training on he- man Services. Dietary Guidelines for Americans Diabetes Care 2011;34:861–866 moglobin A1c levels in patients with type 2 [Internet], 2010. Available from http://www 89. Ekinci EI, Clarke S, Thomas MC, et al. Dietary diabetes: a randomized controlled trial. JAMA .health.gov/dietaryguidelines. Accessed 1 Octo- salt intake and mortality in patients with type 2 2010;304:2253–2262 ber 2014 diabetes. Diabetes Care 2011;34:703–709 104. Bax JJ, Young LH, Frye RL, Bonow RO, 77. Ros E. Dietary cis-monounsaturated fatty 90. Whelton PK, Appel LJ, Sacco RL, et al. Steinberg HO, Barrett EJ. Screening for coronary acids and metabolic control in type 2 diabetes. Sodium, blood pressure, and cardiovascular artery disease in patients with diabetes. Diabe- Am J Clin Nutr 2003;78(Suppl.):617S–625S disease: further evidence supporting the tes Care 2007;30:2729–2736 78. Shai I, Schwarzfuchs D, Henkin Y, et al.; American Heart Association sodium reduction 105. Chu L, Hamilton J, Riddell MC. Clinical man- Dietary Intervention Randomized Controlled recommendations. Circulation 2012;126:2880– agement of the physically active patient with type Trial (DIRECT) Group. Weight loss with a low- 2889 1 diabetes. Phys Sportsmed 2011;39:64–77 carbohydrate, Mediterranean, or low-fat diet. 91. Knowler WC, Barrett-Connor E, Fowler SE, 106. Colberg SR. Exercise and Diabetes: A Clini- N Engl J Med 2008;359:229–241 et al.; Diabetes Prevention Program Research cian’s Guide to Prescribing Physical Activity,1st 79. Brunerova L, Smejkalova V, Potockova J, Group. Reduction in the incidence of type 2 di- ed. Alexandria, VA, American Diabetes Associa- Andel M. A comparison of the influence of a abetes with lifestyle intervention or metformin. tion, 2013 high-fat diet enriched in monounsaturated fatty N Engl J Med 2002;346:393–403 107. Lemaster JW, Reiber GE, Smith DG, acids and conventional diet on weight loss and 92. Tuomilehto J, Lindstrom¨ J, Eriksson JG, Heagerty PJ, Wallace C. Daily weight-bearing metabolic parameters in obese non-diabetic et al.; Finnish Diabetes Prevention Study Group. activity does not increase the risk of diabetic and type 2 diabetic patients. Diabet Med Prevention of type 2 diabetes mellitus by foot ulcers. Med Sci Sports Exerc 2003;35: 2007;24:533–540 changes in lifestyle among subjects with im- 1093–1099 80. Harris WS, Mozaffarian D, Rimm E, et al. paired glucose tolerance. N Engl J Med 2001; 108. Spallone V, Ziegler D, Freeman R, et al.; Omega-6 fatty acids and risk for cardiovascular 344:1343–1350 Toronto Consensus Panel on Diabetic Neuropa- disease: a science advisory from the American 93. Pan X-R, Li G-W, Hu Y-H, et al. Effects of diet thy. Cardiovascular autonomic neuropathy in Heart Association Nutrition Subcommittee of and exercise in preventing NIDDM in people diabetes: clinical impact, assessment, diagnosis, the Council on Nutrition, Physical Activity, and with impaired glucose tolerance: the Da Qing and management. Diabetes Metab Res Rev Metabolism; Council on Cardiovascular Nursing; IGT and Diabetes Study. Diabetes Care 1997; 2011;27:6392653 and Council on Epidemiology and Prevention. 20:537–544 109. Pop-Busui R, Evans GW, Gerstein HC, Circulation 2009;119:902–907 94. Boule´ NG, Haddad E, Kenny GP, Wells GA, et al.; Action to Control Cardiovascular Risk in 81. Crochemore ICC, Souza AFP, de Souza ACF, Sigal RJ. Effects of exercise on glycemic control Diabetes Study Group. Effects of cardiac auto- Rosado EL. v-3 polyunsaturated fatty acid sup- and body mass in type 2 diabetes mellitus: nomic dysfunction on mortality risk in the Ac- plementation does not influence body compo- a meta-analysis of controlled clinical trials. tion to Control Cardiovascular Risk in Diabetes sition, insulin resistance, and lipemia in women JAMA 2001;286:1218–1227 (ACCORD) trial. Diabetes Care 2010;33:1578– with type 2 diabetes and obesity. Nutr Clin Pract 95. Colberg SR, Riddell MC. Physical activity: 1584 2012;27:553–560 regulation of glucose metabolism, clinicial man- 110. Jankowich M, Choudhary G, Taveira TH, 82. Bot M, Pouwer F, Assies J, Jansen EHJM, agement strategies, and weight control. In Type Wu W-C. Age-, race-, and gender-specificprev- Beekman ATF, de Jonge P. Supplementation 1 Diabetes Sourcebook. Peters AL, Laffel LM, alence of diabetes among smokers. Diabetes with eicosapentaenoic omega-3 fatty acid Eds. Alexandria, VA, American Diabetes Associ- Res Clin Pract 2011;93:e101–e105 does not influence serum brain-derived ation, 2013 111. Voulgari C, Katsilambros N, Tentolouris N. neurotrophic factor in diabetes mellitus pa- 96. Boule´ NG, Kenny GP, Haddad E, Wells GA, Smoking cessation predicts amelioration of mi- tients with major depression: a randomized Sigal RJ. Meta-analysis of the effect of struc- croalbuminuria in newly diagnosed type 2 dia- controlled pilot study. Neuropsychobiology tured exercise training on cardiorespiratory fit- betes mellitus: a 1-year prospective study. 2011;63:219–223 ness in type 2 diabetes mellitus. Diabetologia Metabolism 2011;60:1456–1464 83. Holman RR, Paul S, Farmer A, Tucker L, 2003;46:1071–1081 112. Ranney L, Melvin C, Lux L, McClain E, Lohr Stratton IM, Neil HA; Atorvastatin in Factorial 97. Rejeski WJ, Ip EH, Bertoni AG, et al.; Look KN. Systematic review: smoking cessation inter- with Omega-3 EE90 Risk Reduction in Diabetes AHEAD Research Group. Lifestyle change and vention strategies for adults and adults in spe- Study Group. Atorvastatin in Factorial with mobility in obese adults with type 2 diabetes. cial populations. Ann Intern Med 2006;145: Omega-3EE90RiskReduction in Diabetes N Engl J Med 2012;366:1209–1217 845–856 (AFORRD): a randomised controlled trial. Diabe- 98.ColbergSR,SigalRJ,FernhallB,etal. 113. Clair C, Rigotti NA, Porneala B, et al. Asso- tologia 2009;52:50–59 Exercise and type 2 diabetes: the American Col- ciation of smoking cessation and weight change 84. Kromhout D, Geleijnse JM, de Goede J, et al. lege of Sports Medicine and the American Di- with cardiovascular disease among adults with n-3 fatty acids, ventricular arrhythmia-related abetes Association: joint position statement and without diabetes. JAMA 2013;309:1014– events, and fatal myocardial infarction in post- executive summary. Diabetes Care 2010;33: 1021 myocardial infarction patients with diabetes. Di- 2692–2696 114. Palazzolo DL. Electronic cigarettes and abetes Care 2011;34:2515–2520 99. Janssen I, Leblanc AG. Systematic review of vaping: a new challenge in clinical medicine 85. Bosch J, Gerstein HC, Dagenais GR, et al.; the health benefits of physical activity and fit- and public health. A literature review. Front ORIGIN Trial Investigators. n-3 fatty acids and ness in school-aged children and youth. Int J Public Health 2013;1:56 cardiovascular outcomes in patients with dys- Behav Nutr Phys Act 2010;7:40 115. Anderson RJ, Grigsby AB, Freedland KE, glycemia. N Engl J Med 2012;367:309–318 100. Office of Disease Prevention and Health et al. Anxiety and poor glycemic control: 86. Maillot M, Drewnowski A. A conflict be- Promotion; U.S. Department of Health and a meta-analytic review of the literature. Int J tween nutritionally adequate diets and meeting Human Services. 2008 Physical Activity Guide- Psychiatry Med 2002;32:235–247 the 2010 dietary guidelines for sodium. Am J lines for Americans [Internet], 2008. Available 116. Delahanty LM, Grant RW, Wittenberg E, Prev Med 2012;42:174–179 from http://www.health.gov/paguidelines/ et al. Association of diabetes-related emotional 87. Bray GA, Vollmer WM, Sacks FM, guidelines/default.aspx. Accessed 1 October 2014 distress with diabetes treatment in primary care Obarzanek E, Svetkey LP, Appel LJ; DASH Collab- 101. Katzmarzyk PT, Church TS, Craig CL, patients with type 2 diabetes. Diabet Med 2007; orative Research Group. A further subgroup Bouchard C. Sitting time and mortality from all 24:48–54 analysis of the effects of the DASH diet and causes, cardiovascular disease, and cancer. Med 117. Anderson RJ, Freedland KE, Clouse RE, three dietary sodium levels on blood pressure: Sci Sports Exerc 2009;41:998–1005 Lustman PJ. The prevalence of comorbid depres- results of the DASH-Sodium Trial. Am J Cardiol 102. Sigal RJ, Kenny GP, Wasserman DH, sion in adults with diabetes: a meta-analysis. Di- 2004;94:222–227 Castaneda-Sceppa C. Physical activity/exercise abetes Care 2001;24:1069–1078 S30 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

118. Kovacs Burns K, Nicolucci A, Holt RIG, meaningful? Establishing cut points for the Di- difficulties: a qualitative study. Diabetes Care et al.; DAWN2 Study Group. Diabetes Attitudes, abetes Distress Scale. Diabetes Care 2012;35: 2011;34:1086–1088 Wishes and Needs second study (DAWN2Ô): 259–264 136. Ciechanowski P. Diapression: an inte- cross-national benchmarking indicators for fam- 127. Fisher L, Glasgow RE, Strycker LA. The re- grated model for understanding the experience ily members living with people with diabetes. lationship between diabetes distress and clini- of individuals with co-occurring diabetes and Diabet Med 2013;30:778–788 cal depression with glycemic control among depression. Clinical Diabetes 2011;29:43–49 119. Harkness E, Macdonald W, Valderas J, patients with type 2 diabetes. Diabetes Care 137. Katon WJ, Lin EHB, Von Korff M, et al. Col- Coventry P, Gask L, Bower P. Identifying psycho- 2010;33:1034–1036 laborative care for patients with depression and social interventions that improve both physical 128. Aikens JE. Prospective associations be- chronic illnesses. N Engl J Med 2010;363:2611– andmentalhealthinpatientswithdiabetes: tween emotional distress and poor outcomes 2620 a systematic review and meta-analysis. Diabe- in type 2 diabetes. Diabetes Care 2012;35: 138. Akinsanya-Beysolow I; Advisory Commit- tes Care 2010;33:926–930 2472–2478 tee on Immunization Practices (ACIP); ACIP 120. Bot M, Pouwer F, Zuidersma M, van Melle 129. Gary TL, Safford MM, Gerzoff RB, et al. Child/Adolescent Immunization Work Group; JP, de Jonge P. Association of coexisting diabe- Perception of neighborhood problems, health Centers for Disease Control and Prevention tes and depression with mortality after myocar- behaviors, and diabetes outcomes among (CDC). Advisory Committee on Immunization dial infarction. Diabetes Care 2012;35:503–509 adults with diabetes in managed care: the Practices recommended immunization sched- 121. Scherrer JF, Garfield LD, Chrusciel T, et al. TranslatingResearchIntoActionforDiabetes ules for persons aged 0 through 18 years - Increased risk of myocardial infarction in de- (TRIAD) study. Diabetes Care 2008;31:273–278 United States, 2014. MMWR Morb Mortal pressed patients with type 2 diabetes. Diabetes 130. Zhang X, Norris SL, Gregg EW, Cheng YJ, Wkly Rep 2014;63:108–109 Care 2011;34:1729–1734 Beckles G, Kahn HS. Depressive symptoms and 139. Bridges CB, Coyne-Beasley T; Advisory 122. Sullivan MD, O’Connor P, Feeney P, et al. mortality among persons with and without di- Committee on Immunization Practices (ACIP); Depression predicts all-cause mortality: epide- abetes. Am J Epidemiol 2005;161:652–660 ACIP Adult Immunization Work Group; Centers miological evaluation from the ACCORD HRQL 131. Fisher L, Glasgow RE, Mullan JT, Skaff MM, for Disease Control and Prevention (CDC). Advi- substudy. Diabetes Care 2012;35:1708–1715 Polonsky WH. Development of a brief diabetes sory Committee on Immunization Practices rec- 123. Chen P-C, Chan Y-T, Chen H-F, Ko M-C, Li C-Y. distress screening instrument. Ann Fam Med ommended immunization schedule for adults Population-based cohort analyses of the bidi- 2008;6:246–252 aged 19 years or older - United States, 2014. rectional relationship between type 2 diabetes 132. McGuire BE, Morrison TG, Hermanns N, MMWR Morb Mortal Wkly Rep 2014;63:110– and depression. Diabetes Care 2013;36:376– et al. Short-form measures of diabetes-related 112 382 emotional distress: the Problem Areas in Diabe- 140. Smith SA, Poland GA. Use of influenza and 124. Pan A, Keum N, Okereke OI, et al. Bidirec- tes Scale (PAID)-5 and PAID-1. Diabetologia pneumococcal vaccines in people with diabetes. tional association between depression and met- 2010;53:66–69 Diabetes Care 2000;23:95–108 abolic syndrome: a systematic review and meta- 133. Rubin RR, Peyrot M. Psychological issues 141. Colquhoun AJ, Nicholson KG, Botha JL, analysis of epidemiological studies. Diabetes and treatments for people with diabetes. J Clin Raymond NT. Effectiveness of influenza vaccine Care 2012;35:1171–1180 Psychol 2001;57:457–478 in reducing hospital admissions in people with 125. Nicolucci A, Kovacs Burns K, Holt RIG, 134. Young-Hyman DL, Davis CL. Disordered diabetes. Epidemiol Infect 1997;119:335–341 et al.; DAWN2 Study Group. Diabetes Attitudes, eating behavior in individuals with diabetes: im- 142. Tomczyk S, Bennett NM, Stoecker C, et al. Wishes and Needs second study (DAWN2Ô): portance of context, evaluation, and classifica- Use of 13-valent pneumococcal conjugate vac- cross-national benchmarking of diabetes- tion. Diabetes Care 2010;33:683–689 cine and 23-valent pneumococcal polysaccha- related psychosocial outcomes for people with 135. Beverly EA, Hultgren BA, Brooks KM, ride vaccine among adults aged $65 years: diabetes. Diabet Med 2013;30:767–777 Ritholz MD, Abrahamson MJ, Weinger K. Under- recommendations of the Advisory Committee 126. Fisher L, Hessler DM, Polonsky WH, standing physicians’ challenges when treating on Immunization Practices (ACIP). MMWR Mullan J. When is diabetes distress clinically type 2 diabetic patients’ social and emotional Morb Mortal Wkly Rep 2014;63:822–825 Diabetes Care Volume 38, Supplement 1, January 2015 S31

5. Prevention or Delay of Type 2 American Diabetes Association Diabetes Diabetes Care 2015;38(Suppl. 1):S31–S32 | DOI: 10.2337/dc15-S008

Recommendations c Patients with impaired glucose tolerance (IGT) A, impaired fasting glucose (IFG) E, or an A1C 5.7–6.4% E should be referred to an intensive diet and physical activity behavioral counseling program targeting loss of 7% of body weight and increasing moderate-intensity physical activity (such as brisk walk- ing) to at least 150 min/week. c Follow-up counseling may be important for success. B c Based on the cost-effectiveness of diabetes prevention, such programs should OIINSTATEMENT POSITION be covered by third-party payers. B c Metformin therapy for prevention of type 2 diabetes may be considered in those with IGT A,IFGE, or an A1C 5.7–6.4% E, especially for those with BMI .35 kg/m2, aged ,60 years, and women with prior gestational diabetes mellitus (GDM). A c At least annual monitoring for the development of diabetes in those with prediabetes is suggested. E c Screening for and treatment of modifiable risk factors for cardiovascular dis- ease is suggested. B c Diabetes self-management education (DSME) and support (DSMS) programs are appropriate venues for people with prediabetes to receive education and support to develop and maintain behaviors that can prevent or delay the onset of diabetes. C

LIFESTYLE MODIFICATIONS Randomized controlled trials have shown that individuals at high risk for developing type 2 diabetes (IFG, IGT, or both) can significantly decrease the rate of diabetes onset with particular interventions (1–5). These include intensive lifestyle modifi- cation programs that have been shown to be very effective (;58% reduction after 3 years). Follow-up of all three large studies of lifestyle intervention has shown sus- tained reduction in the rate of conversion to type 2 diabetes: 43% reduction at 20 years in the Da Qing study (6), 43% reduction at 7 years in the Finnish Diabetes Prevention Study (DPS) (7), and 34% reduction at 10 years in the U.S. Diabetes Pre- vention Program Outcomes Study (DPPOS) (8). A cost-effectiveness model suggested that lifestyle interventions in the Diabetes Prevention Program (DPP) are cost-effective (9). Actual cost data from the DPP and DPPOS confirm that the lifestyle interventions are highly cost-effective (10). Group delivery of the DPP intervention in community settings has the potential to be significantly less expensive while still achieving similar weight loss (11). The Centers for Disease Control and Prevention (CDC) helps coordinate the National Diabetes Prevention Program, a resource designed to bring evidence- based lifestyle change programs for preventing type 2 diabetes to communities (http://www.cdc.gov/diabetes/prevention/index.htm). Given the clinical trial results and the known risks of progression of prediabetes to diabetes, people with an A1C 5.7–6.4%, IGT, or IFG should be counseled on lifestyle Suggested citation: American Diabetes Associa- changes with goals similar to those of the DPP (7% weight loss and moderate- tion. Prevention or delay of type 2 diabetes. Sec. intensity physical activity of at least 150 min/week). 5. In Standards of Medical Care in Diabetesd2015. Diabetes Care 2015;38(Suppl. 1):S31–S32 PHARMACOLOGICAL INTERVENTIONS © 2015 by the American Diabetes Association. Readers may use this article as long as the work Pharmacological agents, such as metformin, a-glucosidase inhibitors, orlistat, and is properly cited, the use is educational and not thiazolidinediones, have each been shown to decrease incident diabetes to various for profit, and the work is not altered. S32 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

degrees. Metformin has the strongest supporting successful behavior change diabetes by lifestyle intervention: follow-up of evidence base and demonstrated long- and the healthy behaviors recommended the Finnish Diabetes Prevention Study. Lancet – term safety as pharmacological therapy for people with prediabetes are largely 2006;368:1673 1679 8. Knowler WC, Fowler SE, Hamman RF, et al.; for diabetes prevention (12). For other identical to those for people with diabe- Diabetes Prevention Program Research Group. drugs, cost, side effects, and lack of a tes. Given their training and experience, 10-year follow-up of diabetes incidence and persistent effect require consideration. providers of DSME and DSMS are partic- weight loss in the Diabetes Prevention Program Metformin was less effective than ularly well equipped to assist people with Outcomes Study. Lancet 2009;374:1677–1686 lifestyle modification in the DPP and prediabetes in developing and maintain- 9. Herman WH, Hoerger TJ, Brandle M, et al.; Diabetes Prevention Program Research Group. DPPOS but may be cost-saving over a ing behaviors that can prevent or delay The cost-effectiveness of lifestyle modification 10-year period (10). It was as effective the onset of diabetes (14–16). or metformin in preventing type 2 diabetes in as lifestyle modification in participants adults with impaired glucose tolerance. Ann In- 2 – with BMI $35 kg/m but not signifi- References tern Med 2005;142:323 332 cantly better than placebo in those 10. Diabetes Prevention Program Research 1. Knowler WC, Barrett-Connor E, Fowler SE, Group. The 10-year cost-effectiveness of life- over 60 years of age (1). In the DPP, for et al.; Diabetes Prevention Program Research style intervention or metformin for diabetes women with a history of GDM, metfor- Group. Reduction in the incidence of type 2 di- prevention: an intent-to-treat analysis of the min and intensive lifestyle modification abetes with lifestyle intervention or metformin. DPP/DPPOS. Diabetes Care 2012;35:723–730 N Engl J Med 2002;346:393–403 11. Ackermann RT, Finch EA, Brizendine E, Zhou led to an equivalent 50% reduction in 2. Buchanan TA, Xiang AH, Peters RK, et al. diabetes risk (13). Metformin may be H, Marrero DG. Translating the Diabetes Pre- Preservation of pancreatic b-cell function and vention Program into the community. The recommended for very high-risk individu- prevention of type 2 diabetes by pharma- DEPLOY Pilot Study. Am J Prev Med 2008;35: als (e.g., with history of GDM, who are very cological treatment of insulin resistance in 357–363 obese, and/or those with more severe or high-risk hispanic women. Diabetes 2002;51: 12. Diabetes Prevention Program Research – progressive hyperglycemia). 2796 2803 Group. Long-term safety, tolerability, and 3. Chiasson J-L, Josse RG, Gomis R, Hanefeld M, People with prediabetes often have weight loss associated with metformin in the Karasik A, Laakso M; STOP-NIDDM Trial Re- Diabetes Prevention Program Outcomes Study. other cardiovascular risk factors, such as search Group. Acarbose for prevention of type Diabetes Care 2012;35:731–737 obesity, hypertension, and dyslipidemia, 2 diabetes mellitus: the STOP-NIDDM random- 13. Ratner RE, Christophi CA, Metzger BE, et al.; and are at an increased risk for cardiovas- ised trial. Lancet 2002;359:2072–2077 Diabetes Prevention Program Research Group. ’ cular disease events. While treatment 4. Lin JS, O Connor E, Evans CV, Senger CA, Prevention of diabetes in women with a history Rowland MG, Groom HC. Behavioral counseling goals are the same as for other patients of gestational diabetes: effects of metformin to promote a healthy lifestyle in persons with and lifestyle interventions. J Clin Endocrinol without diabetes, increased vigilance is cardiovascular risk factors: a systematic review Metab 2008;93:4774–4779 warranted to identify and treat these for the U.S. Preventive Services Task Force. Ann 14. Parekh D, Sarathi V, Shivane VK, Bandgar and other risk factors (e.g., smoking). Intern Med 2014;161:5682578 TR, Menon PS, Shah NS. Pilot study to evaluate 5. Paulweber B, Valensi P, Lindstrom¨ J, et al. A the effect of short-term improvement in vita- DIABETES SELF-MANAGEMENT European evidence-based guideline for the pre- min D status on glucose tolerance in patients EDUCATION AND SUPPORT vention of type 2 diabetes. Horm Metab Res with type 2 diabetes mellitus. Endocr Pract 2010;42(Suppl. 1):S3–S36 2010;16:600–608 The standards for DSME and DSMS (see 6. Li G, Zhang P, Wang J, et al. The long-term 15. Shah M, Kaselitz E, Heisler M. The role of Section 4. Foundations of Care) can also effect of lifestyle interventions to prevent dia- community health workers in diabetes: update apply to the education and support of betes in the China Da Qing Diabetes Prevention on current literature. Curr Diab Rep 2013;13: Study: a 20-year follow-up study. Lancet 2008; 163–171 people with prediabetes. Currently, there – fi 371:1783 1789 16. Heisler M. Overview of peer support mod- are signi cant barriers to the provision of 7. Lindstrom¨ J, Ilanne-Parikka P, Peltonen M, els to improve diabetes self-management and education and support to those with pre- et al.; Finnish Diabetes Prevention Study Group. clinical outcomes. Diabetes Spectrum 2007;20: diabetes. However, the strategies for Sustained reduction in the incidence of type 2 214–221 Diabetes Care Volume 38, Supplement 1, January 2015 S33

6. Glycemic Targets American Diabetes Association Diabetes Care 2015;38(Suppl. 1):S33–S40 | DOI: 10.2337/dc15-S009

ASSESSMENT OF GLYCEMIC CONTROL Two primary techniques are available for health providers and patients to assess the effectiveness of the management plan on glycemic control: patient self-monitoring of blood glucose (SMBG) or interstitial glucose and A1C. Continuous glucose mon- itoring (CGM) may be a useful adjunct to SMBG in selected patients.

Recommendations c When prescribed as part of a broader educational context, SMBG results may help guide treatment decisions and/or self-management for patients using less frequent insulin injections B or noninsulin therapies. E OIINSTATEMENT POSITION c When prescribing SMBG, ensure that patients receive ongoing instruction and regular evaluation of SMBG technique, SMBG results, and their ability to use SMBG data to adjust therapy. E c Patients on multiple-dose insulin or insulin pump therapy should perform SMBG prior to meals and snacks, occasionally postprandially, at bedtime, prior to ex- ercise, when they suspect low blood glucose, after treating low blood glucose until they are normoglycemic, and prior to critical tasks such as driving. B c When used properly, CGM in conjunction with intensive insulin regimens is a useful tool to lower A1C in selected adults (aged $25 years) with type 1 diabetes. A c Although the evidence for A1C lowering is less strong in children, teens, and younger adults, CGM may be helpful in these groups. Success correlates with adherence to ongoing use of the device. B c CGM may be a supplemental tool to SMBG in those with hypoglycemia un- awareness and/or frequent hypoglycemic episodes. C c Given variable adherence to CGM, assess individual readiness for continuing use of CGM prior to prescribing. E c When prescribing CGM, robust diabetes education, training, and support are required for optimal CGM implementation and ongoing use. E

Self-monitoring of Blood Glucose Major clinical trials of insulin-treated patients have included SMBG as part of the multifactorial interventions to demonstrate the benefit of intensive glycemic con- trol on diabetes complications. SMBG is thus an integral component of effective therapy (1). SMBG allows patients to evaluate their individual response to therapy and assess whether glycemic targets are being achieved. Integrating SMBG results into diabetes management can be a useful tool for guiding medical nutrition therapy and physical activity, preventing hypoglycemia, and adjusting medications (partic- ularly prandial insulin doses). Evidence supports a correlation between greater SMBG frequency and lower A1C (2). The patient’s specific needs and goals should dictate SMBG frequency and timing.

Optimization SMBG accuracy is dependent on the instrument and user (3), so it is important to evaluate each patient’s monitoring technique, both initially and at regular intervals thereafter. Optimal use of SMBG requires proper review and interpretation of the Suggested citation: American Diabetes Associa- data, both by the patient and provider. Among patients who check their blood tion. Glycemic targets. Sec. 6. In Standards of Medical Care in Diabetesd2015.DiabetesCare glucose at least once daily, many report taking no action when results are high or 2015;38(Suppl. 1):S33–S40 low (4). In a yearlong study of insulin-na¨ıve patients with suboptimal initial glycemic © 2015 by the American Diabetes Association. control, a group trained in structured SMBG (a paper tool was used at least quarterly Readers may use this article as long as the work to collect and interpret 7-point SMBG profiles taken on 3 consecutive days) reduced is properly cited, the use is educational and not their A1C by 0.3 percentage points more than the control group (5). Patients should for profit, and the work is not altered. S34 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

be taught how to use SMBG data to SMBG, with the latter still required for A1C Testing adjust food intake, exercise, or phar- making acute treatment decisions. macological therapy to achieve specific A 26-week randomized trial of 322 Recommendations at least goals. The ongoing need for and fre- type 1 diabetic patients showed that c Perform the A1C test two quency of SMBG should be reevaluated adults aged $25 years using intensive times a year in patients who are at each routine visit. SMBG is especially insulin therapy and CGM experienced a meeting treatment goals (and who E important for insulin-treated patients 0.5% reduction in A1C (from ;7.6% to have stable glycemic control). to monitor for and prevent asymptom- 7.1%), compared with those using inten- c Perform the A1C test quarterly in pa- atic hypoglycemia and hyperglycemia. sive insulin therapy with SMBG (12). Sen- tients whose therapy has changed or E sor use in those aged ,25 years (children, who are not meeting glycemic goals. For Patients on Intensive Insulin Regimens teens, and adults) did not result in signif- c Use of point-of-care testing for Most patients on intensive insulin regi- icant A1C lowering, and there was no A1C provides the opportunity for E mens (multiple-dose insulin or insulin significant difference in hypoglycemia more timely treatment changes. pump therapy, including patients with in any group. The greatest predictor of type 1 diabetes) should consider SMBG A1C lowering for all age-groups was fre- fl prior to meals and snacks, occasionally quency of sensor use, which was highest A1C re ects average glycemia over sev- postprandially, at bedtime, prior to exer- in those aged $25yearsandlowerin eral months (3) and has strong predictive cise, when they suspect low blood glu- younger age-groups. value for diabetes complications (22,23). cose, after treating low blood glucose A recent registry study of 17,317 partic- Thus, A1C testing should be performed d until they are normoglycemic, and prior ipants confirmed that more frequent CGM routinely in all patients with diabetes at to critical tasks such as driving. For many use is associated with lower A1C (13), initial assessment and as part of continu- – patients, this will require testing 6 10 (or while another study showed that children ing care. Measurement approximately more) times daily, although individual with .70% sensor use missed fewer every 3 months determines whether pa- ’ needs may vary. A database study of school days (14). Small randomized con- tients glycemic targets have been almost 27,000 children and adolescents trolled trials in adults and children with reached and maintained. The frequency with type 1 diabetes showed that, after baseline A1C 7.0–7.5% have confirmed fa- of A1C testing should depend on the clin- adjustment for multiple confounders, in- vorable outcomes (A1C and hypoglycemia ical situation, the treatment regimen, and ’ creased daily frequency of SMBG was occurrence) in groups using CGM, suggest- the clinician s judgment. Some patients fi signi cantly associated with lower A1C ing that CGM may provide further benefit with stable glycemia well within target 2 ( 0.2% per additional test per day) for individuals with type 1 diabetes who may do well with testing only twice per and with fewer acute complications (6). already have tight control (15,16). year. Unstable or highly intensively man- aged patients (e.g., pregnant women with For Patients Using Basal Insulin or A meta-analysis suggests that, com- pared with SMBG, CGM is associ- type 1 diabetes) may require testing more Oral Agents frequently than every 3 months (24). The evidence is insufficient regarding ated with short-term A1C lowering of when to prescribe SMBG and how often ;0.26% (17). The long-term effective- A1C Limitations testing is needed for patients who do ness of CGM needs to be determined. The A1C test is subject to certain limita- not use an intensive insulin regimen, This technology may be particularly tions. Conditions that affect red blood cell such as those with type 2 diabetes using useful in those with hypoglycemia turnover (hemolysis, blood loss) and he- basal insulin or oral agents. unawareness and/or frequent hypogly- moglobin variants must be considered, Several randomized trials have called cemic episodes, although studies have particularly when the A1C result does into question the clinical utility and cost- not shown significant reductions in se- not correlate with the patient’s blood glu- effectiveness of routine SMBG in noninsulin- vere hypoglycemia (17,18). A CGM de- cose levels (3). For patients in whom A1C/ treated patients (7–9). A meta-analysis vice equipped with an automatic low estimated average glucose (eAG) and suggested that SMBG reduced A1C by glucose suspend feature has been ap- measured blood glucose appear discrep- 0.25% at 6 months (10), but the reduction proved by the U.S. Food and Drug Admin- ant, clinicians should consider the possi- subsides after 12 months (11). A key con- istration. The AutomationtoSimulate bilities of hemoglobinopathy or altered sideration is that performing SMBG alone Pancreatic Insulin Response (ASPIRE) trial red blood cell turnover and the options does not lower blood glucose levels. To be of 247 patients showed that sensor- of more frequent and/or different timing useful, the information must be integrated augmented insulin pump therapy with a of SMBG or CGM use. Other measures of into clinical and self-management plans. low glucose suspend significantly reduced chronic glycemia such as fructosamine nocturnal hypoglycemia, without increas- are available, but their linkage to average Continuous Glucose Monitoring ing A1C levels for those over 16 years of glucose and their prognostic significance Real-time CGM measures interstitial glu- age (19). These devices may offer the op- are not as clear as for A1C. cose (which correlates well with plasma portunity to reduce severe hypoglycemia The A1C does not provide a measure glucose) and includes sophisticated for those with a history of nocturnal of glycemic variability or hypoglycemia. alarms for hypo- and hyperglycemic ex- hypoglycemia. Due to variable adher- For patients prone to glycemic variabil- cursions, but the devices are still not ence, optimal CGM use requires an as- ity, especially type 1 diabetic patients or approved by the U.S. Food and Drug Ad- sessment of individual readiness for the type 2 diabetic patients with severe in- ministration as a sole agent to monitor technology as well as initial and ongoing sulin deficiency, glycemic control is best glucose. CGMs require calibration with education and support (13,20,21). evaluated by the combination of results care.diabetesjournals.org Position Statement S35

from self-monitoring and the A1C. The comparing A1C to CGM data in children hypoglycemia or other adverse ef- A1C may also confirm the accuracy of with type 1 diabetes found a highly sta- fects of treatment. Appropriate the patient’s meter (or the patient’sre- tistically significant correlation between patients might include those with ported SMBG results) and the adequacy A1C and mean blood glucose, although short duration of diabetes, type 2 of the SMBG testing schedule. the correlation (r 5 0.7) was significantly diabetes treated with lifestyle or lower than in the ADAG trial (26). metformin only, long life expec- Whether there are significant differences A1C and Mean Glucose tancy, or no significant cardiovas- Table 6.1 shows the correlation between in how A1C relates to average glucose in cular disease (CVD). C A1C levels and mean glucose levels based children or in different ethnicities is an c Less stringent A1C goals (such as on two studies: the international A1C- area for further study (27,28). For the ,8%) may be appropriate for pa- Derived Average Glucose (ADAG) trial, time being, the question has not led to tients with a history of severe hypo- which based the correlation with A1C different recommendations about testing glycemia, limited life expectancy, on frequent SMBG and CGM in 507 adults A1C or to different interpretations of the advanced microvascular or macro- (83% non-Hispanic whites) with type 1, clinical meaning of given levels of A1C in vascular complications, extensive co- type 2, and no diabetes (25), and an em- those populations. morbid conditions, or long-standing pirical study of the average blood glucose A1C GOALS diabetes in whom the general goal levels at premeal, postmeal, and bedtime is difficult to attain despite diabetes associated with specified A1C levels using For glycemic goals in children, please refer self-management education, ap- data from the ADAG trial (21). The Amer- to Section 11. Children and Adolescents. For propriate glucose monitoring, ican Diabetes Association (ADA) and the glycemic goals in pregnant women, please and effective doses of multiple American Association for Clinical Chemis- refer to Section 12. Management of Diabe- glucose-lowering agents including try have determined that the correlation tes in Pregnancy. insulin. B (r 5 0.92) in the ADAG trial is strong enough to justify reporting both the A1C Recommendations c Lowering A1C to approximately 7% result and the eAG result when a clinician A1C and Microvascular Complications or less has been shown to reduce orders the A1C test. Clinicians should Hyperglycemia defines diabetes, and microvascular complications of dia- note that the mean plasma glucose num- glycemic control is fundamental to betes, and, if implemented soon af- bers in the table are based on ;2,800 diabetes management. The Diabetes ter the diagnosis of diabetes, it is readings per A1C in the ADAG trial. Control and Complications Trial (DCCT) associated with long-term reduc- (1), a prospective randomized controlled tion in macrovascular disease. trial of intensive versus standard glyce- A1C Differences in Ethnic Populations and Therefore, a reasonable A1C goal Children mic control in patients with relatively for many nonpregnant adults is In the ADAG study, there were no signif- recently diagnosed type 1 diabetes ,7%. B icant differences among racial and ethnic showed definitively that improved glyce- c Providers might reasonably sug- groups in the regression lines between mic control is associated with signifi- gest more stringent A1C goals A1C and mean glucose, although there cantly decreased rates of microvascular (such as ,6.5%) for selected in- was a trend toward a difference between (retinopathy and diabetic kidney dis- dividual patients if this can the African/African American and non- ease) and neuropathic complications. be achieved without significant Hispanic white cohorts. A small study Follow-up of the DCCT cohorts in the

Table 6.1—Mean glucose levels for specified A1C levels (21,25) Mean plasma glucose* Mean fasting glucose Mean premeal glucose Mean postmeal glucose Mean bedtime glucose A1C (%) mg/dL mmol/L mg/dL mg/dL mg/dL mg/dL 6 126 7.0 ,6.5 122 118 144 136 6.5–6.99 142 139 164 153 7 154 8.6 7.0–7.49 152 152 176 177 7.5–7.99 167 155 189 175 8 183 10.2 8–8.5 178 179 206 222 9 212 11.8 10 240 13.4 11 269 14.9 12 298 16.5 A calculator for converting A1C results into eAG, in either mg/dL or mmol/L, is available at http://professional.diabetes.org/eAG. *These estimates are based on ADAG data of ;2,700 glucose measurements over 3 months per A1C measurement in 507 adults with type 1, type 2, and no diabetes. The correlation between A1C and average glucose was 0.92 (25). S36 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

Epidemiology of Diabetes Interventions more intensive glycemic targets (e.g., among intensive control subjects was and Complications (EDIC) study (29,30) A1C target ,6.5%) as long as signifi- ,6% in ACCORD, ,6.5% in ADVANCE, demonstrated persistence of these cant hypoglycemia does not become a and a 1.5% reduction in A1C compared microvascular benefits in previously barrier. with control subjects in VADT. Details of intensively treated subjects, even these studies are reviewed extensively though their glycemic control approxi- A1C and Cardiovascular Disease in the ADA position statement “Intensive mated that of previous standard arm Outcomes Glycemic Control and the Prevention subjects during follow-up. CVD is a more common cause of death of Cardiovascular Events: Implications The Kumamoto Study (31) and UK than microvascular complications in of the ACCORD, ADVANCE, and VA Prospective Diabetes Study (UKPDS) populations with diabetes. There is evi- Diabetes Trials: A Position Statement (32,33) confirmed that intensive dence for a cardiovascular benefitofin- of the American Diabetes Association glycemic control was associated with sig- tensive glycemic control after long-term and a Scientific Statement of the nificantly decreased rates of microvascu- follow-up of study cohorts treated early American College of Cardiology Foun- lar and neuropathic complications in inthecourseoftype1andtype2di- dation and the American Heart type 2 diabetic patients. Long-term abetes. In the DCCT, there was a trend Association” (42). follow-up of the UKPDS cohorts showed toward lower risk of CVD events with The glycemic control comparison in enduring effects of early glycemic con- intensive control. In the 9-year post- ACCORDwashaltedearlyduetoan trol on most microvascular complica- DCCT follow-up of the EDIC cohort, par- increased mortality rate in the inten- tions (34). ticipants previously randomized to the sive compared with the standard Three landmark trials (Action to Con- intensive arm had a significant 57% re- arm (1.41% vs. 1.14% per year; hazard trol Cardiovascular Risk in Diabetes duction in the risk of nonfatal myocar- ratio 1.22 [95% CI 1.01–1.46]), with a [ACCORD], Action in Diabetes and Vas- dial infarction (MI), stroke, or CVD similar increase in cardiovascular cular Disease: Preterax and Diamicron death compared with those previously deaths. MR Controlled Evaluation [ADVANCE], in the standard arm (40). The benefitof andVeteransAffairsDiabetesTrial intensive glycemic control in this type 1 Key Points [VADT]) showed that lower A1C levels diabetic cohort has recently been 1. Analysis of the ACCORD data did not were associated with reduced onset or shown to persist for several decades identify a clear explanation for the progression of microvascular complica- (41). excess mortality in the intensive tions (35–37). In type 2 diabetes, there is evidence arm (39). Epidemiological analyses of the DCCT that more intensive treatment of 2. A group-level meta-analysis of (1) and UKPDS (38) demonstrate a glycemia in newly diagnosed patients ACCORD, ADVANCE, and VADT curvilinear relationship between A1C mayreducelong-termCVDrates.Dur- suggested that glucose lowering and microvascular complications. ing the UKPDS trial, there was a 16% had a modest (9%) but statisti- Such analyses suggest that, on a popu- reduction in CVD events (combined cally significant reduction in major lation level, the greatest number of fatal or nonfatal MI and sudden death) CVD outcomes, primarily nonfatal complications will be averted by taking in the intensive glycemic control MI, with no significant effect on patients from very poor control to fair/ arm that did not reach statistical sig- mortality. good control. These analyses also sug- nificance (P 5 0.052), and there was 3. Heterogeneity of the mortality ef- gest that further lowering of A1C from no suggestion of benefitonother fects across studies was noted. 7% to 6% is associated with further re- CVD outcomes (e.g., stroke). However, 4. A prespecified subgroup analy- duction in the risk of microvascular after 10 years of follow-up, those orig- sis suggested that major CVD complications, though the absolute inally randomized to intensive glyce- outcome reduction occurred in pa- risk reductions become much smaller. mic control had significant long-term tients without known CVD at base- Given the substantially increased risk reductions in MI (15% with sulfo- line (hazard ratio 0.84 [95% CI of hypoglycemia in type 1 diabetes tri- nylurea or insulin as initial pharmaco- 0.74–0.94]) (43). als and in recent type 2 diabetes trials, therapy, 33% with metformin as initial 5. Mortality findings in ACCORD (39) the risks of lower glycemic targets may, pharmacotherapy) and in all-cause and subgroup analyses of the VADT on a population level, outweigh the mortality (13% and 27%, respectively) (44) suggested that the potential potential benefits on microvascular (34). risks of intensive glycemic control complications. The ACCORD, ADVANCE, and VADT may outweigh its benefits in some The concerning mortality findings in suggested no significant reduction in patients. the ACCORD trial, discussed below CVD outcomes with intensive glycemic 6. Those with long duration of diabetes, (39), and the relatively intense efforts control in participants followed for known history of severe hypoglyce- required to achieve near-euglycemia 3.525.6 years who had more advanced mia, advanced atherosclerosis, or ad- should also be considered when setting type 2 diabetes than UKPDS partici- vanced age/frailty may benefit from glycemic targets. However, based on pants. All three trials were conducted less aggressive targets. physician judgment and patient prefer- in participants with more long-standing 7. Severe hypoglycemia was signifi- ences, select patients, especially those diabetes (mean duration 8–11 years) cantly more likely in participants in with little comorbidity and long life ex- and either known CVD or multiple car- all three trials randomized to the in- pectancy, may benefit from adopting diovascular risk factors. The target A1C tensive glycemic control arm. care.diabetesjournals.org Position Statement S37

Table 6.2—Summary of glycemic recommendations for nonpregnant adults with targeting postprandial glucose com- diabetes pared with those targeting prepran- A1C ,7.0%* dial glucose (48). Therefore, it is Preprandial capillary plasma glucose 80–130 mg/dL* (4.4–7.2 mmol/L) reasonable for postprandial testing Peak postprandial capillary plasma glucose† ,180 mg/dL* (,10.0 mmol/L) to be recommended for individuals who have premeal glucose values *More or less stringent glycemic goals may be appropriate for individual patients. Goals should be individualized based on duration of diabetes, age/life expectancy, comorbid conditions, within target but have A1C values known CVD or advanced microvascular complications, hypoglycemia unawareness, and above target. Taking postprandial individual patient considerations. plasma glucose measurements 1–2h †Postprandial glucose may be targeted if A1C goals are not met despite reaching preprandial glucose goals. Postprandial glucose measurements should be made 1–2 h after the beginning of after the start of a meal and using the meal, generally peak levels in patients with diabetes. treatments aimed at reducing post- prandial plasma glucose values to ,180 mg/dL (10 mmol/L) may help lower A1C. Providers should be vigilant in negatively affected by postprandial An analysis of data from 470 par- preventing severe hypoglycemia in hyperglycemia (47). It is clear that post- ticipants of the ADAG study (237 patients with advanced disease and prandial hyperglycemia, like prepran- with type 1 diabetes and 147 with should not aggressively attempt to dial hyperglycemia, contributes to type 2 diabetes) found that actual achieve near-normal A1C levels in pa- elevated A1C levels, with its relative average glucose levels associated tients in whom such targets cannot be contribution being greater at A1C levels with conventional A1C targets were safely and reasonably achieved. Severe that are closer to 7%. However, outcome higher than older DCCT and ADA or frequent hypoglycemia is an abso- studies have clearly shown A1C to be targets (Table 6.1) (21,25). These find- lute indication for the modification of the primary predictor of complications, ings support that premeal glucose treatment regimens, including setting and landmark glycemic control trials targets may be relaxed without un- higher glycemic goals. Many factors, such as the DCCT and UKPDS relied dermining overall glycemic control as including patient preferences, should overwhelmingly on preprandial SMBG. measured by A1C. These data have be taken into account when develop- Additionally, a randomized controlled prompted a revision in the ADA- ing a patient’s individualized goals trial in patients with known CVD found recommended premeal target to 80– (Table 6.2). no CVD benefit of insulin regimens 130 mg/dL (4.4–7.2 mmol/L).

A1C and Glycemic Targets Numerous aspects must be considered when setting glycemic targets. The ADA proposes optimal targets, but each target must be individualized to the needs of each patient and their disease factors. When possible, such decisions should be made with the patient, reflecting his or her preferences, needs, and values. Figure 6.1 is not designed to be applied rigidly but used as a broad construct to guide clinical decision making (45), both in type 1 and type 2 diabetes. Recommended glycemic targets for many nonpregnant adults are shown in Table 6.2. The recommendations include blood glucose levels that ap- pear to correlate with achievement of an A1C of ,7%. The issue of prepran- dial versus postprandial SMBG targets is complex (46). Elevated postchal- lenge (2-h oral glucose tolerance test) glucose values have been associ- ated with increased cardiovascular risk independent of fasting plasma glu- cose in some epidemiological studies. Figure 6.1—Depicted are patient and disease factors used to determine optimal A1C targets. In subjects with diabetes, surrogate Characteristics and predicaments toward the left justify more stringent efforts to lower A1C; measures of vascular pathology, such those toward the right suggest less stringent efforts. Adapted with permission from Inzucchi as endothelial dysfunction, are et al. (45). S38 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

HYPOGLYCEMIA dementia (50). Conversely, in a substudy recurrent hypoglycemia unless further of the ACCORD trial, cognitive impair- food is ingested after recovery. Recommendations ment at baseline or decline in cognitive c Individuals at risk for hypoglycemia function during the trial was significantly Glucagon should be asked about symptom- associated with subsequent episodes of Those in close contact with, or having cus- atic and asymptomatic hypoglyce- severe hypoglycemia (51). Evidence from todial care of, people with hypoglycemia- mia at each encounter. C the DCCT/EDIC, which involved younger prone diabetes (family members, c Glucose (15–20 g) is the preferred adults and adolescents with type 1 diabe- roommates, school personnel, child care treatment for the conscious individ- tes, found no association between fre- providers, correctional institution staff, or ual with hypoglycemia, although any quency of severe hypoglycemia and coworkers) should be instructed on the form of carbohydrate that contains cognitive decline (52), as discussed in use of glucagon kits. An individual does glucose may be used. Fifteen minutes Section 11. Children and Adolescents. not need to be a health care professional after treatment, if SMBG shows con- Severe hypoglycemia was associated to safely administer glucagon. A glucagon tinued hypoglycemia, the treatment withmortalityinparticipantsinboththe kit requires a prescription. Care should be should be repeated. Once SMBG re- standard and intensive glycemia arms taken to ensure that glucagon kits are not turns to normal, the individual should oftheACCORDtrial,buttherelation- expired. consume a meal or snack to prevent ships between hypoglycemia, achieved Hypoglycemia Prevention E recurrence of hypoglycemia. A1C, and treatment intensity were not Hypoglycemia prevention is a critical c Glucagon should be prescribed for straightforward. An association of severe component of diabetes management. all individuals at an increased risk of hypoglycemia with mortality was also SMBG and, for some patients, CGM are severe hypoglycemia, and care- found in the ADVANCE trial (53). An asso- essential tools to assess therapy and de- givers or family members of these ciation between self-reported severe hy- tect incipient hypoglycemia. Patients individuals should be instructed on poglycemia and 5-year mortality has also should understand situations that its administration. Glucagon admin- been reported in clinical practice (54). increase their risk of hypoglycemia, istration is not limited to health In 2013, the ADA and the Endocrine such as fasting for tests or procedures, E care professionals. Society published the consensus report during or after intense exercise, and c Hypoglycemia unawareness or one “Hypoglycemia and Diabetes: A Report during sleep. Hypoglycemia may in- or more episodes of severe hypo- of a Workgroup of the American Diabe- crease the risk of harm to self or others, glycemia should trigger reevalua- tes Association and the Endocrine Soci- such as with driving. Teaching people E tion of the treatment regimen. ety” (55) on the effect and treatment of with diabetes to balance insulin use c Insulin-treated patients with hypo- hypoglycemia in patients with diabetes. and carbohydrate intake and exercise glycemia unawareness or an episode Severe hypoglycemia was defined as an are necessary, but these strategies are of severe hypoglycemia should be event requiring the assistance of an- not always sufficient for prevention. advised to raise their glycemic tar- other person. Young children with type In type 1 diabetes and severely gets to strictly avoid further hypogly- 1 diabetes and the elderly were noted insulin-deficient type 2 diabetes, hypo- cemia for at least several weeks in as particularly vulnerable due to their glycemia unawareness (or hypoglycemia- order to partially reverse hypoglyce- limited ability to recognize hypogly- associated autonomic failure) can mia unawareness and reduce risk of cemic symptoms and effectively com- severely compromise stringent diabe- A future episodes. municate their needs. Individualized tes control and quality of life. This syn- c Ongoing assessment of cognitive patient education, dietary interven- drome is characterized by deficient function is suggested with increased tion (e.g., bedtime snack to prevent counterregulatory hormone release, es- vigilance for hypoglycemia by the cli- overnight hypoglycemia), exercise pecially in older adults, and a dimin- nician, patient, and caregivers if low management, medication adjustment, ished autonomic response, which both cognition and/or declining cognition glucose monitoring, and routine clini- are risk factors for, and caused by, hy- B is found. cal surveillance may improve patient poglycemia. A corollary to this “vicious outcomes. cycle” is that several weeks of avoid- ance of hypoglycemia has been demon- Hypoglycemia is the leading limiting fac- Hypoglycemia Treatment strated to improve counterregulation tor in the glycemic management of type Hypoglycemia treatment requires inges- and awareness to some extent in 1 and insulin-treated type 2 diabetes tion of glucose- or carbohydrate- many patients (56). Hence, patients (49). Mild hypoglycemia may be incon- containing foods. The acute glycemic with one or more episodes of severe venient or frightening to patients with response correlates better with the glu- hypoglycemia may benefitfromatleast diabetes. Severe hypoglycemia can cose content of food than with the car- short-term relaxation of glycemic cause acute harm to the person with di- bohydrate content of food. Pure glucose targets. abetes or others, especially if it causes is the preferred treatment, but any form falls, motor vehicle accidents, or other of carbohydrate that contains glucose INTERCURRENT ILLNESS injury. A large cohort study suggested will raise blood glucose. Added fat may For further information on management that among older adults with type 2 retard and then prolong the acute gly- of patients with hyperglycemia in the diabetes, a history of severe hypoglycemia cemic response. Ongoing insulin activity hospital, please refer to Section 13. Di- was associated with greater risk of or insulin secretagogues may lead to abetes Care in the Hospital, Nursing care.diabetesjournals.org Position Statement S39

Home, and Skilled Nursing Facility. 6. Ziegler R, Heidtmann B, Hilgard D, Hofer S, insulin-pump interruption for reduction of hy- Stressful events (e.g., illness, trauma, Rosenbauer J, Holl R; DPV-Wiss-Initiative. Fre- poglycemia. N Engl J Med 2013;369:224–232 surgery, etc.) frequently aggravate quency of SMBG correlates with HbA1c and 20. McQueen RB, Ellis SL, Maahs DM, Anderson acute complications in children and adolescents HD, Nair KV, Campbell JD. Frequency of contin- glycemic control and may precipitate with type 1 diabetes. Pediatr Diabetes 2011;12: uous glucose monitoring use and change in he- diabetic ketoacidosis or nonketotic hy- 11–17 moglobin A1c for adults with type 1 diabetes in perosmolar state, life-threatening con- 7. Farmer A, Wade A, Goyder E, et al. Impact of a clinical practice setting. Endocr Pract 2014;20: ditions that require immediate medical self monitoring of blood glucose in the manage- 1007–1015 ment of patients with non-insulin treated dia- 21. Wei N, Zheng H, Nathan DM. Empirically care to prevent complications and death. betes: open parallel group randomised trial. establishing blood glucose targets to achieve Any condition leading to deterioration in BMJ 2007;335:132 HbA1c goals. Diabetes Care 2014;37:1048–1051 glycemic control necessitates more fre- 8. O’Kane MJ, Bunting B, Copeland M, Coates 22. Albers JW, Herman WH, Pop-Busui R, quent monitoring of blood glucose; VE; ESMON Study Group. Efficacy of self moni- et al.; Diabetes Control and Complications Trial/ ketosis-prone patients also require urine toring of blood glucose in patients with newly Epidemiology of Diabetes Interventions and diagnosed type 2 diabetes (ESMON study): Complications Research Group. Effect of prior or blood ketone monitoring. If accompa- randomised controlled trial. BMJ 2008;336: intensive insulin treatment during the Diabetes nied by ketosis, vomiting, or alteration in 1174–1177 Control and Complications Trial (DCCT) on pe- level of consciousness, marked hypergly- 9. Simon J, Gray A, Clarke P, Wade A, Neil A, ripheral neuropathy in type 1 diabetes during cemia requires temporary adjustment of Farmer A; Diabetes Glycaemic Education and the Epidemiology of Diabetes Interventions the treatment regimen and immediate Monitoring Trial Group. Cost effectiveness of and Complications (EDIC) study. Diabetes Care self monitoring of blood glucose in patients 2010;33:1090–1096 interaction with the diabetes care with non-insulin treated type 2 diabetes: eco- 23. Stratton IM, Adler AI, Neil HAW, et al. As- team. The patient treated with noninsu- nomic evaluation of data from the DiGEM trial. sociation of glycaemia with macrovascular and lin therapies or medical nutrition ther- BMJ 2008;336:1177–1180 microvascular complications of type 2 diabetes apy alone may temporarily require 10. Willett LR. ACP Journal Club. Meta-analysis: (UKPDS 35): prospective observational study. – insulin. Adequate fluid and caloric intake self-monitoring in non-insulin-treated type 2 di- BMJ 2000;321:405 412 abetes improved HbA1c by 0.25%. Ann Intern 24. Jovanovicˇ L, Savas H, Mehta M, Trujillo A, must be assured. Infection or dehydra- Med 2012;156:JC6–JC12 Pettitt DJ. Frequent monitoring of A1C during tion is more likely to necessitate hospi- 11. Malanda UL, Welschen LM, Riphagen II, pregnancy as a treatment tool to guide therapy. talization of the person with diabetes Dekker JM, Nijpels G, Bot SD. Self-monitoring Diabetes Care 2011;34:53–54 than the person without diabetes. of blood glucose in patients with type 2 diabetes 25. Nathan DM, Kuenen J, Borg R, Zheng H, mellitus who are not using insulin. Cochrane Schoenfeld D, Heine RJ; A1c-Derived Average A physician with expertise in diabetes Database Syst Rev 2012;1:CD005060 Glucose Study Group. Translating the A1C assay management should treat the hospital- 12. Tamborlane WV, Beck RW, Bode BW, et al.; into estimated average glucose values. Diabetes ized patient. For further information on Juvenile Diabetes Research Foundation Contin- Care 2008;31:1473–1478 diabetic ketoacidosis management or hy- uous Glucose Monitoring Study Group. Con- 26. Wilson DM, Kollman; Diabetes Research perglycemic nonketotic hyperosmolar tinuous glucose monitoring and intensive in Children Network (DirecNet) Study Group. treatment of type 1 diabetes. N Engl J Med Relationship of A1C to glucose concentrations state, please refer to the ADA statement 2008;359:1464–1476 in children with type 1 diabetes: assessments by “Hyperglycemic Crises in Adult Patients 13. Wong JC, Foster NC, Maahs DM, et al.; T1D high-frequency glucose determinations by sen- With Diabetes” (57). Exchange Clinic Network. Real-time continuous sors. Diabetes Care 2008;31:381–385 glucose monitoring among participants in the 27. Buse JB, Kaufman FR, Linder B, Hirst K, El T1D Exchange clinic registry. Diabetes Care Ghormli L, Willi S; HEALTHY Study Group. Dia- References 2014;37:2702–2709 betes screening with hemoglobin A(1c) versus 1. The Diabetes Control and Complications Trial 14. Hommel E, Olsen B, Battelino T, et al.; fasting plasma glucose in a multiethnic middle- Research Group. The effect of intensive treatment SWITCH Study Group. Impact of continuous glu- school cohort. Diabetes Care 2013;36:429–435 of diabetes on the development and progression cose monitoring on quality of life, treatment 28. Kamps JL, Hempe JM, Chalew SA. Racial dis- of long-term complications in insulin-dependent satisfaction, and use of medical care resources: parity in A1C independent of mean blood glu- diabetes mellitus. N Engl J Med 1993;329:977–986 analyses from the SWITCH study. Acta Diabetol cose in children with type 1 diabetes. Diabetes 2. Miller KM, Beck RW, Bergenstal RM, et al.; 2014;51:845–851 Care 2010;33:1025–1027 T1D Exchange Clinic Network. Evidence of a 15. Battelino T, Phillip M, Bratina N, Nimri R, 29. The Diabetes Control and Complications strong association between frequency of self- Oskarsson P, Bolinder J. Effect of continuous Trial/Epidemiology of Diabetes Interventions monitoring of blood glucose and hemoglobin glucose monitoring on hypoglycemia in type 1 and Complications Research Group. Retinopa- A1c levels in T1D Exchange clinic registry partic- diabetes. Diabetes Care 2011;34:795–800 thy and nephropathy in patients with type 1 di- ipants. Diabetes Care 2013;36:2009–2014 16. Beck RW, Hirsch IB, Laffel L, et al.; Juvenile abetes four years after a trial of intensive 3. Sacks DB, Arnold M, Bakris GL, et al.; National Diabetes Research Foundation Continuous Glu- therapy. N Engl J Med 2000;342:381–389 Academy of Clinical Biochemistry. Position cose Monitoring Study Group. The effect of con- 30. Martin CL, Albers J, Herman WH, et al.; statement executive summary: guidelines and tinuous glucose monitoring in well-controlled DCCT/EDIC Research Group. Neuropathy among recommendations for laboratory analysis in type 1 diabetes. Diabetes Care 2009;32:1378– the Diabetes Control and Complications Trial the diagnosis and management of diabetes mel- 1383 cohort 8 years after trial completion. Diabetes litus. Diabetes Care 2011;34:1419–1423 17. Yeh H-C, Brown TT, Maruthur N, et al. Com- Care 2006;29:340–344 4. Wang J, Zgibor J, Matthews JT, Charron- parative effectiveness and safety of methods of 31. Ohkubo Y, Kishikawa H, Araki E, et al. Inten- Prochownik D, Sereika SM, Siminerio L. Self- insulin delivery and glucose monitoring for di- sive insulin therapy prevents the progression of monitoring of blood glucose is associated with abetes mellitus: a systematic review and meta- diabetic microvascular complications in Japa- problem-solving skills in hyperglycemia and hy- analysis. Ann Intern Med 2012;157:336–347 nese patients with non-insulin-dependent dia- poglycemia. Diabetes Educ 2012;38:207–218 18. Choudhary P, Ramasamy S, Green L, et al. betes mellitus: a randomized prospective 6-year 5. Polonsky WH, Fisher L, Schikman CH, et al. Real-time continuous glucose monitoring study. Diabetes Res Clin Pract 1995;28:103–117 Structured self-monitoring of blood glucose sig- significantly reduces severe hypoglycemia in 32. UK Prospective Diabetes Study (UKPDS) nificantly reduces A1C levels in poorly con- hypoglycemia-unaware patients with type 1 di- Group. Effect of intensive blood-glucose control trolled, noninsulin-treated type 2 diabetes: abetes. Diabetes Care 2013;36:4160–4162 with metformin on complications in overweight results from the Structured Testing Program 19. Bergenstal RM, Klonoff DC, Garg SK, et al.; patients with type 2 diabetes (UKPDS 34). Lan- study. Diabetes Care 2011;34:262–267 ASPIRE In-Home Study Group. Threshold-based cet 1998;352:854–865 S40 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

33. UK Prospective Diabetes Study (UKPDS) Epidemiology of Diabetes Interventions and 48. Raz I, Wilson PWF, Strojek K, et al. Effects of Group. Intensive blood-glucose control with sul- Complications (DCCT/EDIC) Research Group. prandial versus fasting glycemia on cardiovas- phonylureas or insulin compared with conven- Modern-day clinical course of type 1 diabetes cular outcomes in type 2 diabetes: the HEART2D tional treatment and risk of complications in mellitus after 30 years’ duration: the Diabetes trial. Diabetes Care 2009;32:381–386 patients with type 2 diabetes (UKPDS 33). Lan- Control and Complications Trial/Epidemiology 49. Cryer PE. Hypoglycaemia: the limiting factor cet 1998;352:837–853 of Diabetes Interventions and Complications in the glycaemic management of type I and type II 34. Holman RR, Paul SK, Bethel MA, Matthews and Pittsburgh Epidemiology of Diabetes Com- diabetes. Diabetologia 2002;45:937–948 DR, Neil HAW. 10-year follow-up of intensive plications Experience (1983-2005). Arch Intern 50. Whitmer RA, Karter AJ, Yaffe K, Quesenberry glucose control in type 2 diabetes. N Engl Med 2009;169:1307–1316 CP Jr, Selby JV. Hypoglycemic episodes and risk J Med 2008;359:1577–1589 42. Skyler JS, Bergenstal R, Bonow RO, et al. of dementia in older patients with type 2 diabe- 35. Duckworth W, Abraira C, Moritz T, et al.; Intensive glycemic control and the prevention tes mellitus. JAMA 2009;301:1565–1572 VADT Investigators. Glucose control and vascu- of cardiovascular events: implications of the 51. Punthakee Z, Miller ME, Launer LJ, et al.; lar complications in veterans with type 2 diabe- ACCORD, ADVANCE, and VA Diabetes Trials: ACCORD Group of Investigators; ACCORD- tes. N Engl J Med 2009;360:129–139 a position statement of the American Diabetes MIND Investigators. Poor cognitive function 36. Patel A, MacMahon S, Chalmers J, et al.; Association and a scientific statement of the and risk of severe hypoglycemia in type 2 dia- ADVANCE Collaborative Group. Intensive blood American College of Cardiology Foundation betes: post hoc epidemiologic analysis of the glucose control and vascular outcomes in pa- and the American Heart Association. Diabetes ACCORD trial. Diabetes Care 2012;35:787–793 tients with type 2 diabetes. N Engl J Med Care 2009;32:187–192 52. Jacobson AM, Musen G, Ryan CM, et al.; 2008;358:2560–2572 43. Turnbull FM, Abraira C, Anderson RJ, et al. Diabetes Control and Complications Trial/ 37. Ismail-Beigi F, Craven T, Banerji MA, et al.; Intensive glucose control and macrovascular Epidemiology of Diabetes Interventions and Com- ACCORD trial group. Effect of intensive treat- outcomes in type 2 diabetes. Diabetologia plications Study Research Group. Long-term ef- ment of hyperglycaemia on microvascular out- 2009;52:2288–2298 fect of diabetes and its treatment on cognitive comes in type 2 diabetes: an analysis of the 44. Duckworth WC, Abraira C, Moritz TE, et al.; function. N Engl J Med 2007;356:1842–1852 ACCORD randomised trial. Lancet 2010;376: Investigators of the VADT. The duration of di- 53. Zoungas S, Patel A, Chalmers J, et al.; 419–430 abetes affects the response to intensive glucose ADVANCE Collaborative Group. Severe hypo- 38. Adler AI, Stratton IM, Neil HAW, et al. As- control in type 2 subjects: the VA Diabetes Trial. glycemia and risks of vascular events and death. sociation of systolic blood pressure with macro- J Diabetes Complications 2011;25:355–361 N Engl J Med 2010;363:1410–1418 vascular and microvascular complications of 45. Inzucchi SE, Bergenstal RM, Buse JB, et al. 54. McCoy RG, Van Houten HK, Ziegenfuss JY, type 2 diabetes (UKPDS 36): prospective obser- Management of hyperglycemia in type 2 diabe- ShahND,WermersRA,SmithSA.Increased vational study. BMJ 2000;321:412–419 tes, 2015: a patient-centered approach. Update mortality of patients with diabetes reporting 39. Gerstein HC, Miller ME, Byington RP, et al.; to a position statement of the American Diabe- severe hypoglycemia. Diabetes Care 2012;35: Action to Control Cardiovascular Risk in Diabe- tes Association and the European Association 1897–1901 tes Study Group. Effects of intensive glucose for the Study of Diabetes. Diabetes Care 2015; 55. Seaquist ER, Anderson J, Childs B, et al. Hy- lowering in type 2 diabetes. N Engl J Med 38:140–149 poglycemia and diabetes: a report of a work- 2008;358:2545–2559 46. American Diabetes Association. Postpran- group of the American Diabetes Association 40. Nathan DM, Cleary PA, Backlund J-YC, dial blood glucose. Diabetes Care 2001;24: and the Endocrine Society. Diabetes Care et al.; Diabetes Control and Complications 775–778 2013;36:1384–1395 Trial/Epidemiology of Diabetes Interventions 47. Ceriello A, Taboga C, Tonutti L, et al. Evi- 56. Cryer PE. Diverse causes of hypoglycemia- and Complications (DCCT/EDIC) Study Research dence for an independent and cumulative effect associated autonomic failure in diabetes. N Engl Group. Intensive diabetes treatment and cardio- of postprandial hypertriglyceridemia and hyper- J Med 2004;350:2272–2279 vascular disease in patients with type 1 diabetes. glycemia on endothelial dysfunction and oxida- 57. Kitabchi AE, Umpierrez GE, Miles JM, N Engl J Med 2005;353:2643–2653 tive stress generation: effects of short- and Fisher JN. Hyperglycemic crises in adult pa- 41. Nathan DM, Zinman B, Cleary PA, et al.; long-term simvastatin treatment. Circulation tients with diabetes. Diabetes Care 2009;32: Diabetes Control and Complications Trial/ 2002;106:1211–1218 1335–1343 Diabetes Care Volume 38, Supplement 1, January 2015 S41

7. Approaches to Glycemic American Diabetes Association Treatment Diabetes Care 2015;38(Suppl. 1):S41–S48 | DOI: 10.2337/dc15-S010

PHARMACOLOGICAL THERAPY FOR TYPE 1 DIABETES

Recommendations c Most people with type 1 diabetes should be treated with multiple-dose insulin (MDI) injections (three to four injections per day of basal and prandial insulin) or continuous subcutaneous insulin infusion (CSII). A c Most people with type 1 diabetes should be educated in how to match pran- dial insulin dose to carbohydrate intake, premeal blood glucose, and antici- E

pated activity. STATEMENT POSITION c Most people with type 1 diabetes should use insulin analogs to reduce hypo- glycemia risk. A

Insulin Therapy There are excellent reviews to guide the initiation and management of insulin therapy to achieve desired glycemic goals (1,2,3). Although most studies of MDI versus pump therapy have been small and of short duration, a systematic review and meta-analysis concluded that there were no systematic differences in A1C or severe hypoglycemia rates in children and adults between the two forms of intensive in- sulin therapy (4). A large randomized trial in type 1 diabetic patients with nocturnal hypoglycemia reported that sensor-augmented insulin pump therapy with the threshold suspend feature reduced nocturnal hypoglycemia, without increasing glycated hemoglobin values (5). Overall, intensive management through pump therapy/continuous glucose monitoring and active patient/family participation should be strongly encouraged (6–8). For selected individuals who have mastered carbohydrate counting, education on the impact of protein and fat on glycemic excursions can be incorporated into diabetes management (9). The Diabetes Control and Complications Trial (DCCT) clearly showed that intensive insulin therapy (three or more injections per day of insulin) or CSII (insulin pump therapy) was a key part of improved glycemia and better outcomes (10,11). The study was carried out with short- and intermediate-acting human insulins. Despite better microvascular outcomes, intensive insulin therapy was associated with a high rate of severe hypogly- cemia (62 episodes per 100 patient-years of therapy). Since the DCCT, a number of rapid- acting and long-acting insulin analogs have been developed. These analogs are associated with less hypoglycemia in type 1 diabetes, while matching the A1C lowering of human insulins (1,12).

Recommended therapy for type 1 diabetes consists of the following: 1. Use MDI injections (three to four injections per day of basal and prandial insulin) or CSII therapy. 2. Match prandial insulin to carbohydrate intake, premeal blood glucose, and an- ticipated physical activity. 3. For most patients (especially those at an elevated risk of hypoglycemia), use Suggested citation: American Diabetes Associa- insulin analogs. tion. Approaches to glycemic treatment. Sec. 7. 4. For patients with frequent nocturnal hypoglycemia and/or hypoglycemia unawareness, In Standards of Medical Care in Diabetesd2015. a sensor-augmented low glucose threshold suspend pump may be considered. Diabetes Care 2015;38(Suppl. 1):S41–S48 © 2015 by the American Diabetes Association. Pramlintide Readers may use this article as long as the work Pramlintide, an amylin analog, is an agent that delays gastric emptying, blunts is properly cited, the use is educational and not pancreatic secretion of glucagon, and enhances satiety. It is a U.S. Food and Drug for profit, and the work is not altered. S42 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

Administration (FDA)-approved therapy A1C around 0.9–1.1%. A comprehensive achieve or maintain the A1C target for use in type 1 diabetes. It has been listing, including the cost, is available in over 3 months, add a second oral shown to induce weight loss and lower Table 7.1. agent, a GLP-1 receptor agonist, or insulin dose; however, it is only indi- If the A1C target is not achieved after basal insulin. A cated in adults. Concurrent reduction approximately 3 months, consider a c A patient-centered approach of prandial insulin dosing is required to combination of metformin and one of should be used to guide choice reduce the risk of severe hypoglycemia. these six treatment options: sulfonyl- of pharmacological agents. Con- urea, thiazolidinedione, DPP-4 inhibi- siderations include efficacy, tors, SGLT2 inhibitors, GLP-1 receptor Investigational Agents cost, potential side effects, weight, agonists, or basal insulin (Fig. 7.1). Metformin comorbidities, hypoglycemia risk, Drug choice is based on patient prefer- Adding metformin to insulin therapy may and patient preferences. E ences as well as various patient, disease, reduce insulin requirements and improve c Duetotheprogressivenatureof and drug characteristics, with the goal of metabolic control in overweight/obese type 2 diabetes, insulin therapy is reducing blood glucose levels while patients with poorly controlled type 1 eventually indicated for many pa- minimizing side effects, especially hypo- diabetes. In a meta-analysis, metformin tients with type 2 diabetes. B in type 1 diabetes was found to reduce glycemia. Figure 7.1 emphasizes drugs commonly used in the U.S. and/or Europe. insulin requirements (6.6 U/day, P , An updated American Diabetes Asso- Rapid-acting secretagogues (megliti- 0.001) and led to small reductions in ciation/European Association for the nides) may be used instead of sulfonyl- weight and total and LDL cholesterol but Study of Diabetes position statement ureas in patients with irregular meal not to improved glycemic control (abso- (15) evaluated the data and developed P 5 schedules or who develop late post- lute A1C reduction 0.11%, 0.42) (13). recommendations, including advan- prandial hypoglycemia on a sulfonyl- Incretin-Based Therapies tages and disadvantages, for antihyper- urea. Other drugs not shown in the Therapies approved for the treatment of glycemic agents for type 2 diabetic figure (e.g., a-glucosidase inhibitors, co- type 2 diabetes are currently being eval- patients. A patient-centered approach lesevelam, bromocriptine, pramlintide) uated in type 1 diabetes. Glucagon-like is stressed, including patient prefer- may be tried in specific situations, but peptide 1 (GLP-1) agonists and dipep- ences, cost and potential side effects are generally not favored due to modest tidyl peptidase 4 (DPP-4) inhibitors are of each class, effects on body weight, efficacy, the frequency of administra- not currently FDA approved for those and hypoglycemia risk. Lifestyle modifi- tion, and/or side effects. with type 1 diabetes, but are being stud- cations that improve health (see Section For all patients, consider initiating ied in this population. 4. Foundations of Care) should be em- therapy with a dual combination when – phasized along with any pharmacologi- Sodium Glucose Cotransporter 2 Inhibitors A1C is $9% to more expeditiously Sodium–glucose cotransporter 2 (SGLT2) cal therapy. achieve the target A1C level. Insulin inhibitors provide insulin-independent has the advantage of being effective glucose lowering by blocking glucose Initial Therapy where other agents may not be and reabsorption in the proximal renal tubule Most patients should begin with life- should be considered as part of any by inhibiting SGLT2. These agents provide style changes (lifestyle counseling, combination regimen when hyperglyce- modest weight loss and blood pressure weight-loss education, exercise, etc.). mia is severe, especially if symptoms are reduction. Although there are two FDA- When lifestyle efforts alone have not present or any catabolic features approved agents for use in patients with achieved or maintained glycemic goals, (weight loss, ketosis) are in evidence. type 2 diabetes, there are insufficient metformin monotherapy should be Consider initiating combination insulin data to recommend clinical use in type 1 added at, or soon after, diagnosis, un- injectable therapy when blood glucose diabetes at this time (14). less there are contraindications or intol- is $300–350 mg/dL (16.7–19.4 mmol/L) erance. Metformin has a long-standing and/or A1C is $10–12%. As the pa- fi PHARMACOLOGICAL THERAPY FOR evidence base for ef cacy and safety, is tient’s glucose toxicity resolves, the TYPE 2 DIABETES inexpensive, and may reduce risk of car- regimen can, potentially, be subse- diovascular events (16). In patients with quently simplified. Recommendations metformin intolerance or contraindica- c Metformin, if not contraindicated tions, consider an initial drug from other Insulin Therapy and if tolerated, is the preferred classes depicted in Fig. 7.1 under “Dual Many patients with type 2 diabetes even- initial pharmacological agent for therapy” and proceed accordingly. tually require and benefit from insulin type 2 diabetes. A therapy. Providers may wish to consider c In patients with newly diagnosed Combination Therapy regimen flexibility when devising a plan type 2 diabetes and markedly symp- Although there are numerous trials for the initiation and adjustment of insu- tomatic and/or elevated blood glu- comparing dual therapy with metformin lin therapy in people with type 2 diabetes cose levels or A1C, consider initiating alone, few directly compare drugs as (Fig. 7.2). The progressive nature of type insulin therapy (with or without add-on therapy. A comparative effec- 2 diabetes and its therapies should be additional agents). E tiveness meta-analysis (17) suggests regularly and objectively explained to pa- c If noninsulin monotherapy at max- that overall each new class of noninsulin tients. Providers should avoid using insu- imum tolerated dose does not agents added to initial therapy lowers lin as a threat or describing it as a failure care.diabetesjournals.org Position Statement S43

Figure 7.1—Antihyperglycemic therapy in type 2 diabetes: general recommendations (15). The order in the chart was determined by historical availability and the route of administration, with injectables to the right; it is not meant to denote any specific preference. Potential sequences of antihyperglycemic therapy for patients with type 2 diabetes are displayed, with the usual transition moving vertically from top to bottom (although horizontal movement within therapy stages is also possible, depending on the circumstances). DPP-4-i, DPP-4 inhibitor; fxs, fractures; GI, gastro- intestinal; GLP-1-RA, GLP-1 receptor agonist; GU, genitourinary; HF, heart failure; Hypo, hypoglycemia; SGLT2-i, SGLT2 inhibitor; SU, sulfonylurea; TZD, thiazolidinedione. *See ref. 15 for description of efficacy categorization. †Consider starting at this stage when A1C is $9%. ‡Consider starting at this stage when blood glucose is $300–350 mg/dL (16.7–19.4 mmol/L) and/or A1C is $10–12%, especially if symptomatic or catabolic features are present, in which case basal insulin 1 mealtime insulin is the preferred initial regimen. §Usually a basal insulin (NPH, glargine, detemir, degludec). Adapted with permission from Inzucchi et al. (15). or punishment. Equipping patients with combination injectable therapy (Fig. 7.2) premixed insulin analogs, respectively, an algorithm for self-titration of insulin to cover postprandial glucose excur- but their pharmacodynamic profiles doses based on self-monitoring of blood sions. Options include adding a GLP-1 make them suboptimal for the coverage glucose (SMBG) improves glycemic con- receptor agonist or mealtime insulin, of postprandial glucose excursions. A trol in type 2 diabetic patients initiating consisting of one to three injections of less commonly used and more costly insulin (18). rapid-acting insulin analog (lispro, as- alternative to “basal–bolus” therapy Basal insulin alone is the most conve- part, or glulisine) administered just be- with multiple daily injections is CSII nient initial insulin regimen, beginning fore eating. A less studied alternative, (insulin pump). In addition to the sug- at 10 U or 0.1–0.2 U/kg, depending on transitioning from basal insulin to gestions provided for determining the degree of hyperglycemia. Basal in- twice-daily premixed (or biphasic) insu- the starting dose of mealtime insulin sulin is usually prescribed in conjunction lin analog (70/30 aspart mix, 75/25 under a basal–bolus regimen, another with metformin and possibly one addi- or 50/50 lispro mix), could also be con- method consists of adding up the total tional noninsulin agent. If basal insulin sidered. Regular human insulin and current insulin dose and then providing has been titrated to an acceptable fast- human NPH-Regular premixed formula- one-half of this amount as basal and ing blood glucose level, but A1C remains tions (70/30) are less costly alternatives one-half as mealtime insulin, the latter above target, consider advancing to to rapid-acting insulin analogs and split evenly between three meals. 4 oiinStatement Position S44

Table 7.1—Properties of available glucose-lowering agents in the U.S. and Europe that may guide individualized treatment choices in patients with type 2 diabetes (15) Class Compound(s) Cellular mechanism(s) Primary physiological action(s) Advantages Disadvantages Cost* Biguanides c Metformin Activates AMP-kinase c ↓ Hepatic glucose production c Extensive experience c Gastrointestinal side effects (diarrhea, Low (? other) c No hypoglycemia abdominal cramping) c ↓ CVD events (UKPDS) c Lactic acidosis risk (rare) c Vitamin B12 deficiency c Multiple contraindications: CKD, acidosis, hypoxia, dehydration, etc.

Sulfonylureas 2nd Generation Closes KATP channels on c ↑ Insulin secretion c Extensive experience c Hypoglycemia Low c Glyburide/glibenclamide b-cell plasma membranes c ↓ Microvascular risk c ↑ Weight c Glipizide (UKPDS) c ? Blunts myocardial ischemic c Gliclazide† preconditioning c Glimepiride c Low durability

Meglitinides c Repaglinide Closes KATP channels on c ↑ Insulin secretion c ↓Postprandial glucose c Hypoglycemia Moderate (glinides) c Nateglinide b-cell plasma membranes excursions c ↑ Weight c Dosing flexibility c ? Blunts myocardial ischemic preconditioning c Frequent dosing schedule TZDs c Pioglitazone‡ Activates the nuclear c ↑ Insulin sensitivity c No hypoglycemia c ↑ Weight Low c Rosiglitazone§ transcription factor PPAR-g c Durability c Edema/heart failure c ↑ HDL-C c Bone fractures c ↓ Triglycerides c ↑ LDL-C (rosiglitazone) (pioglitazone) c ? ↑ MI (meta-analyses, rosiglitazone) c ? ↓ CVD events (PROactive, pioglitazone) a-Glucosidase c Acarbose Inhibits intestinal c Slows intestinal carbohydrate c No hypoglycemia c Generally modest A1C efficacy Moderate inhibitors c Miglitol a-glucosidase digestion/absorption c ↓Postprandial glucose c Gastrointestinal side effects Care Diabetes excursions (flatulence, diarrhea) c ? ↓ CVD events c Frequent dosing schedule (STOP-NIDDM) c Nonsystemic DPP-4 inhibitors c Sitagliptin Inhibits DPP-4 activity, c ↑ Insulin secretion c No hypoglycemia c Angioedema/urticaria and other High 2015 January 1, Supplement 38, Volume c Vildagliptin† increasing postprandial (glucose-dependent) c Well tolerated immune-mediated dermatological c Saxagliptin active incretin (GLP-1, GIP) c ↓ Glucagon secretion effects c Linagliptin concentrations (glucose-dependent) c ? Acute pancreatitis c Alogliptin c ? ↑ Heart failure hospitalizations Bile acid c Colesevelam Binds bile acids in c ? ↓ Hepatic glucose c No hypoglycemia c Generally modest A1C efficacy High sequestrants intestinal tract, increasing production c ↓ LDL-C c Constipation hepatic bile acid c ? ↑ Incretin levels c ↑ Triglycerides production c May ↓ absorption of other medications Continued on p. S45 care.diabetesjournals.org Table 7.1—Continued Class Compound(s) Cellular mechanism(s) Primary physiological action(s) Advantages Disadvantages Cost* Dopamine-2 c Bromocriptine (quick release)§ Activates dopaminergic c Modulates hypothalamic c No hypoglycemia c Generally modest A1C efficacy High agonists receptors regulation of metabolism c ? ↓ CVD events c Dizziness/syncope c ↑ Insulin sensitivity (Cycloset Safety Trial) c Nausea c Fatigue c Rhinitis SGLT2 inhibitors c Canagliflozin Inhibits SGLT2 in the c Blocks glucose reabsorption c No hypoglycemia c Genitourinary High c Dapagliflozin‡ proximal nephron by the kidney, increasing c ↓ Weight c Polyuria c Empagliflozin glucosuria c ↓ Blood pressure c Volume depletion/hypotension/ c Effective at all stages dizziness of T2DM c ↑ LDL-C c ↑ Creatinine (transient) GLP-1 receptor c Exenatide Activates GLP-1 receptors c ↑ Insulin secretion (glucose- c No hypoglycemia c Gastrointestinal side effects (nausea/ High agonists c Exenatide extended release dependent) c ↓ Weight vomiting/diarrhea) c Liraglutide c ↓ Glucagon secretion c ↓ Postprandial glucose c ↑ Heart rate c Albiglutide (glucose-dependent) excursions c ? Acute pancreatitis c Lixisenatide† c Slows gastric emptying c ↓ Some cardiovascular c C-cell hyperplasia/medullary thyroid c Dulaglutide c ↑ Satiety risk factors tumors in animals c Injectable c Training requirements Amylin mimetics c Pramlintide§ Activates amylin receptors c ↓ Glucagon secretion c ↓ Postprandial glucose c Generally modest A1C efficacy High c Slows gastric emptying excursions c Gastrointestinal side effects (nausea/ c ↑ Satiety c ↓ Weight vomiting) c Hypoglycemia unless insulin dose is simultaneously reduced c Injectable c Frequent dosing schedule c Training requirements Insulins c Rapid-acting analogs Activates insulin receptors c ↑ Glucose disposal c Nearly universal c Hypoglycemia Variable# - Lispro c ↓ Hepatic glucose production response c Weight gain - Aspart c Other c Theoretically unlimited c ? Mitogenic effects - Glulisine efficacy c Injectable c Short-acting c ↓ Microvascular risk c Patient reluctance - Human Regular (UKPDS) c Training requirements c Intermediate-acting - Human NPH c Basal insulin analogs - Glargine - Detemir - Degludec† c

Premixed (several types) S45 Statement Position CKD, chronic kidney disease; CVD, cardiovascular disease; GIP, glucose-dependent insulinotropic peptide; HDL-C, HDL cholesterol; LDL-C, LDL cholesterol; MI, myocardial infarction; PPAR-g, peroxisome proliferator–activated receptor g; PROactive, Prospective Pioglitazone Clinical Trial in Macrovascular Events (30); STOP-NIDDM, Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (31); TZD, thiazolidinedione; T2DM, type 2 diabetes mellitus; UKPDS, UK Prospective Diabetes Study (32,33). Cycloset trial of quick-release bromocriptine (34). *Cost is based on lowest-priced member of the class (see ref. 15). †Not licensed in the U.S. ‡Initial concerns regarding bladder cancer risk are decreasing after subsequent study. §Not licensed in Europe for type 2 diabetes. #Cost is highly dependent on type/brand (analogs . human insulins) and dosage. Adapted with permission from Inzucchi et al. (15). S46 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

Figure 7.2—Approach to starting and adjusting insulin in type 2 diabetes (15). FBG, fasting blood glucose; GLP-1-RA, GLP-1 receptor agonist; hypo, hypoglycemia; mod., moderate; PPG, postprandial glucose; #, number. Adapted with permission from Inzucchi et al. (15).

Figure 7.2 focuses solely on sequen- inhibitors may be helpful in improving need lifelong lifestyle support tial insulin strategies, describing the control and reducing the amount of in- and medical monitoring. B number of injections and the relative sulin needed. Comprehensive educa- c Although small trials have shown complexity and flexibility of each stage. tion regarding SMBG, diet, exercise, glycemic benefit of bariatric surgery Once an insulin regimen is initiated, and the avoidance of and response to in patients with type 2 diabetes and dose titration is important, with adjust- hypoglycemia are critically important in BMI 30–35 kg/m2, there is currently ments made in both mealtime and basal any patient using insulin. insufficient evidence to generally insulins based on the prevailing blood recommend surgery in patients glucose levels and an understanding of BARIATRIC SURGERY with BMI ,35 kg/m2. E the pharmacodynamic profile of each Recommendations formulation (pattern control). c Bariatric surgery may be con- Noninsulin agents may be continued, Bariatricandmetabolicsurgeries, sidered for adults with BMI .35 although sulfonylureas, DPP-4 inhibitors, either gastric banding or procedures kg/m2 and type 2 diabetes, espe- and GLP-1 receptor agonists are typically that involve resecting, bypassing, or cially if diabetes or associated co- stopped once more complex insulin regi- transposing sections of the stomach morbidities are difficult to control mens beyond basal are used. In patients and small intestine, can be effective with lifestyle and pharmacological with suboptimal blood glucose control, weight-loss treatments for severe therapy. B especially those requiring increasing insu- obesity when performed as part of a c Patients with type 2 diabetes who lin doses, adjunctive use of thiazolidine- comprehensive weight-management have undergone bariatric surgery diones (usually pioglitazone) or SGLT2 program with lifelong lifestyle support care.diabetesjournals.org Position Statement S47

and medical monitoring. National guide- studies attempting to match surgical 10. The Diabetes Control and Complications lines support consideration for bariatric and nonsurgical subjects suggest that Trial Research Group. The effect of intensive surgery for people with type 2 diabetes the procedure may reduce longer-term treatment of diabetes on the development . 2 and progression of long-term complications in with BMI 35 kg/m . mortality rates (19). In contrast, a pro- insulin-dependent diabetes mellitus. N Engl J pensity score-adjusted analysis of older, Med 1993;329:977–986 Advantages severely obese patients in Veterans Af- 11. Nathan DM, Cleary PA, Backlund J-YC, et al.; Treatment with bariatric surgery has fairs Medical Centers found that bariatric Diabetes Control and Complications Trial/Epi- been shown to achieve near- or com- surgery was not associated with de- demiology of Diabetes Interventions and Com- plications (DCCT/EDIC) Study Research Group. plete normalization of glycemia 2 years creased mortality compared with usual Intensive diabetes treatment and cardiovascu- following surgery in 72% of patients care (mean follow-up 6.7 years) (24). Ret- lar disease in patients with type 1 diabetes. (compared with 16% in a matched con- rospective analyses and modeling studies N Engl J Med 2005;353:2643–2653 trol group treated with lifestyle and suggest that bariatric surgery may be 12. Rosenstock J, Dailey G, Massi-Benedetti M, pharmacological interventions) (19). A cost-effective for patients with type 2 Fritsche A, Lin Z, Salzman A. Reduced hypoglyce- mia risk with insulin glargine: a meta-analysis study evaluated the long-term (3-year) diabetes, but the results are largely de- comparing insulin glargine with human NPH outcomes of surgical intervention pendent on assumptions about the insulin in type 2 diabetes. Diabetes Care 2005; (Roux-en-Y gastric bypass or sleeve gas- long-term effectiveness and safety of 28:950–955 trectomy) and intensive medical ther- the procedures (25–27). Understanding 13. Vella S, Buetow L, Royle P, Livingstone S, apy (quarterly visits, pharmacological the long-term benefits and risks of bariat- Colhoun HM, Petrie JR. The use of metformin in type 1 diabetes: a systematic review of effi- therapy, SMBG, diabetes education, life- ric surgery in individuals with type 2 diabe- cacy. Diabetologia 2010;53:809–820 style counseling, and encouragement to tes, especially those who are not severely 14. Chiang JL, Kirkman MS, Laffel LM, Peters AL; participate in Weight Watchers) com- obese, will require well-designed clinical Type 1 Diabetes Sourcebook Authors. Type 1 pared with just intensive medical ther- trials, with optimal medical therapy as diabetes through the life span: a position state- apy on achieving a target A1C #6% the comparator (28). Unfortunately, such ment of the American Diabetes Association. Di- abetes Care 2014;37:2034–2054 among obese patients with uncon- studies may not be feasible (29). 15. Inzucchi SE, Bergenstal RM, Buse JB, et al. trolled type 2 diabetes (mean A1C Management of hyperglycemia in type 2 diabe- 9.3%). This A1C target was achieved by tes, 2015: a patient-centered approach. Update 38% (P , 0.001) in the gastric bypass References to a position statement of the American Diabe- group, 24% (P 5 0.01) in the sleeve gas- 1. DeWitt DE, Hirsch IB. Outpatient insulin ther- tes Association and the European Association apy in type 1 and type 2 diabetes mellitus: sci- for the Study of Diabetes. Diabetes Care 2015; trectomy group, and 5% in those receiv- – entific review. JAMA 2003;289:2254–2264 38:140 149 ing medical therapy (20). Diabetes 2. American Diabetes Association. Intensive 16. Holman RR, Paul SK, Bethel MA, Matthews remission rates tend to be higher with Diabetes Management.4thed.WolfsdorfJI,Ed. DR, Neil HA. 10-year follow-up of intensive glu- procedures that bypass portions of the Alexandria, VA, American Diabetes Association, cose control in type 2 diabetes. N Engl J Med 2008;359:1577–1589 small intestine and lower with proce- 2009 3. Mooradian AD, Bernbaum M, Albert SG. Nar- 17. Bennett WL, Maruthur NM, Singh S, et al. dures that only restrict the stomach. Comparative effectiveness and safety of medi- rative review: a rational approach to starting in- Younger age, shorter duration of type cations for type 2 diabetes: an update including sulin therapy. Ann Intern Med 2006;145:125–134 new drugs and 2-drug combinations. Ann Intern 2 diabetes, lower A1C, higher serum in- 4. Yeh H-C, Brown TT, Maruthur N, et al. Com- Med 2011;154:602–613 sulin levels, and nonuse of insulin have parative effectiveness and safety of methods of 18. Blonde L, Merilainen M, Karwe V, Raskin P; insulin delivery and glucose monitoring for di- all been associated with higher remis- TITRATE Study Group. Patient-directed titration abetes mellitus: a systematic review and meta- sion rates after bariatric surgery (21). for achieving glycaemic goals using a once-daily analysis. Ann Intern Med 2012;157:336–347 Although bariatric surgery has been basal insulin analogue: an assessment of two dif- 5. Bergenstal RM, Klonoff DC, Garg SK, et al.; fi ferent fasting plasma glucose targets - the TITRATE shown to improve the metabolic pro les ASPIRE In-Home Study Group. Threshold-based of morbidly obese patients with type 1 study. Diabetes Obes Metab 2009;11:623–631 insulin-pump interruption for reduction of hy- 19. Sjostr¨ om¨ L, Peltonen M, Jacobson P, et al. – diabetes, the role of bariatric surgery in poglycemia. N Engl J Med 2013;369:224 232 Association of bariatric surgery with long-term such patients will require larger and lon- 6. Wood JR, Miller KM, Maahs DM, et al.; T1D remission of type 2 diabetes and with microvas- ger studies (22). Exchange Clinic Network. Most youth with type 1 cular and macrovascular complications. JAMA diabetes in the T1D Exchange clinic registry do 2014;311:2297–2304 not meet American Diabetes Association or In- Disadvantages 20. Schauer PR, Bhatt DL, Kirwan JP, et al.; ternational Society for Pediatric and Adolescent STAMPEDE Investigators. Bariatric surgery Bariatric surgery is costly and has asso- Diabetes clinical guidelines. Diabetes Care 2013; versus intensive medical therapy for diabetesd ciated risks. Morbidity and mortality 36:2035–2037 3-year outcomes. N Engl J Med 2014;370:2002– rates directly related to the surgery 7. Kmietowicz Z. Insulin pumps improve control 2013 have decreased considerably in recent and reduce complications in children with type 21. Still CD, Wood GC, Benotti P, et al. Preop- 1 diabetes. BMJ 2013;347:f5154 years, with 30-day mortality rates now erative prediction of type 2 diabetes remission 8. Phillip M, Battelino T, Atlas E, et al. Nocturnal after Roux-en-Y gastric bypass surgery: a retro- 0.28%, similar to those for laparoscopic glucose control with an artificial pancreas at a spective cohort study. Lancet Diabetes Endocri- cholecystectomy (23). Outcomes vary diabetes camp. N Engl J Med 2013;368:824–833 nol 2014;2:38–45 depending on the procedure and the 9. Wolpert HA, Atakov-Castillo A, Smith SA, 22. Brethauer SA, Aminian A, Rosenthal RJ, experience of the surgeon and center. Steil GM. Dietary fat acutely increases glucose Kirwan JP, Kashyap SR, Schauer PR. Bariatric Longer-term concerns include vitamin concentrations and insulin requirements in surgery improves the metabolic profile of mor- fi patients with type 1 diabetes: implications for bidly obese patients with type 1 diabetes. Di- and mineral de ciencies, osteoporosis, carbohydrate-based bolus dose calculation and abetes Care 2014;37:e51–e52 and rare but often severe hypoglycemia intensive diabetes management. Diabetes Care 23. Buchwald H, Estok R, Fahrbach K, Banel D, from insulin hypersecretion. Cohort 2013;36:810–816 Sledge I. Trends in mortality in bariatric surgery: S48 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

a systematic review and meta-analysis. Surgery 28. Wolfe BM, Belle SH. Long-term risks and in a population with impaired glucose tolerance: 2007;142:621–632 benefits of bariatric surgery: a research chal- rationale, design, and preliminary screening 24. Maciejewski ML, Livingston EH, Smith VA, lenge. JAMA 2014;312:1792–1793 data. Diabetes Care 1998;21:1720–1725 et al. Survival among high-risk patients after 29. Courcoulas AP, Goodpaster BH, Eagleton JK, 32. UK Prospective Diabetes Study (UKPDS) bariatric surgery. JAMA 2011;305:2419–2426 et al. Surgical vs medical treatments for type 2 Group. Intensive blood-glucose control with sul- 25. Hoerger TJ, Zhang P, Segel JE, Kahn HS, diabetes mellitus: a randomized clinical trial. phonylureas or insulin compared with conven- Barker LE, Couper S. Cost-effectiveness of bari- JAMA Surg 2014;149:707–715 tional treatment and risk of complications in atric surgery for severely obese adults with di- 30. Dormandy JA, Charbonnel B, Eckland DJ, patients with type 2 diabetes (UKPDS 33). Lan- abetes. Diabetes Care 2010;33:1933–1939 et al.; PROactive Investigators. Secondary pre- cet 1998;352:837–853 26. Makary MA, Clark JM, Shore AD, et al. Med- vention of macrovascular events in patients 33. UK Prospective Diabetes Study (UKPDS) ication utilization and annual health care costs with type 2 diabetes in the PROactive Study Group. Effect of intensive blood-glucose control in patients with type 2 diabetes mellitus before (PROspective pioglitAzone Clinical Trial In mac- with metformin on complications in overweight and after bariatric surgery. Arch Surg 2010;145: rovascular Events): a randomised controlled tri- patients with type 2 diabetes (UKPDS 34). Lan- 726–731 al. Lancet 2005;366:1279–1289 cet 1998;352:854–865 27. Keating CL, Dixon JB, Moodie ML, Peeters A, 31. Chiasson JL, Gomis R, Hanefeld M, Josse RG, 34. Gaziano JM, Cincotta AH, O’Connor CM, Playfair J, O’Brien PE. Cost-efficacy of surgically Karasik A, Laakso M;STOP-NIDDMTrial et al. Randomized clinical trial of quick-release induced weight loss for the management of Research Group. The STOP-NIDDM Trial: an in- bromocriptine among patients with type 2 di- type 2 diabetes: a randomized controlled trial. ternational study on the efficacy of an alpha- abetes on overall safety and cardiovascular out- Diabetes Care 2009;32:580–584 glucosidase inhibitor to prevent type 2 diabetes comes. Diabetes Care 2010;33:1503–1508 Diabetes Care Volume 38, Supplement 1, January 2015 S49

8. Cardiovascular Disease and Risk American Diabetes Association Management Diabetes Care 2015;38(Suppl. 1):S49–S57 | DOI: 10.2337/dc15-S011

For prevention and management of diabetes complications in children and adoles- cents, please refer to Section 11. Children and Adolescents.

Cardiovascular disease (CVD) is the major cause of morbidity and mortality for individuals with diabetes and is the largest contributor to the direct and indirect costs of diabetes. The common conditions coexisting with type 2 diabetes (e.g., hypertension and dyslipidemia) are clear risk factors for CVD, and diabetes itself confers independent risk. Numerous studies have shown the efficacy of con-

trolling individual cardiovascular risk factors in preventing or slowing CVD in people STATEMENT POSITION with diabetes. Large benefits are seen when multiple risk factors are addressed globally (1,2). There is evidence that measures of 10-year coronary heart disease (CHD) risk among U.S. adults with diabetes have improved significantly over the past decade (3).

HYPERTENSION/BLOOD PRESSURE CONTROL

Recommendations Screening and Diagnosis c Blood pressure should be measured at every routine visit. Patients found to have elevated blood pressure should have blood pressure confirmed on a separate day. B

Goals c People with diabetes and hypertension should be treated to a systolic blood pressure (SBP) goal of ,140 mmHg. A c Lower systolic targets, such as ,130 mmHg, may be appropriate for certain individuals, such as younger patients, if they can be achieved without undue treatment burden. C c Individuals with diabetes should be treated to a diastolic blood pressure (DBP) ,90 mmHg. A c Lower diastolic targets, such as ,80 mmHg, may be appropriate for certain individuals, such as younger patients, if they can be achieved without undue treatment burden. B

Treatment c Patients with blood pressure .120/80 mmHg should be advised on lifestyle changes to reduce blood pressure. B c Patients with confirmed office-based blood pressure higher than 140/90 mmHg should, in addition to lifestyle therapy, have prompt initiation and timely subsequent titration of pharmacological therapy to achieve blood pres- sure goals. A c Lifestyle therapy for elevated blood pressure consists of weight loss, if over- weight or obese; a Dietary Approaches to Stop Hypertension (DASH)-style dietary pattern including reducing sodium and increasing potassium intake; B Suggested citation: American Diabetes Associa- moderation of alcohol intake; and increased physical activity. tion. Cardiovascular disease and risk manage- c Pharmacological therapy for patients with diabetes and hypertension should ment. Sec. 8. In Standards of Medical Care in comprise a regimen that includes either an ACE inhibitor or an angiotensin Diabetesd2015. Diabetes Care 2015;38(Suppl. 1): receptor blocker (ARB). B If one class is not tolerated, the other should be S49–S57 substituted. C © 2015 by the American Diabetes Association. c Multiple-drug therapy (including a thiazide diuretic and ACE inhibitor/ARB, at Readers may use this article as long as the work maximal doses) is generally required to achieve blood pressure targets. B is properly cited, the use is educational and not for profit, and the work is not altered. S50 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

demonstrated the benefit (reduction of cardiovascular causes (10). The baseline c If ACE inhibitors, ARBs, or diuretics CHD events, stroke, and diabetic kidney blood pressure among the study sub- are used, serum creatinine/estimated disease) of lowering blood pressure to jects was 145/81 mmHg. Compared glomerular filtration rate (eGFR) and ,140 mmHg systolic and ,90 mmHg with the placebo group, the patients serum potassium levels should be diastolic in individuals with diabetes treated with a single-pill, fixed-dose monitored. E (6). There is limited prespecified clinical combination of perindopril and indapa- c In pregnant patients with diabetes trial evidence for the benefits of lower mide experienced an average reduction and chronic hypertension, blood SBP or DBP targets (7). A meta-analysis of 5.6 mmHg in SBP and 2.2 mmHg in pressure targets of 110–129/65– of randomized trials of adults with type DBP. The final blood pressure in the 79 mmHg are suggested in the 2 diabetes comparing intensive blood treated group was 136/73 mmHg, not interest of optimizing long-term pressure targets (upper limit of 130 quite the intensive or tight control maternal health and minimizing mmHg systolic and 80 mmHg diastolic) achieved in ACCORD. Recently published impaired fetal growth. ACE inhibi- to standard targets (upper limit of 140– 6-year follow-up of the ADVANCE-BP tors and ARBs are contraindicated 160 mmHg systolic and 85–100 mmHg study reported that the reductions in during pregnancy. E diastolic)foundnosignificant reduction the risk of death from any cause and of in mortality or nonfatal myocardial in- death from cardiovascular causes in the Hypertension is a common diabetes farction (MI). There was a statistically intervention group were attenuated, but comorbidity that affects the majority significant 35% relative risk (RR) reduc- remained significant (11). of patients, with the prevalence de- tion in stroke with intensive targets, but These results underscore the impor- pending on type of diabetes, age, obe- the absolute risk reduction was only 1%, tant clinical difference between patients sity, and ethnicity. Hypertension is a and intensive targets were associated who are able to easily achieve lower major risk factor for both CVD and mi- with an increased risk for adverse events blood pressure levels (e.g., as seen in crovascular complications. In type 1 di- such as hypotension and syncope (8). observational epidemiology studies) abetes, hypertension is often the result Given the epidemiological relation- and patients who require intensive of underlying nephropathy, while in ship between lower blood pressure medical management to achieve these type 2 diabetes it usually coexists with and better long-term clinical outcomes, goals (e.g., the clinical trials). other cardiometabolic risk factors. two landmark trials, Action to Control Cardiovascular Risk in Diabetes (ACCORD) Systolic Blood Pressure Screening and Diagnosis The clear body of evidence that SBP .140 andActioninDiabetesandVascular Blood pressure measurement should be mmHg is harmful suggests that clinicians Disease: Preterax and Diamicron MR done by a trained individual and follow should promptly initiate and titrate ther- Controlled Evaluation–Blood Pressure the guidelines established for the gen- apyinanongoingfashiontoachieveand (ADVANCE-BP), were conducted in the eral population: measurement in the maintain SBP ,140 mmHg in virtually all past decade to examine the benefitof seated position, with feet on the floor patients. Patients with long life expectancy tighter blood pressure control in pa- and arm supported at heart level, after 5 may have renal benefits from long-term tients with type 2 diabetes. min of rest. Cuff size should be appro- intensive blood pressure control. Addi- The ACCORD trial examined whether a priate for the upper arm circumference. tionally, individuals in whom stroke risk lower SBP of ,120 mmHg, in type 2 di- Elevated values should be confirmed is a concern may, as part of shared deci- abetic patients at high risk for CVD, pro- on a separate day. sion making, have appropriately lower sys- vided greater cardiovascular protection Home blood pressure self-monitoring tolic targets such as ,130 mmHg. This is than an SBP level of 130–140 mmHg (9). and 24-h ambulatory blood pressure especially true if lower blood pressure can The study did not find a benefitinprimary monitoring may provide evidence of be achieved with few drugs and without end point (nonfatal MI, nonfatal stroke, white coat hypertension, masked hyper- side effects of therapy. tension, or other discrepancies between and cardiovascular death) comparing in- office and “true” blood pressure. Stud- tensive blood pressure treatment (goal Diastolic Blood Pressure ies in individuals without diabetes found ,120 mmHg, average blood pressure Similarly, the clearest evidence from ran- that home measurements may better achieved 5 119/64 mmHg on 3.4 medica- domized clinical trials supports DBP correlate with CVD risk than office tions) with standard treatment (average targets of ,90 mmHg. Prior recommen- measurements (4,5). However, most of blood pressure achieved 5 143/70 mmHg dations for lower DBP targets (,80 the evidence of benefits of hypertension on 2.1 medications). In ACCORD, there was mmHg) were based primarily on a post treatment in people with diabetes is no benefit of aggressive blood pressure hoc analysis of the Hypertension Optimal based on office measurements. lowering, despite the extra cost and efforts. Treatment (HOT) trial (12). This level may InADVANCE,theactivebloodpres- still be appropriate for patients with long Treatment Goals sure intervention arm (a single-pill, life expectancy and those with chronic Epidemiological analyses show that fixed-dose combination of perindopril kidney disease and elevated urine albu- blood pressure .115/75 mmHg is asso- and indapamide) showed a significant min excretion (12). The 2015 American ciated with increased cardiovascular reduction in the risk of the primary com- Diabetes Association (ADA) Standards of event rates and mortality in individuals posite end point (major macrovascular Care have been revised to reflect the with diabetes and that SBP .120 mmHg or microvascular event), as well as sig- higher-quality evidence that exists to predicts long-term end-stage renal dis- nificant reductions in the risk of death support a goal of DBP ,90 mmHg, al- ease. Randomized clinical trials have from any cause and of death from though lower targets may be appropriate care.diabetesjournals.org Position Statement S51

for certain individuals. This is in harmoni- that ACE inhibitors may be superior to pressure medications should be made in zation with a recent publication by the dihydropyridine calcium channel blockers timely fashion to overcome clinical inertia Eighth Joint National Committee that rec- in reducing cardiovascular events (15–17). in achieving blood pressure targets. ommended, for individuals over 18 years However, several studies have also Growing evidence suggests that there is of age with diabetes, a DBP threshold of shown no specific advantage to ACE inhib- an association between increase in sleep- ,90 mmHg and SBP ,140 mmHg (7). itors as initial treatment of hypertension time blood pressure and incidence of CVD in the general hypertensive population, events. A randomized controlled trial of Treatment Strategies while showing an advantage of initial 448 participants with type 2 diabetes and Lifestyle Modifications therapy with low-dose thiazide diuretics hypertension demonstrated reduced Although there are no well-controlled on cardiovascular outcomes (14,18,19). cardiovascular events and mortality with studies of diet and exercise in the treat- In people with diabetes, inhibitors of median follow-up of 5.4 years if at least ment of elevated blood pressure or hy- the renin-angiotensin system (RAS) may one antihypertensive medication was pertension in individuals with diabetes, have unique advantages for initial or given at bedtime (26). Consider adminis- the DASH study evaluated the impact of early treatment of hypertension. In a tri- tering one or more antihypertensive med- healthy dietary patterns in individuals al of individuals at high risk for CVD, ications at bedtime (27). without diabetes and has shown antihy- including a large subset with diabetes, An important caveat is that most pa- pertensive effects similar to those of phar- an ACE inhibitor reduced CVD outcomes tients with hypertension require multiple- macological monotherapy. (20). In patients with congestive heart drug therapy to reach treatment goals (13). Lifestyle therapy consists of restrict- failure (CHF), including subgroups with Identifying and addressing barriers to , ing sodium intake ( 2,300 mg/day); re- diabetes, ARBs have been shown to re- medication adherence (such as cost and ducing excess body weight; increasing duce major CVD outcomes (21–24). In side effects) should routinely be done. If – consumption of fruits, vegetables (8 type 2 diabetic patients with significant blood pressure remains uncontrolled de- 10 servings per day), and low-fat dairy diabetic kidney disease, ARBs were su- spite confirmed adherence to optimal – products (2 3 servings per day); avoid- perior to calcium channel blockers for doses of at least three antihypertensive ing excessive alcohol consumption (no reducing heart failure (25). Although ev- agents of different classifications, one of more than 2 servings per day in men idence for distinct advantages of RAS which should be a diuretic, clinicians should and no more than 1 serving per day in inhibitors on CVD outcomes in diabetes consider an evaluation for secondary forms women) (13); and increasing activity lev- remains conflicting (10,19), the high of hypertension. els (14). For individuals with diabetes CVD risks associated with diabetes, and Pregnancy and Antihypertensive and hypertension, setting a sodium in- thehighprevalenceofundiagnosed , Medications take goal of 1,500 mg/day should be CVD, may still favor recommendations In a pregnancy complicated by diabetes considered on an individual basis. for their use as first-line hypertension and chronic hypertension, target blood These lifestyle (nonpharmacological) therapy in people with diabetes (14). pressure goals of SBP 110–129 mmHg strategies may also positively affect gly- The blood pressure arm of the and DBP 65–79 mmHg are reasonable, as cemia and lipid control and should be ADVANCE trial demonstrated that rou- they contribute to improved long-term encouraged in those with even mildly tine administration of a fixed combina- maternal health. Lower blood pressure elevated blood pressure. The effects of tion of the ACE inhibitor perindopril and levels may be associated with im- lifestyle therapy on cardiovascular the diuretic indapamide significantly re- paired fetal growth. During pregnancy, events have not been established. Non- duced combined microvascular and treatment with ACE inhibitors and ARBs pharmacological therapy is reasonable macrovascular outcomes, as well as death is contraindicated, since they may cause in individuals with diabetes and mildly from cardiovascular causes and total fetal damage. Antihypertensive drugs . elevated blood pressure (SBP 120 mortality. The improved outcomes could known to be effective and safe in preg- . mmHg or DBP 80 mmHg). If the blood also have been due to lower achieved nancy include methyldopa, labetalol, dil- fi $ pressure is con rmed to be 140 mmHg blood pressure in the perindopril- tiazem, clonidine, and prazosin. Chronic $ systolic and/or 90 mmHg diastolic, indapamide arm (10). Another trial diuretic use during pregnancy has been pharmacological therapy should be ini- showed a decrease in morbidity and mor- associated with restricted maternal tiated along with nonpharmacological tality in those receiving benazepril and plasma volume, which may reduce therapy(14).Toenablelong-term amlodipine versus benazepril and hydro- uteroplacental perfusion (28). adherence, lifestyle therapy should chlorothiazide (HCTZ). The compelling DYSLIPIDEMIA/LIPID be adapted to suit the needs of the pa- benefits of RAS inhibitors in diabetic pa- MANAGEMENT tient and discussed as part of diabetes tients with albuminuria or renal insuffi- management. ciency provide additional rationale for Recommendations Pharmacological Interventions these agents (see Section 9. Microvascu- Screening Lowering of blood pressure with regi- lar Complications and Foot Care). If c In adults, a screening lipid profile is mens based on a variety of antihyper- needed to achieve blood pressure targets, reasonable at the time of first diag- tensive agents, including ACE inhibitors, amlodipine, HCTZ, or chlorthalidone can nosis, at the initial medical evalua- ARBs, b-blockers, diuretics, and calcium be added. If eGFR is ,30 mL/min/m2,a tion, and/or at age 40 years and channel blockers, has been shown to be loop diuretic, rather than HCTZ or chlor- periodically (e.g., every 1–2years) effective in reducing cardiovascular thalidone, should be prescribed. Titration thereafter. E events. Several studies have suggested of and/or addition of further blood S52 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

patients in larger trials (31–35) and trials Treatment Recommendations and adherence to therapy, but may in patients with diabetes (36,37) Goals not be needed once the patient showed significant primary and second- c Lifestyle modification focusing on E is stable on therapy. ary prevention of CVD events 1/2 CHD the reduction of saturated fat, trans c Combination therapy (statin/ deaths in patients with diabetes. Meta- fat, and cholesterol intake; increase fi brate and statin/niacin) has not analyses, including data from over of omega-3 fatty acids, viscous fiber, been shown to provide additional 18,000 patients with diabetes from 14 and plant stanols/sterols; weight fi cardiovascular bene tabovestatin randomized trials of statin therapy loss (if indicated); and increased therapy alone and is not generally (mean follow-up 4.3 years), demonstrate physical activity should be recom- A recommended. a 9% proportional reduction in all-cause mended to improve the lipid profile c Statin therapy is contraindicated mortality and 13% reduction in vascular in patients with diabetes. A B in pregnancy. mortality, for each mmol/L reduction in c Intensify lifestyle therapy and opti- Lifestyle Intervention LDL cholesterol (38). As in those without mize glycemic control for patients diabetes, absolute reductions in objective with elevated triglyceride levels Lifestyle intervention, including MNT, in- CVD outcomes (CHD death and nonfatal ($150 mg/dL [1.7 mmol/L]) and/or creased physical activity, weight loss, and MI) are greatest in people with high base- low HDL cholesterol (,40 mg/dL smoking cessation, may allow some pa- line CVD risk (known CVD and/or very high [1.0 mmol/L] for men, ,50 mg/dL tients to reduce CVD risk factors, such as LDL cholesterol levels), but the overall ben- [1.3 mmol/L] for women). C For by lowering LDL cholesterol. Nutrition in- efits of statin therapy in people with diabe- patients with fasting triglyceride tervention should be tailored according to ’ tes at moderate or high risk for CVD are levels $500 mg/dL (5.7 mmol/L), each patient s age, diabetes type, pharma- convincing (39,40). Statins are the drugs of evaluate for secondary causes cological treatment, lipid levels, and medi- choice for LDL cholesterol lowering and car- and consider medical therapy to cal conditions. Recommendations should dioprotection. reduce risk of pancreatitis. C focus on reducing saturated fat, choles- terol, and trans unsaturated fat intake Most trials of statins and CVD out- c For patients of all ages with diabe- comes tested specific doses of statins tes and overt CVD, high-intensity and increasing omega-3 fatty acids and vis- fi against placebo or other statins, rather statin therapy should be added to cous ber (such as in oats, legumes, and fi than aiming for specific LDL cholesterol lifestyle therapy. A citrus). Glycemic control can also bene - goals (41). In light of this fact, the 2015 c For patients with diabetes aged cially modify plasma lipid levels, particularly ADA Standards of Care have been revised ,40 years with additional CVD risk in patients with very high triglycerides and to recommend when to initiate and inten- factors, consider using moderate- poor glycemic control. sify statin therapy (high versus moderate) or high-intensity statin and lifestyle Statin Treatment basedonriskprofile (Table 8.1). therapy. C Initiating Statin Therapy Based on Risk The American College of Cardiology/ c For patients with diabetes aged Patients with type 2 diabetes have an American Heart Association new Pooled 40–75 years without additional increased prevalence of lipid abnormal- Cohort Equation, the “Risk Calculator,” CVD risk factors, consider using ities, contributing to their high risk of may be a useful tool to estimate 10- moderate-intensity statin and life- CVD. Multiple clinical trials have demon- year atherosclerotic CVD (http://my style therapy. A strated significant effects of pharmaco- .americanheart.org). Since diabetes it- c For patients with diabetes aged 40– logical (primarily statin) therapy on CVD self confers increased risk for CVD, the 75 years with additional CVD risk fac- outcomes in individual subjects with Risk Calculator has limited use for as- tors, consider using high-intensity CHD and for primary CVD prevention sessing risk in individuals with diabetes. statin and lifestyle therapy. B (29,30). Subgroup analyses of diabetic The following recommendations are c For patients with diabetes aged .75 years without additional CVD risk factors, consider using moderate-intensity statin therapy Table 8.1—Recommendations for statin treatment in people with diabetes and lifestyle therapy. B Recommended c For patients with diabetes aged .75 Age Risk factors statin dose* Monitoring with lipid panel years with additional CVD risk fac- ,40 years None None Annually or as needed to monitor tors, consider using moderate- or CVD risk factor(s)** Moderate or high for adherence high-intensity statin therapy and life- Overt CVD*** High style therapy. B 40–75 years None Moderate As needed to monitor adherence c In clinical practice, providers may CVD risk factors High need to adjust intensity of statin Overt CVD High . therapy based on individual patient 75 years None Moderate As needed to monitor adherence CVD risk factors Moderate or high response to medication (e.g., side Overt CVD High effects, tolerability, LDL cholesterol levels). E *In addition to lifestyle therapy. **CVD risk factors include LDL cholesterol $100 mg/dL (2.6 mmol/L), high blood pressure, c Cholesterol laboratory testing smoking, and overweight and obesity. may be helpful in monitoring ***Overt CVD includes those with previous cardiovascular events or acute coronary syndromes. care.diabetesjournals.org Position Statement S53

supported by evidence from trials focus- Ongoing Therapy and Monitoring However, the evidence base for drugs ing specifically on patients with diabetes. With Lipid Panel that target these lipid fractions is signifi- In adults with diabetes, a screening lipid Age ‡40 Years cantly less robust than that for statin ther- fi fi In all patients with diabetes aged $40 pro le (total cholesterol, LDL cholesterol, apy (48). In a large trial speci ctodiabetic fi years, and if clinically indicated, moderate- HDL cholesterol, and triglycerides) is rea- patients, feno brate failed to reduce over- fi intensity statin treatment should be sonable at the time of rst diagnosis, at all cardiovascular outcomes (49). the initial medical evaluation, and/or at considered, in addition to lifestyle ther- Combination Therapy – apy. Clinical trials in high-risk patients, age 40 and periodically (e.g., every 1 2 years) thereafter. Once a patient is on a Statin and Fibrate such as those with acute coronary syn- Combination therapy (statin and fibrate) statin, testing for LDL cholesterol may be dromes or previous cardiovascular maybeefficacious for treatment for LDL considered on an individual basis to, for events (42–44), have demonstrated cholesterol, HDL cholesterol, and triglycer- example, monitor adherence and efficacy. that more aggressive therapy with high ides, but this combination is associated In cases where patients are adherent, but doses of statins led to a significant re- with an increased risk for abnormal trans- LDL cholesterol level is not responding, clin- duction in further events. Therefore, in aminase levels, myositis, or rhabdomyoly- ical judgment is recommended to deter- patients with increased cardiovascular sis. The risk of rhabdomyolysis is more mine the need for and timing of lipid panels. risk (e.g., LDL cholesterol $100 mg/dL common with higher doses of statins and In individual patients, the highly variable [2.6 mmol/L], high blood pressure, smok- with renal insufficiency and seems to be LDL cholesterol–lowering response seen ing, and overweight/obesity) or with overt lower when statins are combined with fe- with statins is poorly understood (46). Re- CVD, high-dose statins are recommended. nofibrate than gemfibrozil (50). duction of CVD events with statins corre- For adults with diabetes over 75 years of In the ACCORD study, in patients with lates very closely with LDL cholesterol age, there are limited data regarding statin type 2 diabetes who were at high risk for lowering (29). Clinicians should attempt to therapy. Statin therapy should be individ- CVD, the combination of fenofibrate and find a dose or alternative statin that is tol- ualized based on risk profile. High-dose simvastatin did not reduce the rate of fatal erable, if side effects occur. There is evi- statins, if well tolerated, may still be appro- cardiovascular events, nonfatal MI, or non- dence for significant LDL cholesterol priate and are recommended for older fatal stroke, as compared with simvastatin lowering from even extremely low, less adults with overt CVD. However, the risk- alone. Prespecified subgroup analyses sug- than daily, statin doses (47). benefitprofile should be routinely evalu- gested heterogeneity in treatment effects When maximally tolerated doses of sta- ated in this population, with downward accordingtosex,withabenefit of combi- tins fail to significantly lower LDL choles- titration (e.g., high to moderate intensity) nation therapy for men and possible harm terol (,30% reduction from the patient’s performed as needed. See Section 10. for women, and a possible benefitforpa- baseline), there is no strong evidence that Older Adults for more details on clinical tients with both triglyceride level $204 combination therapy should be used to considerations for this unique population. mg/dL (2.3 mmol/L) and HDL cholesterol achieve additional LDL cholesterol lower- level #34 mg/dL (0.9 mmol/L) (51). Age <40 Years and/or Type 1 Diabetes ing. Although niacin, fenofibrate, ezeti- Very little clinical trial evidence exists mibe, and bile acid sequestrants all offer Statin and Niacin for type 2 diabetic patients under the additional LDL cholesterol lowering to sta- The Atherothrombosis Intervention in Met- age of 40 years or for type 1 diabetic tins alone, there is insufficient evidence abolic Syndrome With Low HDL/High Triglyc- patients of any age. In the Heart Protec- that such combination therapy provides a erides: Impact on Global Health Outcomes tion Study (lower age limit 40 years), the significant increment in CVD risk reduction (AIM-HIGH) trial randomized over 3,000 pa- subgroup of ;600 patients with type 1 over statin therapy alone. tients (about one-third with diabetes) with diabetes had a proportionately similar, Treatment of Other Lipoprotein established CVD, low LDL cholesterol levels although not statistically significant, re- Fractions or Targets (,180 mg/dL [4.7 mmol/L]), low HDL cho- duction in risk to patients with type 2 Hypertriglyceridemia should be addressed lesterol levels (men ,40 mg/dL [1.0 mmol/L] diabetes (32). Even though the data with dietary and lifestyle changes. Severe and women ,50 mg/dL [1.3 mmol/L]), are not definitive, similar statin treat- hypertriglyceridemia (.1,000 mg/dL) may and triglyceride levels of 150–400 mg/dL ment approaches should be considered warrant immediate pharmacological ther- (1.7–4.5 mmol/L) to statin therapy plus for both type 1 and type 2 diabetic pa- apy (fibric acid derivatives or fish oil) to extended-release niacin or matching pla- tients, particularly in the presence of reduce the risk of acute pancreatitis. If se- cebo. The trial was halted early due to cardiovascular risk factors. Please refer vere hypertriglyceridemia is absent, then lack of efficacy on the primary CVD out- to “Type 1 Diabetes Mellitus and Cardio- therapy targeting HDL cholesterol or triglyc- come (first event of the composite of death vascular Disease: A ScientificStatement erides lacks the strong evidence base of from CHD, nonfatal MI, ischemic stroke, From the American Heart Association statin therapy. If HDL cholesterol is ,40 hospitalization for an acute coronary syn- andAmericanDiabetesAssociation” mg/dL and LDL cholesterol is between drome, or symptom-driven coronary or ce- (45) for additional discussion. 100 and 129 mg/dL, a fibrate or niacin rebral revascularization) and a possible Treatment with a moderate dose of sta- might be used, especially if a patient is increase in ischemic stroke in those on tin should be considered if the patient has intolerant to statins. combination therapy (52). Hence, combi- increased cardiovascular risk (e.g., cardio- Low levels of HDL cholesterol, often as- nation therapy with niacin is not recom- vascular risk factors such as LDL cholesterol sociated with elevated triglyceride levels, mended given the lack of efficacy on $100 mg/dL) and with a high dose of statin are the most prevalent pattern of dyslipi- major CVD outcomes, possible increase in if the patient has overt CVD. demia in persons with type 2 diabetes. risk of ischemic stroke, and side effects. S54 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

Diabetes With Statin Use Aspirin appears to have a modest ef- c In patients in these age-groups There is an increased risk of incident dia- fect on ischemic vascular events with with multiple other risk factors betes with statin use (53,54), which may the absolute decrease in events depend- (e.g., 10-year risk 5–10%), clinical be limited to those with diabetes risk fac- ing on the underlying CVD risk. The main judgment is required. E tors. These patients may benefitfromdi- adverse effects appear to be an in- c Use aspirin therapy (75–162 mg/day) abetes screening when on statin therapy. creased risk of gastrointestinal bleeding. as a secondary prevention strategy An analysis of one of the initial studies The excess risk may be as high as 1–5per in those with diabetes and a his- suggested that statins were linked to di- 1,000 per year in real-world settings. In tory of CVD. A abetes risk, the cardiovascular event rate adults with CVD risk greater than 1% per c For patients with CVD and docu- reduction with statins far outweighed the year, the number of CVD events pre- mented aspirin allergy, clopidogrel risk of incident diabetes even for patients vented will be similar to or greater (75 mg/day) should be used. B at highest risk for diabetes (55). The abso- than the number of episodes of bleeding c Dual antiplatelet therapy is rea- lute risk increase was small (over 5 years of induced, although these complications sonable for up to a year after an follow-up, 1.2% of participants on placebo do not have equal effects on long-term acute coronary syndrome. B developed diabetes and 1.5% on rosuvas- health (61). tatin) (56). A meta-analysis of 13 random- ized statin trials with 91,140 participants Risk Reduction Treatment Considerations showed an odds ratio of 1.09 for a new Aspirin has been shown to be effective in In 2010, a position statement of the ADA, diagnosis of diabetes, so that (on average) reducing cardiovascular morbidity and the American Heart Association, and the treatment of 255 patients with statins for mortality in high-risk patients with previ- American College of Cardiology Founda- 4 years resulted in one additional case of ous MI or stroke (secondary prevention). tion recommended that low-dose (75–162 diabetes, while simultaneously prevent- Its net benefit in primary prevention mg/day) aspirin for primary prevention is ing 5.4 vascular events among those 255 among patients with no previous cardio- reasonable for adults with diabetes and patients (54). The RR-benefit ratio favor- vascular events is more controversial, no previous history of vascular disease ing statins is further supported by meta- both for patients with and without a his- who are at increased CVD risk (10-year analysis of individual data of over 170,000 tory of diabetes (57,58). Two randomized risk of CVD events over 10%) and who persons from 27 randomized trials. This controlled trials of aspirin specifically in are not at increased risk for bleeding. demonstrated that individuals at low risk patients with diabetes failed to show a This generally includes most men over of vascular disease, including those un- significant reduction in CVD end points, age 50 years and women over age 60 dergoing primary prevention, received raising questions about the efficacy of as- years who also have one or more of the benefits from statins that included reduc- pirin for primary prevention in people following major risk factors: smoking, hy- tions in major vascular events and vascu- with diabetes (59,60). pertension, dyslipidemia, family history of lar death without increase in incidence of The Antithrombotic Trialists’ (ATT) col- premature CVD, and albuminuria (62). cancer or deaths from other causes (30). laborators published an individual patient- However, aspirin is no longer recom- level meta-analysis of the six large trials of mended for those at low CVD risk ANTIPLATELET AGENTS aspirin for primary prevention in the gen- (women under age 60 years and men Recommendations eral population. These trials collectively under age 50 years with no major CVD c Consider aspirin therapy (75–162 enrolled over 95,000 participants, includ- risk factors; 10-year CVD risk under 5%) mg/day) as a primary prevention ing almost 4,000 with diabetes. Overall, as the low benefit is likely to be out- strategy in those with type 1 or they found that aspirin reduced the risk weighed by the risks of significant bleed- type 2 diabetes at increased car- of vascular events by 12% (RR 0.88 [95% ing. Clinical judgment should be used for diovascular risk (10-year risk CI 0.82–0.94]). The largest reduction was those at intermediate risk (younger pa- .10%). This includes most men for nonfatal MI with little effect on CHD tients with one or more risk factors or aged .50 years or women aged death (RR 0.95 [95% CI 0.78–1.15]) or total older patients with no risk factors; those .60 years who have at least one stroke. There was some evidence of a dif- with 10-year CVD risk of 5–10%) until additional major risk factor (family ference in aspirin effect by sex: aspirin further research is available. Aspirin history of CVD, hypertension, significantly reduced CVD events in men, use in patients under the age of 21 years smoking, dyslipidemia, or albu- but not in women. Conversely, aspirin had is contraindicated due to the associated minuria). C no effect on stroke in men but significantly risk of Reye syndrome. c Aspirin should not be recom- reduced stroke in women. Sex differences Average daily dosages used in most mended for CVD prevention for in aspirin’s effects have not been observed clinical trials involving patients with di- adults with diabetes at low CVD in studies of secondary prevention (57). In abetes ranged from 50 to 650 mg but risk (10-year CVD risk ,5%, such the six trials examined by the ATT collab- were mostly in the range of 100 to as in men aged ,50 years and orators, the effects of aspirin on major 325 mg/day. There is little evidence to women aged ,60 years with no vascular events were similar for patients support any specific dose, but using the major additional CVD risk factors), with or without diabetes: RR 0.88 (95% CI lowest possible dose may help reduce since the potential adverse effects 0.67–1.15) and RR 0.87 (95% CI 0.79– side effects (63). In the U.S., the most from bleeding likely offset the 0.96), respectively. The confidence inter- common low dose tablet is 81 mg. potential benefits. C val was wider for those with diabetes Although platelets from patients with because of smaller numbers. diabetes have altered function, it is care.diabetesjournals.org Position Statement S55

unclear what, if any, impact that finding albuminuria. Abnormal risk factors caloric intake and increased physical ac- has on the required dose of aspirin for should be treated as described else- tivity as performed in the Action for cardioprotective effects in the patient where in these guidelines. Health in Diabetes (Look AHEAD) trial with diabetes. Many alternate pathways may be considered for improving glu- for platelet activation exist that are in- Screening cose control, fitness, and some CVD Candidates for advanced or invasive car- dependent of thromboxane A2 and thus risk factors. Patients at increased CVD not sensitive to the effects of aspirin diac testing include those with 1)typical risk should receive aspirin and a statin, (64). Therefore, while “aspirin resis- or atypical cardiac symptoms and 2)an and ACE inhibitor or ARB therapy if hy- tance” appears higher in patients with abnormal resting ECG. The screening of pertensive, unless there are contraindi- diabetes when measured by a variety of asymptomatic patients with high CVD cations to a particular drug class. While ex vivo and in vitro methods (platelet risk is not recommended (39), in part clear benefit exists for ACE inhibitor and aggregometry, measurement of throm- because these high-risk patients should ARB therapy in patients with nephropa- alreadybereceivingintensivemedical boxane B2), these observations alone thy or hypertension, the benefits in pa- are insufficient to empirically recom- therapy, an approach that provides sim- tients with CVD in the absence of these mend that higher doses of aspirin be ilar benefit as invasive revascularization conditions are less clear, especially used in this group at this time. (66,67). There is also some evidence when LDL cholesterol is concomitantly A P2Y12 receptor antagonist in com- that silent MI may reverse over time, controlled (75,76). In patients with a bination with aspirin should be used for adding to the controversy concerning prior MI, b-blockers should be contin- at least 1 year in patients following an aggressive screening strategies (68). A ued for at least 2 years after the event acute coronary syndrome. Evidence randomized observational trial demon- (77). A systematic review of 34,000 pa- supports use of either ticagrelor or clo- strated no clinical benefit to routine tients showed that metformin is as safe pidogrel if no percutaneous coronary screening of asymptomatic patients as other glucose-lowering treatments in intervention (PCI) was performed and with type 2 diabetes and normal ECGs patients with diabetes and CHF, even in the use of clopidogrel, ticagrelor, or (69). Despite abnormal myocardial per- those with reduced left ventricular ejec- prasugrel if PCI was performed (65). fusion imaging in more than one in five tion fraction or concomitant chronic patients, cardiac outcomes were essen- kidney disease; however, metformin CORONARY HEART DISEASE tially equal (and very low) in screened should be avoided in hospitalized versus unscreened patients. Accord- Recommendations patients (78). ingly, indiscriminate screening is not Screening considered cost-effective. Studies have References c In asymptomatic patients, routine found that a risk factor–based approach screening for coronary artery dis- 1. Buse JB, Ginsberg HN, Bakris GL, et al.; Amer- to the initial diagnostic evaluation and ican Heart Association; American Diabetes As- ease (CAD) is not recommended subsequent follow-up for CAD fails to sociation. Primary prevention of cardiovascular because it does not improve out- identify which patients with type 2 di- diseases in people with diabetes mellitus: fi comes as long as CVD risk factors abetes will have silent ischemia on a scienti c statement from the American Heart are treated. A fi Association and the American Diabetes Associ- screening tests (70,71). Any bene tof ation. Diabetes Care 2007;30:162–172 Treatment newer noninvasive CAD screening meth- 2. Gaede P, Lund-Andersen H, Parving H-H, c In patients with known CVD, use ods, such as computed tomography and Pedersen O. Effect of a multifactorial interven- computed tomography angiography, to tion on mortality in type 2 diabetes. N Engl J aspirin and statin therapy (if not – identify patient subgroups for different Med 2008;358:580 591 contraindicated) A and consider 3. Ali MK, Bullard KM, Saaddine JB, Cowie CC, ACE inhibitor therapy C to reduce treatment strategies, remain unproven. Imperatore G, Gregg EW. Achievement of goals the risk of cardiovascular events. Although asymptomatic diabetic pa- in U.S. diabetes care, 1999-2010. N Engl J Med 2013;368:1613–1624 c In patients with a prior MI, b-blockers tients with higher coronary disease bur- den have more future cardiac events 4. Bobrie G, Genes` N, Vaur L, et al. Is “isolated should be continued for at least 2 ” “ – home hypertension as opposed to isolated of- years after the event. B (72 74), the role of these tests beyond fice” hypertension a sign of greater cardiovascular fi c In patients with symptomatic risk strati cation is not clear. Their rou- risk? Arch Intern Med 2001;161:2205–2211 heart failure, thiazolidinedione tine use leads to radiation exposure and 5. Sega R, Facchetti R, Bombelli M, et al. Prog- A may result in unnecessary invasive test- nostic value of ambulatory and home blood treatment should not be used. fi ing such as coronary angiography and pressures compared with of ce blood pressure c In patients with stable CHF, met- in the general population: follow-up results formin may be used if renal func- revascularization procedures. The ulti- from the Pressioni Arteriose Monitorate e fi tion is normal but should be mate balance of bene t, cost, and risks Loro Associazioni (PAMELA) study. Circulation avoided in unstable or hospital- of such an approach in asymptomatic 2005;111:1777–1783 6. Arguedas JA, Leiva V, Wright JM. Blood pres- ized patients with CHF. B patients remains controversial, particu- larly in the modern setting of aggressive sure targets for hypertension in people with di- abetes mellitus. Cochrane Database Syst Rev In all patients with diabetes, cardio- CVD risk factor control. 2013;10:CD008277 vascular risk factors should be assessed 7. James PA, Oparil S, Carter BL, et al. 2014 at least annually. These risk factors Lifestyle and Pharmacological evidence-based guideline for the management of high blood pressure in adults: report from the Interventions include dyslipidemia, hypertension, panel members appointed to the Eighth Joint smoking, a family history of premature Intensive lifestyle intervention focusing National Committee (JNC 8). JAMA 2014;311: coronary disease, and the presence of on weight loss through decreased 507–520 S56 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

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Cardiovascular outcomes in of cardiovascular disease with atorvastatin in National Committee on Prevention, Detection, the Irbesartan Diabetic Nephropathy Trial of pa- type 2 diabetes in the Collaborative Atorvasta- Evaluation, and Treatment of High Blood Pres- tients with type 2 diabetes and overt nephrop- tin Diabetes Study (CARDS): multicentre rando- sure; National High Blood Pressure Education athy. Ann Intern Med 2003;138:542–549 mised placebo-controlled trial. Lancet 2004; Program Coordinating Committee. The Seventh 26. Hermida RC, Ayala DE, Mojon´ A, Fernandez´ 364:685–696 Report of the Joint National Committee on Pre- JR. Influence of time of day of blood pressure- 38. Kearney PM, Blackwell L, Collins R, et al.; vention, Detection, Evaluation, and Treatment lowering treatment on cardiovascular risk in Cholesterol Treatment Trialists’ (CTT) Collabo- of High Blood Pressure: the JNC 7 report. JAMA hypertensive patients with type 2 diabetes. rators. 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Nat Clin Cholesterol Treatment Trialists’ (CTT) Collabo- 520–530 Pract Nephrol 2007;3:428–438 rators. The effects of lowering LDL cholesterol 42. Cannon CP, Braunwald E, McCabe CH, et al.; 18. ALLHAT Officers and Coordinators for the with statin therapy in people at low risk of vas- Pravastatin or Atorvastatin Evaluation and In- ALLHAT Collaborative Research Group. Major cular disease: meta-analysis of individual data fection Therapy-Thrombolysis in Myocardial In- outcomes in high-risk hypertensive patients from 27 randomised trials. Lancet 2012;380: farction 22 Investigators. Intensive versus randomized to angiotensin-converting enzyme 581–590 moderate lipid lowering with statins after acute inhibitor or calcium channel blocker vs diuretic: 31. Pyor˘ al¨ a¨ K, Pedersen TR, Kjekshus J, coronary syndromes. N Engl J Med 2004;350: the Antihypertensive and Lipid-Lowering Treat- Faergeman O, Olsson AG, Thorgeirsson G. Cho- 1495–1504 ment to Prevent Heart Attack Trial (ALLHAT). lesterol lowering with simvastatin improves 43. de Lemos JA, Blazing MA, Wiviott SD, et al.; JAMA 2002;288:2981–2997 prognosis of diabetic patients with coronary Investigators. Early intensive vs a delayed con- 19.PsatyBM,SmithNL,SiscovickDS,etal. heart disease. A subgroup analysis of the Scan- servative simvastatin strategy in patients with Health outcomes associated with antihyperten- dinavian Simvastatin Survival Study (4S). Diabe- acute coronary syndromes: phase Z of the A to Z sive therapies used as first-line agents. A sys- tes Care 1997;20:614–620 trial. JAMA 2004;292:1307–1316 tematic review and meta-analysis. JAMA 1997; 32. Collins R, Armitage J, Parish S, Sleigh P, Peto 44. Nissen SE, Tuzcu EM, Schoenhagen P, et al.; 277:739–745 R; Heart Protection Study Collaborative Group. REVERSAL Investigators. Effect of intensive 20. Heart Outcomes Prevention Evaluation MRC/BHF Heart Protection Study of cholesterol- compared with moderate lipid-lowering ther- Study Investigators. Effects of ramipril on car- lowering with simvastatin in 5963 people with di- apy on progression of coronary atherosclerosis: diovascular and microvascular outcomes in peo- abetes: a randomised placebo-controlled trial. a randomized controlled trial. JAMA 2004;291: ple with diabetes mellitus: results of the HOPE Lancet 2003;361:2005–2016 1071–1080 care.diabetesjournals.org Position Statement S57

45. de Ferranti SD, de Boer IH, Fonseca V, et al. on cardiovascular disease prevention in clinical asymptomatic myocardial ischemia in patients Type 1 diabetes mellitus and cardiovascular dis- practice (version 2012). The Fifth Joint Task with type 2 diabetes in the Detection of Ische- ease: a scientific statement from the American Force of the European Society of Cardiology mia in Asymptomatic Diabetics (DIAD) study. Heart Association and American Diabetes Asso- and Other Societies on Cardiovascular Disease Diabetes Care 2007;30:2892–2898 ciation. Circulation 2014;130:1110–1130 Prevention in Clinical Practice (constituted by 69. Young LH, Wackers FJT, Chyun DA, et al.; 46. Chasman DI, Posada D, Subrahmanyan L, representatives of nine societies and by invited DIAD Investigators. Cardiac outcomes after Cook NR, Stanton VP Jr, Ridker PM. Pharmaco- experts). Eur Heart J 2012;33:1635–1701 screening for asymptomatic coronary artery dis- genetic study of statin therapy and cholesterol 59. Ogawa H, Nakayama M, Morimoto T, et al.; ease in patients with type 2 diabetes: the DIAD reduction. JAMA 2004;291:2821–2827 Japanese Primary Prevention of Atherosclerosis study: a randomized controlled trial. JAMA 47. Meek C, Wierzbicki AS, Jewkes C, et al. Daily With Aspirin for Diabetes (JPAD) Trial Investiga- 2009;301:1547–1555 and intermittent rosuvastatin 5 mg therapy in tors. Low-dose aspirin for primary prevention of 70. Wackers FJT, Young LH, Inzucchi SE, et al.; statin intolerant patients: an observational atherosclerotic events in patients with type 2 DetectionofIschemiainAsymptomaticDia- study. Curr Med Res Opin 2012;28:371–378 diabetes: a randomized controlled trial. JAMA betics Investigators. Detection of silent myocar- 48. Singh IM, Shishehbor MH, Ansell BJ. High- 2008;300:2134–2141 dial ischemia in asymptomatic diabetic subjects: density lipoprotein as a therapeutic target: a sys- 60. Belch J, MacCuish A, Campbell I, et al. The the DIAD study. Diabetes Care 2004;27:1954– tematic review. JAMA 2007;298:786–798 prevention of progression of arterial disease 1961 49.KeechA,SimesRJ,BarterP,etal.;FIELD and diabetes (POPADAD) trial: factorial rando- 71. Scognamiglio R, Negut C, Ramondo A, study investigators. Effects of long-term fenofi- misedplacebocontrolledtrialofaspirinand Tiengo A, Avogaro A. Detection of coronary ar- brate therapy on cardiovascular events in 9795 antioxidants in patients with diabetes and tery disease in asymptomatic patients with type people with type 2 diabetes mellitus (the FIELD asymptomatic peripheral arterial disease. BMJ 2 diabetes mellitus. J Am Coll Cardiol 2006;47: study): randomised controlled trial. Lancet 2008;337:a1840 65–71 2005;366:1849–1861 61. Pignone M, Earnshaw S, Tice JA, Pletcher 72. Hadamitzky M, Hein F, Meyer T, et al. Prog- 50. Jones PH, Davidson MH. Reporting rate of MJ. Aspirin, statins, or both drugs for the pri- nostic value of coronary computed tomographic rhabdomyolysis with fenofibrate 1 statin ver- mary prevention of coronary heart disease angiography in diabetic patients without known sus gemfibrozil 1 any statin. Am J Cardiol 2005; events in men: a cost-utility analysis. Ann Intern coronary artery disease. Diabetes Care 2010;33: 95:120–122 Med 2006;144:326–336 1358–1363 51. Ginsberg HN, Elam MB, Lovato LC, et al.; 62. Pignone M, Alberts MJ, Colwell JA, et al.; 73. Elkeles RS, Godsland IF, Feher MD, et al.; ACCORD Study Group. Effects of combination American Diabetes Association; American Heart PREDICT Study Group. Coronary calcium mea- lipid therapy in type 2 diabetes mellitus. N Association; American College of Cardiology surement improves prediction of cardiovascular Engl J Med 2010;362:1563–1574 Foundation. Aspirin for primary prevention of events in asymptomatic patients with type 2 52. Boden WE, Probstfield JL, Anderson T, et al.; cardiovascular events in people with diabetes: diabetes: the PREDICT study. Eur Heart J 2008; AIM-HIGH Investigators. Niacin in patients with a position statement of the American Diabetes 29:2244–2251 low HDL cholesterol levels receiving intensive Association, a scientific statement of the Amer- 74. Choi E-K, Chun EJ, Choi S-I, et al. Assessment statin therapy. N Engl J Med 2011;365:2255– ican Heart Association, and an expert consensus of subclinical coronary atherosclerosis in 2267 document of the American College of Cardiol- asymptomatic patients with type 2 diabetes 53. Rajpathak SN, Kumbhani DJ, Crandall J, ogy Foundation. Diabetes Care 2010;33:1395– mellitus with single photon emission computed Barzilai N, Alderman M, Ridker PM. Statin therapy 1402 tomography and coronary computed tomogra- and risk of developing type 2 diabetes: a meta- 63. Campbell CL, Smyth S, Montalescot G, phy angiography. Am J Cardiol 2009;104:890– analysis. Diabetes Care 2009;32:1924–1929 Steinhubl SR. Aspirin dose for the prevention 896 54. Sattar N, Preiss D, Murray HM, et al. Statins of cardiovascular disease: a systematic review. 75. Braunwald E, Domanski MJ, Fowler SE, and risk of incident diabetes: a collaborative JAMA 2007;297:2018–2024 et al.; PEACE Trial Investigators. Angiotensin- meta-analysis of randomised statin trials. Lan- 64. Dav`ı G, Patrono C. Platelet activation and converting-enzyme inhibition in stable coronary cet 2010;375:735–742 atherothrombosis. N Engl J Med 2007;357: artery disease. N Engl J Med 2004;351:2058– 55. Ridker PM, Danielson E, Fonseca FAH, et al.; 2482–2494 2068 JUPITER Study Group. Rosuvastatin to prevent 65. Vandvik PO, Lincoff AM, Gore JM, et al.; 76. Telmisartan Randomised AssessmeNt vascular events in men and women with ele- American College of Chest Physicians. Primary Study in ACE iNtolerant subjects with cardiovas- vated C-reactive protein. N Engl J Med 2008; and secondary prevention of cardiovascular dis- cular Disease (TRANSCEND) Investigators; Yusuf 359:2195–2207 ease: antithrombotic therapy and prevention of S, Teo K, et al. Effects of the angiotensin-receptor 56. Ridker PM, Pradhan A, MacFadyen JG, Libby thrombosis, 9th ed: American College of Chest blocker telmisartan on cardiovascular events in P, Glynn RJ. Cardiovascular benefits and diabe- Physicians Evidence-Based Clinical Practice high-risk patients intolerant to angiotensin- tes risks of statin therapy in primary prevention: Guidelines. Chest 2012;141(Suppl.):e637S– converting enzyme inhibitors: a randomised con- an analysis from the JUPITER trial. Lancet 2012; e668S trolled trial. Lancet 2008;372:1174–1183 380:565–571 66. Boden WE, O’Rourke RA, Teo KK, et al.; 77. Kezerashvili A, Marzo K, De Leon J. Beta 57. Baigent C, Blackwell L, Collins R, et al.; An- COURAGE Trial Research Group. Optimal medi- blocker use after acute myocardial infarction tithrombotic Trialists’ (ATT) Collaboration. Aspi- cal therapy with or without PCI for stable coro- in the patient with normal systolic function: rin in the primary and secondary prevention of nary disease. N Engl J Med 2007;356:1503–1516 when is it “ok” to discontinue? Curr Cardiol vascular disease: collaborative meta-analysis of 67. BARI 2D Study Group; Frye RL, August P, Rev 2012;8:77–84 individual participant data from randomised tri- et al. A randomized trial of therapies for type 78. Eurich DT, Weir DL, Majumdar SR, et al. als. Lancet 2009;373:1849–1860 2 diabetes and coronary artery disease. N Engl J Comparative safety and effectiveness of met- 58. Perk J, De Backer G, Gohlke H, et al.; Euro- Med 2009;360:2503–2515 formin in patients with diabetes mellitus and pean Association for Cardiovascular Prevention 68. Wackers FJT, Chyun DA, Young LH, et al.; heart failure: systematic review of observa- & Rehabilitation (EACPR); ESC Committee for Detection of Ischemia in Asymptomatic Dia- tional studies involving 34,000 patients. Circ Practice Guidelines (CPG). European Guidelines betics (DIAD) Investigators. Resolution of Heart Fail 2013;6:395–402 S58 Diabetes Care Volume 38, Supplement 1, January 2015

9. Microvascular Complications American Diabetes Association and Foot Care Diabetes Care 2015;38(Suppl. 1):S58–S66 | DOI: 10.2337/dc15-S012

NEPHROPATHY

Recommendations c Optimize glucose control to reduce the risk or slow the progression of diabetic kidney disease. A c Optimize blood pressure control to reduce the risk or slow the progression of diabetic kidney disease. A Screening c At least once a year, quantitatively assess urinary albumin (e.g., urine albumin- to-creatinine ratio [UACR]) and estimated glomerular filtration rate (eGFR) in patients with type 1 diabetes duration of $5 years and in all patients with type 2diabetes.B Treatment c An ACE inhibitor or angiotensin receptor blocker (ARB) is not recommended POSITION STATEMENT for the primary prevention of diabetic kidney disease in patients with diabetes who have normal blood pressure and normal UACR (,30 mg/g). B c Either an ACE inhibitor or ARB is suggested for the treatment of the non- pregnant patient with modestly elevated urinary albumin excretion (30–299 mg/day) C and is recommended for those with urinary albumin excretion .300 mg/day. A c When ACE inhibitors, ARBs, or diuretics are used, monitor serum creatinine and potassium levels for the development of increased creatinine or changes in potassium. E c Continued monitoring of UACR in patients with albuminuria is reasonable to assess progression of diabetic kidney disease. E c When eGFR is ,60 mL/min/1.73 m2, evaluate and manage potential compli- cations of chronic kidney disease (CKD). E c Consider referral to a physician experienced in the care of kidney disease when there is uncertainty about the etiology of kidney disease, difficult manage- ment issues, or advanced kidney disease. B Nutrition c For people with diabetic kidney disease, reducing the amount of dietary pro- tein below the recommended daily allowance of 0.8 g/kg/day (based on ideal body weight) is not recommended because it does not alter glycemic mea- sures, cardiovascular risk measures, or the course of GFR decline. A

The terms “microalbuminuria” (30–299 mg/24 h) and “macroalbuminuria” (.300 mg/24 h) will no longer be used, since albuminuria occurs on a continuum. Albuminuria is defined as UACR $30 mg/g. Diabetic kidney disease occurs in 20–40% of patients with diabetes and is the leading cause of end-stage renal disease (ESRD). Persistent increased albumin- Suggested citation: American Diabetes Association. uria in the range of UACR 30–299 mg/g is an early indicator of diabetic kidney Microvascular complications and foot care. Sec. 9. In Standards of Medical Care in Diabetesd2015. disease in type 1 diabetes and a marker for development of diabetic kidney Diabetes Care 2015;38(Suppl. 1):S58–S66 diseaseintype2diabetes.Itisawell-established marker of increased cardiovas- – © 2015 by the American Diabetes Association. cular disease (CVD) risk (1 3). However, there is increasing evidence of sponta- Readers may use this article as long as the work neous remission of UACR levels 30–299 mg/g in up to 40% of patients with type 1 is properly cited, the use is educational and not diabetes. About 30–40% remain with UACR levels of 30–299 mg/g and do not for profit, and the work is not altered. care.diabetesjournals.org Position Statement S59

progress to higher levels ($300 mg/g) and normoalbuminuria, renin-angiotensin (31–34), although more recent studies over 5–10 years of follow-up (4–7). Pa- system inhibition has been demon- have provided conflicting results (35). tients with persistent albuminuria are strated to delay onset of elevated al- Dietary protein limitation, if protein likely to develop ESRD (8,9). buminuria (20,21). Of note, in the intake is high, is a consideration par- latter study, there was an unexpected ticularly in patients whose diabetic Interventions higher rate of fatal cardiovascular kidney disease is progressing despite Glycemia events with olmesartan compared optimal glucose and blood pressure A number of interventions have been with placebo among patients with pre- control and use of an ACE inhibitor or demonstrated to reduce the risk and existing CVD. ARB (34). slow the progression of diabetic kid- ACE inhibitors have been shown to ney disease. Intensive diabetes man- reduce major CVD outcomes (i.e., Assessment of Albuminuria Status and agement with the goal of achieving myocardial infarction, stroke, death) Renal Function near-normoglycemia has been shown in patients with diabetes (22), thus Screening for increased urinary albu- in large prospective randomized stud- further supporting the use of these min excretion can be performed by ies to delay the onset and progression agents in patients with elevated UACR in a random spot urine collec- of increased urinary albumin excre- albuminuria, a CVD risk factor. ARBs tion; 24-h or timed collections are tion and reduced eGFR in patients do not have the same beneficial effect more burdensome and add little to with type 1 (9) and type 2 diabetes on cardiovascular outcomes or pre- prediction or accuracy (36,37). Mea- – (10 14). vent the onset of elevated albuminuria surement of a spot urine sample for Despite prior concerns and published in normotensive patients with type 1 albumin alone (whether by immunoas- case reports, current data indicate that or type 2 diabetes (23). However, ARBs say or by using a sensitive dipstick test the overall risk of metformin-associated have been shown to reduce the pro- specific for albuminuria) without si- lactic acidosis is low (14). GFR may be a gression of albuminuria, as well as multaneously measuring urine creati- more appropriate measure to assess ESRD,inpatientswithtype2diabetes nine is less expensive but susceptible to continued metformin use than serum (24–26). In those with diabetic kidney false-negative and false-positive deter- creatinine considering that the serum disease, some evidence suggests that minations as a result of variation in creatinine level can translate into ARBs are associated with a smaller in- urine concentration due to hydration widely varying eGFR levels depending crease in serum potassium levels com- and other factors. on age, ethnicity, and muscle mass pared with ACE inhibitors (27). Abnormalities of albumin excretion (15). A recent review (16) proposes and the linkage between UACR and fi that metformin use should be reeval- Combination Therapy 24-h albumin excretion are de ned in , 2 uated at an eGFR 45 mL/min/1.73 m Drug combinations that block the renin- Table 9.1. Because of variability in urinary with a reduction in maximum dose to angiotensin system (e.g., an ACE inhibi- albumin excretion, two of three speci- 1,000 mg/day and discontinued when torplusanARB,amineralocorticoid mens collected within a 3- to 6-month , 2 eGFR 30 mL/min/1.73 m or in clini- antagonist, or a direct renin inhibitor) period should be abnormal before cal situations in which there is an in- provide additional lowering of albumin- considering a patient to have developed creased risk of lactic acidosis, such as uria (28). However, compared with albuminuria. Exercise within 24 h, infec- sepsis, hypotension, and hypoxia, or in single-agent use, such combinations tion, fever, congestive heart failure, which there is a high risk of acute kid- have been found to provide no addi- marked hyperglycemia, and marked hy- ney injury resulting in a worsening tional benefit on CVD or diabetic kid- pertension may elevate urinary albumin of GFR, such as administration of ney disease and have higher adverse excretion over baseline values. radiocontrast dye in those with eGFR event rates (hyperkalemia or acute kid- Abnormal urine albumin excretion , 2 60 mL/min/1.73 m . ney injury) (29). Therefore, the com- and GFR level may be used to stage Blood Pressure bined use of different inhibitors of the CKD. The National Kidney Foundation The UK Prospective Diabetes Study renin-angiotensin system should be classification (Table 9.2) is primarily (UKPDS) provided strong evidence that avoided. based on GFR levels and may be super- blood pressure control can reduce the Diuretics, calcium channel blockers, seded by other systems in which staging development of diabetic kidney disease and b-blockers can be used as additional (17). In addition, large prospective ran- therapy to further lower blood pressure Table 9.1—Definitions of abnormalities domized studies in patients with type 1 in patients already treated with maxi- in albumin excretion diabetes have shown that ACE inhibitors mum doses of ACE inhibitors or ARBs Spot collection have achieved lower systolic blood pres- (30) or as alternate therapy in the rare Category (mg/g creatinine) sure levels (,140 mmHg) and have individual unable to tolerate ACE inhib- Normal ,30 provided a selective benefit over other itors and ARBs. Increased urinary antihypertensive drug classes in delay- Studies in patients with varying albumin excretion* $30 ing the progression of increased urinary stages of diabetic kidney disease *Historically, ratios between 30 and 299 albumin excretion and can slow the de- have shown that the limitation of di- mg/g have been called “microalbuminuria” cline in GFR in patients with higher lev- etary protein to avoid excess intake and those .300 mg/g have been called els of albuminuria (18,19). In patients slows the progression of albuminuria, “macroalbuminuria” (or clinical albuminuria). with type 2 diabetes, hypertension, GFR decline, and occurrence of ESRD S60 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

includes other variables such as urinary Table 9.2—Stages of CKD albumin excretion (38). Studies have Stage Description GFR (mL/min/1.73 m2) found decreased GFR without increased $ urine albumin excretion in a substantial 1 Kidney damage* with normal or increased GFR 90 – percentage of adults with type 2 diabe- 2 Kidney damage* with mildly decreased GFR 60 89 tes (39). Substantial evidence shows 3 Moderately decreased GFR 30–59 that in patients with type 1 diabetes 4 Severely decreased GFR 15–29 and persistent UACR 30–299 mg/g, 5 Kidney failure ,15 or dialysis screening with albumin excretion rate *Kidney damage is defined as abnormalities on pathological, urine, blood, or imaging tests. alone would miss .20% of progressive Adapted from Levey et al. (37). disease (7). Serum creatinine with eGFR should therefore be assessed at least indicatedinpatientslikelytoprogress treatment of blood pressure and blood annually in all adults with diabetes, re- to ESRD. glucose, and the potential need for renal gardless of the degree of urine albumin transplant. excretion. Referral to Nephrologist Serum creatinine should be used to Consider referral to a physician experi- estimate GFR and to stage the level enced in the care of kidney disease RETINOPATHY of CKD, if present. eGFR is commonly when there is uncertainty about the coreported by laboratories or can be etiology of kidney disease (heavy pro- Recommendations estimated using formulae such as the teinuria, active urine sediment, absence c Optimize glycemic control to re- Modification of Diet in Renal Disease of retinopathy, rapid decline in GFR). duce the risk or slow the progres- (MDRD) study equation (40) or the Other triggers for referral may include sion of retinopathy. A Chronic Kidney Disease Epidemiology difficult management issues (anemia, c Optimize blood pressure control Collaboration (CKD-EPI) equation. The secondary hyperparathyroidism, meta- to reduce the risk or slow the pro- latter is the current preferred GFR es- bolic bone disease, resistant hyperten- gression of retinopathy. A timating equation. GFR calculators are sion, or electrolyte disturbance) or Screening available at http://www.nkdep.nih advanced kidney disease. The threshold c Adults with type 1 diabetes .gov. for referral may vary depending on should have an initial dilated and The need for annual quantitative as- the frequency with which a provider comprehensive eye examination sessment of albumin excretion after encounters diabetic patients with sig- by an ophthalmologist or optom- diagnosis of albuminuria and institu- nificant kidney disease. Consultation etrist within 5 years after the on- tion of ACE inhibitor or ARB therapy with a nephrologist when stage 4 CKD set of diabetes. B and blood pressure control is a subject develops has been found to reduce cost, c Patients with type 2 diabetes of debate. Continued surveillance can improve quality of care, and delay dial- should have an initial dilated and assess both response to therapy and ysis (41). However, other specialists and comprehensive eye examination disease progression and may aid in as- providers should not delay educating by an ophthalmologist or optom- sessing adherence to ACE inhibitor or their patients about the progressive na- etrist shortly after the diagnosis of ARB therapy. Some suggest that reduc- ture of diabetic kidney disease, the kid- diabetes. B ing UACR to normal (,30 mg/g) or ney preservation benefits of proactive near normal may improve CKD and CVD prognosis, but this approach has Table 9.3—Management of CKD in diabetes (7) not been formally evaluated in pro- 2 spective trials, and evidence demon- GFR (mL/min/1.73 m ) Recommended management strates spontaneous remission of All patients Yearly measurement of creatinine, urinary albumin excretion, potassium albuminuria in up to 40% of type 1 di- 45–60 Referral to a nephrologist if possibility for nondiabetic kidney abetic patients. disease exists (duration of type 1 diabetes ,10 years, persistent fi Conversely, patients with increasing albuminuria, abnormal ndings on renal ultrasound, resistant hypertension, rapid fall in GFR, or active urinary sediment on albumin levels, declining GFR, increas- ultrasound) ing blood pressure, retinopathy, macro- Consider the need for dose adjustment of medications vascular disease, elevated lipids and/or Monitor eGFR every 6 months uric acid concentrations, or a family his- Monitor electrolytes, bicarbonate, hemoglobin, calcium, tory of CKD are more likely to ex- phosphorus, parathyroid hormone at least yearly perience a progression of diabetic Assure vitamin D sufficiency kidney disease (7). Consider bone density testing Referral for dietary counseling Complications of kidney disease cor- 30–44 Monitor eGFR every 3 months relate with level of kidney function. , 2 Monitor electrolytes, bicarbonate, calcium, phosphorus, parathyroid When the eGFR is 60 mL/min/1.73 m , hormone, hemoglobin, albumin, weight every 3–6 months screening for complications of CKD Consider the need for dose adjustment of medications is indicated (Table 9.3). Early vacci- ,30 Referral to a nephrologist nation against hepatitis B virus is care.diabetesjournals.org Position Statement S61

Diabetic retinopathy is a highly specific in a population with well-controlled c If there is no evidence of retinopathy vascular complication of both type 1 type 2 diabetes, there was essentially for one or more eye exams, then ex- and type 2 diabetes, with prevalence no risk of development of significant ret- ams every 2 years may be consid- strongly related to the duration of dia- inopathy with a 3-year interval after a ered. If diabetic retinopathy is betes. Diabetic retinopathy is the most normal examination (49). Examinations present, subsequent examinations frequent cause of new cases of blind- will be required more frequently if reti- for patients with type 1 and type 2 ness among adults aged 20–74 years. nopathy is progressing. diabetes should be repeated annually Glaucoma, cataracts, and other disor- Retinal photography, with remote by an ophthalmologist or optome- ders of the eye occur earlier and more reading by experts, has great potential trist. If retinopathy is progressing or frequently in people with diabetes. in areas where qualified eye care profes- sight-threatening, then examinations In addition to diabetes duration, fac- sionals are not readily available (50). It will be required more frequently. B tors that increase the risk of, or are as- also may enhance efficiency and reduce c High-quality fundus photographs sociated with, retinopathy include costs when the expertise of ophthalmol- can detect most clinically signifi- chronic hyperglycemia (42), nephropa- ogistscanbeusedformorecomplex cant diabetic retinopathy. Inter- thy (43), and hypertension (44). Inten- examinations and for therapy (51). In- pretation of the images should sive diabetes management with the person exams are still necessary when be performed by a trained eye goal of achieving near-normoglycemia the photos are unacceptable and for care provider. While retinal pho- has been shown in large prospective follow-up if abnormalities are detected. tography may serve as a screening randomized studies to prevent and/or Photos are not a substitute for a com- tool for retinopathy, it is not a sub- delay the onset and progression of di- prehensive eye exam, which should be stitute for a comprehensive eye abetic retinopathy (11,45). Lowering performed at least initially and at inter- exam, which should be performed bloodpressurehasbeenshowntode- vals thereafter as recommended by an at least initially and at intervals crease retinopathy progression, al- eye care professional. Results of eye ex- thereafter as recommended by though tight targets (systolic ,120 aminations should be documented and an eye care professional. E mmHg) do not impart additional benefit transmitted to the referring health care c Women with preexisting diabetes (45). Several case series and a con- professional. who are planning pregnancy or trolled prospective study suggest that who have become pregnant pregnancy in type 1 diabetic patients Treatment should have a comprehensive eye may aggravate retinopathy (46,47). La- One of the main motivations for screening examination and be counseled on ser photocoagulation surgery can mini- for diabetic retinopathy is the long- the risk of development and/or mize this risk (47). established efficacy of laser photocoag- progression of diabetic retinopa- ulation surgery in preventing visual loss. thy. Eye examination should occur Screening Two large trials, the Diabetic Retinopa- in the first trimester with close The preventive effects of therapy and thy Study (DRS) in patients with PDR and follow-up throughout pregnancy the fact that patients with PDR or mac- the Early Treatment Diabetic Retinopathy and for 1 year postpartum. B ular edema may be asymptomatic pro- Study (ETDRS) in patients with macular Treatment vide strong support for a screening edema, provide the strongest support program to detect diabetic retinopathy. for the therapeutic benefits of photoco- c Promptly refer patients with any Because retinopathy is estimated to agulation surgery. The DRS (52) showed level of macular edema, severe take at least 5 years to develop after that panretinal photocoagulation surgery nonproliferative diabetic retinop- the onset of hyperglycemia, patients reduced the risk of severe vision loss from athy (NPDR), or any proliferative with type 1 diabetes should have an ini- PDR from 15.9% in untreated eyes to diabetic retinopathy (PDR) to an tial dilated and comprehensive eye ex- 6.4% in treated eyes, with the greatest ophthalmologist who is knowl- amination within 5 years after the risk-benefit ratio in those with baseline edgeable and experienced in the diabetes diagnosis (48). Patients with disease (disc neovascularization or vitre- management and treatment of di- type 2 diabetes who may have had years ous hemorrhage). abetic retinopathy. A of undiagnosed diabetes and have a sig- The ETDRS (53) established the ben- c Laser photocoagulation therapy is nificant risk of prevalent diabetic ret- efit of focal laser photocoagulation sur- indicated to reduce the risk of vision inopathy at the time of diagnosis gery in eyes with macular edema, loss in patients with high-risk PDR, should have an initial dilated and com- particularly those with clinically signif- clinically significant macular edema, prehensive eye examination shortly af- icant macular edema, with reduction of and, in some cases, severe NPDR. A ter diagnosis. Examinations should be doubling of the visual angle (e.g., 20/50 c Antivascular endothelial growth performed by an ophthalmologist or op- to 20/100) from 20% in untreated eyes factor (VEGF) therapy is indicated tometrist who is knowledgeable and to 8% in treated eyes. The ETDRS also for diabetic macular edema. A experienced in diagnosing diabetic reti- verified the benefits of panretinal pho- c The presence of retinopathy is nopathy. Subsequent examinations for tocoagulation for high-risk PDR and in not a contraindication to aspirin type 1 and type 2 diabetic patients are older-onset patients with severe NPDR therapy for cardioprotection, as generally repeated annually. Exams ev- or less-than-high-risk PDR. aspirin does not increase the risk ery 2 years may be cost-effective after Laser photocoagulation surgery in of retinal hemorrhage. A oneormorenormaleyeexams,and both trials was beneficial in reducing S62 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

the risk of further visual loss, but gener- 4. Autonomic neuropathy, particularly examination. Major clinical manifesta- ally not beneficial in reversing already CAN, is an independent risk factor tions of diabetic autonomic neuropathy diminished acuity. Recombinant mono- for cardiovascular mortality (58,59). include resting tachycardia, exercise clonal neutralizing antibody to VEGF im- intolerance, orthostatic hypotension, proves vision and reduces the need for Specific treatment for the underlying gastroparesis, constipation, erectile dys- laser photocoagulation in patients with nerve damage, other than improved gly- function, sudomotor dysfunction, im- macular edema (54). Other emerging cemic control, is currently not available. paired neurovascular function, and, therapies for retinopathy include sus- Glycemic control was shown to effec- potentially, autonomic failure in response tained intravitreal delivery of fluocin- tively prevent DPN and CAN in type 1 to hypoglycemia. diabetes (60,61) and may modestly olone (55) and the possibility of Cardiovascular Autonomic Neuropathy fi prevention with feno brate (56,57). slow progression in type 2 diabetes CAN is the most studied and clinically NEUROPATHY (13) but does not reverse neuronal important form of diabetic autonomic loss. Therapeutic strategies (pharmaco- neuropathy because of its association Recommendations logical and nonpharmacological) for the with mortality independent of other fi c All patients should be screened for relief of speci c symptoms related to cardiovascular risk factors (58,68). In diabetic peripheral neuropathy painful DPN or autonomic neuropathy early stages, CAN may be completely (DPN) starting at diagnosis of are recommended because they can po- asymptomatic and detected by changes type 2 diabetes and 5 years after tentially reduce pain (62) and improve in heart rate variability with deep the diagnosis of type 1 diabetes quality of life. breathing and abnormal cardiovascular and at least annually thereafter, Diagnosis reflex tests (R-R interval response to using simple clinical tests, such deep breathing, standing, and Valsalva as a 10-g monofilament. B Diabetic Peripheral Neuropathy Patients with diabetes should be maneuver tests). Advanced disease may c Screening for signs and symptoms screened annually for DPN symptoms be indicated by resting tachycardia (e.g., orthostasis, resting tachycar- . using simple clinical tests. Symptoms ( 100 bpm) and orthostasis (a fall in dia) of cardiovascular autonomic systolic blood pressure .20 mmHg or neuropathy (CAN) should be consid- vary according to the class of sensory fi diastolic blood pressure of at least 10 ered with more advanced disease. E bers involved. The most common symptoms are induced by the involve- mmHg upon standing without an appro- c Tight glycemic control is the only ment of small fibers and include pain, priate heart rate response). The stan- strategy convincingly shown to dard cardiovascular reflex tests (deep prevent or delay the development dysesthesias (unpleasant abnormal sen- sations of burning and tingling), and breathing, standing, and Valsalva of DPN and CAN in patients with maneuver) are noninvasive, easy to type 1 diabetes A and to slow the numbness. Clinical tests include assess- ment of pinprick sensation, vibration perform, reliable, and reproducible, es- progression of neuropathy in some pecially the deep breathing test, and patients with type 2 diabetes. B threshold using a 128-Hz tuning fork, light touch perception using a 10-g have prognostic value (69). Although c Assess and treat patients to re- monofilament, and ankle reflexes. As- some societies have developed guide- duce pain related to DPN B and lines for screening for CAN, the benefits symptoms of autonomic neuropa- sessment should follow the typical DPN pattern, starting distally (the dorsal of sophisticated testing beyond risk thy and to improve quality of life. E fi aspect of the hallux) on both sides and strati cation are not clear (69). The diabetic neuropathies are heteroge- move proximally until threshold is de- Gastrointestinal Neuropathies Gastrointestinal neuropathies (e.g., neous with diverse clinical manifestations. tected. Several clinical instruments esophageal enteropathy, gastroparesis, They may be focal or diffuse. The most that combine more than one test have . constipation, diarrhea, fecal inconti- prevalent neuropathies are DPN and auto- 87% sensitivity in detecting DPN – nence) may involve any section of the nomic neuropathy. Although DPN is a diag- (63 65). Electrophysiological testing or gastrointestinal tract. Gastroparesis nosis of exclusion, complex investigations referral to a neurologist is rarely needed, should be suspected in individuals with or referral for neurology consultation to ex- except in situations where the clinical erratic glucose control or with upper gas- clude other conditions is rarely needed. features are atypical or the diagnosis is trointestinal symptoms without another The early recognition and appropriate unclear. identified cause. Evaluation of solid- management of neuropathy in the pa- In patients with severe or atypical neu- phase gastric emptying using double- tient with diabetes is important for a ropathy, causes other than diabetes isotope scintigraphy may be done if number of reasons: should always be considered, such as neu- rotoxic medications, heavy metal poison- symptoms are suggestive, but test re- fi sults often correlate poorly with symp- 1. Nondiabetic neuropathies may be ing, alcohol abuse, vitamin B12 de ciency fl present in patients with diabetes (66), renal disease, chronic in ammatory toms. Constipation is the most common and may be treatable. demyelinating neuropathy, inherited neu- lower-gastrointestinal symptom but can 2. A number of treatment options exist ropathies, and vasculitis (67). alternate with episodes of diarrhea. for symptomatic . Diabetic Autonomic Neuropathy Genitourinary Tract Disturbances 3. Up to 50% of DPN may be asymptom- The symptoms and signs of autonomic Diabetic autonomic neuropathy is also atic, and patients are at risk for in- dysfunction should be elicited care- associated with genitourinary tract dis- sensate injury to their feet. fully during the history and physical turbances. In men, diabetic autonomic care.diabetesjournals.org Position Statement S63

neuropathy may cause erectile dysfunc- Autonomic Neuropathy FOOT CARE tion and/or retrograde ejaculation. Eval- An intensive multifactorial cardiovascu- Recommendations lar risk intervention targeting glucose, uation of bladder dysfunction should be c For all patients with diabetes, per- performed for individuals with diabetes blood pressure, lipids, smoking, and form an annual comprehensive who have recurrent urinary tract infec- other lifestyle factors has been shown foot examination to identify risk tions, pyelonephritis, incontinence, or a to reduce the progression and develop- factors predictive of ulcers and palpable bladder. ment of CAN among patients with type 2 amputations. The foot examina- fi diabetes (79). For those with signi cant tion should include inspection Treatment CAN, referral to a cardiologist may be and assessment of foot pulses. B indicated. Glycemic Control c Patients with insensate feet, foot Tight glycemic control, implemented deformities, and ulcers should early in the course of diabetes, has Orthostatic Hypotension have their feet examined at every been shown to effectively prevent or de- Treatment of orthostatic hypotension is visit. E lay the development of DPN and CAN in challenging. The therapeutic goal is to c Provide general foot self-care patients with type 1 diabetes (70–73). minimize postural symptoms rather education to all patients with di- While the evidence is not as strong for than to restore normotension. Most pa- abetes. B type 2 diabetes, some studies have tients require the use of both pharma- c A multidisciplinary approach is demonstrated a modest slowing of pro- cological and nonpharmacological recommended for individuals gression (74,75) without reversal of measures (e.g., avoiding medications with foot ulcers and high-risk feet neuronal loss. Several observational that aggravate hypotension, using com- (e.g., dialysis patients and those studies further suggest that neuropathic pressive garments over the legs and ab- with Charcot foot, prior ulcers, or symptoms improve not only with opti- domen). Midodrine is the only drug amputation). B mization of glycemic control but also approved by the U.S. Food and Drug c Refer patients who smoke or who with the avoidance of extreme blood Administration for the treatment of have a loss of protective sensation glucose fluctuations. orthostatic hypotension. (LOPS), structural abnormalities, or a history of prior lower- Diabetic Peripheral Neuropathy Gastroparesis Symptoms extremity complications to foot DPN symptoms, and especially neuro- Gastroparesis symptoms may improve care specialists for ongoing pre- pathic pain, can be severe, have sudden with dietary changes and prokinetic agents ventive care and lifelong surveil- onset, and are associated with lower such as erythromycin. Recently, the Euro- lance. C quality of life, limited mobility, depres- pean Medicines Agency (www.ema.europa c Initial screening for peripheral sion, and social dysfunction (76). There .eu/docs/en_GB/document_library/ arterial disease (PAD) should is limited clinical evidence regarding the Press_release/2013/07/WC500146614.pdf) include a history for claudication most effective treatments for individual decided that risks of extrapyramidal symp- and an assessment of the pedal patients given the wide range of avail- toms with metoclopramide outweigh ben- pulses. C fi able medications (77,78). Several drugs e ts. In Europe, metoclopramide use is c Refer patients with significant fi have been approved speci cally for re- now restricted to a maximum of 5 days claudication or a positive ankle- lief of DPN pain in the U.S. (pregabalin, andisnolongerindicatedforthelong- brachial index (ABI) for further duloxetine, and tapentadol), but none term treatment of gastroparesis. Although vascular assessment and consider ’ affords complete relief, even when the U.S. Food and Drug Administration s exercise, medications, and surgical used in combination. Venlafaxine, ami- decision is pending, it is suggested that options. C triptyline, gabapentin, valproate, and metoclopramide be reserved for only the other opioids (morphine sulfate, trama- most severe cases that are unresponsive Amputation and foot ulceration, which dol, oxycodone controlled release) may to other therapies. Side effects should be are consequences of diabetic neuropa- be effective and may be considered for closely monitored. thy and/or PAD, are common and repre- treatment of painful DPN. Head-to- sent major causes of morbidity and head treatment comparisons and stud- Erectile Dysfunction disability in people with diabetes. Loss ies that include quality-of-life outcomes Treatments for erectile dysfunction may of 10-g monofilament perception and are rare, so treatment decisions must include phosphodiesterase type 5 inhibi- reduced vibration perception predict consider each patient’spresentation tors, intracorporeal or intraurethral prosta- foot ulcers (78). Early recognition and and comorbidities and often follow a glandins, vacuum devices, or penile management of risk factors can prevent trial-and-error approach. Given the prostheses. Interventions for other mani- or delay adverse outcomes. range of partially effective treatment festations of autonomic neuropathy are The risk of ulcers or amputations is options, a tailored and stepwise phar- described in the American Diabetes Asso- increasedinpeoplewhohavethefol- macological strategy with careful atten- ciation (ADA) statement on neuropathy lowing risk factors: tion to relative symptom improvement, (78). As with DPN treatments, these inter- medication adherence, and medication ventions do not change the underlying ○ Previous amputation side effects is recommended to achieve pathology and natural history of the dis- ○ Past foot ulcer history pain reduction and improve quality of ease process but may have a positive im- ○ Peripheral neuropathy life (62). pact on the quality of life of the patient. ○ Foot deformities S64 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

○ Peripheral vascular disease A diagnostic ABI should be considered commercial therapeutic footwear may ○ Visual impairment in patients with PAD. Due to the high need custom-molded shoes. ○ Diabetic nephropathy (especially pa- estimated prevalence of PAD in patients Most infections are poly- tients on dialysis) with diabetes and the fact that many microbial, with aerobic gram-positive ○ Poor glycemic control patients with PAD are asymptomatic, cocci (GPC). Staphylococci are the most ○ Cigarette smoking an ADA consensus report on PAD (81) common causative organisms. Wounds suggested that a screening ABI be per- without evidence of soft-tissue or bone formed in patients over 50 years of age infection do not require antibiotic ther- Clinicians are encouraged to review and be considered in patients under 50 apy. Empiric antibiotic therapy can be ADA screening recommendations for years of age who have other PAD risk narrowly targeted at GPC in many further details and practical descriptions factors (e.g., smoking, hypertension, hy- acutely infected patients, but those at of how to perform components of the perlipidemia, or duration of diabetes risk for infection with antibiotic-resistant comprehensive foot examination (80). .10 years). Refer patients with signifi- organisms or with chronic, previously Examination cant symptoms or a positive ABI for fur- treated, or severe infections require All adults with diabetes should ther vascular assessment and consider broader-spectrum regimens and should undergo a comprehensive foot exami- exercise, medications, and surgical be referred to specialized care centers nation at least annually to identify options (81). (82). Foot ulcers and wound care may require care by a podiatrist, orthopedic high-risk conditions. Clinicians should Patient Education or vascular surgeon, or rehabilitation ask about history of previous foot ulcer- Patients with diabetes and high-risk foot specialist experienced in the manage- ation or amputation, neuropathic or pe- conditions should be educated about ment of individuals with diabetes. ripheral vascular symptoms, impaired their risk factors and appropriate man- Guidelines for treatment of diabetic vision, tobacco use, and foot care prac- agement. Patients at risk should under- foot ulcers have recently been updated tices. A general inspection of skin integ- stand the implications of LOPS; the (82). rity and musculoskeletal deformities importance of foot monitoring on a daily should be done in a well-lit room. Vas- basis; the proper care of the foot, includ- References cular assessment would include inspec- ing nail and skin care; and the selection 1. Krolewski AS, Niewczas MA, Skupien J, et al. tion and assessment of pedal pulses. of appropriate footwear. Patients with The neurological exam recommended Early progressive renal decline precedes the onset LOPS should be educated on ways to of microalbuminuria and its progression to mac- is designed to identify LOPS rather than substitute other sensory modalities roalbuminuria. Diabetes Care 2014;37:226–234 early neuropathy. The clinical examination (hand palpation, visual inspection) for 2. Garg JP, Bakris GL. Microalbuminuria: to identify LOPS is simple and requires no surveillance of early foot problems. Pa- marker of vascular dysfunction, risk factor for cardiovascular disease. Vasc Med 2002;7:35–43 expensive equipment. Five simple clinical tients’ understanding of these issues fi 3. Klausen K, Borch-Johnsen K, Feldt-Rasmussen B, tests (use of a 10-g mono lament, vibra- and their physical ability to conduct et al. Very low levels of microalbuminuria are tion testing using a 128-Hz tuning fork, proper foot surveillance and care should associated with increased risk of coronary heart fl tests of pinprick sensation, ankle re ex as- be assessed. Patients with visual difficul- disease and death independently of renal func- sessment, and testing vibration percep- tion, hypertension, and diabetes. Circulation ties, physical constraints preventing – tion threshold with a biothesiometer), 2004;110:32 35 movement, or cognitive problems that 4. de Boer IH, Rue TC, Cleary PA, et al.; Diabetes each with evidence from well-conducted impair their ability to assess the condi- Control and Complications Trial/Epidemiology prospective clinical cohort studies, are tion of the foot and to institute appro- of Diabetes Interventions and Complications considered useful in the diagnosis of priate responses will need other people, Study Research Group. Long-term renal out- fi comes of patients with type 1 diabetes mellitus LOPS in the diabetic foot. Any of the ve such as family members, to assist in tests listed above could be used by clini- and microalbuminuria: an analysis of the Diabetes their care. Control and Complications Trial/Epidemiology of cians to identify LOPS, although ideally Diabetes Interventions and Complications cohort. Treatment two of these should be regularly per- Arch Intern Med 2011;171:412–420 formed during the screening examd People with neuropathy or evidence of 5. Molitch ME, Steffes M, Sun W, et al.; Epide- normally the 10-g monofilament and one increased plantar pressure (e.g., ery- miology of Diabetes Interventions and Com- other test. One or more abnormal tests thema, warmth, callus, or measured plications Study Group. Development and progression of renal insufficiency with and with- would suggest LOPS, while at least two pressure) may be adequately managed fi out albuminuria in adults with type 1 diabetes in normal tests (and no abnormal test) would with well- tted walking shoes or athletic the Diabetes Control and Complications Trial rule out LOPS. The last test listed, vibration shoes that cushion the feet and redis- and the Epidemiology of Diabetes Interventions assessment using a biothesiometer or sim- tribute pressure. Calluses can be de- and Complications Study. Diabetes Care 2010; 33:1536–1543 ilar instrument, is widely used in the U.S.; brided with a scalpel by a foot care specialist or other health professional 6. de Boer IH, Sun W, Cleary PA, et al.; DCCT/ however, identification of the patient with EDIC Research Group. Intensive diabetes ther- LOPS can easily be carried out without this with experience and training in foot apy and glomerular filtration rate in type 1 di- or other expensive equipment. care. People with bony deformities (e.g., abetes. N Engl J Med 2011;365:2366–2376 hammertoes, prominent metatarsal 7. National Kidney Foundation. KDOQI clinical Screening heads, bunions) may need extra wide practice guideline for diabetes and CKD: 2012 update. Am J Kidney Dis 2012;60:850–886 Initial screening for PAD should or deep shoes. People with extreme 8. Gall M-A, Hougaard P, Borch-Johnsen K, include a history for claudication and bony deformities (e.g., Charcot foot) Parving H-H. Risk factors for development of an assessment of the pedal pulses. who cannot be accommodated with incipient and overt diabetic nephropathy in care.diabetesjournals.org Position Statement S65

patients with non-insulin dependent diabetes study and MICRO-HOPE substudy. Lancet 2000; 36. Eknoyan G, Hostetter T, Bakris GL, et al. Pro- mellitus: prospective, observational study. 355:253–259 teinuria and other markers of chronic kidney BMJ 1997;314:783–788 23. Bilous R, Chaturvedi N, Sjølie AK, et al. Ef- disease: a position statement of the National 9. The Diabetes Control and Complications fect of candesartan on microalbuminuria and Kidney Foundation (NKF) and the National In- (DCCT) Research Group. Effect of intensive ther- albumin excretion rate in diabetes: three ran- stitute of Diabetes and Digestive and Kidney apy on the development and progression of di- domized trials. Ann Intern Med 2009;151: Diseases (NIDDK). Am J Kidney Dis 2003;42: abetic nephropathy in the Diabetes Control and 11220 617–622 Complications Trial. Kidney Int 1995;47:1703– 24. Lewis EJ, Hunsicker LG, Clarke WR, et al.; 37. Levey AS, Coresh J, Balk E, et al.; National 1720 Collaborative Study Group. Renoprotective ef- Kidney Foundation. National Kidney Foundation 10. UK Prospective Diabetes Study (UKPDS) fect of the angiotensin-receptor antagonist ir- practice guidelines for chronic kidney disease: Group. Effect of intensive blood-glucose control besartan in patients with nephropathy due to evaluation, classification, and stratification. Ann with metformin on complications in overweight type 2 diabetes. N Engl J Med 2001;345:851– Intern Med 2003;139:137–147 patients with type 2 diabetes (UKPDS 34). Lan- 860 38. Kramer H, Molitch ME. Screening for kidney cet 1998;352:854–865 25. Brenner BM, Cooper ME, de Zeeuw D, et al.; disease in adults with diabetes. Diabetes Care 11. UK Prospective Diabetes Study (UKPDS) RENAAL Study Investigators. Effects of losartan 2005;28:1813–1816 Group. Intensive blood-glucose control with sul- on renal and cardiovascular outcomes in pa- 39. Kramer HJ, Nguyen QD, Curhan G, Hsu C-Y. phonylureas or insulin compared with conven- tients with type 2 diabetes and nephropathy. Renal insufficiency in the absence of albumin- tional treatment and risk of complications in N Engl J Med 2001;345:861–869 uria and retinopathy among adults with type 2 patients with type 2 diabetes (UKPDS 33). Lan- 26. Parving HH, Lehnert H, Brochner-¨ diabetes mellitus. JAMA 2003;289:3273–3277 cet 1998;352:837–853 Mortensen J, Gomis R, Andersen S, Arner P; Ir- 40. Levey AS, Bosch JP, Lewis JB, Greene T, 12. Patel A, MacMahon S, Chalmers J, et al.; besartan in Patients with Type 2 Diabetes and Rogers N, Roth D; Modification of Diet in Renal ADVANCE Collaborative Group. Intensive blood Microalbuminuria Study Group. The effect of Disease Study Group. A more accurate method glucose control and vascular outcomes in pa- irbesartan on the development of diabetic ne- to estimate glomerular filtration rate from se- tients with type 2 diabetes. N Engl J Med phropathy in patients with type 2 diabetes. N rum creatinine: a new prediction equation. Ann 2008;358:2560–2572 Engl J Med 2001;345:870–878 Intern Med 1999;130:461–470 13. Ismail-Beigi F, Craven T, Banerji MA, et al.; 27. Pepine CJ, Handberg EM, Cooper-DeHoff 41. Smart NA, Dieberg G, Ladhani M, Titus T. ACCORD Trial Group. Effect of intensive treat- RM, et al.; INVEST Investigators. A calcium an- Early referral to specialist nephrology services ment of hyperglycaemia on microvascular out- tagonist vs a non-calcium antagonist hyperten- for preventing the progression to end-stage kid- comes in type 2 diabetes: an analysis of the sion treatment strategy for patients with ney disease. Cochrane Database Syst Rev 2014; ACCORD randomised trial. Lancet 2010;376: coronary artery disease. The International 6:CD007333 419–430 Verapamil-Trandolapril Study (INVEST): a ran- 42. Klein R. Hyperglycemia and microvascular 14. Tuttle KR, Bakris GL, Bilous RW, et al. 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Hyperglycemia, blood 16. Lipska KJ, Bailey CJ, Inzucchi SE. Use of met- patients at high risk for vascular events. N Engl J pressure, and the 9-year incidence of diabetic formin in the setting of mild-to-moderate renal Med 2008;358:1547–1559 retinopathy: the Barbados Eye Studies. Oph- insufficiency. Diabetes Care 2011;34:1431– 30. Berl T, Hunsicker LG, Lewis JB, et al.; Irbe- thalmology 2005;112:799–805 1437 sartan Diabetic Nephropathy Trial. Collabora- 45. Chew EY, Ambrosius WT, Davis MD, et al.; 17. UK Prospective Diabetes Study Group. tive Study Group. Cardiovascular outcomes ACCORD Study Group; ACCORD Eye Study Tight blood pressure control and risk of macro- in the Irbesartan Diabetic Nephropathy Trial Group. Effects of medical therapies on retinop- vascular and microvascular complications in of patients with type 2 diabetes and overt athy progression in type 2 diabetes. N Engl J type 2 diabetes: UKPDS 38. BMJ 1998;317: nephropathy. Ann Intern Med 2003;138:542– Med 2010;363:233–244 703–713 549 46. Fong DS, Aiello LP, Ferris FL 3rd, Klein R. 18. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD; 31. Pijls LT, de Vries H, Donker AJ, van Eijk JT. Diabetic retinopathy. Diabetes Care 2004;27: Collaborative Study Group. The effect of The effect of protein restriction on albuminuria 2540–2553 angiotensin-converting-enzyme inhibition on in patients with type 2 diabetes mellitus: a ran- 47. Diabetes Control and Complications Trial diabetic nephropathy. N Engl J Med 1993;329: domized trial. Nephrol Dial Transplant 1999;14: Research Group. Effect of pregnancy on micro- 1456–1462 1445–1453 vascular complications in the diabetes control 19. Laffel LM, McGill JB, Gans DJ; North Amer- 32. Pedrini MT, Levey AS, Lau J, Chalmers TC, and complications trial. Diabetes Care 2000;23: ican Microalbuminuria Study Group. The bene- Wang PH. The effect of dietary protein restric- 1084–1091 ficial effect of angiotensin-converting enzyme tion on the progression of diabetic and nondia- 48. Hooper P, Boucher MC, Cruess A, et al. inhibition with captopril on diabetic nephropa- betic renal diseases: a meta-analysis. Ann Intern Canadian Ophthalmological Society evidence- thy in normotensive IDDM patients with micro- Med 1996;124:627–632 based clinical practice guidelines for the albuminuria. Am J Med 1995;99:497–504 33. Hansen HP, Tauber-Lassen E, Jensen BR, management of diabetic retinopathy. Can J 20. Remuzzi G, Macia M, Ruggenenti P. Preven- Parving H-H. Effect of dietary protein restriction Ophthalmol 2012;47(Suppl. 2):S12S30 tion and treatment of diabetic renal disease in on prognosis in patients with diabetic nephrop- 49. Agardh E, Tababat-Khani P. Adopting 3-year type 2 diabetes: the BENEDICT study. J Am Soc athy. Kidney Int 2002;62:220–228 screening intervals for sight-threatening retinal Nephrol 2006;17(Suppl. 2):S90–S97 34. Kasiske BL, Lakatua JD, Ma JZ, Louis TA. A vascular lesions in type 2 diabetic subjects with- 21. Haller H, Ito S, Izzo JL Jr; et al.; ROADMAP meta-analysis of the effects of dietary protein out retinopathy. Diabetes Care 2011;34:1318– Trial Investigators. Olmesartan for the delay or restriction on the rate of decline in renal func- 1319 prevention of microalbuminuria in type 2 tion. Am J Kidney Dis 1998;31:954–961 50. Bragge P, Gruen RL, Chau M, Forbes A, diabetes. N Engl J Med 2011;364:907–917 35. Wheeler ML, Dunbar SA, Jaacks LM, et al. Taylor HR. Screening for presence or absence 22. Heart Outcomes Prevention Evaluation Macronutrients, food groups, and eating pat- of diabetic retinopathy: a meta-analysis. Arch Study Investigators. Effects of ramipril on car- terns in the management of diabetes: a system- Ophthalmol 2011;129:435–444 diovascular and microvascular outcomes in peo- atic review of the literature, 2010. Diabetes 51. Ahmed J, Ward TP, Bursell S-E, Aiello LM, ple with diabetes mellitus: results of the HOPE Care 2012;35:434–445 Cavallerano JD, Vigersky RA. The sensitivity and S66 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

specificity of nonmydriatic digital stereoscopic American Academy of Physical Medicine and the Epidemiology of Diabetes Interventions and retinal imaging in detecting diabetic retinopa- Rehabilitation [published correction appears in Complications (EDIC) study. Diabetes Care thy. Diabetes Care 2006;29:2205–2209 Neurology 2011;77:603]. Neurology 2011;76: 2010;33:1090–1096 52. The Diabetic Retinopathy Study Research 1758–1765 73. Pop-Busui R, Low PA, Waberski BH, et al.; Group. Preliminary report on effects of photo- 63. Pop-Busui R, Lu J, Brooks MM, et al.; BARI DCCT/EDIC Research Group. Effects of prior in- coagulation therapy. Am J Ophthalmol 1976;81: 2D Study Group. Impact of glycemic control tensive insulin therapy on cardiac autonomic 383–396 strategies on the progression of diabetic periph- nervous system function in type 1 diabetes mel- 53. Early Treatment Diabetic Retinopathy eral neuropathy in the Bypass Angioplasty Re- litus: the Diabetes Control and Complications Study Research Group. Photocoagulation for di- vascularization Investigation 2 Diabetes (BARI Trial/Epidemiology of Diabetes Interventions abetic macular edema. Early Treatment Diabetic 2D) cohort. Diabetes Care 2013;36:3208–3215 and Complications study (DCCT/EDIC). Circula- Retinopathy Study report number 1. Arch Oph- 64. Martin CL, Albers J, Herman WH, et al.; tion 2009;119:2886–2893 thalmol 1985;103:1796–1806 DCCT/EDIC Research Group. Neuropathy among 74. Callaghan BC, Little AA, Feldman EL, Hughes 54. Nguyen QD, Brown DM, Marcus DM, et al.; the diabetes control and complications trial co- RAC. Enhanced glucose control for preventing RISE and RIDE Research Group. Ranibizumab for hort 8 years after trial completion. Diabetes and treating diabetic neuropathy. Cochrane Da- diabetic macular edema: results from 2 phase III Care 2006;29:340–344 tabase Syst Rev 2012;6:CD007543 randomized trials: RISE and RIDE. Ophthalmol- 65. Herman WH, Pop-Busui R, Braffett BH, 75. Riddle MC, Ambrosius WT, Brillon DJ, et al.; ogy 2012;119:789–801 et al.; DCCT/EDIC Research Group. Use of the Action to Control Cardiovascular Risk in Diabe- 55. Pearson PA, Comstock TL, Ip M, et al. Fluo- Michigan Neuropathy Screening Instrument as a tes Investigators. Epidemiologic relationships cinolone acetonide intravitreal implant for dia- measure of distal symmetrical peripheral neu- between A1C and all-cause mortality during a betic macular edema: a 3-year multicenter, ropathy in type 1 diabetes: results from the Di- median 3.4-year follow-up of glycemic treat- randomized, controlled clinical trial. Ophthal- abetes Control and Complications Trial/ ment in the ACCORD trial. Diabetes Care 2010; mology 2011;118:1580–1587 Epidemiology of Diabetes Interventions and 33:983–990 56. Chew EY, Ambrosius WT. Update of the Complications. Diabet Med 2012;29:937–944 76. Sadosky A, Schaefer C, Mann R, et al. Bur- ACCORD Eye Study. N Engl J Med 2011;364: 66. Wile DJ, Toth C. Association of metformin, den of illness associated with painful diabetic 188–189 elevated homocysteine, and methylmalonic peripheral neuropathy among adults seeking 57. Keech AC, Mitchell P, Summanen PA, et al.; acid levels and clinically worsened diabetic pe- treatment in the US: results from a retrospec- FIELD study investigators. Effect of fenofibrate ripheral neuropathy. Diabetes Care 2010;33: tive chart review and cross-sectional survey. Di- on the need for laser treatment for diabetic 156–161 abetes Metab Syndr Obes 2013;6:79–92 retinopathy (FIELD study): a randomised con- 67. Freeman R. Not all neuropathy in diabetes 77. Snedecor SJ, Sudharshan L, Cappelleri JC, trolled trial. Lancet 2007;370:1687–1697 is of diabetic etiology: differential diagnosis of Sadosky A, Mehta S, Botteman M. Systematic 58. Pop-Busui R, Evans GW, Gerstein HC, et al.; diabetic neuropathy. Curr Diab Rep 2009;9: review and meta-analysis of pharmacological Action to Control Cardiovascular Risk in Diabetes 423–431 therapies for painful diabetic peripheral neu- Study Group. Effects of cardiac autonomic dys- 68. Young LH, Wackers FJT, Chyun DA, et al.; ropathy. Pain Pract 2014;14:167–184 function on mortality risk in the Action to Control DIAD Investigators. Cardiac outcomes after 78. Boulton AJM, Vinik AI, Arezzo JC, et al.; Cardiovascular Risk in Diabetes (ACCORD) trial. screening for asymptomatic coronary artery dis- American Diabetes Association. Diabetic Diabetes Care 2010;33:1578–1584 ease in patients with type 2 diabetes: the DIAD neuropathies: a statement by the American 59. Spallone V, Ziegler D, Freeman R, et al.; study: a randomized controlled trial. JAMA Diabetes Association. Diabetes Care 2005;28: Toronto Consensus Panel on Diabetic Neuropa- 2009;301:1547–1555 956–962 thy. Cardiovascular autonomic neuropathy in 69. Spallone V, Bellavere F, Scionti L, et al.; Di- 79. Gaede P, Vedel P, Larsen N, Jensen GVH, diabetes: clinical impact, assessment, diagnosis, abetic Neuropathy Study Group of the Italian Parving H-H, Pedersen O. Multifactorial inter- and management. Diabetes Metab Res Rev Society of Diabetology. Recommendations for vention and cardiovascular disease in patients 2011;27:6392653 the use of cardiovascular tests in diagnosing di- with type 2 diabetes. N Engl J Med 2003;348: 60. Ang L, Jaiswal M, Martin C, Pop-Busui R. abetic autonomic neuropathy. Nutr Metab Car- 383–393 Glucose control and diabetic neuropathy: les- diovasc Dis 2011;21:69–78 80. Boulton AJM, Armstrong DG, Albert SF, sons from recent large clinical trials. Curr Diab 70. Diabetes Control and Complications Trial et al.; American Diabetes Association; American Rep 2014;14:528 (DCCT) Research Group. Effect of intensive di- Association of Clinical Endocrinologists. Com- 61. Martin CL, Albers JW, Pop-Busui R; DCCT/ abetes treatment on nerve conduction in the prehensive foot examination and risk assess- EDIC Research Group. Neuropathy and related Diabetes Control and Complications Trial. Ann ment: a report of the task force of the foot findings in the Diabetes Control and Complica- Neurol 1995;38:869–880 care interest group of the American Diabetes tions Trial/Epidemiology of Diabetes Interven- 71. CDC Study Group. The effect of intensive Association, with endorsement by the American tions and Complications study. Diabetes Care diabetes therapy on measures of autonomic Association of Clinical Endocrinologists. Diabe- 2014;37:31–38 nervous system function in the Diabetes Control tes Care 2008;31:1679–1685 62. Bril V, England J, Franklin GM, et al.; Amer- and Complications Trial (DCCT). Diabetologia 81. American Diabetes Association. Peripheral ican Academy of Neurology; American Associa- 1998;41:416–423 arterial disease in people with diabetes. Diabe- tion of Neuromuscular and Electrodiagnostic 72. Albers JW, Herman WH, Pop-Busui R, et al.; tes Care 2003;26:3333–3341 Medicine; American Academy of Physical Med- Diabetes Control and Complications Trial/ 82. Lipsky BA, Berendt AR, Cornia PB, et al.; In- icine and Rehabilitation. Evidence-based guide- Epidemiology of Diabetes Interventions and fectious Diseases Society of America. 2012 In- line: treatment of painful diabetic neuropathy: Complications Research Group. Effect of prior fectious Diseases Society of America clinical report of the American Academy of Neurology, intensive insulin treatment during the Diabetes practice guideline for the diagnosis and treat- the American Association of Neuromuscular Control and Complications Trial (DCCT) on pe- ment of diabetic foot infections. Clin Infect Dis and Electrodiagnostic Medicine, and the ripheral neuropathy in type 1 diabetes during 2012;54:e132–e173 Diabetes Care Volume 38, Supplement 1, January 2015 S67

10. Older Adults American Diabetes Association Diabetes Care 2015;38(Suppl. 1):S67–S69 | DOI: 10.2337/dc15-S013

Recommendations c Older adults who are functional and cognitively intact and have significant life expectancy should receive diabetes care with goals similar to those developed for younger adults. E c Glycemic goals for some older adults might reasonably be relaxed, using in- dividual criteria, but hyperglycemia leading to symptoms or risk of acute hyperglycemic complications should be avoided in all patients. E c Other cardiovascular risk factors should be treated in older adults with con- sideration of the time frame of benefit and the individual patient. Treatment of hypertension is indicated in virtually all older adults, and lipid-lowering and aspirin therapy may benefit those with life expectancy at least equal to the STATEMENT POSITION time frame of primary or secondary prevention trials. E c Screening for diabetes complications should be individualized in older adults, but particular attention should be paid to complications that would lead to functional impairment. E c Older adults ($65 years of age) with diabetes should be considered a high- priority population for depression screening and treatment. B

Diabetes is an important health condition for the aging population; at least 20% of patients over the age of 65 years have diabetes, and this number is expected to grow rapidly in the coming decades. Older individuals with diabetes have higher rates of premature death, functional disability, and coexisting illnesses, such as hyperten- sion, coronary heart disease, and stroke, than those without diabetes. Older adults with diabetes are also at a greater risk than other older adults for several common geriatric syndromes, such as polypharmacy, cognitive impairment, urinary inconti- nence, injurious falls, and persistent pain. Screening for diabetes complications in older adults also should be individualized. Older adults are at an increased risk for depression and should therefore be screened and treated accordingly (1). Particular attention should be paid to complications that can develop over short periods of time and/or that would significantly impair functional status, such as visual and lower-extremity complications. Please refer to the American Diabetes Association consensus report “Diabetes in Older Adults” for details (2). The care of older adults with diabetes is complicated by their clinical and func- tional heterogeneity. Some older individuals developed diabetes years earlier and may have significant complications; others are newly diagnosed and may have had years of undiagnosed diabetes with resultant complications; and still other older adults may have truly recent-onset disease with few or no complications. Some older adults with diabetes are frail and have other underlying chronic conditions, substantial diabetes-related comorbidity, or limited physical or cognitive functioning. Other older individuals with diabetes have little comorbidity and are active. Life expectancies are highly variable for this population but are often longer than clinicians realize. Providers caring for older adults with diabetes must take this hetero- geneity into consideration when setting and prioritizing treatment goals (Table 10.1).

Suggested citation: American Diabetes Associa- TREATMENT GOALS tion. Older adults. Sec. 10. In Standards of Med- fi ical Care in Diabetesd2015. Diabetes Care There are few long-term studies in older adults demonstrating the bene ts of in- 2015;38(Suppl. 1):S67–S69 tensive glycemic, blood pressure, and lipid control. Patients who can be expected to fi © 2015 by the American Diabetes Association. live long enough to reap the bene ts of long-term intensive diabetes management, Readers may use this article as long as the work who have good cognitive and physical function, and who choose to do so via shared is properly cited, the use is educational and not decision making may be treated using therapeutic interventions and goals similar to for profit, and the work is not altered. S68 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

Table 10.1—Framework for considering treatment goals for glycemia, blood pressure, and dyslipidemia in older adults with diabetes Fasting or Bedtime Blood Patient characteristics/ Reasonable preprandial glucose pressure health status Rationale A1C goal‡ glucose (mg/dL) (mg/dL) (mmHg) Lipids Healthy (few coexisting Longer remaining life ,7.5% 90–130 90–150 ,140/90 Statin unless chronic illnesses, intact expectancy contraindicated cognitive and functional or not tolerated status) Complex/intermediate Intermediate remaining ,8.0% 90–150 100–180 ,140/90 Statin unless (multiple coexisting life expectancy, high contraindicated chronic illnesses* or 21 treatment burden, or not tolerated instrumental ADL hypoglycemia impairments or mild-to- vulnerability, fall risk moderate cognitive impairment) Very complex/poor health Limited remaining life ,8.5%† 100–180 110–200 ,150/90 Consider likelihood of (long-term care or end- expectancy makes benefit with statin stage chronic illnesses** benefit uncertain (secondary prevention or moderate-to-severe more so than primary) cognitive impairment or 21 ADL dependencies) This represents a consensus framework for considering treatment goals for glycemia, blood pressure, and dyslipidemia in older adults with diabetes. The patient characteristic categories are general concepts. Not every patient will clearly fall into a particular category. Consideration of patient and caregiver preferences is an important aspect of treatment individualization. Additionally, a patient’s health status and preferences may change over time. ADL, activities of daily living. ‡A lower A1C goal may be set for an individual if achievable without recurrent or severe hypoglycemia or undue treatment burden. *Coexisting chronic illnesses are conditions serious enough to require medications or lifestyle management and may include arthritis, cancer, congestive heart failure, depression, emphysema, falls, hypertension, incontinence, stage 3 or worse chronic kidney disease, myocardial infarction, and stroke. By “multiple,” we mean at least three, but many patients may have five or more (6). **The presence of a single end-stage chronic illness, such as stage 3–4 congestive heart failure or oxygen-dependent lung disease, chronic kidney disease requiring dialysis, or uncontrolled metastatic cancer, may cause significant symptoms or impairment of functional status and significantly reduce life expectancy. †A1C of 8.5% equates to an estimated average glucose of ;200 mg/dL. Looser glycemic targets than this may expose patients to acute risks from glycosuria, dehydration, hyperglycemic hyperosmolar syndrome, and poor wound healing.

those for younger adults with diabetes. factors rather than from tight glycemic caregivers. Hypoglycemic events should As with all diabetic patients, diabetes control alone. There is strong evidence be diligently monitored, and glycemic tar- self-management education and ongo- from clinical trials of the value of treat- gets may need to be adjusted to accom- ing diabetes self-management support inghypertensionintheelderly(3,4). modate for the changing needs of the are vital components of diabetes care There is less evidence for lipid-lowering older adult (2). for older adults and their caregivers. and aspirin therapy, although the bene- For patients with advanced diabetes fits of these interventions for primary PHARMACOLOGICAL THERAPY complications, life-limiting comorbid ill- and secondary prevention are likely to Special care is required in prescribing and ness, or substantial cognitive or func- apply to older adults whose life expec- monitoring pharmacological therapy in tional impairment, it is reasonable to tancies equal or exceed the time frames older adults. Cost may be a significant set less intensive glycemic target goals. seen in clinical trials. factor, especially as older adults tend to These patients are less likely to benefit be on many medications. Metformin may from reducing the risk of microvascular HYPOGLYCEMIA be contraindicated because of renal insuf- complications and more likely to suffer Older adults are at a higher risk of hypo- ficiency or significant heart failure. Thia- serious adverse effects from hypoglyce- glycemia for many reasons, including in- zolidinediones, if used at all, should be mia. However, patients with poorly con- sulin deficiency and progressive renal used very cautiously in those with, or at trolled diabetes may be subject to acute insufficiency. In addition, older adults risk for, congestive heart failure and have complications of diabetes, including tend to have higher rates of unidentified been associated with fractures. Sulfonyl- dehydration, poor wound healing, and cognitive deficits, causing difficulty in ureas, other insulin secretagogues, and hyperglycemic hyperosmolar coma. complex self-care activities (e.g., glucose insulin can cause hypoglycemia. Insulin Glycemic goals at a minimum should monitoring, adjusting insulin doses, etc.). use requires that patients or caregivers avoid these consequences. These deficits have been associated with have good visual and motor skills and cog- Although hyperglycemia control may increased risk of hypoglycemia and with nitive ability. GLP-1 agonists and dipep- be important in older individuals with severe hypoglycemia linked to increased tidyl peptidase-4 inhibitors have few diabetes, greater reductions in morbid- dementia. Therefore, it is important to side effects, but their costs may be a bar- ity and mortality are likely to result from routinely screen older adults for cognitive rier to some older patients. A clinical trial, control of other cardiovascular risk dysfunction and discuss findings with the Saxagliptin Assessment of Vascular care.diabetesjournals.org Position Statement S69

Outcomes Recorded in Patients with References 4. James PA, Oparil S, Carter BL, et al. 2014 Diabetes Mellitus–Thrombolysis in Myo- 1. Kimbro LB, Mangione CM, Steers WN, et al. evidence-based guideline for the management of cardial Infarction 53 (SAVOR-TIMI 53), Depression and all-cause mortality in persons high blood pressure in adults: report from the panel members appointed to the Eighth Joint Na- evaluated saxagliptin (a dipeptidyl with diabetes mellitus: are older adults at higher risk? Results from the Translating Research Into tional Committee (JNC 8). JAMA 2014;311:507–520 peptidase-4 inhibitor) and its impact Action for Diabetes Study. J Am Geriatr Soc 2014; 5. Scirica BM, Bhatt DL, Braunwald E, et al.; on cardiovascular outcomes (5). Pa- 62:1017–1022 SAVOR-TIMI 53 Steering Committee and Investi- tients treated with saxagliptin were 2. Kirkman MS, Briscoe VJ, Clark N, et al. Diabetes gators. Saxagliptin and cardiovascular outcomes more likely to be hospitalized for heart in older adults. Diabetes Care 2012;35:2650– in patients with type 2 diabetes mellitus. N Engl J – failure than were those given a placebo 2664 Med 2013;369:1317 1326 3. Beckett NS, Peters R, Fletcher AE, et al.; 6. Laiteerapong N, Iveniuk J, John PM, Laumann (3.5% vs. 2.8%, respectively, according to HYVET Study Group. Treatment of hypertension EO, Huang ES. Classification of older adults who 2-year Kaplan-Meier estimates; hazard in patients 80 years of age or older. N Engl J Med have diabetes by comorbid conditions, United ratio 1.27 [95% CI 1.0721.51]; P 5 0.007). 2008;358:1887–1898 States, 2005-2006. Prev Chronic Dis 2012;9:E100 S70 Diabetes Care Volume 38, Supplement 1, January 2015

11. Children and Adolescents American Diabetes Association Diabetes Care 2015;38(Suppl. 1):S70–S76 | DOI: 10.2337/dc15-S014

TYPE 1 DIABETES Three-quarters of all cases of type 1 diabetes are diagnosed in individuals ,18 years of age.The provider mustconsider theunique aspects ofcare andmanagement ofchildren and adolescents with type 1 diabetes, such as changes in insulin sensitivity related to sexual maturityandphysical growth,ability toprovide self-care,supervisionin childcare and school, and unique neurological vulnerability to hypoglycemia and possibly hyper- glycemia as well as diabetic ketoacidosis. Attention to family dynamics, developmental stages, and physiological differences related to sexual maturity are all essential in de- veloping and implementing an optimal diabetes regimen. Due to the paucity of clinical researchinchildren, therecommendations forchildrenandadolescents are lesslikely to be based on clinical trial evidence. However, expert opinion and a review of available and relevant experimental data are summarized in the American Diabetes Association (ADA) position statement “Care of Children and Adolescents With Type 1 Diabetes” (1) and have been updated in the recently published ADA position statement “Type 1 Diabetes Through the Life Span” (2). A multidisciplinary team of specialists trained in pediatric diabetes management

POSITION STATEMENT and sensitive to the challenges of children and adolescents with type 1 diabetes should provide care for this population. It is essential that diabetes self-management educa- tion (DSME) and support (DSMS), medical nutrition therapy (MNT), and psychosocial support be provided at diagnosis and regularly thereafter by individuals experienced with the educational, nutritional, behavioral, and emotional needs of the growing child and family. The balance between adult supervision and self-care should be de- fined at the first interaction and reevaluated at each clinic visit. This relationship will evolve as the child reaches physical, psychological, and emotional maturity.

Glycemic Control

Recommendation c An A1C goal of ,7.5% is recommended across all pediatric age-groups. E

Current standards for diabetes management reflect the need to lower glucose as safely as possible. This should be done with stepwise goals. Special consideration should be given to the unique risks of hypoglycemia in young children (aged ,6 years), as they are often unable to recognize, articulate, and/or manage their hy- poglycemic symptoms. This “hypoglycemia unawareness” should be considered when establishing individualized glycemic targets. Although it was previously thought that young children were at risk for cognitive impairment after episodes of severe hypoglycemia, current data have not confirmed this (3–5). Furthermore, new therapeutic modalities, such as rapid- and long-acting insulin analogs, technological advances (e.g., continuous glucose monitors, low glucose suspend insulin pumps), and education, may mitigate the incidence of severe hypoglycemia (6). The Diabetes Control and Complications Trial (DCCT) demonstrated that near-normalization of blood glucose levels was more difficult to achieve in adolescents than in adults. Nevertheless, the increased use of basal–bolus regimens and insulin pumps in youth from infancy through adolescence has been associated with more children reaching the blood Suggested citation: American Diabetes Associa- glucose targets set by the ADA (7–9) in those families in which both parents and the child tion. Children and adolescents. Sec. 11. In Stan- dards of Medical Care in Diabetesd2015. with diabetes participate jointly to perform the required diabetes-related tasks. Further- Diabetes Care 2015;38(Suppl. 1):S70–S76 more, studies documenting neurocognitive imaging differences related to hyperglycemia © 2015 by the American Diabetes Association. in children provide another compelling motivation for lowering glycemic targets (10). Readers may use this article as long as the work In selecting glycemic goals, the long-term health benefits of achieving a lower A1C is properly cited, the use is educational and not should be balanced against the risks of hypoglycemia and the developmental burdens for profit, and the work is not altered. care.diabetesjournals.org Position Statement S71

of intensive regimens in children and frequent unexplained hypoglycemia peroxidase and antithyroglobulin youth. In addition, achieving lower A1C or deterioration in glycemic control. E antibodies soon after diagnosis. E levels is more likely to be related to set- c Children with biopsy-confirmed c Measuring thyroid-stimulating hor- ting lower A1C targets (11). A1C goals are celiac disease should be placed mone concentrations soon after presented in Table 11.1. on a gluten-free diet and have diagnosis of type 1 diabetes is Autoimmune Conditions consultation with a dietitian expe- reasonable. If normal, consider re- rienced in managing both diabetes checking every 1–2yearsorsooner Recommendation and celiac disease. B if the patient develops symptoms c Assess for the presence of addi- of thyroid dysfunction, thyrome- tional autoimmune conditions at di- Celiac disease is an immune-mediated galy, an abnormal growth rate, or agnosis and if symptoms develop. E disorder that occurs with increased fre- unusual glycemic variation. E quency in patients with type 1 diabetes Because of the increased frequency of (1–16% of individuals compared with 0.3– Autoimmune thyroid disease is the most other autoimmune diseases in type 1 di- 1% in the general population) (12,13). common autoimmune disorder associ- abetes, screening for thyroid dysfunc- Testing for celiac disease includes mea- ated with diabetes, occurring in 17– tion, vitamin B12 deficiency (due to suring serum levels of IgA antitissue 30% of patients with type 1 diabetes autoimmune gastritis), and celiac dis- transglutaminase antibodies or, with IgA (17). About one-quarter of children ease should be considered based on deficiency, screening can include measur- with type 1 diabetes have thyroid auto- signs and symptoms. Periodic screening ing IgG tissue transglutaminase antibodies antibodies at the time of diagnosis (18), in asymptomatic individuals has been or IgG deamidated gliadin peptide antibod- and the presence of thyroid autoantibod- recommended, but the effectiveness ies. A small-bowel biopsy in antibody- ies is predictive of thyroid dysfunctiond and optimal frequency are unclear. positive children is recommended to most commonly hypothyroidism, al- Although less common than celiac confirm the diagnosis (14). European guide- though hyperthyroidism may occur (19). disease and thyroid dysfunction, there lines on screening for celiac disease in chil- Subclinical hypothyroidism may be asso- are other autoimmune conditions that dren (not specific to children with type 1 ciated with increased risk of symptomatic occur more commonly in type 1 diabe- diabetes) suggested that biopsy may not be hypoglycemia (20) and reduced linear tes, such as Addison’s disease (primary necessary in symptomatic children with growth. Hyperthyroidism alters glucose adrenal insufficiency), autoimmune high-positive antibody titers as long as fur- metabolism, potentially resulting in dete- hepatitis, dermatomyositis, myasthenia ther testing such as genetic or HLA testing rioration of metabolic control. gravis, etc., which should be assessed was supportive, but that asymptomatic at- and monitored as clinically indicated. risk children should have biopsies (15). Management of Cardiovascular Risk In symptomatic children with type 1 di- Celiac Disease Factors fi abetes and con rmed celiac disease, Hypertension Recommendations gluten-free diets reduce symptoms and Recommendations c Consider screening children with rates of hypoglycemia (16). The challenging type 1 diabetes for celiac disease dietary restrictions associated with having Screening by measuring tissue transglutami- both type 1 diabetes and celiac disease c Blood pressure should be mea- nase or deamidated gliadin antibod- place a significant burden on individuals. sured at each routine visit. Chil- ies, with documentation of normal Therefore, we recommend a biopsy con- dren found to have high-normal total serum IgA levels, soon after the firming the diagnosis of celiac disease be- blood pressure (systolic blood diagnosis of diabetes. E fore endorsing significant dietary changes, pressure [SBP] or diastolic blood c Consider screening in children with a especially in asymptomatic children. pressure [DBP] $90th percentile positive family history of celiac dis- for age, sex, and height) or hyper- Thyroid Disease ease, growth failure, failure to gain tension (SBP or DBP $95th per- weight, weight loss, diarrhea, flatu- Recommendations centileforage,sex,andheight) lence, abdominal pain, or signs of c Consider testing children with should have blood pressure con- malabsorption or in children with type 1 diabetes for antithyroid firmed on three separate days. B

Table 11.1—Plasma blood glucose and A1C goals for type 1 diabetes across all pediatric age-groups Plasma blood glucose goal range Before meals Bedtime/overnight A1C Rationale 90–130 mg/dL 90–150 mg/dL ,7.5% A lower goal (,7.0%) is reasonable if it can be (5.0–7.2 mmol/L) (5.0–8.3 mmol/L) achieved without excessive hypoglycemia Key concepts in setting glycemic goals: c Goals should be individualized, and lower goals may be reasonable based on benefit-risk assessment. c Blood glucose goals should be modified in children with frequent hypoglycemia or hypoglycemia unawareness. c Postprandial blood glucose values should be measured when there is a discrepancy between preprandial blood glucose values and A1C levels and to help assess glycemia in those on basal–bolus regimens. S72 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

Treatment Treatment prevention are paramount, as statins are category X in pregnancy (see Section c Initial treatment of high-normal c Initial therapy may consist of opti- blood pressure (SBP or DBP consis- mization of glucose control and 12. Management of Diabetes in Preg- tently $90th percentile for age, MNT using a Step 2 American Heart nancy for more information). sex, and height) includes dietary Association (AHA) diet aimed at a Smoking intervention and exercise, aimed decrease in the amount of satu- at weight control and increased rated fat in the diet. B Recommendation physical activity, if appropriate. If c After the age of 10 years, the addi- c Elicit smoking history at initial and target blood pressure is not tion of a statin in patients who, after follow-up diabetes visits and dis- reachedwith3–6 months of MNT and lifestyle changes, have courage smoking in nonsmoking lifestyle intervention, pharmaco- LDL cholesterol .160 mg/dL (4.1 youth and encourage smoking ces- logical treatment should be con- mmol/L) or LDL cholesterol .130 sation in those who smoke. B sidered. E mg/dL (3.4 mmol/L) and one or c Pharmacological treatment of hy- more cardiovascular disease (CVD) The adverse health effects of smoking pertension (SBP or DBP consistently risk factors is reasonable. E are well recognized with respect to fu- $95th percentile for age, sex, and c The goal of therapy is an LDL cho- ture cancer and CVD risk. In youth with height) should be considered as lesterol value ,100 mg/dL (2.6 diabetes, it remains important to avoid soon as hypertension is confirmed. E mmol/L). E additional CVD risk factors; thus, dis- c ACE inhibitors or angiotensin recep- couraging cigarette smoking, including tor blockers (ARBs) should be consid- Children diagnosed with type 1 diabetes e-cigarettes, is important as part of rou- ered for the initial pharmacological have a high risk of early subclinical (21,22) tine diabetes care. In younger children, treatment of hypertension, following and clinical (23) CVD. Although intervention it is important to assess exposure to cig- appropriate reproductive counsel- data are lacking, the AHA categorizes chil- arette smoke in the home due to the ing due to its potential teratogenic dren with type 1 diabetes in the highest tier adverse effects of secondhand smoke effects. E for cardiovascular risk and recommends and to discourage youth from adopting c The goal of treatment is blood both lifestyle and pharmacological treat- smoking behaviors if exposed to them in pressure consistently ,90th per- ment for those with elevated LDL choles- childhood. In addition, smoking has centile for age, sex, and height. E terol levels (24,25). Initial therapy should be been associated with onset of albumin- with a Step 2 AHA diet, which restricts sat- uria; therefore, avoiding smoking is im- Blood pressure measurements should urated fat to 7% of total calories and re- portant to prevent both microvascular be determined correctly, using the ap- stricts dietary cholesterol to 200 mg/day. and macrovascular complications (31,32). propriate size cuff, and with the child Data from randomized clinical trials in chil- seated and relaxed. Hypertension dren as young as 7 months of age indicate Microvascular Complications should be confirmed on at least three that this diet is safe and does not interfere Nephropathy separate days. Evaluation should pro- with normal growth and development (26). Recommendations ceed as clinically indicated. Treatment Forchildrenwithsignificant family his- Screening is generally initiated with an ACE inhibi- tory of CVD, the National Heart, Lung, and c At least an annual screening for tor, but an ARB can be used if the ACE Blood Institute recommends a fasting lipid albuminuria, with a random spot inhibitor is not tolerated (e.g., due to panel beginning at 2 years of age (27). urine sample for albumin-to- cough). Normal blood pressure levels for Abnormal results from a random lipid creatinine ratio (UACR), should age, sex, and height and appropriate panel should be confirmed with a fasting be considered once the child has methods for measurement are available lipid panel. Evidence has shown that im- had diabetes for 5 years. B online at www.nhlbi.nih.gov/health/ proved glucose control correlates with a fi c Measure creatinine clearance/es- prof/heart/hbp/hbp_ped.pdf. more favorable lipid pro le. However, im- proved glycemic control alone will not re- timated glomerular filtration rate Dyslipidemia verse significant dyslipidemia (28). at initial evaluation and then Neither long-term safety nor cardiovas- based on age, diabetes duration, Recommendations cular outcome efficacy of statin therapy and treatment. E Testing has been established for children. How- c Obtain a fasting lipid profile on Treatment ever, studies have shown short-term children $2 years of age soon af- c Treatment with an ACE inhibitor, safety equivalent to that seen in adults ter the diagnosis (after glucose titrated to normalization of albumin and efficacy in lowering LDL cholesterol control has been established). E excretion, should be considered levels, improving endothelial function, c If lipids are abnormal, annual when elevated UACR (.30 mg/g) and causing regression of carotid intimal monitoring is reasonable. If LDL is documented with at least two thickening (29,30). Statins are not ap- cholesterol values are within of three urine samples. This should proved for use in patients under the age the accepted risk levels (,100 be obtained over a 6-month inter- of 10 years, and statin treatment should mg/dL [2.6 mmol/L]), a lipid val following efforts to improve generally not be used in children with profile repeated every 5 years is glycemic control and normalize type 1 diabetes prior to this age. For post- reasonable. E blood pressure for age. B pubertal girls, issues of pregnancy care.diabetesjournals.org Position Statement S73

Recent research demonstrates the im- tibial pulses, assessment of the pres- and “Care of Young Children With portance of tight glycemic and blood ence or absence of patellar and Achilles Diabetes in the Child Care Setting” (39) pressure control, especially as diabetes reflexes, and determination of proprio- for additional details. duration increases (33). A creatinine ception, vibration, and monofilament clearance using an estimated glomeru- sensation, should be performed annu- Transition From Pediatric to Adult lar filtration rate can be obtained with ally along with assessment of symptoms Care the serum creatinine, height, age, and of neuropathic pain. Foot inspection can sex of the patient (34) and should be be performed at each visit as education Recommendations obtained at baseline and repeated as in- for youth regarding the importance of c As teens transition into emerging dicated based on clinical status, age, di- foot care. adulthood, health care providers abetes duration, and therapies. There and families must recognize their Diabetes Self-management are ongoing clinical trials assessing the many vulnerabilities B and prepare Education and Support efficacy of early treatment with ACE in- the developing teen, beginning in hibitors for persistent albuminuria (35). Recommendation early to mid-adolescence and at E c Youth with type 1 diabetes and least 1 year prior to the transition. Retinopathy parents/caregivers (for patients c Both pediatricians and adult health care providers should assist Recommendations aged ,18 years) should receive culturally sensitive and develop- in providing support and links to c An initial dilated and comprehen- mentally appropriate individual- resources for the teen and emerg- sive eye examination should be ing adult. B considered for the child at the ized DSME and DSMS according to national standards when their start of puberty or at age $10 Care and close supervision of diabetes years, whichever is earlier, once diabetes is diagnosed and rou- tinely thereafter. B management are increasingly shifted the youth has had diabetes for 3– from parents and other adults to the 5 years. B No matter how sound the medical youth with diabetes throughout child- c After the initial examination, an- regimen, it can only be as good as hood and adolescence. However, the nual routine follow-up is generally the ability of the family and/or indi- shift from pediatrics to adult health recommended. Less frequent ex- vidual to implement it. Family in- care providers often occurs very abruptly aminations, every 2 years, may be volvement remains an important as the older teen enters the next devel- acceptable on the advice of an eye component of optimal diabetes man- opmental stage referred to as emerging care professional. E agement throughout childhood and adulthood (40), which is a critical period for young people who have diabetes. Although retinopathy (like albuminuria) adolescence. Health care providers who care for children and adoles- During this period of major life transi- most commonly occurs after the onset tions, youth begin to move out of their – cents, therefore, must be capable of of puberty and after 5 10 years of diabe- parents’ home and must become fully tes duration (36), it has been reported in evaluating the educational, behav- ioral, emotional, and psychosocial fac- responsible for their diabetes care. Their prepubertal children and with diabetes new responsibilities include the many as- duration of only 1–2 years. Referrals tors that impact implementation of a treatment plan and must work with pects of managing self-care, making should be made to eye care professionals medical appointments, and financing with expertise in diabetic retinopathy, an the individual and family to overcome barriers or redefine goals as appropri- health care, once they are no longer cov- understanding of retinopathy risk in the ’ ate. DSME and DSMS are activities ered under their parents health insur- pediatric population, and experience in ance (although ongoing coverage until counseling the pediatric patient and fam- that require ongoing reassessment, especially as the youth grows, devel- age 26 years is possible with recent ily on the importance of early prevention/ U.S. health care reform). In addition to intervention. ops, and acquires need for greater self-care skills. In addition, it may be lapses in health care, this is also a period Neuropathy necessary to assess the educational of deterioration in glycemic control; in- needs and skills of day care providers, creased occurrence of acute complica- Recommendation school nurses, or school personnel who tions and psychosocial, emotional, and c Consider an annual comprehen- may participate in the care of the young behavioral issues; and emergence of – sive foot exam for the child at child with diabetes (37). chronic complications (41 44). the start of puberty or at age Although scientific evidence contin- $10 years, whichever is earlier, School and Child Care ues to be limited, it is clear that compre- once the youth has had type 1 di- As a large portion of a child’s day is spent hensive and coordinated planning, abetes for 5 years. E in school, close communication with and beginning early and with ongoing atten- cooperation of school or day care per- tion, facilitates a seamless transition Neuropathy rarely occurs in prepubertal sonnel is essential for optimal diabetes from pediatric to adult health care children or in youth with 1–2 years of management, safety, and maximal aca- (41,42). Transition planning should be- duration of diabetes (36). A comprehen- demic opportunities. Please refer to the gin in early adolescence. Even after the sive foot exam, including inspection, ADA position statements “Diabetes Care transition to adult care is made, support palpation of dorsalis pedis and posterior in the School and Day Care Setting” (38) and reinforcement are recommended. S74 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

A comprehensive discussion regarding ADA consensus report “Type 2 Diabetes in disordered eating behaviors using avail- the challenges faced during this period, Children and Adolescents” (48) provides able screening tools, and, with respect including specific recommendations, is guidance on the prevention, screening, to disordered eating, it is important to found in the ADA position statement “Di- and treatment of type 2 diabetes and its recognize the unique and dangerous abetes Care for Emerging Adults: Recom- comorbidities in young people. disordered eating behavior of insulin mendations for Transition From Pediatric omission for weight control in type 1 to Adult Diabetes Care Systems” (42). PSYCHOSOCIAL ISSUES diabetes (49,56). The presence of a The National Diabetes Education mental health professional on pediatric Program (NDEP) has materials avail- Recommendations multidisciplinary teams highlights the able to facilitate the transition process c At diagnosis and during routine importance of attending to the psycho- (http://ndep.nih.gov/transitions), and follow-up care, assess psychoso- social issues of diabetes. These psycho- the Endocrine Society in collaboration cial issues and family stresses social factors are significantly related to with ADA and other organizations has thatcouldimpactadherencewith nonadherence, suboptimal glycemic developed transition tools for clini- diabetes management and pro- control, reduced quality of life, and higher cians and youth and families (http:// vide appropriate referrals to rates of acute and chronic diabetes www.endo-society.org/clinicalpractice/ trained mental health professionals, complications. transition_of_care.cfm). preferably experienced in child- hood diabetes. E TYPE 2 DIABETES References c Encourage developmentally ap- For information on testing for type 2 di- 1. Silverstein J, Klingensmith G, Copeland K, propriate family involvement in di- et al. Care of children and adolescents with abetes and prediabetes in children and abetes management tasks for type 1 diabetes: a statement of the American adolescents, please refer to Section 2. children and adolescents, recog- Diabetes Association. Diabetes Care 2005;28: Classification and Diagnosis of Diabetes. nizing that premature transfer of 186–212 The Centers for Disease Control and diabetes care to the child can re- 2. Chiang JL, Kirkman MS, Laffel LMB, Peters AL; Type 1 Diabetes Sourcebook Authors. Type 1 Prevention recently published projec- sult in nonadherence and deterio- diabetes through the life span: a position state- tions for type 2 diabetes prevalence us- ration in glycemic control. B ment of the American Diabetes Association. Di- ing the SEARCH database. Assuming a abetes Care 2014;37:203422054 2.3% annual increase, the prevalence Diabetes management throughout 3. Seaquist ER, Anderson J, Childs B, et al. Hy- of type 2 diabetes in those under 20 childhood and adolescence places sub- poglycemia and diabetes: a report of a work- group of the American Diabetes Association years of age will quadruple in 40 years stantial burdens on the youth and fam- and the Endocrine Society. Diabetes Care (45,46). Given the current obesity epi- ily, necessitating ongoing assessment of 2013;36:1384–1395 demic, distinguishing between type 1 psychosocial issues and distress during 4. Wysocki T, Harris MA, Mauras N, et al. Ab- and type 2 diabetes in children can be routine diabetes visits (49–51). Further, sence of adverse effects of severe hypoglycemia on cognitive function in school-aged children fi the complexities of diabetes manage- dif cult. For example, autoantibodies with diabetes over 18 months. Diabetes Care and ketosis may be present in patients ment require ongoing parental involve- 2003;26:1100–1105 with features of type 2 diabetes (includ- ment in care throughout childhood with 5. Blasetti A, Chiuri RM, Tocco AM, et al. The ing obesity and acanthosis nigricans). developmentally appropriate family effect of recurrent severe hypoglycemia on cog- Nevertheless, accurate diagnosis is crit- teamwork between the growing child/ nitive performance in children with type 1 di- abetes: a meta-analysis. J Child Neurol 2011;26: ical as treatment regimens, educational teen and parent in order to maintain 1383–1391 approaches, dietary counsel, and out- adherence and prevent deterioration 6. Cooper MN, O’Connell SM, Davis EA, Jones comes will differ markedly between in glycemic control (52,53). In addition, TW. A population-based study of risk factors for the two diagnoses. as diabetes-specific family conflict is re- severe hypoglycaemia in a contemporary cohort Significant comorbidities may already lated to poorer adherence and glycemic of childhood-onset type 1 diabetes. 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It is 2131 demia, albumin excretion, and retinopathy important to consider the impact of di- 9. Doyle EA, Weinzimer SA, Steffen AT, Ahern in youth with type 2 diabetes are similar to abetes on quality of life as well as the JAH, Vincent M, Tamborlane WVA. A random- ized, prospective trial comparing the efficacy of those for youth with type 1 diabetes. Ad- development of mental health problems continuous subcutaneous insulin infusion with ditional problems that may need to be ad- related to diabetes distress, fear of hy- multiple daily injections using insulin glargine. dressed include polycystic ovary disease poglycemia (and hyperglycemia), symp- Diabetes Care 2004;27:1554–1558 and the various comorbidities associated toms of anxiety, disordered eating 10. Barnea-Goraly N, Raman M, Mazaika P, et al.; Diabetes Research in Children Network with pediatric obesity, such as sleep behaviors as well as eating disorders, (DirecNet). Alterations in white matter struc- apnea, hepatic steatosis, orthopedic com- and symptoms of depression (55). Con- ture in young children with type 1 diabetes. plications, and psychosocial concerns. The sider screening for depression and Diabetes Care 2014;37:332–340 care.diabetesjournals.org Position Statement S75

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Am Psychol 2000;55:469–480 pean Society for Pediatric Gastroenterology, Lipids and lipoproteins. In Expert Panel on Inter- 41. Weissberg-Benchell J, Wolpert H, Anderson Hepatology, and Nutrition guidelines for the di- grated Guidelines for Cardiovascular Health and BJ. Transitioning from pediatric to adult care: agnosis of coeliac disease. J Pediatr Gastroen- Risk Reduction in Children and Adolescents: a new approach to the post-adolescent young terol Nutr 2012;54:136–160 Summary Report [Internet]. Available from person with type 1 diabetes. Diabetes Care 16. Abid N, McGlone O, Cardwell C, McCallion http://www.nhlbi.nih.gov/health-pro/guidelines/ 2007;30:2441–2446 W, Carson D. Clinical and metabolic effects of current/cardiovascular-health-pediatric- 42. Peters A, Laffel L; American Diabetes Asso- gluten free diet in children with type 1 diabetes guidelines/summary.htm#chap9. Accessed 17 ciation Transitions Working Group. Diabetes and coeliac disease. Pediatr Diabetes 2011;12: October 2014 care for emerging adults: recommendations 322–325 28. Maahs DM, Dabelea D, D’Agostino RB, for transition from pediatric to adult diabetes 17. Roldan´ MB, Alonso M, Barrio R. Thyroid au- et al.; SEARCH for Diabetes in Youth Study. Glu- care systems: a position statement of the Amer- toimmunity in children and adolescents with cose control predicts 2-year change in lipid pro- ican Diabetes Association, with representation type 1 diabetes mellitus. Diabetes Nutr Metab file in youth with type 1 diabetes. J Pediatr 2013; by the American College of Osteopathic Family 1999;12:27–31 162:101–107.e1 Physicians, the American Academy of Pediatrics, 18. Triolo TM, Armstrong TK, McFann K, et al. 29. McCrindle BW, Ose L, Marais AD. Efficacy the American Association of Clinical Endocrinol- Additional autoimmune disease found in 33% of and safety of atorvastatin in children and ado- ogists, the American Osteopathic Association, patients at type 1 diabetes onset. Diabetes Care lescents with familial hypercholesterolemia or the Centers for Disease Control and Prevention, 2011;34:1211–1213 severe hyperlipidemia: a multicenter, random- Children with Diabetes, The Endocrine Society, 19. Kordonouri O, Deiss D, Danne T, Dorow A, ized, placebo-controlled trial. J Pediatr 2003; the International Society for Pediatric and Ado- Bassir C, Gruters-Kieslich¨ A. Predictivity of 143:74–80 lescent Diabetes, Juvenile Diabetes Research thyroid autoantibodies for the development of 30. Wiegman A, Hutten BA, de Groot E, et al. Foundation International, the National Diabetes thyroid disorders in children and adolescents with Efficacy and safety of statin therapy in children Education Program, and the Pediatric Endocrine type 1 diabetes. Diabet Med 2002;19:518–521 with familial hypercholesterolemia: a random- Society (formerly Lawson Wilkins Pediatric Endo- 20. Mohn A, Di Michele S, Di Luzio R, Tumini S, ized controlled trial. JAMA 2004;292:331–337 crine Society). Diabetes Care 2011;34:2477–2485 Chiarelli F. The effect of subclinical hypothyroid- 31. Scott LJ, Warram JH, Hanna LS, Laffel LM, 43. Bryden KS, Peveler RC, Stein A, Neil A, ism on metabolic control in children and adoles- Ryan L, Krolewski AS. A nonlinear effect of hy- Mayou RA, Dunger DB. Clinical and psychologi- cents with type 1 diabetes mellitus. Diabet Med perglycemia and current cigarette smoking are cal course of diabetes from adolescence to 2002;19:70–73 major determinants of the onset of microalbu- young adulthood: a longitudinal cohort study. 21. Hortenhuber¨ T, Rami-Mehar B, Satler M, minuria in type 1 diabetes. Diabetes 2001;50: Diabetes Care 2001;24:1536–1540 et al. Endothelial progenitor cells are related to 2842–2849 44. Laing SP, Jones ME, Swerdlow AJ, Burden glycemic control in children with type 1 diabetes 32. Expert Panel on Integrated Guidelines for AC, Gatling W. Psychosocial and socioeconomic over time. Diabetes Care 2013;36:1647–1653 Cardiovascular Health and Risk Reduction in risk factors for premature death in young peo- 22. Haller MJ, Samyn M, Nichols WW, et al. Ra- Children and Adolescents; National Heart, ple with type 1 diabetes. Diabetes Care 2005;28: dial artery tonometry demonstrates arterial Lung, and Blood Institute. Expert panel on in- 1618–1623 stiffness in children with type 1 diabetes. Dia- tegrated guidelines for cardiovascular health 45. Imperatore G, Boyle JP, Thompson TJ, et al.; betes Care 2004;27:2911–2917 and risk reduction in children and adolescents: SEARCH for Diabetes in Youth Study Group. Pro- 23. Orchard TJ, Forrest KY-Z, Kuller LH, Becker summary report. Pediatrics 2011;128(Suppl. 5): jections of type 1 and type 2 diabetes burden in DJ; Pittsburgh Epidemiology of Diabetes Com- S213–S256 the U.S. population aged ,20 years through plications Study. Lipid and blood pressure 33. Daniels M, DuBose SN, Maahs DM, et al.; 2050: dynamic modeling of incidence, mortal- treatment goals for type 1 diabetes: 10-year T1D Exchange Clinic Network. Factors associ- ity, and population growth. Diabetes Care 2012; incidence data from the Pittsburgh Epidemiol- ated with microalbuminuria in 7,549 children 35:2515–2520 ogy of Diabetes Complications Study. Diabetes and adolescents with type 1 diabetes in the 46. Pettitt DJ, Talton J, Dabelea D, et al.; Care 2001;24:1053–1059 T1D Exchange clinic registry. Diabetes Care SEARCH for Diabetes in Youth Study Group. 24. Kavey R-EW, Allada V, Daniels SR, et al. Car- 2013;36:2639–2645 Prevalence of diabetes in U.S. youth in 2009: diovascular risk reduction in high-risk pediatric 34. Schwartz GJ, Work DF. Measurement and the SEARCH for Diabetes In Youth study. Diabe- patients: a scientific statement from the Amer- estimation of GFR in children and adolescents. tes Care 2014;37:402–408 ican Heart Association Expert Panel on Popula- Clin J Am Soc Nephrol 2009;4:1832–1843 47. Eppens MC, Craig ME, Cusumano J, et al. tion and Prevention Science; the Councils 35. Marcovecchio ML, Woodside J, Jones T, Prevalence of diabetes complications in adoles- on Cardiovascular Disease in the Young, Ep- et al.; AdDIT Investigators. Adolescent Type 1 cents with type 2 compared with type 1 diabe- idemiology and Prevention, Nutrition, Physical Diabetes Cardio-Renal Intervention Trial tes. Diabetes Care 2006;29:1300–1306 S76 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

48. American Diabetes Association. Type 2 di- 52. Katz ML, Volkening LK, Butler DA, Anderson short duration type 1 diabetes. Diabet Med abetes in children and adolescents. Diabetes BJ, Laffel LM. Family-based psychoeducation 2002;19:635–642 Care 2000;23:381–389 and care ambassador intervention to improve 55. Lawrence JM, Yi-Frazier JP, Black MH, et al. 49. Corathers SD, Kichler J, Jones N-HY, et al. Im- glycemic control in youth with type 1 diabetes: Demographic and clinical correlates of proving depression screening for adolescents with a randomized trial. Pediatr Diabetes 2014;15: diabetes-related quality of life among youth type 1 diabetes. Pediatrics 2013;132:e13952e1402 142–150 with type 1 diabetes. J Pediatr 2012;161:201– 50. Hood KK, Beavers DP, Yi-Frazier J, et al. Psy- 53. Laffel LMB, Vangsness L, Connell A, Goebel- 207.e2 chosocial burden and glycemic control during Fabbri A, Butler D, Anderson BJ. Impact of 56. Markowitz JT, Butler DA, Volkening LK, the first 6 years of diabetes: results from the ambulatory, family-focused teamwork inter- Antisdel JE, Anderson BJ, Laffel LMB. Brief SEARCH for Diabetes in Youth Study. J Adolesc vention on glycemic control in youth with type screening tool for disordered eating in diabetes: Health 2014;55:498–504 1 diabetes. J Pediatr 2003;142:409–416 internal consistency and external validity in a 51. Ducat L, Philipson LH, Anderson BJ. The 54. Anderson BJ, Vangsness L, Connell A, Butler contemporary sample of pediatric patients mental health comorbidities of diabetes. JAMA D, Goebel-Fabbri A, Laffel LMB. Family conflict, with type 1 diabetes. Diabetes Care 2010;33: 2014;312:691–692 adherence, and glycaemic control in youth with 495–500 Diabetes Care Volume 38, Supplement 1, January 2015 S77

12. Management of Diabetes in American Diabetes Association Pregnancy

Diabetes Care 2015;38(Suppl. 1):S77–S79 | DOI: 10.2337/dc15-S015

For guidelines related to the diagnosis of gestational diabetes mellitus (GDM), please refer to Section 2. Classification and Diagnosis of Diabetes.

Recommendations c Provide preconception counseling that addresses the importance of tight control in reducing the risk of congenital anomalies with an emphasis on achieving A1C ,7%, if this can be achieved without hypoglycemia. B c Potentially teratogenic medications (ACE inhibitors, statins, etc.) should be

avoided in sexually active women of childbearing age who are not using reli- STATEMENT POSITION able contraception. B c GDM should be managed first with diet and exercise, and medications should be added if needed. A c Women with pregestational diabetes should have a baseline ophthalmology exam in the first trimester and then be monitored every trimester as indicated by degree of retinopathy. B c Due to alterations in red blood cell turnover that lower the normal A1C level in pregnancy, the A1C target in pregnancy is ,6% if this can be achieved without significant hypoglycemia. B c Medications widely used in pregnancy include insulin, metformin, and glybur- ide; most oral agents cross the placenta or lack long-term safety data. B

DIABETES IN PREGNANCY The prevalence of diabetes in pregnancy has been increasing in the U.S. The majority is GDM with the remainder divided between pregestational type 1 diabetes and type 2 diabetes. Both pregestational type 1 diabetes and type 2 diabetes confer significantly greater risk than GDM, with differences according to type as outlined below. PRECONCEPTION COUNSELING All women of childbearing age with diabetes should be counseled about the impor- tance of strict glycemic control prior to conception. Observational studies show an increased risk of diabetic embryopathy, especially anencephaly, microcephaly, and congenital heart disease, that increases directly with elevations in A1C. Spontane- ous abortion is also increased in the setting of uncontrolled diabetes. While obser- vational studies are confounded by the relationship between elevated periconceptional A1C and other poor self-care behaviors, the quantity and consistency of data are convincing, and the recommendation remains to aim for an A1C ,7% prior to conception to minimize risk (1,2). There are opportunities to educate adolescents of reproductive age with diabetes about the risks of unplanned pregnancies and the opportunities for healthy maternal and fetal outcomes with pregnancy planning (3). Targeted preconception counseling visits should include routine rubella, rapid plasma reagin, hepatitis B virus, and HIV testing as well as Pap smear, cervical cultures, blood typing, and prescription of prenatal vitamins (with at least 400 mg of folic acid). Diabetes- Suggested citation: American Diabetes Asso- specific management should include A1C, thyroid-stimulating hormone, creatinine, and ciation. Management of diabetes in preg- urine albumin-to-creatinine ratio testing; review of the medication list for potentially nancy. Sec. 12. In Standards of Medical Care in Diabetesd2015. Diabetes Care 2015;38 teratogenic drugs (i.e., ACE inhibitors, statins); and referral for an ophthalmologic exam. (Suppl. 1):S77–S79 Specific risks of uncontrolled diabetes include fetal anomalies, preeclampsia, © 2015 by the American Diabetes Association. macrosomia, intrauterine fetal demise, neonatal hypoglycemia, and neonatal hy- Readers may use this article as long as the work perbilirubinemia, among others. In addition, diabetes in pregnancy increases the is properly cited, the use is educational and not risk of obesity and type 2 diabetes in offspring later in life (4,5). for profit, and the work is not altered. S78 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

GLYCEMIC TARGETS IN Due to increases in red blood cell the recommended treatment for GDM PREGNANCY turnover associated with pregnancy, in the U.S. Randomized controlled trials The goals for glycemic control for GDM A1C levels fall during pregnancy. Addi- support the efficacy and short-term are based on recommendations from the tionally, as A1C represents an average, it safety of glyburide (11) (pregnancy cat- Fifth International Workshop-Conference may not fully capture physiologically rel- egory B) and metformin (12,13) (preg- on Gestational Diabetes Mellitus (6) and evant glycemic parameters in pregnancy. nancy category B) for the treatment have the following targets for maternal A1C should be used as a secondary mea- of GDM. However, both agents cross capillary glucose concentrations: sure, next to self-monitoring of blood glu- the placenta, and long-term safety cose. The recommended A1C target in data are not available (14). Insulin also ○ Preprandial #95 mg/dL (5.3 mmol/L) pregnancy is ,6% if this can be achieved maybeusedandshouldfollowthe and either without hypoglycemia. Given the alter- guidelines below. ○ One-hour postmeal #140 mg/dL ation in red blood cell kinetics during (7.8 mmol/L) or pregnancy, A1C levels may need to be MANAGEMENT OF PREGESTATIONAL TYPE 1 ○ Two-hour postmeal #120 mg/dL monitored more frequently than usual (6.7 mmol/L) (e.g., monthly). DIABETES AND TYPE 2 DIABETES IN PREGNANCY For women with preexisting type 1 PREGNANCY AND Insulin Use in Pregnancy ANTIHYPERTENSIVE DRUGS diabetes or type 2 diabetes who be- Insulin is the preferred agent for man- come pregnant, the following are rec- In a pregnancy complicated by diabetes agement of diabetes in pregnancy be- ommended as optimal glycemic goals and chronic hypertension, target blood cause of the lack of long-term safety if they can be achieved without exces- pressure goals of systolic blood pres- data for noninsulin agents. The physiol- sive hypoglycemia (7): sure 110–129 mmHg and diastolic blood ogy of pregnancy requires frequent ti- pressure 65–79 mmHg are reasonable, tration of insulin to match changing ○ Premeal, bedtime, and overnight as they contribute to improved long- requirements. In the first trimester, glucose 60–99 mg/dL (3.3–5.4 term maternal health. Lower blood there is often a decrease in total daily mmol/L) pressure levels may be associated with dose of insulin. In the second trimester, ○ Peak postprandial glucose 100–129 impaired fetal growth. During preg- rapidly increasing insulin resistance re- mg/dL (5.4–7.1 mmol/L) nancy, treatment with ACE inhibitors quires weekly or biweekly increase in ○ A1C ,6.0% and angiotensin receptor blockers is insulin dose to achieve glycemic targets. contraindicated because they may In general, a small proportion of the to- Metabolic physiology of pregnancy is cause fetal damage. Antihypertensive tal daily dose should be given as basal characterized by fasting hypoglycemia drugs known to be effective and safe in insulin and a greater proportion as pran- due to insulin-independent glucose up- pregnancy include methyldopa, labetalol, dial insulin. Due to the complexity of take by the placenta, postprandial hyper- diltiazem, clonidine, and prazosin. insulin management in pregnancy, re- glycemia, and carbohydrate intolerance Chronic diuretic use during pregnancy ferral to a specialized center is recom- as a result of diabetogenic placental hor- has been associated with restricted ma- mended if this resource is available. All mones. In addition, insulin resistance in- ternal plasma volume, which may reduce insulins are pregnancy category B ex- creases exponentially during the second uteroplacental perfusion (8). cept for glargine and glulisine, which trimester and levels off toward the end of are labeled C. the third trimester. MANAGEMENT OF GESTATIONAL Concerns Related to Type 1 Diabetes Reflecting this physiology, pre- and DIABETES MELLITUS in Pregnancy postprandial monitoring of blood glucose As highlighted in Section 2. Classification Women with type 1 diabetes have an is recommended to achieve metabolic and Diagnosis of Diabetes, GDM is char- increased risk of hypoglycemia in the control. The American College of acterized by increased risk of macrosomia first trimester. Frequent hypoglycemia Obstetricians and Gynecologists (ACOG) and birth complications, without a risk can be associated with intrauterine recommends the following targets: fast- threshold (9). Treatment starts with med- growth restriction. In addition, rapid im- ing ,90 mg/dL, preprandial ,105 mg/dL, ical nutrition therapy, exercise, and glu- plementation of tight glycemic control 1-h postprandial ,130–140 mg/dL, and cose monitoring aiming for the targets in the setting of retinopathy is associ- 2-h postprandial ,120 mg/dL. If women described previously. A total of 70 to ated with worsening of retinopathy cannot achieve these targets without 85% of women diagnosed with GDM un- (15). Insulin resistance drops rapidly significant hypoglycemia, the American der older criteria can control GDM with with delivery of the placenta, and Diabetes Association (ADA) suggests lifestyle modification alone; it is antici- women become very insulin sensitive, consideration of slightly higher targets: pated that this number will increase using requiring much less insulin than in the fasting ,105 mg/dL, 1-h postprandial the lower International Association of the prepartum period. ,155 mg/dL, and 2-h postprandial Diabetes and Pregnancy Study Groups ,130 mg/dL. Until harmonization of (IADPSG) thresholds. Treatment has Concerns Related to Type 2 Diabetes these guidelines is achieved, the ADA been demonstrated to improve perinatal in Pregnancy recommends setting targets based outcomes in randomized studies and in a Pregestational type 2 diabetes is often on clinical experience, individualizing U.S. Preventive Services Task Force re- associated with obesity. Recommended care, as needed. view (10). Historically, insulin has been weight gain during pregnancy for care.diabetesjournals.org Position Statement S79

overweight women is 15–25 lb and for and many women will require signifi- 9. Metzger BE, Lowe LP, Dyer AR, et al.; HAPO obese women is 10–20 lb. Glycemic con- cantly less insulin at this time than Study Cooperative Research Group. Hyperglyce- trol is often easier to achieve in type 2 during the prepartum period. Breast- mia and adverse pregnancy outcomes. N Engl J Med 2008;358:1991–2002 diabetes than in type 1 diabetes, but feeding may cause hypoglycemia, which 10. Hartling L, Dryden DM, Guthrie A, Muise M, hypertension and other comorbidities maybeamelioratedbyconsumingasnack Vandermeer B, Donovan L. Benefits and harms often render pregestational type 2 dia- (such as milk) prior to nursing. Diabetes of treating gestational diabetes mellitus: a sys- betes as high or higher risk than preges- self-management often suffers in the tematic review and meta-analysis for the U.S. tational type 1 diabetes (16,17). postpartum period. Preventive Services Task Force and the National Institutes of Health Office of Medical Applica- POSTPARTUM CARE tions of Research. Ann Intern Med 2013;159: Type 2 Diabetes 123–129 Lactation If the pregnancy has motivated the adop- 11. Langer O, Conway DL, Berkus MD, Xenakis All women should be supported in at- tion of a healthier diet, building on these EM-J, Gonzales O. A comparison of glyburide tempts to nurse their babies, given im- gains to support weight loss is recom- and insulin in women with gestational diabetes mellitus. N Engl J Med 2000;343:1134–1138 mediate nutritional and immunological mended in the postpartum period. 12. Rowan JA, Hague WM, Gao W, Battin MR, benefits of breastfeeding for the baby; Moore MP; MiG Trial Investigators. Metformin there may also be a longer-term meta- Contraception versus insulin for the treatment of gestational bolic benefit to both mother (18) and All women of childbearing age, including diabetes. N Engl J Med 2008;358:2003–2015 offspring (19), though data are mixed. those who are postpartum, should have 13. Gui J, Liu Q, Feng L. Metformin vs insulin in contraception options reviewed at reg- the management of gestational diabetes: Gestational Diabetes Mellitus a meta-analysis. PLoS One 2013;8:e64585 ular intervals. Because GDM may represent preexisting 14. Coustan DR. Pharmacological management of gestational diabetes: an overview. Diabetes undiagnosed type 2 diabetes, women References Care 2007;30(Suppl. 2):S206–S208 with GDM should be screened for persis- 1. Guerin A, Nisenbaum R, Ray JG. Use of ma- 15. Chew EY, Mills JL, Metzger BE, et al.; Na- tent diabetes or prediabetes at 6–12 ternal GHb concentration to estimate the risk of tional Institute of Child Health and Human De- weeks postpartum using nonpregnancy congenital anomalies in the offspring of women velopment Diabetes in Early Pregnancy Study. criteria and every 1–3 years thereafter with prepregnancy diabetes. Diabetes Care Metabolic control and progression of retinopa- – thy: the Diabetes in Early Pregnancy Study. Di- depending on other risk factors. Women 2007;30:1920 1925 2. Jensen DM, Korsholm L, Ovesen P, et al. abetes Care 1995;18:631–637 with a history of GDM have a greatly in- Peri-conceptional A1C and risk of serious ad- 16. Clausen TD, Mathiesen E, Ekbom P, Hellmuth creased risk of conversion to type 2 dia- verse pregnancy outcome in 933 women with E, Mandrup-Poulsen T, Damm P. Poor pregnancy betes over time and not solely within the type 1 diabetes. Diabetes Care 2009;32:1046– outcome in women with type 2 diabetes. Diabe- – 6–12 weeks’ postpartum time frame 1048 tes Care 2005;28:323 328 17. Cundy T, Gamble G, Neale L, et al. Differing (20). In the prospective Nurses’ Health 3. Charron-Prochownik D, Sereika SM, Becker D, et al. Long-term effects of the booster- causes of pregnancy loss in type 1 and type 2 Study II (21), subsequent diabetes – enhanced READY-Girls preconception counsel- diabetes. Diabetes Care 2007;30:2603 2607 fi risk after a history of GDM was signi - ing program on intentions and behaviors for 18. Stuebe AM, Rich-Edwards JW, Willett WC, cantly lower in women who followed family planning in teens with diabetes. Diabetes Manson JE, Michels KB. Duration of lactation and incidence of type 2 diabetes. JAMA 2005; healthy eating patterns. Adjusting for Care 2013;36:3870–3874 294:2601–2610 4. Holmes VA, Young IS, Patterson CC, et al.; BMI moderately, but not completely, 19. Pereira PF, Alfenas R de CG, Araujo´ RMA. Diabetes and Pre-eclampsia Intervention Trial attenuated this association. Interpreg- Does breastfeeding influence the risk of develop- Study Group. Optimal glycemic control, pre- ing diabetes mellitus in children? A review of cur- nancy or postpartum weight gain is as- eclampsia, and gestational hypertension in rent evidence. J Pediatr (Rio J) 2014;90:7–15 sociated with increased risk of adverse women with type 1 diabetes in the diabetes pregnancy outcomes in subsequent 20. Kim C, Newton KM, Knopp RH. Gestational and pre-eclampsia intervention trial. Diabetes diabetes and the incidence of type 2 diabetes: – pregnancies (22) and earlier progression Care 2011;34:1683 1688 a systematic review. Diabetes Care 2002;25: to type 2 diabetes. Both metformin and 5. Dabelea D, Hanson RL, Lindsay RS, et al. In- 1862–1868 intensive lifestyle intervention prevent trauterine exposure to diabetes conveys risks 21. Tobias DK, Hu FB, Chavarro J, Rosner B, for type 2 diabetes and obesity: a study of dis- Mozaffarian D, Zhang C. Healthful dietary pat- or delay progression to diabetes in cordant sibships. Diabetes 2000;49:2208–2211 women with a history of GDM. Of women terns and type 2 diabetes mellitus risk among 6. Metzger BE, Buchanan TA, Coustan DR, et al. women with a history of gestational diabetes with a history of GDM and impaired glu- Summary and recommendations of the Fifth In- mellitus. Arch Intern Med 2012;172:1566–1572 cose tolerance, only 5–6 individuals need ternational Workshop-Conference on Gesta- 22. Villamor E, Cnattingius S. Interpregnancy to be treated with either intervention tional Diabetes Mellitus. Diabetes Care 2007; weight change and risk of adverse pregnancy – to prevent one case of diabetes over 30(Suppl. 2):S251 S260 outcomes: a population-based study. Lancet 7. Kitzmiller JL, Block JM, Brown FM, et al. 2006;368:1164–1170 3 years (23). Managing preexisting diabetes for pregnancy: 23. Ratner RE, Christophi CA, Metzger BE, et al.; Type 1 Diabetes summary of evidence and consensus recom- Diabetes Prevention Program Research Group. mendations for care. Diabetes Care 2008;31: Prevention of diabetes in women with a history Insulin sensitivity increases in the imme- 1060–1079 of gestational diabetes: effects of metformin diate postpartum period and then returns 8. Sibai BM. Treatment of hypertension in preg- and lifestyle interventions. J Clin Endocrinol to normal over the following 1–2 weeks, nant women. N Engl J Med 1996;335:257–265 Metab 2008;93:477424779 S80 Diabetes Care Volume 38, Supplement 1, January 2015

13. Diabetes Care in the Hospital, American Diabetes Association Nursing Home, and Skilled Nursing Facility Diabetes Care 2015;38(Suppl. 1):S80–S85 | DOI: 10.2337/dc15-S016

Recommendations c Diabetes discharge planning should start at hospital admission, and clear diabetes management instructions should be provided at discharge. E c The sole use of sliding scale insulin (SSI) in the inpatient hospital setting is strongly discouraged. A c All patients with diabetes admitted to the hospital should have their diabetes type clearly identified in the medical record. E POSITION STATEMENT Critically Ill Patients c Insulin therapy should be initiated for treatment of persistent hyperglycemia starting at a threshold of no greater than 180 mg/dL (10 mmol/L). Once insulin therapy is started, a glucose range of 140–180 mg/dL (7.8–10 mmol/L) is recom- mended for the majority of critically ill patients. A c More stringent goals, such as 110–140 mg/dL (6.1–7.8 mmol/L), may be appropriate for selected patients, as long as this can be achieved without significant hypoglycemia. C c Critically ill patients require an intravenous insulin protocol that has demon- strated efficacy and safety in achieving the desired glucose range without increasing risk for severe hypoglycemia. E Noncritically Ill Patients c If treated with insulin, generally premeal blood glucose targets of ,140 mg/dL (7.8 mmol/L) with random blood glucose ,180 mg/dL (10.0 mmol/L) are reasonable, provided these targets can be safely achieved. More stringent targets may be appropriate in stable patients with previous tight glycemic control. Less stringent targets may be appropriate in those with severe co- morbidities. C c A basal plus correction insulin regimen is the preferred treatment for patients with poor oral intake or who are taking nothing by mouth (NPO). An insulin regimen with basal, nutritional, and correction components is the preferred treatment for patients with good nutritional intake. A c A hypoglycemia management protocol should be adopted and implemented by each hospital or hospital system. A plan for preventing and treating hypoglycemia should be established for each patient. Episodes of hypoglycemia in the hospital should be documented in the medical record and tracked. E c Consider obtaining an A1C in patients with diabetes admitted to the hospital if Suggested citation: American Diabetes Associa- tion. Diabetes care in the hospital, nursing home, the result of testing in the previous 3 months is not available. E and skilled nursing facility. Sec. 13. In Standards c Consider obtaining an A1C in patients with risk factors for undiagnosed of Medical Care in Diabetesd2015. Diabetes diabetes who exhibit hyperglycemia in the hospital. E Care 2015;38(Suppl. 1):S80–S85 c Patients with hyperglycemia in the hospital who do not have a prior diagnosis © 2015 by the American Diabetes Association. of diabetes should have appropriate follow-up testing and care documented at Readers may use this article as long as the work discharge. E is properly cited, the use is educational and not for profit, and the work is not altered. care.diabetesjournals.org Position Statement S81

HYPERGLYCEMIA IN THE HOSPITAL mean blood glucose attained 115 mg/dL and persistently above this may re- Hyperglycemia in the hospital can re- [6.4 mmol/L]) to standard glycemic con- quire treatment in hospitalized pa- flect previously known or previously un- trol (target 144–180 mg/dL [8.0–10.0 tients. A1C values $6.5% suggest, in diagnosed diabetes or may be hospital mmol/L]; mean blood glucose attained undiagnosed patients, that diabetes related. The difficulty distinguishing be- 144 mg/dL [8.0 mmol/L]) on outcomes preceded hospitalization (1). Hypoglyce- tween the second and third categories among 6,104 critically ill participants, mia has been defined as any blood glu- , during the hospitalization may be over- almost all of whom required mechanical cose 70 mg/dL (3.9 mmol/L). This is fi come by measuring A1C, as long as con- ventilation (6). the standard de nition in outpatients fi ditions interfering with A1C equilibrium Ninety-day mortality was signi - and correlates with the initial threshold (such as hemolysis, blood transfusion, cantly higher in the intensive versus for the release of counterregulatory blood loss, or erythropoietin therapy) the conventional treatment group in hormones. Severe hypoglycemia in hos- fi have not occurred. A1C values $6.5% both surgical and medical patients, as pitalized patients has been de ned by , in undiagnosed patients suggest that was mortality from cardiovascular many as 40 mg/dL (2.2 mmol/L), ; diabetes preceded hospitalization (1). causes. Severe hypoglycemia was also although this is lower than the 50 Hyperglycemia management in the hos- more common in the intensively treated mg/dL (2.8 mmol/L) level at which cog- P , pital has often been considered second- group (6.8% vs. 0.5%; 0.001). nitive impairment begins in normal in- The study results lie in stark contrast dividuals (10). Both hyperglycemia and ary in importance to the condition that to a 2001 single-center study that re- hypoglycemia among inpatients are as- prompted admission. However, a body ported a 42% relative reduction in inten- sociated with adverse short- and long- of literature now supports targeted glu- sive care unit (ICU) mortality in critically ill term outcomes. Early recognition and cose control in the hospital setting for surgical patients treated to a target blood treatment of mild to moderate hypogly- improved clinical outcomes (2). Hyper- glucose of 80–110 mg/dL (3). The NICE- cemia (40–69 mg/dL [2.2–3.8 mmol/L]) glycemia in the hospital may result SUGAR findings do not disprove the no- can prevent deterioration to a more from stress or decompensation of tion that glycemic control in the ICU is severe episode with potential adverse type 1, type 2, or other forms of diabe- important. However, they do strongly sequelae (11). tes and/or may be iatrogenic due to with- suggest that it may not be necessary to holding of antihyperglycemic medications target blood glucose values ,140 mg/dL Critically Ill Patients or administration of hyperglycemia- (7.8 mmol/L) and that a highly stringent Based on available evidence, for the ma- provoking agents, such as glucocorticoids, target of ,110 mg/dL (6.1 mmol/L) may jority of critically ill patients in the ICU vasopressors, and enteral or parenteral actually be dangerous. setting, intravenous insulin infusion nutrition. In a meta-analysis of 26 trials (n 5 should be used to control hyperglyce- There is substantial observational 13,567), which included the NICE- mia, with a starting threshold of no evidence linking hyperglycemia in hos- SUGAR data, the pooled relative risk higher than 180 mg/dL (10.0 mmol/L). pitalized patients (with or without dia- [RR] of death with intensive insulin ther- Once intravenous insulin is started, the betes) to poor outcomes. Cohort studies apy was 0.93 as compared with conven- glucose level should be maintained be- as well as a few early randomized con- tional therapy (95% CI 0.83–1.04) (9). tween 140–180 mg/dL (7.8–10.0 mmol/L). trolled trials (RCTs) suggested that in- Approximately half of these trials re- Greater benefit may be realized at the tensive treatment of hyperglycemia ported hypoglycemia, with a pooled lower end of this range. Although strong improved hospital outcomes (3,4). In RR of intensive therapy of 6.0 (95% CI evidence is lacking, lower glucose targets general, these studies were heteroge- 4.5–8.0). The specific ICU setting influ- may be appropriate in select patients. neous in terms of patient population, enced the findings, with patients in sur- One small study suggested that ICU pa- blood glucose targets, insulin protocols, gical ICUs appearing to benefitfrom tients treated to targets of 120–140 provision of nutritional support, and the intensive insulin therapy (RR 0.63 [95% mg/dL (6.7–7.8 mmol/L) had less nega- proportion of patients receiving insulin, CI 0.44–0.91]), while those in other tive nitrogen balance than those treated which limits the ability to make mean- medical and mixed critical care settings to higher targets (12). However, targets ingful comparisons among them. Trials did not. It was concluded that, overall, ,110 mg/dL (6.1 mmol/L) are not rec- in critically ill patients have failed to intensive insulin therapy increased the ommended. Insulin infusion protocols show a significant improvement in mor- risk of hypoglycemia and provided no with demonstrated safety and efficacy, tality with intensive glycemic control or overall benefit on mortality in the criti- resulting in low rates of hypoglycemia, have even shown increased mortality cally ill, although a possible mortality are highly recommended (11). risk (5). Moreover, RCTs have high- benefit to patients admitted to the sur- lighted the risk of severe hypoglycemia gical ICU was suggested. Noncritically Ill Patients resulting from such efforts (6–9). With no prospective RCT data to inform The largest study to date, Normo- GLYCEMIC TARGETS IN specific glycemic targets in noncritically glycemia in Intensive Care Evaluation- HOSPITALIZED PATIENTS ill patients, recommendations are Survival Using Glucose Algorithm Definition of Glucose Abnormalities in based on clinical experience and judg- Regulation (NICE-SUGAR), a multicen- the Hospital Setting ment (13). For the majority of noncriti- ter, multinational RCT, compared the Hyperglycemia in the hospital has been de- cally ill patients treated with insulin, effect of intensive glycemic control fined as any blood glucose .140 mg/dL premeal glucose targets should gener- (target 81–108 mg/dL [4.5–6.0 mmol/L]; (7.8 mmol/L). Levels that are significantly ally be ,140 mg/dL (7.8 mmol/L) with S82 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

random blood glucose ,180 mg/dL Forpatientswithtype1diabetes, Despite the preventable nature of (10.0 mmol/L), as long as these targets dosing insulin solely based on premeal many inpatient episodes of hypoglyce- can be safely achieved. To avoid hypo- glucose levels does not account for basal mia, institutions are more likely to have glycemia, consideration should be given insulin requirements or caloric intake, nursing protocols for hypoglycemia treat- to reassessing the insulin regimen if increasing both hypoglycemia and hy- ment than for its prevention. Tracking blood glucose levels fall below 100 perglycemia risks and potentially lead- such episodes and analyzing their causes mg/dL (5.6 mmol/L). Modifying the reg- ing to diabetic ketoacidosis. It has are important quality-improvement imen is required when blood glucose been shown in an RCT that basal–bolus activities (22). values are ,70 mg/dL (3.9 mmol/L), un- treatment improved glycemic control less the event is easily explained by and reduced hospital complications DIABETES CARE PROVIDERS IN THE other factors (such as a missed meal). compared with SSI in general surgery HOSPITAL There is some evidence that systematic patients with type 2 diabetes (17). Typ- Inpatient diabetes management may be attention to hyperglycemia in the emer- ical dosing schemes are based on body effectively championed and/or provided gency room leads to better glycemic weight, with some evidence that pa- by primary care physicians, endocrinol- control in the hospital for those subse- tients with renal insufficiency should ogists, intensive care specialists, or hos- quently admitted (14). be treated with lower doses (18). The pitalists. Involvement of appropriately Patients with a prior history of suc- reader is referred to publications and trained specialists or specialty teams cessful tight glycemic control in the out- reviews that describe available insulin may reduce length of stay, improve gly- patient setting who are clinically stable preparations and protocols and provide cemic control, and improve outcomes may be maintained with a glucose range guidance in the use of insulin therapy (11). Standardized orders for scheduled below the aforementioned cut points. in specific clinical settings, including and correction-dose insulin should be Conversely, higher glucose ranges may parenteral nutrition (19), enteral tube implemented, while sole reliance on an be acceptable in terminally ill patients or feedings, and high-dose glucocorticoid SSI regimen is strongly discouraged. As in patients with severe comorbidities, as therapy (11). hospitals move to comply with “mean- well as in those in patient-care settings Recent studies have investigated the ingful use” regulations for electronic where frequent glucose monitoring or safety and efficacy of oral agents and in- health records, as mandated by the close nursing supervision is not feasible. jectable noninsulin therapies, such as GLP- Health Information Technology for Eco- Clinical judgment combined with on- 1 analogs, in the hospital. A small study in nomic and Clinical Health Act, efforts going assessment of the patient’s clini- general medicine and surgical wards should be made to ensure that all com- cal status, including changes in the showed that treatment with sitagliptin re- ponents of structured insulin order sets trajectory of glucose measures, the se- sulted in similar glycemic control as a are incorporated into electronic insulin verity of illness, nutritional status, or basal–bolusregimeninpatientswithtype order sets (23,24). concomitant medications that might af- 2 diabetes who had an A1C ,7.5% and, in To achieve glycemic targets associ- fect glucose levels (e.g., glucocorticoids, addition to a nutrition intervention, were ated with improved hospital outcomes, octreotide), must be incorporated into treated with oral agents or low doses of hospitals will need a multidisciplinary the day-to-day decisions regarding insu- insulin prior to hospitalization (20). Use of approach to develop insulin manage- lin dosing (11). intravenous exenatide infusion resulted in ment protocols that effectively and improved glycemic control in patients ad- safely enable achievement of glycemic ANTIHYPERGLYCEMIC AGENTS IN mitted to a cardiac ICU (21). Further stud- targets (25). HOSPITALIZED PATIENTS ies are needed to define the role of In most clinical situations in the hospital, incretin mimetics in the inpatient manage- SELF-MANAGEMENT IN THE insulin therapy is the preferred method ment of hyperglycemia. HOSPITAL of glycemic control (11). In the ICU, in- Diabetes self-management in the hospi- travenous infusion is the preferred PREVENTING HYPOGLYCEMIA tal may be appropriate for competent route of insulin administration. When Patients with or without diabetes may youth and adult patients who have a sta- the patient is transitioned off intrave- experience hypoglycemia in the hospital ble level of consciousness and reason- nous insulin to subcutaneous therapy, setting in association with altered nutri- ably stable daily insulin requirements, precautions should be taken to prevent tional state, heart failure, renal or liver successfully conduct self-management hyperglycemia (15,16). Outside of criti- disease, malignancy, infection, or sepsis. of diabetes at home, have physical skills cal care units, scheduled subcutaneous Additional triggering events leading to needed to successfully self-administer insulin that delivers basal, nutritional, iatrogenic hypoglycemia include sudden insulin and perform self-monitoring of and correction components (basal–bolus reduction of corticosteroid dose, altered blood glucose, have adequate oral in- regimen) is recommended for patients ability of the patient to report symp- take, are proficient in carbohydrate with good nutritional intake. A basal toms, reduced oral intake, emesis, new counting, use multiple daily insulin in- plus correction insulin regimen is the NPO status, inappropriate timing of jections or insulin pump therapy, and preferred treatment for patients with short- or rapid-acting insulin in relation understand sick-day management. The poor oral intake or who are NPO. SSI to meals, reduced infusion rate of intra- patient and physician, in consultation is strongly discouraged in hospitalized venous dextrose, and unexpected inter- with nursing staff, must agree that pa- patients as the sole method of insulin ruption of enteral feedings or parenteral tient self-management is appropriate treatment. nutrition. while hospitalized. care.diabetesjournals.org Position Statement S83

Patients who use continuous subcuta- that prohibit the sharing of finger-stick living, rehabilitation, or skilled nursing neous insulin infusion (CSII) pump therapy lancing devices, lancets, needles, and me- facilities. For the patient who is dis- in the outpatient setting can be candi- ters to reduce the risk of transmission of charged to assisted living or to home, dates for diabetes self-management in blood-borne diseases. Shared lancing de- the optimal program will need to con- the hospital, provided that they have vices carry essentially the same risk as sider the type and severity of diabetes, the mental and physical capacity to do sharing syringes and needles (31). the effects of the patient’s illness on so (11). Hospital policy and procedures Accuracy of blood glucose measure- blood glucose levels, and the capacities delineating inpatient guidelines for CSII ments using POC meters has limitations and desires of the patient. Smooth tran- therapy are advisable, and availability of that must be considered. Although the sition to outpatient care should be hospital personnel with expertise in CSII U.S. Food and Drug Administration cur- ensured. therapy is essential. It is important that rently allows a 620% error for blood An outpatient follow-up visit with the nursing personnel document basal rates glucose meters, questions about the ap- primary care provider, endocrinologist, and bolus doses taken on a daily basis. propriateness of these criteria have or diabetes educator within 1 month of been raised, especially for lower blood discharge is advised for all patients hav- MEDICAL NUTRITION THERAPY IN glucose readings (32). Glucose mea- ing hyperglycemia in the hospital. Clear THE HOSPITAL sures differ significantly between plasma communication with outpatient pro- The goals of medical nutrition therapy and whole blood, terms that are often viders either directly or via hospital are to optimize glycemic control, pro- used interchangeably and can lead to discharge summaries facilitates safe vide adequate calories to meet meta- misinterpretation. Most commercially transitions to outpatient care. Providing bolic demands, and create a discharge available capillary blood glucose meters information regarding the cause of hy- plan for follow-up care (2,26). The introduce a correction factor of ;1.12 perglycemia (or the plan for determin- American Diabetes Association (ADA) to report a “plasma-adjusted” value (33). ing the cause), related complications does not endorse any single meal plan Significant discrepancies between and comorbidities, and recommended or specified percentages of macronu- capillary, venous, and arterial plasma treatments can assist outpatient pro- trients, and the term “ADA diet” should samples have been observed in patients viders as they assume ongoing care. no longer be used. Current nutrition rec- with low or high hemoglobin concentra- The Agency for Healthcare Research ommendations advise individualization tions, hypoperfusion, and interfering and Quality recommends that, at a based on treatment goals, physiological substances such as maltose (contained minimum, discharge plans include the parameters, and medication use. Con- in immunoglobulins) (34). Analytical var- following: sistent carbohydrate meal plans are iability has been described with several preferred by many hospitals as they fa- meters (35). Increasingly, newer-generation Medication Reconciliation cilitate matching the prandial insulin POC blood glucose meters correct for ○ The patient’s medications must be dose to the amount of carbohydrate variation in hematocrit and for interfer- cross-checked to ensure that no consumed (27). Because of the complex- ing substances. Any glucose result that chronic medications were stopped ity of nutrition issues in the hospital, a does not correlate with the patient’s and to ensure the safety of new registered dietitian, knowledgeable and status should be confirmed through prescriptions. skilled in medical nutrition therapy, conventional laboratory sampling of ○ Prescriptions for new or changed should serve as an inpatient team plasma glucose. The U.S. Food and Drug medication should be filled and re- member. The dietitian is responsible Administration has become increasingly viewed with the patient and family for integrating information about the concerned about POC blood glucose at or before discharge. patient’s clinical condition, meal plan- meter use in the hospital and is presently ning, and lifestyle habits and for estab- reviewing matters related to their use. Structured Discharge Communication lishing treatment goals to determine a ○ Information on medication changes, realistic plan for nutrition therapy (28). DISCHARGE PLANNING pending tests and studies, and follow- Transition from the acute care setting up needs must be accurately and BEDSIDE BLOOD GLUCOSE is a high-risk time for all patients, not promptly communicated to outpatient MONITORING just those with diabetes or new hyper- physicians. Bedside point-of-care (POC) blood glu- glycemia. Although there is extensive ○ Discharge summaries should be trans- cose monitoring is used to guide insulin literature concerning safe transition mitted to the primary physician as soon dosing. In the patient receiving nutri- within and from the hospital, little of it as possible after discharge. tion, the timing of glucose monitoring is specific to diabetes (36). Diabetes dis- ○ Appointment-keeping behavior is should match carbohydrate exposure. charge planning is not a separate entity enhanced when the inpatient team In the patient not receiving nutrition, but is an important part of an overall schedules outpatient medical follow- glucose monitoring is performed every discharge plan. As such, discharge plan- up prior to discharge. Ideally, the inpa- 4–6 h (29,30). More frequent blood glu- ning begins at admission to the hospital tient care providers or case managers/ cose testing ranging from every 30 min andisupdatedasprojectedpatient discharge planners will schedule to every 2 h is required for patients on needs change. follow-up visit(s) with the appropriate intravenous insulin infusions. Inpatients may be discharged to var- professionals, including primary care Safety standards should be estab- ied settings, including home (with or provider, endocrinologist, and diabetes lished for blood glucose monitoring without visiting nurse services), assisted educator (37). S84 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

DIABETES SELF-MANAGEMENT discharge in order to avoid a poten- 12. Hsu C-W, Sun S-F, Lin S-L, Huang H-H, Wong EDUCATION tially dangerous hiatus in care. These K-F. Moderate glucose control results in less negative nitrogen balances in medical intensive Teaching diabetes self-management to supplies/prescriptions should include care unit patients: a randomized, controlled patients in hospitals is a challenging the following: study. Crit Care 2012;16:R56 task. Patients are ill, under increased 13. Umpierrez GE, Hellman R, Korytkowski MT, stress related to their hospitalization ○ Insulin (vials or pens), if needed et al.; Endocrine Society. Management of hyper- ○ Syringes or pen needles, if needed glycemia in hospitalized patients in non-critical and diagnosis, and in an environment care setting: an endocrine society clinical prac- ○ Oral medications, if needed not conducive to learning. Ideally, people tice guideline. J Clin Endocrinol Metab 2012;97: with diabetes should be taught at a time ○ Blood glucose meter and strips 16–38 and place conducive to learning: as an ○ Lancets and lancing devices 14. Bernard JB, Munoz C, Harper J, Muriello M, outpatient in a recognized program of di- ○ Urine ketone strips (type 1 diabetes) Rico E, Baldwin D. Treatment of inpatient hyper- ○ Glucagon emergency kit (insulin- glycemia beginning in the emergency depart- abetes education. For the hospitalized pa- ment: a randomized trial using insulins aspart tient, diabetes “survival skills” education treated patients) and detemir compared with usual care. J Hosp is generally a feasible approach to provide ○ Medical alert application/charms Med 2011;6:279–284 sufficient information and training to en- 15. Czosnowski QA, Swanson JM, Lobo BL, able safe care at home. Patients hospital- References Broyles JE, Deaton PR, Finch CK. Evaluation of glycemic control following discontinuation of an 1. Saudek CD, Herman WH, Sacks DB, ized because of a crisis related to diabetes intensive insulin protocol. J Hosp Med 2009;4: Bergenstal RM, Edelman D, Davidson MB. A management or poor care at home re- 28–34 new look at screening and diagnosing diabetes 16. Shomali ME, Herr DL, Hill PC, Pehlivanova quire education to prevent subsequent mellitus. J Clin Endocrinol Metab 2008;93: M, Sharretts JM, Magee MF. Conversion from episodes of hospitalization. Assessing 2447–2453 intravenous insulin to subcutaneous insulin af- the need for a home health referral 2. Clement S, Braithwaite SS, Magee MF, et al.; ter cardiovascular surgery: Transition to Target American Diabetes Association Diabetes in or referral to an outpatient diabetes ed- Study. Diabetes Technol Ther 2011;13:121–126 ucation program should be part of Hospitals Writing Committee. Management of 17. Umpierrez GE, Smiley D, Jacobs S, et al. Ran- discharge planning for all patients. Ex- diabetes and hyperglycemia in hospitals [pub- domized Study of Basal-Bolus Insulin Therapy in lished correction in Diabetes Care 2004;27: the Inpatient Management of Patients with Type 2 panded diabetes education can be ar- 856]. Diabetes Care 2004;27:553–591 ranged in the community. Diabetes undergoing general surgery (RABBIT 2 3. van den Berghe G, Wouters P, Weekers F, Surgery). Diabetes Care 2011;34:256–261 Diabetes self-management education et al. Intensive insulin therapy in critically ill 18. Baldwin D, Zander J, Munoz C, et al. A ran- – should start upon admission or as soon patients. N Engl J Med 2001;345:1359 1367 domized trial of two weight-based doses of in- as feasible, especially in those new to 4. Malmberg K, Norhammar A, Wedel H, sulin glargine and glulisine in hospitalized Ryden´ L. Glycometabolic state at admission: insulin therapy or in whom the diabetes subjects with type 2 diabetes and renal insuffi- important risk marker of mortality in conven- ciency. Diabetes Care 2012;35:1970–1974 regimen has been substantially altered tionally treated patients with diabetes melli- 19. Pasquel FJ, Spiegelman R, McCauley M, during the hospitalization. tus and acute myocardial infarction: long-term et al. Hyperglycemia during total parenteral nu- It is recommended that the following results from the Diabetes and Insulin-Glucose trition: an important marker of poor outcome areas of knowledge be reviewed and ad- Infusion in Acute Myocardial Infarction and mortality in hospitalized patients. Diabetes – – dressed prior to hospital discharge: (DIGAMI) study. Circulation 1999;99:2626 Care 2010;33:739 741 2632 20. Umpierrez GE, Gianchandani R, Smiley D, 5. Finar S, Liu B, Chittock DR, et al.; NICE-SUGAR et al. Safety and efficacy of sitagliptin therapy ○ fi Identi cation of the health care pro- Study Investigators. Hypoglycemia and risk of for the inpatient management of general med- vider who will provide diabetes care deathincriticallyillpatients.NEnglJMed icine and surgery patients with type 2 diabetes: after discharge 2012;367:1108–1118 a pilot, randomized, controlled study. Diabetes ○ Level of understanding related to the 6. Finfer S, Chittock DR, Su SY, et al.; Care 2013;36:3430–3435 diagnosis of diabetes, self-monitoring NICE-SUGAR Study Investigators. Intensive 21. Abuannadi M, Kosiborod M, Riggs L, et al. versus conventional glucose control in criti- Management of hyperglycemia with the admin- of blood glucose, and explanation of cally ill patients. N Engl J Med 2009;360: istration of intravenous exenatide to patients in home blood glucose goals 1283–1297 the cardiac intensive care unit. Endocr Pract ○ Definition, recognition, treatment, 7. Krinsley JS, Grover A. Severe hypoglycemia in 2013;19:81–90 and prevention of hyperglycemia critically ill patients: risk factors and outcomes. 22. Seaquist ER, Anderson J, Childs B, et al. Hy- – and hypoglycemia Crit Care Med 2007;35:2262 2267 poglycemia and diabetes: a report of a work- 8. Van den Berghe G, Wilmer A, Hermans G, group of the American Diabetes Association ○ Informationonconsistenteatingpat- et al. Intensive insulin therapy in the medical and the Endocrine Society. Diabetes Care terns ICU. N Engl J Med 2006;354:449–461 2013;36:1384–1395 ○ When and how to take blood 9. Griesdale DE, de Souza RJ, van Dam RM, et al. 23. Schnipper JL, Liang CL, Ndumele CD, glucose–lowering medications, in- Intensive insulin therapy and mortality among crit- Pendergrass ML. Effects of a computerized or- cluding insulin administration (if go- ically ill patients: a meta-analysis including NICE- der set on the inpatient management of hyper- SUGAR study data. CMAJ 2009;180:821–827 glycemia: a cluster-randomized controlled trial. ing home on insulin) 10. Cryer PE, Davis SN, Shamoon H. Hypoglyce- Endocr Pract 2010;16:209–218 ○ Sick-day management mia in diabetes. Diabetes Care 2003;26:1902– 24. Wexler DJ, Shrader P, Burns SM, Cagliero E. ○ Proper use and disposal of needles 1912 Effectiveness of a computerized insulin order and syringes 11. Moghissi ES, Korytkowski MT, DiNardo M, template in general medical inpatients with et al.; American Association of Clinical Endocri- type 2 diabetes: a cluster randomized trial. Di- – It is important that patients be pro- nologists; American Diabetes Association. abetes Care 2010;33:2181 2183 American Association of Clinical Endocrinolo- 25. Furnary AP, Braithwaite SS. Effects of out- vided with appropriate durable medi- gists and American Diabetes Association con- come on in-hospital transition from intravenous cal equipment, medication, supplies, sensus statement on inpatient glycemic insulin infusion to subcutaneous therapy. Am J and prescriptions at the time of control. Diabetes Care 2009;32:1119–1131 Cardiol 2006;98:557–564 care.diabetesjournals.org Position Statement S85

26. Schafer RG, Bohannon B, Franz MJ, et al.; 30. Umpierrez GE. Basal versus sliding-scale results for blood glucose (abbreviated). Clin American Diabetes Association. Diabetes regular insulin in hospitalized patients with hy- Chem 2005;51:1573–1576 nutrition recommendations for health care in- perglycemia during enteral nutrition therapy. 34. Dungan K, Chapman J, Braithwaite SS, Buse stitutions. Diabetes Care 2004;27(Suppl. 1): Diabetes Care 2009;32:751–753 J. Glucose measurement: confounding issues in S55–S57 31. Klonoff DC, Perz JF. Assisted monitoring of setting targets for inpatient management. Dia- 27. Curll M, Dinardo M, Noschese M, blood glucose: special safety needs for a new betes Care 2007;30:403–409 Korytkowski MT. Menu selection, glycaemic paradigm in testing glucose. J Diabetes Sci 35. Boyd JC, Bruns DE. Quality specifications for control and satisfaction with standard and Tech 2010;4:1027–1031 glucose meters: assessment by simulation mod- patient-controlled consistent carbohydrate 32. Vandvik PO, Lincoff AM, Gore JM, et al.; eling of errors in insulin dose. Clin Chem 2001; meal plans in hospitalised patients with diabe- American College of Chest Physicians. Primary 47:209–214 tes. Qual Saf Health Care 2010;19:355–359 and secondary prevention of cardiovascular dis- 36.ShepperdS,LanninNA,ClemsonLM, 28. Evert AB, Boucher JL, Cypress M, et al. Nu- ease: Antithrombotic Therapy and Prevention of McCluskey A, Cameron ID, Barras SL. Discharge trition therapy recommendations for the man- Thrombosis, 9th ed: American College of Chest planning from hospital to home. Cochrane Da- agement of adults with diabetes. Diabetes Care Physicians Evidence-Based Clinical Practice Guide- tabase Syst Rev 2013;1:CD000313 2014;37(Suppl. 1):S120–S143 lines. Chest 2012;141(Suppl.):e637S–e668S 37. Agency for Healthcare Research and Qual- 29. Korytkowski MT, Salata RJ, Koerbel GL, 33. D’Orazio P, Burnett RW, Fogh-Andersen N, ity. AHRQ Patient Safety Networkdadverse et al. Insulin therapy and glycemic control et al.; International Federation of Clinical Chem- events after hospital discharge [Internet], in hospitalized patients with diabetes during istry Scientific Division Working Group on Selec- 2014. Available from http://psnet.ahrq.gov/ enteral nutrition therapy: a randomized controlled tive Electrodes and Point of Care Testing. primer.aspx?primerID511. Accessed 1 October clinical trial. Diabetes Care 2009;32:594–596 Approved IFCC recommendation on reporting 2014 S86 Diabetes Care Volume 38, Supplement 1, January 2015

14. Diabetes Advocacy American Diabetes Association

Diabetes Care 2015;38(Suppl. 1):S86–S87 | DOI: 10.2337/dc15-S017

Managing the daily health demands of diabetes can be challenging. People living with diabetes should not have to face additional discrimination due to diabetes. By advocating for the rights of those with diabetes at all levels, the American Diabetes Association (ADA) can help ensure that they live a healthy and productive life. A strategic goal of the ADA is that by the end of 2015, more children and adults with diabetes will be living free from the burden of discrimination. One tactic for achieving this goal is to implement the ADA’s Standards of Medical Care through advocacy-oriented position statements. The ADA publishes evidence- based, peer-reviewed statements on topics such as diabetes and employment, di- abetes and driving, and diabetes management in certain settings such as schools, child care programs, and correctional institutions. In addition to ADA’sclinical position statements, these advocacy position statements are important tools in educating schools, employers, licensing agencies, policy makers, and others about the intersection of diabetes medicine and the law. ADVOCACY POSITION STATEMENTS Partial list, with most recent publications appearing first

POSITION STATEMENT Care of Young Children With Diabetes in the Child Care Setting (1) First publication: 2014 Very young children (aged ,6 years) with diabetes have legal protections and can be safely cared for by child care providers with appropriate training, access to resources, and a system of communication with parents and the child’s diabetes provider. See theADA positionstatement “Care ofYoung Children WithDiabetes in theChild CareSet- ting” for further discussion: http://care.diabetesjournals.org/content/37/10/2834. Diabetes and Driving (2) First publication: 2012 People with diabetes who wish to operate motor vehicles are subject to a great variety of licensing requirements applied by both state and federal jurisdictions, which may lead to loss of employment or significant restrictions on a person’s license. Presence of a medical condition that can lead to significantly impaired consciousness or cognition may lead to drivers being evaluated for fitness to drive. People with diabetes should be individually assessed by a health care professional knowledgeable in diabetes if license restrictions are being considered, and patients should be counseled about detecting and avoiding hypoglycemia while driving. See the ADA position statement “Diabetes and Driving” for further discussion: http://care.diabetesjournals.org/content/37/Supplement_1/S97. Diabetes and Employment (3) First publication: 1984 (revised 2009) Any person with diabetes, whether insulin-treated or noninsulin-treated, should be eligible for any employment for which he or she is otherwise qualified. Employment decisions should never be based on generalizations or stereotypes regarding the effects of diabetes. When questions arise about the medical fitness of a person with diabetes for a particular job, a health care professional with expertise in treating diabetes should perform an individualized assessment. See the ADA position statement “ ” Diabetes and Employment for further discussion: http://care.diabetesjournals.org/ Suggested citation: American Diabetes Associa- content/37/Supplement_1/S112. tion. Diabetes advocacy. Sec. 14. In Standards of d . Diabetes Care Diabetes Care in the School and Day Care Setting (4)* Medical Care in Diabetes 2015 2015;38(Suppl. 1):S86–S87 First publication: 1998 (revised 2008) © 2015 by the American Diabetes Association. As a sizeable portion of a child’s day is spent in school, close communication with and Readers may use this article as long as the work cooperation of school personnel are essential for optimal diabetes management, is properly cited, the use is educational and not safety, and maximal academic opportunities. See the ADA position statement “Diabetes for profit, and the work is not altered. care.diabetesjournals.org Position Statement S87

Care in the School and Day Care Setting” that nearly 80,000 inmates have diabetes, child care setting: a position statement of the for further discussion: http://care correctional institutions should have writ- American Diabetes Association. Diabetes Care – .diabetesjournals.org/content/37/ ten policies and procedures for the man- 2014;37:2834 2842 2. American Diabetes Association. Diabetes Supplement_1/S91. agement of diabetes and for training of and driving. Diabetes Care 2014;37(Suppl. 1): *In October 2014, a separate statement medical and correctional staff in diabetes S972S103 on the care of young children with diabetes care practices. See the ADA position 3. American Diabetes Association. Diabetes in the child care setting was published. statement “Diabetes Management in and employment. Diabetes Care 2014;37(Suppl. Correctional Institutions” for further dis- 1):S112–S117 Diabetes Management in Correctional cussion: http://care.diabetesjournals 4. American Diabetes Association. Diabetes Institutions (5) care in the school and day care setting. Diabetes .org/content/37/Supplement_1/S104. – First publication: 1989 (revised 2008) Care 2014;37(Suppl. 1):S91 S96 5. American Diabetes Association. Diabetes People with diabetes in correctional facili- References management in correctional institutions. ties should receive care that meets na- 1. Siminerio LM, Albanese-O’Neill A, Chiang JL, Diabetes Care 2014;37(Suppl. 1):S104– tional standards. Because it is estimated et al. Care of young children with diabetes in the S111 S88 Diabetes Care Volume 38, Supplement 1, January 2015

Professional Practice Committee

PROFESSIONAL PRACTICE COMMITTEE for the Standards of Medical Care in Diabetesd2015 Diabetes Care 2015;38(Suppl. 1):S88–S89 | DOI: 10.2337/dc15-S018

Committee members disclosed the following financial or other conflicts of interest covering the period 12 months before 7 September 2014 Member Employment Research grant Other research support Richard W. Grant, MD, MPH (Chair) Division of Research, Kaiser NIDDK, NHLBI None Permanente, Oakland, CA Thomas W. Donner, MD Johns Hopkins University School of Novo Nordisk*# None Medicine, Baltimore, MD Judith E. Fradkin, MD National Institutes of Health, None None Bethesda, MD Charlotte Hayes, MMSc, MS, RD, Private practice: (NF)2 Nutrition and None None CDE, ACSM CES Fitness Consulting, Atlanta, GA William H. Herman, MD, MPH University of Michigan, Ann Arbor, MI None None William C. Hsu, MD Joslin Diabetes Center, Boston, MA None None Eileen Kim, MD Kaiser Permanente Northern None None California Region, Oakland, CA Lori Laffel, MD, MPH Joslin Diabetes Center and Harvard Dexcom, Boehringer None Medical School, Boston, MA Ingelheim Rodica Pop-Busui, MD, PhD University of Michigan, Ann Arbor, MI NHLBI, NIDDK, ADA, None Bristol-Myers Squibb Neda Rasouli, MD University of Colorado, Denver, CO Novo Nordisk,# Bristol- None Myers Squibb,# Merck Sharp & Dohme,# NIDDK,# Pfizer# Desmond Schatz, MD University of Florida, Gainesville, FL None NIDDK, NIAID, Jaeb Center for Health Research, JDRF, Helmsley Charitable Trust Joseph A. Stankaitis, MD, MPH Monroe Plan for Medical Care, Milbank Memorial Fund None Rochester, NY Tracey H. Taveira, PharmD, University of Rhode Island College of AHA None CDOE, CVDOE Pharmacy, Kingston, RI; Providence VA Medical Center, Warren Alpert Medical School of Brown University, Providence, RI Deborah J. Wexler, MD Massachusetts General Hospital, NIDDK None Boston, MA Jane L. Chiang, MD (Staff) ADA, Alexandria, VA None None Erika Gebel Berg, PhD (Staff) ADA, Alexandria, VA None None ADA, American Diabetes Association; AHA, American Heart Association; MEDCAC, Medicare Evidence Development & Coverage Advisory Committee; NHLBI, National Heart, Lung, and Blood Institute; NIAID, National Institute of Allergy and Infectious Diseases; NIDDK, National Institute of Diabetes and Digestive and Kidney Diseases. *$$10,000 per year from company to individual. #Grant or contract is to university or other employer. care.diabetesjournals.org Professional Practice Committee S89

Speakers’ bureau/ Ownership Member honoraria interest Consultant/advisory board Other R.W.G. None None None None T.W.D. None None None None J.E.F. None None None None C.H. Scherer Clinical None Emory University, Emory Diabetes Receives royalties from the ADA, Communications Course at Grady, Team Novo Nordisk Academy of Nutrition and Dietetics (Chair, Legislative and Public Policy Committee) W.H.H. None None AstraZeneca, Novo Nordisk (self and National Committee for Quality spouse), Merck Sharp & Dohme,* GI Assurance (Chair, Diabetes Panel), Dynamics, Boehringer Ingelheim Centers for Medicare & Medicaid Services (member, MEDCAC), Diabetic Medicine (Editor for the Americas) W.C.H. None None Novo Nordisk None E.K. None None None None L.L. None None Johnson & Johnson, Eli Lilly, Sanofi, None Bristol-Myers Squibb, Menarini, Novo Nordisk, AstraZeneca, LifeScan/ Animas, Boehringer Ingelheim, Dexcom R.P.-B. None None Acorda Therapeutics, AstraZeneca, None T1D Exchange N.R. None None None None D.S. None None Daiichi Sankyo, Andromeda Biotech ADA Board of Directors, ADA officer J.A.S. None None TPG National Payor Roundtable, National Committee for Quality Amgen, Celgene, Gilead, Salix Assurance (physician surveyor and Pharmaceuticals, Janssen member of Reconsideration Pharmaceuticals, Bayer, Medtronic Committee), New York State Department of Health Medicaid Redesign Team’s Evidence-Based Benefit Review Workgroup, Board member (Chair-Elect) for St. Ann’s Community, Rochester, NY, a non- profit senior living/long-term care organization T.H.T. None None None None D.J.W. None None None Diabetes Care (Editorial Board) J.L.C. None None None None E.G.B. None None None None S90 Diabetes Care Volume 38, Supplement 1, January 2015

Index

A1C. see also glycemic targets cardiovascular disease changes, initiatives, S6 CGM, S34 A1C relationship to, S36 demographic changes, S5 children and adolescents, S35, S71 autonomic neuropathy, S25, S62–S63 improvement strategies, S5 glycemic target determination, S37 children and adolescents, S72 patient-centeredness, S5 goals, S35 dietary fat management, S23–S24 regime reevaluation, S6–S7 limitations, S34–S35 patient-centeredness, S5 resources, S6 macrovascular complications, S36 pharmacological therapy, S51–S55, S59 clonidine, S78 mean glucose levels, S35 postprandial plasma glucose testing, S37 clopidogrel, S54, S55 microvascular complications, S35–S36 revisions summary, S4 cognitive impairment, S19, S38, S70 race/ethnicity differences, S9, S35 risk calculator, S52 colesevelam, S42, S44 recommendations, S34, S35, S37 risk factors, S10, S12, S25, S32 comorbidities, S17–S19, S26 SMBG, S33–S34 risk management, S49–S55 congestive heart failure, S51, S55 testing, S8–S10, S12, S34–S35 screening, S31, S55 consensus reports, S1 acarbose, S44 testing frequency, S9 continuous glucose monitoring (CGM), S4, ACCORD trial, S19, S36, S38, S50, S53 Care of Young Children With Diabetes in the S33, S34 A1C Derived Average Glucose (ADAG) trial, Child Care Setting,S86 continuous subcutaneous insulin infusion S35, S37 celiac disease, S71 (CSII), S83 ACE inhibitors, S49–S51, S55, S58–S60, Charcot foot, S64 contraception, S79 S72, S78 children and adolescents coronary heart disease, S55 acute coronary syndrome, S54, S55 A1C goals, S35, S71 cystic fibrosis–related diabetes, S15 adolescents. see children and autoimmune conditions, S71 adolescents cardiovascular disease, S72 dapagliflozin, S45 ADVANCE-BP trial, S50, S51 celiac disease, S71 Da Qing study, S31 ADVANCE trial, S36, S38 cognitive impairment, S70 DAWN2 study, S26 advocacy, S5, S86–S87 DSME/DSMS, S73 day care, S73, S86–S87 African Americans, S9, S11, S12, S24, S35 dyslipidemia, S72 degludec, S45 age. see older adults family stresses, S74 depression, S18, S26, S67, S74 AIM-HIGH trial, S53 glycemic control, S70–S71 detemir, S45 albiglutide, S45 hypertension, S71–S72 Diabetes and Driving, S86 albuminuria, S25, S58–S60, S73 hypoglycemia, S70 Diabetes and Employment, S86 alcohol, S23, S51 nephropathy, S72–S73 Diabetes Care in the School and Day Care alogliptin, S44 neuropathy, S73 Setting, S86–S87 amlodipine, S51 pediatric to adult care transition, Diabetes Control and Complications Trial amputations, S63–S64 S73–S74 (DCCT), S35, S36, S38, S41, S70 amylin mimetics, S45 plasma blood glucose goals, S71 Diabetes Management in Correctional anemia, S9 psychosocial issues, S74 Institutions, S87 angiotensin receptor blockers (ARBs), resources, S86 Diabetes Prevention Program (DPP), S49–S51, S55, S58–S60, S72, S78 retinopathy, S73 S31, S32 ankle-brachial index (ABI), S63, S64 revisions summary, S4 Diabetes Prevention Program Outcomes antihypertensive medications, S51, school, child care, S73 Study (DPPOS), S31, S32 S59, S78 smoking, S72 diabetes-related distress, S26 antiplatelet agents, S54–S55, S61 statins, S72 diabetes self-management education Antithrombotic Trialists’ (ATT) Collaboration, S54 thyroid disease, S71 (DSME) Asian Americans, S9–S12 type 1 diabetes, S10–S11, S70–S74 benefits, S6, S20–S21 aspart, S43, S45 type 2 diabetes, S12–S13, S74 carbohydrate management, S21–S23 aspirin resistance, S55 chlorthalidone, S51 children and adolescents, S73 aspirin therapy, S54–S55, S61 cholesterol. see also dyslipidemia dietary fat management, S23–S24 assisted living. see hospital care children and adolescents, S72 eating patterns, S21–S23 autoimmune disease, S10–S11 control, S51 herbal supplements, S23 Automation to Simulate Pancreatic Insulin monitoring, S53 hospital care, S84 Response (ASPIRE) trial, S34 screening, S10, S52 medical nutrition therapy, S21–S23, S52, autonomic neuropathy, S25, S62–S63 treatment, S52, S55 S72, S83 Chronic Care Model (CCM), S5, S6 micronutrients, S23 bariatric surgery, S46–S47 chronic kidney disease, S23, S25, S58–S60 national standards, S21 benazepril, S51 classification, diagnosis overview, S17, S20–S21 biguanides, S31, S32, S42–S44 overview, S8 prediabetes, S32 bile acid sequestrants, S42, S44, S53 prediabetes, S9–S10, S12–S13 protein management, S22, S23, S59 b-blockers, S51, S55 revisions summary, S4 recommendations, S20, S31 blood pressure control. see hypertension testing, S8–S10 reimbursement, S21 body mass index (BMI), S12 testing frequency, S9 sodium, S23, S24, S51 bromocriptine, S42, S45 claudication, S63 weight loss, S21, S55

INDEX clinical management diabetes self-management support (DSMS). calcium channel blockers, S51, S59 advocacy, S5, S86–S87 see diabetes self-management education canagliflozin, S45 behavior change support, S6 (DSME) cancer, S18 behavior optimization, S6 Diabetic Retinopathy Study (DRS), S61 carbohydrates, S21–S23 care delivery systems, S6 diastolic blood pressure goals, S4 care.diabetesjournals.org Index S91

diet, nutrition, S21–S23 postpartum care, S79 diastolic blood pressure, S50–S51 diltiazem, S78 recommendations, S13 goals, S49, S50 dipeptidyl peptidase 4 (DPP-4) inhibitors, screening, S10 lifestyle modification, S49, S51 S42–S44, S46, S68 two-step strategy, S13–S14 older adults, S67 disordered eating, S74 glargine, S45 overview, S49–S50 diuretics, S49–S51, S58, S59, S78 gliclazide, S44 pharmacological therapy, S49–S51 dopamine-2 agonists, S45 glimepiride, S44 recommendations, S49 driving, S86 glipizide, S44 screening, S10, S49, S50 dulaglutide, S45 glucagon, S38 sodium guidelines, S24, S51 dyslipidemia. see also cholesterol; glucagon-like peptide 1 (GLP-1) agonists, S42, systolic blood pressure, S50, S59 triglycerides S43, S45, S46, S68, S82 treatment, S49, S50 children and adolescents, S72 a-glucosidase inhibitors, S42, S44 Hypertension Optimal Treatment (HOT) trial, S50 control, S51 glulisine, S43, S45 hypertriglyceridemia, S53 lifestyle modification, S52, S55 glyburide/glibenclamide, S44 hypoglycemia monitoring recommendations, S4, S53 glycemic targets. see also A1C A1C goals, S35, S37 recommendations, S51–S52 A1C/microvascular complications CGM, S34 screening, S51 relationships, S35–S36 children and adolescents, S70 treatment, S52–S55 determination, S37 exercise, S25 glycemic control assessment, S33–S35 hospital care, S80–S82 Early Treatment Diabetic Retinopathy Study hospital care, S80–S82 nocturnal, S34 (ETDRS), S61 intercurrent illness, S39 older adults, S68 eating abnormalities, S74 mean glucose levels, S35 overview, S38 eating patterns, S21–S23 mortality findings, S36 pregnancy, S78 e-cigarettes, S4, S25 older adults, S68 prevention, S38, S82 empagliflozin, S45 pregnancy, S77, S78 recommendations, S38 employment, S86 recommendations, S33, S36–S37 treatment, S38 end-stage renal disease (ESRD), S59 revisions summary, S4 hypoglycemia unawareness Epidemiology of Diabetes Interventions and glycemic treatment approaches CGM, S33, S34 Complications (EDIC) study, S35–S36, S38 bariatric surgery, S46–S47 children and adolescents, S70 erectile dysfunction, S63 pharmacological therapy, S41–S46 effects, characterization, S38 exenatide/exenatide ER, S45, S82 revisions summary, S4 recommendations, S38 exercise gram-positive cocci, S64 albuminuria, S25 immune-mediated diabetes, S10–S11 autonomic neuropathy, S25, S62–S63 hearing impairment, S19 immunization recommendations, S4, benefits, S24 hemoglobinopathies, S9 S26–S27 children, S24 hepatitis B vaccination, S26 impaired fasting glucose (IFG), S10, S31 frequency, type, S24 herbal supplements, S23 impaired glucose tolerance (IGT), S10, S31 glycemic control, S24 hospital care incretin-based therapies, S42 hyperglycemia, S25 bedside blood glucose monitoring, S83 indapamide, S50, S51 hypoglycemia, S25 critically ill patients, S80, S81 infections, S64 kidney disease, S23, S25, S58–S60, discharge planning, S80, S83 influenza vaccine, S26–S27 S72–S73 DSME, S84 insulin peripheral neuropathy, S25, S62–S63 glucose abnormalities definitions, S81 basal–bolus, S43, S45, S46, S70, prediabetes, S24 glycemic targets, S80–S82 S71, S82 pre-exercise evaluation, S24–S25 hyperglycemia, S80–S81 combination therapy, S42 recommendations, S24 hypoglycemia, S80–S82 glycemic targets, S38 retinopathy, S25, S60–S62, S73 insulin therapy, S80–S82 hospital care, S80–S82 ezetimibe, S53 management team, S82 hypoglycemia treatment, S38 medical nutrition therapy, S83 intensive insulin regimens, S34 fasting plasma glucose testing, S9 medication reconciliation, S83 MDI, S41 fatty liver disease, S18 non critically ill patients, S80–S82 older adults, S68 fenofibrate, S53 recommendations, S80 pregnancy, S78 fibrates, S53 self-management, S82–S83 recommendations, S33 Finnish Diabetes Prevention Study (DPS), S31 sliding scale insulin (SSI), S80, S82 sliding scale insulin (SSI), S80, S82 foot care, S4, S63–S64 structured discharge communication, S83 type 1 diabetes, S41 foot infections, S64 type 1 diabetes, S82 type 2 diabetes, S42–S46 foundations of care revisions summary, S4 hydrochlorothiazide, S51 insulin dependent diabetes, S10–S11 fractures, S18–S19 hyperglycemia insulin pump therapy, S33, S41, S43, S83 FRAX score, S18 cognitive impairment, S19 insulin resistance, S10, S78 fundus photographs, S61 exercise, S25 insulin secretagogues, S38, S68 glycemic target determination, S37 International Association of the Diabetes gastrointestinal neuropathies, S62 hospital care, S80–S81 and Pregnancy Study Groups gastroparesis, S63 older adults, S67, S68 (IADPSG), S13 genitourinary tract disturbances, S62–S63 plasma glucose testing, S9 gestational diabetes mellitus (GDM). see also postprandial, S37 jail, S87 pregnancy risk factors, S11 juvenile-onset diabetes, S10–S11 classification, S8 Hyperglycemia and Adverse Pregnancy diagnosis, S13–S14 Outcome (HAPO) study, S13 kidney disease, S23, S25, S58–S60, S72–S73 glycemic targets, S77, S78 hyperglycemic crisis, S9 Kumamoto Study, S36 management, S78 hypertension one-step strategy, S13, S14 children and adolescents, S71–S72 labetalol, S78 overview, S13, S77 diagnosis, S49, S50 lactation, S79 S92 Index Diabetes Care Volume 38, Supplement 1, January 2015

laser photocoagulation therapy, S61–S62 hypoglycemia, S68 repaglinide, S44 lifestyle modifications pharmacological therapy, S68–S69 retinal photography, S61 dyslipidemia, S52, S55 recommendations, S67 retinopathy, S25, S60–S62, S73 hypertension, S49, S51 sodium guidelines, S24 revisions summary, S4 type 2 diabetes, S31, S42 statin therapy, S52, S53 Reye syndrome, S54 linagliptin, S44 treatment goals, S67–S68 risk management, S4, S6, S9, S11 liraglutide, S45 type 2 diabetes screening, S12 rosiglitazone, S44 lispro, S43, S45 orthostatic hypotension, S63 lixisenatide, S45 overweight, obesity, S9, S10, S21, S55, SAVOR-TIMI 53 trial, S68–S69 Look AHEAD trial, S18, S55 S78–S79 saxagliptin, S44, S68–S69 loss of protective sensation (LOPS), school, S73, S86–S87 S63, S64 Patient-Centered Medical Home, S6 scientific evidence grading, perindopril, S50, S51 S1–S2 macrovascular complications, S35, S36, S51 periodontal disease, S19 scientific statements, S1 macular edema, S61 peripheral arterial disease, S63, S64 self-monitoring of blood glucose management planning, S17–S19, S26 peripheral neuropathy, S25, S62–S63 (SMBG) maturity-onset diabetes of the young pharmacological therapy basal insulin/oral agents, S34 (MODY), S14 cardiovascular disease, S51–S55, S59 intensive insulin regimens, S34 medical evaluation, S17, S18, S24–S25 hypertension, S49–S51 optimization, S33–S34 medical nutrition therapy, S21–S23, S52, S72, microvascular complications, S51 overview, S33 S83 older adults, S68–S69 recommendations, S33 Medicare/Medicaid, S21 prediabetes, S32 sickle cell trait, S9 medications, S12. see also pharmacological type 2 diabetes, S31–S32, S42–S46 sitagliptin, S44, S82 therapy; specific medications, conditions pioglitazone, S44, S46 skilled nursing facilities. see hospital care meglitinides, S42, S44 pneumococcal polysaccharide vaccine 23 sliding scale insulin (SSI), S80, S82 mental health specialist referrals, S26 (PPSV23), S26, S27 smoking, S4, S25, S63, S72 metformin, S31, S32, S42–S44, S55, S59, polycystic ovary syndrome, S10 sodium, S23, S24, S51 S68 position statements, S1 sodium–glucose cotransporter 2 (SGLT2) methyldopa, S78 pramlintide, S41–S42, S45 inhibitors, S42, S43, S45, S46 microvascular complications prasugrel, S55 Standards of Care recommendations, S1 A1C goals, S35 prazosin, S78 Staphylococci, S64 A1C relationship to, S35–S36 prediabetes statins, S4, S52–S55, S72 erectile dysfunction, S63 classification, diagnosis, S9–S10, stroke, S36, S54, S59 gastroparesis, S63 S12–S13 sulfonylureas glycemic control, S63 DSME/DSMS, S32 A1C/CVD relationships, S36 kidney disease, S23, S25, S58–S60, exercise, S24 combination therapy, S42, S43 S72–S73 pharmacological therapy, S32 older adults, S68 neuropathy, S25, S62–S63, S73 pre-exercise medical evaluation, S24–S25 type 2 diabetes, S43, S44, S46 orthostatic hypotension, S63 pregnancy patient education, S64 A1C testing, S9, S78 testosterone levels, S19 pharmacological therapy, S51 antihypertensive medications, S51, thiazolidinediones, S43, S44, S46 retinopathy, S25, S60–S62, S73 S78 thyroid disease, S71 revisions summary, S4 contraception, S79 ticagrelor, S55 risk factors, S11 GDM (see gestational diabetes mellitus triglycerides, S10, S52, S53. see also miglitol, S44 [GDM]) dyslipidemia monogenic diabetes syndromes, S14–S15 glycemic targets, S77, S78 2-hour plasma glucose testing, S9 myocardial infarction (MI), S36, S50, S54, S55, hypertension, S50 type 1 diabetes S59 hypoglycemia, S78 A1C/mean glucose relationship, insulin, S78 S35 nateglinide, S44 insulin resistance, S78 autoimmune conditions, S71 National Diabetes Education Program (NDEP), lactation, S79 carbohydrate management, S21 S6, S74 medications contraindicated, S77, S78 CGM, S33, S34 National Diabetes Prevention Program, S31 metabolic physiology, S78 children and adolescents, S10–S11, National Institutes of Health (NIH), overweight, obesity, S78–S79 S70–S74 S13–S14 postpartum care, S79 classification, S8 neonatal diabetes, S14 preconception counseling, S77 diagnosis, S10–S11 nephropathy, S23, S25, S58–S60, S72–S73 recommendations, S77 glycemic control, neuropathy, S25, S62–S63, S73 retinopathy, S25, S60–S62, S73 S70–S71 niacin, S53 revisions summary, S4 hospital care, S82 NICE-SUGAR trial, S81 screening, S10 hypoglycemia, S38 nonproliferative diabetic retinopathy statins, S72 insulin, S41 (NPDR), S61 prison, S87 pharmacological therapy, S41–S42 nursing home. see hospital care Professional Practice Committee, S3, pregnancy, S78–S79 S88–S89 progression estimates, S11 obstructive sleep apnea, S18 proliferative diabetic retinopathy, S61 retinopathy, S25, S60–S62, S73 older adults protein, S22, S23, S59 SMBG, S34 A1C levels, S9 psychosocial screening, care, S25–S26 statin therapy, S53 depression screening, S67 P2Y12 receptor antagonist, S55 testing, S11 diabetes complications screening, S67 type 2 diabetes glycemic targets, S68 race/ethnicity, S9, S12, S35. see also African A1C goals, S35 hyperglycemia, S67, S68 Americans; Asian Americans A1C/macrovascular complications hypertension, S67 RAS inhibitors, S51, S59 relationships, S36 care.diabetesjournals.org Index S93

children and adolescents, S12–S13, overview, S11 UK Prospective Diabetes Study (UKPDS), S74 pharmacological therapy, S31–S32, S36, S59 classification, S8 S42–S46 ulcers, S63–S64 combination therapy, S42, S43 pregnancy, S78–S79 community screening, S12 prevention, delay of, vascular endothelial growth factor (VEGF), comorbidities, S74 S31–S32 S61, S62 diagnosis, S11–S13 recommendations, S11, S31 vascular pathology measures, S37 diagnostic tests, S12 retinopathy, S25, S60–S62, S73 Veterans Affairs Diabetes Trial (VADT), S36 hypoglycemia, S38 risk factors, S11–S12 vildagliptin, S44 ketoacidosis, S11 screening, S12, S31 lifestyle modifications, S31, S42 testing interval, S12 weight loss, S21, S55