Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus

Total Page:16

File Type:pdf, Size:1020Kb

Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus Reviews/Commentaries/ADA Statements POSITION STATEMENT Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus 1 6 DAVID B. SACKS M. SUE KIRKMAN mellitus, formerly known as insulin- 2 7 MARK ARNOLD AKE LERNMARK 3 8 dependent diabetes mellitus (IDDM) or GEORGE L. BAKRIS BOYD E. METZGER 4 9 juvenile-onset diabetes mellitus, is usu- DAVID E. BRUNS DAVID M. NATHAN 5 ally caused by autoimmune destruction ANDREA RITA HORVATH of the pancreatic islet b-cells, rendering the pancreas unable to synthesize and se- crete insulin (2). Type 2 diabetes mellitus, BACKGROUND—Multiple laboratory tests are used to diagnose and manage patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these tests varies formerly known as non-IDDM or adult- substantially. onset diabetes, is caused by a combina- tion of insulin resistance and inadequate APPROACH—An expert committee compiled evidence-based recommendations for the use of insulin secretion (3,4). Gestational diabe- laboratory testing for patients with diabetes. A new system was developed to grade the overall quality tes mellitus (GDM), which resembles type of the evidence and the strength of the recommendations. Draft guidelines were posted on the fi 2diabetesmorethantype1,develops Internet and presented at the 2007 Arnold O. Beckman Conference. The document was modi ed in during approximately 7% (range, 5%– response to oral and written comments, and a revised draft was posted in 2010 and again modified in response to written comments. The National Academy of Clinical Biochemistry and the Evidence- 15%) of pregnancies, usually remits after Based Laboratory Medicine Committee of the American Association for Clinical Chemistry jointly delivery, and constitutes a major risk fac- reviewed the guidelines, which were accepted after revisions by the Professional Practice Committee tor for the development of type 2 diabetes and subsequently approved by the Executive Committee of the American Diabetes Association. later in life. Other types of diabetes are rare. Type 2 is the most common form, — CONTENT In addition to long-standing criteria based on measurement of plasma glucose, accounting for 85%–95% of diabetes in diabetes can be diagnosed by demonstrating increased blood hemoglobin A1c (HbA1c) concen- developed countries. Some patients can- trations. Monitoring of glycemic control is performed by self-monitoring of plasma or blood not be clearly classified as type 1 or type 2 glucose with meters and by laboratory analysis of HbA1c. The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of autoantibodies, urine albumin, insulin, diabetes (5). proinsulin, C-peptide, and other analytes are addressed. Diabetes is a common disease. The current worldwide prevalence is esti- SUMMARY—The guidelines provide specific recommendations that are based on published mated to be approximately 250 x 106, data or derived from expert consensus. Several analytes have minimal clinical value at present, and it is expected to reach 380 x 106 by and their measurement is not recommended. 2025 (6). The prevalence of diabetes Diabetes Care 34:e61–e99, 2011 [based on fasting plasma glucose (FPG) results] in U.S. adults in 1999–2002 was 9.3%, of which 30% of the cases were un- fi iabetes mellitus is a group of met- hyperglycemia. The disease is classi ed diagnosed (7). The most recent data, abolic disorders of carbohydrate into several categories. The revised clas- – D fi which were derived from the 2005 metabolism in which glucose is si cation, published in 1997 (1), is pre- 2006 National Health and Nutrition Ex- underutilized and overproduced, causing sented in Table 1. Type 1 diabetes amination Survey (NHANES) with both ccccccccccccccccccccccccccccccccccccccccccccccccc FPG and 2-h oral glucose tolerance test (OGTT) results, show a prevalence of di- From the 1Department of Laboratory Medicine, National Institutes of Health, Bethesda, Maryland; the 2Department 3 abetes in U.S. persons $20 years old of of Chemistry, University of Iowa, Iowa City, Iowa; the Department of Medicine, Hypertensive Disease Unit, 6 Section of Endocrinology, Diabetes and Metabolism, University of Chicago, Chicago, Illinois; the 4Department 12.9% (approximately 40 x 10 )(8).Of of Pathology, University of Virginia Medical School, Charlottesville, Virginia; the 5Screening and Test Evaluation these individuals, 40% (approximately 16 Program, School of Public Health, University of Sydney, SEALS Department of Clinical Chemistry, Prince million) are undiagnosed. The prevalence of Wales Hospital, Sydney, Australia; the 6American Diabetes Association, Alexandria, Virginia; the 7Department of Clinical Sciences, Lund University/CRC, Skane University Hospital Malmö, Malmö, Sweden; the 8Division of of diabetes has also increased in other Endocrinology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois; and 9Massachusetts parts of the world. For example, recent General Hospital and Harvard Medical School, Diabetes Center, Boston, Massachusetts. estimates suggest 110 x 106 diabetic indi- Corresponding author: David B. Sacks, [email protected]. viduals in Asia in 2007 (9), but the true Received 30 December 2010 and accepted 28 February 2011. DOI: 10.2337/dc11-9998 number is likely to be substantially This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10. greater, because China alone was thought 6 2337/dc11-9998/-/DC1. to have 92.4 x 10 adults with diabetes in This article is simultaneously published in Clinical Chemistry and Diabetes Care, under joint copyright, and by 2008 (10). the National Academy of Clinical Biochemistry. The worldwide costs of diabetes were © 2011 by the American Diabetes Association and the American Association for Clinical Chemistry. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the approximately $232 billion in 2007 and work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. are likely to be $302 billion by 2025 (6). See accompanying article, p. 1419. In 2007, the costs of diabetes in the U.S. care.diabetesjournals.org DIABETES CARE, VOLUME 34, JUNE 2011 e61 Position Statement Table 1—Classification of diabetes quality of the evidence (Table 2) and the several headings and subheadings (in mellitusa strength of recommendations (Table 3). parentheses), which are as follows: use This guideline focuses primarily on (diagnosis, screening, monitoring, and I. Type 1 diabetes the laboratory aspects of testing in di- prognosis); rationale (diagnosis and A. Immune-mediated abetes. It does not address any issues screening); analytical considerations (pre- B. Idiopathic related to the clinical management of analytical, including reference intervals; II. Type 2 diabetes diabetes, which are already covered in and analytical, such as methods); inter- III. Other specifictypes the American Diabetes Association (ADA) pretation (including frequency of mea- A. Genetic defects of b-cell function guidelines. The NACB guideline intends surement and turnaround time); and, B. Genetic defects in insulin action to supplement the ADA guidelines in where applicable, emerging considera- C. Diseases of the exocrine pancreas order to avoid duplication or repetition tions, which alert the reader to ongoing D. Endocrinopathies of information. Therefore, it focuses on studies and potential future aspects rele- E. Drug- or chemical-induced practical aspects of care to assist with vant to that analyte. F. Infections decisions related to the use or interpreta- G. Uncommon forms of immune-mediated tion of laboratory tests while screening, diabetes GLUCOSE diagnosing, or monitoring patients with H. Other genetic syndromes sometimes diabetes. Additional details concerning 1. Use associated with diabetes the scope, purpose, key topics, and tar- IV. GDM a gets of this guideline are described in the From the ADA (378). accompanying Supplementary Data. RECOMMENDATION: WHEN GLUCOSE IS To facilitate comprehension and as- USED TO ESTABLISH THE DIAGNOSIS were estimated to be $174 billion (11). sist the reader, we divide each analyte into OF DIABETES, IT SHOULD BE MEASURED IN The mean annual per capita healthcare VENOUS PLASMA costs for an individual with diabetes are A(high). approximately 2.3-fold higher than those Table 2—Rating scale for the quality of for individuals who do not have diabetes evidence RECOMMENDATION: WHEN GLUCOSE IS (11). Similarly, diabetes in the U.K. ac- USED FOR SCREENING OF HIGH-RISK counts for roughly 10% of the National High: Further research is very unlikely to INDIVIDUALS, IT SHOULD BE MEASURED Health Service budget (equivalent in change our confidence in the estimate of effect. The body of evidence comes from IN VENOUS PLASMA 2008 to £9 billion/year). The high costs B (moderate). of diabetes are attributable to care for both high-level individual studies that are acute conditions (such as hypoglycemia sufficiently powered and provide precise, consistent, and directly applicable results in and ketoacidosis) and debilitating compli- RECOMMENDATION: PLASMA GLUCOSE a relevant population. cations (12). The latter include both micro- SHOULD BE MEASURED IN AN — Moderate: Further research is likely to have an vascular complications predominantly ACCREDITED LABORATORY WHEN USED — important impact on our confidence in the retinopathy, nephropathy, and neuropathy FOR DIAGNOSIS OF OR SCREENING
Recommended publications
  • Liver Glucose Metabolism in Humans
    Biosci. Rep. (2016) / 36 / art:e00416 / doi 10.1042/BSR20160385 Liver glucose metabolism in humans Mar´ıa M. Adeva-Andany*1, Noemi Perez-Felpete*,´ Carlos Fernandez-Fern´ andez*,´ Cristobal´ Donapetry-Garc´ıa* and Cristina Pazos-Garc´ıa* *Nephrology Division, Hospital General Juan Cardona, c/ Pardo Bazan´ s/n, 15406 Ferrol, Spain Synopsis Information about normal hepatic glucose metabolism may help to understand pathogenic mechanisms underlying obesity and diabetes mellitus. In addition, liver glucose metabolism is involved in glycosylation reactions and con- nected with fatty acid metabolism. The liver receives dietary carbohydrates directly from the intestine via the portal vein. Glucokinase phosphorylates glucose to glucose 6-phosphate inside the hepatocyte, ensuring that an adequate flow of glucose enters the cell to be metabolized. Glucose 6-phosphate may proceed to several metabolic path- ways. During the post-prandial period, most glucose 6-phosphate is used to synthesize glycogen via the formation of glucose 1-phosphate and UDP–glucose. Minor amounts of UDP–glucose are used to form UDP–glucuronate and UDP– galactose, which are donors of monosaccharide units used in glycosylation. A second pathway of glucose 6-phosphate metabolism is the formation of fructose 6-phosphate, which may either start the hexosamine pathway to produce UDP-N-acetylglucosamine or follow the glycolytic pathway to generate pyruvate and then acetyl-CoA. Acetyl-CoA may enter the tricarboxylic acid (TCA) cycle to be oxidized or may be exported to the cytosol to synthesize fatty acids, when excess glucose is present within the hepatocyte. Finally, glucose 6-phosphate may produce NADPH and ribose 5-phosphate through the pentose phosphate pathway.
    [Show full text]
  • MODY 2 Presenting As Neonatal Hyperglycaemia: a Need to Reshape the Definition of ªneonatal Diabetesº?
    Letters 1331 MODY 2 presenting as neonatal sidered a stringent criterium for selecting patients. We ob- served that the moderate low birth weight of patients No. 1 hyperglycaemia: a need to reshape and No. 3 was probablyinfluenced bya mutation of paternal the definition of ªneonatal diabetesº? origin and subsequent low fetal insulin secretion. Mutations in the GK represent the more frequent cause of Dear Sir, MODY in some series [3] and it has been calculated that up Neonatal diabetes mellitus is defined as a rare condition to 6% of familial Type II non-insulin-dependent) diabetes 1:400.000 live births) of unknown origin, characterised byhy- mellitus could bear a MODY 2 allele [3]. We and others have perglycaemia occurring in the first month of life that requires ex- frequentlyobserved that the mutation-carryingparent of chil- ogenous insulin therapy[1, 2]. The derangement of glucose me- dren with MODY 2 is unaware of his or her hyperglycaemia. tabolism in newborns affected bythis condition could be perma- As a consequence, some previouslydescribed cases of perma- nent permanent neonatal diabetes mellitus, PNDM) or could nent neonatal diabetes of unknown origin might be linked to orcouldnot)recurafterremissionofhyperglycaemiatransient GK mutations in both alleles, even in the absence of consan- neonataldiabetesmellitus,TNDM)[1,2]. Inapedigreewith ma- guineityloop i.e. compound heterozygous). Neonatal, insu- turityonset diabetes of the youngMODY) harbouring the glu- lin-requiring, permanent diabetes mellitus is the main feature cokinase GK, MODY 2) mutation Q38P, we followed a new of GK knock-out mice models [5]. pregnancyofthenon-mutantmotheroftheindexcase.Wefound We believe that the definition of neonatal diabetes currently that 15 days after delivery her child presented hyperglycaemia inuse[1,2]needstoberevisedinorderto:firstly,permanently in- 11.7 mmol) with dehydration and mild ketosis Table 1, patient corporate the concept that TNDM in some cases linked to pa- No.
    [Show full text]
  • Jeffrey Kleinberger Ph.D. Candidate Molecular Medicine Program, Genome Biology Track Graduate Program in Life Sciences, University of Maryland, Baltimore
    Discovery and Analysis of Patients with Monogenic Diabetes in Multiple Cohorts to Guide Future Diagnosis Item Type dissertation Authors Kleinberger, Jeffrey Publication Date 2017 Abstract Monogenic diabetes is hyperglycemia caused by a variant in a single gene, and it accounts for approximately 1-2% of all diabetes cases. A genetic diagnosis of monogenic diabetes is important because the most common gene etiologies can be effectively ... Keywords MODY; monogenic diabetes; screening; Clinical Trial; Diabetes Mellitus, Type 2; Zebrafish Download date 05/10/2021 09:00:42 Link to Item http://hdl.handle.net/10713/7072 Jeffrey Kleinberger Ph.D. Candidate Molecular Medicine Program, Genome Biology Track Graduate Program in Life Sciences, University of Maryland, Baltimore Contact Information Medical School Teaching Facility 357 685 West Baltimore St. Baltimore, MD 21201 [email protected] Education Juniata College Huntingdon, PA August 2004 – May 2008 Cum Laude distinction (GPA: 3.701) Biochemistry major Coursework included: Organic Chemistry, Bioinorganic Chemistry, Analytical Chemistry, Physical Chemistry, Chemistry Research, Biology, Cell Biology, Genetics, Biostatistics, Molecular Techniques, Physiology, Microbiology, Biochemistry and Molecular Biology (I-III), Calculus (I&II), Physics (I&II), Scientific Glassblowing, College Writing Seminar, Art of Public Speaking, Intro to Psychology, Learning & Conditioning, Mod. Knowledge & The Self, United States to 1877, The American Revolution, Survey of Western Art, Modern Architecture,
    [Show full text]
  • 一般演題(口演)/Oral Sessions
    一般演題(口演)!Oral Sessions ご ! 案 第 60 回大会賞候補セッション(口演) Oral Presentation Award Session 内 日 時:10 月 16 日(金)11:25~12:20 第 2 会場(南館 4 階 錦) 座 長:稲澤 譲治(東京医科歯科大学難治疾患研究所ゲノム応用医学研究部門(分子細胞遺伝)) 田中 敏博(東京医科歯科大学疾患バイオリソースセンター) Date:Oct. 16 (Fri.) 11:25~12:20 Room 2(Nishiki, South Tower 4F) Chairs:Johji Inazawa(Tokyo Medical and Dental University) Toshihiro Tanaka(Tokyo Medical and Dental University) プ ロ BO-1 ゲノムワイド関連解析(GWAS)データを活用した in silico 解析による新規抗パーキンソン病薬 グ の探索 ラ In silico drug discovery for Parkinson’s disease by using genome!wide association study ム (GWAS)data ○上中 健 1(Takeshi Uenaka)、佐竹 渉 1(Wataru Satake)、謝 珮琴 1(Pei"Chieng Cha)、 岡田 随象 2(Yukinori Okada)、戸田 達史 1(Tatsushi Toda) 1 神戸大学大学院医学研究科神経内科!分子脳科学 指 (Division of Neurology, Kobe University Graduate School of Medicine, Kobe, Japan) 定 2 東京医科歯科大学大学院医歯学総合研究科疾患多様性遺伝学分野 演 (Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, 題 Tokyo Medical and Dental University, Tokyo, Japan) 抄 録 BO-2 MIRAGE 症候群:機能亢進型 SAMD9 変異を原因とする新規症候群の発見 MIRAGE syndrome:New genetic syndrome caused by activating SAMD9 mutations ○鳴海 覚志 1(Satoshi Narumi)、天野 直子 1(Naoko Amano)、石井 智弘 1(Tomohiro Ishii)、 一 勝又 規行 2(Noriyuki Katsumata)、福澤 龍二 3(Ryuji Fukuzawa)、芝田 晋介 4(Shinsuke Shibata)、 般 4 5 6 演 岡野 栄之 (Hideyuki Okano)、清水 厚志 (Atsushi Shimizu)、三宅 紀子 (Noriko Miyake)、 題 松本 直通 6(Naomichi Matsumoto)、長谷川 奉延 1(Tomonobu Hasegawa) ( 1 慶應義塾大学医学部小児科 口 (Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan) 演 ) 2 国立成育医療研究センター研究所分子内分泌研究部 抄 (Department of Molecular Endocrinology, National Research
    [Show full text]
  • Maternal Or Paternal Diabetes and Its Crucial Role in Offspring Birth
    H OH metabolites OH Editorial Maternal or Paternal Diabetes and Its Crucial Role in Offspring Birth Weight and MODY Diagnosis Valeria Calcaterra 1,2,* , Angela Zanfardino 3 , Gian Vincenzo Zuccotti 2,4 and Dario Iafusco 3 1 Pediatric and Adolescence Unit, Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy 2 Pediatric Unit, “V. Buzzi” Children’s Hospital, 20154 Milano, Italy; [email protected] 3 Department of Pediatrics, Regional Center of Pediatric Diabetology “G. Stoppoloni”, University of Campania “Luigi Vanvitelli”, 80138 Napoli, Italy; [email protected] (A.Z.); [email protected] (D.I.) 4 Department of Biomedical and Clinical Sciences “L. Sacco”, University of Milan, 20157 Milano, Italy * Correspondence: [email protected] Received: 17 September 2020; Accepted: 26 September 2020; Published: 28 September 2020 Abstract: Maturity-onset diabetes of the young (MODY) represents a heterogenous group of monogenic autosomal dominant diseases, which accounts for 1–2% of all diabetes cases. Pregnancy represents a crucial time to diagnose MODY forms due to the 50% risk of inheritance in offspring of affected subjects and the potential implications on adequate fetal weight. Not only a history of maternal diabetes may affect the birth weight of offspring, paternal diabetes should also be taken into consideration for a correct pathogenetic diagnosis. The crucial role of maternal and paternal diabetes inheritance patterns and the impact of this inherited mutation on birthweight and the MODY diagnosis was discussed. Keywords: mother; father; diabetes; birthweight; MODY Maturity-onset diabetes of the young (MODY) represents a heterogenous group of monogenic autosomal dominant diseases, which accounts for 1–2% of all diabetes cases [1].
    [Show full text]
  • Monogenic Diabetes: a New Pathogenic Variant of HNF1A Gene Raquel Vilela Oliveira, Teresa Bernardo, Sandrina Martins, Ana Sequeira
    Case report BMJ Case Rep: first published as 10.1136/bcr-2019-231837 on 20 January 2021. Downloaded from Monogenic diabetes: a new pathogenic variant of HNF1A gene Raquel Vilela Oliveira, Teresa Bernardo, Sandrina Martins, Ana Sequeira Pediatrics, Unidade Local de SUMMARY hepatic nuclear factor 1 alpha (HNF1A), respec- Saúde do Alto Minho EPE, Viana Maturity onset diabetes of the young defines a tively.2–4 6 7 10 These subtypes account for up to 90% do Castelo, Portugal diabetes mellitus subtype, with no insulin resistance of all MODY cases.10 or autoimmune pancreatic β-cells dysfunction, that One of the challenges is to differentiate MODY Correspondence to from other forms of diabetes. The diagnosis of Dr Raquel Vilela Oliveira; occurs by mutation in a single gene. A 13- year- old Raquelvoliveira07@ gmail. com girl hospitalised due to hyperglycemia plus glycosuria MODY should be suspected in patients with family without ketosis, and with normal glycated haemoglobin history of diabetes of any type, diagnosed at a young Accepted 11 November 2019 of 6.8%. She started a sugar- free fast- absorption diet age (<25 years), lack of type 1 DM characteris- and no insulin therapy was required. Fasting glucose tics (the absence of islet autoantibodies, preserved was normal, but 2 hours after lunch she presented β-cell function with low or no insulin requirements hyperglycemia as after 2 hours of an oral glucose and detectable C- peptide over an extended partial tolerance test, with 217 mg/dL. Family history was remission phase), the absence of typical type 2 DM positive for type 2 diabetes mellitus with an autosomal characteristics (severe obesity, acanthosis nigricans dominant pattern.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2016/0281166 A1 BHATTACHARJEE Et Al
    US 20160281 166A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0281166 A1 BHATTACHARJEE et al. (43) Pub. Date: Sep. 29, 2016 (54) METHODS AND SYSTEMIS FOR SCREENING Publication Classification DISEASES IN SUBJECTS (51) Int. Cl. (71) Applicant: PARABASE GENOMICS, INC., CI2O I/68 (2006.01) Boston, MA (US) C40B 30/02 (2006.01) (72) Inventors: Arindam BHATTACHARJEE, G06F 9/22 (2006.01) Andover, MA (US); Tanya (52) U.S. Cl. SOKOLSKY, Cambridge, MA (US); CPC ............. CI2O 1/6883 (2013.01); G06F 19/22 Edwin NAYLOR, Mt. Pleasant, SC (2013.01); C40B 30/02 (2013.01); C12O (US); Richard B. PARAD, Newton, 2600/156 (2013.01); C12O 2600/158 MA (US); Evan MAUCELI, (2013.01) Roslindale, MA (US) (21) Appl. No.: 15/078,579 (57) ABSTRACT (22) Filed: Mar. 23, 2016 Related U.S. Application Data The present disclosure provides systems, devices, and meth (60) Provisional application No. 62/136,836, filed on Mar. ods for a fast-turnaround, minimally invasive, and/or cost 23, 2015, provisional application No. 62/137,745, effective assay for Screening diseases, such as genetic dis filed on Mar. 24, 2015. orders and/or pathogens, in Subjects. Patent Application Publication Sep. 29, 2016 Sheet 1 of 23 US 2016/0281166 A1 SSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSS S{}}\\93? sau36 Patent Application Publication Sep. 29, 2016 Sheet 2 of 23 US 2016/0281166 A1 &**** ? ???zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz??º & %&&zzzzzzzzzzzzzzzzzzzzzzz &Sssssssssssssssssssssssssssssssssssssssssssssssssssssssss & s s sS ------------------------------ Patent Application Publication Sep. 29, 2016 Sheet 3 of 23 US 2016/0281166 A1 23 25 20 FG, 2. Patent Application Publication Sep. 29, 2016 Sheet 4 of 23 US 2016/0281166 A1 : S Patent Application Publication Sep.
    [Show full text]
  • Download an Example File with Diabetes Mellitus (PDF)
    Legal Disclaimer All diagnostic and therapeutic procedures in the field of science and medicine are continuously evolving: Therefore the herein presented medical evidence is state of the technical and scientific art at the time of the editorial deadline for the respective edition of the book. All details provided herein related to a particular therapeutic mode of administration and dosing of drugs are screened employing utmost measures of accuracy and precision. Unless explicitly specified otherwise, all drug administration and dosing regimens presented herein are for healthy adults with normal renal and hepatic function. Liability cannot be assumed for any type of dosing and administration regimen presented herein. Each reader is advised to carefully consult the respective market authorization holders directions for use of the recommended drugs, medical devices and other means of therapy and diagnosis. This applies in particular also to market authorization holders summaries of product characteristics for pharmaceutical products. Despite all care, there may be translation errors. The reader is advised to carefully check information related to the indication for use, contraindications, dosing recommendations, side effects and interactions with other medications! All modes of medication use and administration are at the consumers risk. The author and his team cannot be held responsible for any damage caused by wrong therapy or diagnosis. Please refer to, i.e: www.leitlinien.de or www.guideline.gov The trade name of a trade name registered product does not provide the legal privilege to employ the trade name as a free trade mark even if it is not specifically marked as such. Drugs which are sold as generics are referred to throughout the book by their generic name and not necessarily by a particular brand name Remark: ICD 10 code version 1.3 has been employed for the index.
    [Show full text]
  • Two MODY 2 Families Identified in Brazilian Subjects
    case report Incidental mild hyperglycemia in children: two MODY 2 families identified in Brazilian subjects Hiperglicemia incidental em crianças: duas famílias com MODY 2 identificadas em brasileiros Lílian A. Caetano1,2, Alexander A. L. Jorge1, Alexsandra C. Malaquias1, Ericka B. Trarbach1, Márcia S. Queiroz2, Márcia Nery2, Milena G. Teles1,2 SUMMARY Maturity-onset diabetes of the young (MODY) is characterized by an autosomal dominant mode 1 Unidade de Endocrinologia of inheritance, early onset of hyperglycemia, and defects of insulin secretion. MODY subtypes Genética e Laboratório de described present genetic, metabolic, and clinical differences. MODY 2 is characterized by mild Endocrinologia Molecular e Celular/LIM25, Disciplina de asymptomatic fasting hyperglycemia, and rarely requires pharmacological treatment. Hence, Endocrinologia, Faculdade precise diagnosis of MODY is important for determining management and prognosis. We report de Medicina da Universidade two heterozygous GCK mutations identified during the investigation of short stature. Case 1: a de São Paulo (FMUSP), São Paulo, SP, Brazil prepubertal 14-year-old boy was evaluated for constitutional delay of growth and puberty. During 2 Unidade de Diabetes, follow-up, he showed abnormal fasting glucose (113 mg/dL), increased level of HbA1c (6.6%), and Hospital das Clínicas, FMUSP, negative β-cell antibodies. His father and two siblings also had slightly elevated blood glucose le- São Paulo, SP, Brazil vels. The mother had normal glycemia. A GCK heterozygous missense mutation, p.Arg191Trp, was identified in the proband. Eighteen family members were screened for this mutation, and 11 had the mutation in heterozygous state. Case 2: a 4-year-old boy investigated for short stature revealed no other laboratorial alterations than elevated glycemia (118 mg/dL); β-cell antibodies were nega- tive.
    [Show full text]
  • Genetic, Metabolic and Clinical Characteristics of Maturity Onset Diabetes of the Young
    European Journal of Endocrinology (1998) 138 233±239 ISSN 0804-4643 REVIEW Genetic, metabolic and clinical characteristics of maturity onset diabetes of the young Gilberto Velho and Philippe Froguel1 INSERM U-342, HoÃpital Saint Vincent de Paul, Paris, France and 1CNRS EP10, Institut Pasteur de Lille et CHU, Lille, France (Correspondence should be addressed to G Velho, INSERM U-342, HoÃpital Saint Vincent de Paul, 82 Avenue Denfert Rochereau, 75014 Paris, France) Abstract Maturity onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of non-insulin-dependent diabetes mellitus (NIDDM) characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. To date, three MODY genes have been identi®ed on chromosomes 20q (MODY1/hepatic nuclear factor (HNF)-4a), 7p (MODY2/glucokinase) and 12q (MODY3/HNF-1a). Mutations in MODY2/glucokinase result in mild chronic hyperglycaemia as a result of reduced pancreatic beta-cell responsiveness to glucose, and decreased net accumulation of hepatic glycogen and increased hepatic gluconeogenesis after meals. In contrast, MODY1 and MODY3 are characterised by severe insulin secretory defects, and by major hyperglycaemia associated with microvascular complications. The role of the three known MODY genes in susceptibility to the more common late-onset NIDDM remain uncertain. Genetic studies seem to exclude a role as major susceptibility genes, but leave unresolved whether they may have a minor role in a polygenic context or an important role in particular populations. European Journal of Endocrinology 138 233±239 MODY is a monogenic form of NIDDM MODY3/HNF-1a (11, 12) respectively, can cause this form of diabetes.
    [Show full text]
  • Mat Kadi Tora Tutti O Al Ut Hit Hitta Atuh
    MAT KADI TORA TUTTI USO AL20180235194A1 UT HIT HITTA ATUH ( 19) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2018 /0235194 A1 Fahrenkrug et al. (43 ) Pub . Date : Aug . 23, 2018 ( 54 ) MULTIPLEX GENE EDITING Publication Classification (51 ) Int. Ci. ( 71 ) Applicant: Recombinetics , Inc ., Saint Paul, MN A01K 67/ 027 (2006 . 01 ) (US ) C12N 15 / 90 ( 2006 .01 ) (72 ) Inventors : Scott C . Fahrenkrug, Minneapolis , (52 ) U . S . CI. MN (US ) ; Daniel F . Carlson , CPC .. .. A01K 67 / 0276 (2013 . 01 ) ; C12N 15 / 907 Woodbury , MN (US ) ( 2013 .01 ) ; A01K 67 /0275 ( 2013 .01 ) ; A01K 2267/ 02 (2013 .01 ) ; AOIK 2217 / 15 (2013 .01 ) ; AOIK 2227 / 108 ( 2013 .01 ) ; AOIK 2217 /07 (21 ) Appl. No. : 15 /923 , 951 ( 2013 .01 ) ; A01K 2227/ 101 (2013 .01 ) ; AOIK ( 22 ) Filed : Mar. 16 , 2018 2217 /075 ( 2013 .01 ) (57 ) ABSTRACT Related U . S . Application Data Materials and methods for making multiplex gene edits in (62 ) Division of application No . 14 /698 ,561 , filed on Apr. cells and are presented . Further methods include animals 28 , 2015, now abandoned . and methods of making the same . Methods of making ( 60 ) Provisional application No . 61/ 985, 327, filed on Apr. chimeric animals are presented , as well as chimeric animals . 28 , 2014 . Specification includes a Sequence Listing . Patent Application Publication Aug . 23 , 2018 Sheet 1 of 13 US 2018 / 0235194 A1 GENERATION OF HOMOZYGOUS CATTLE EDITED AT ONE ALLELE USING SINGLE EDITS Edit allele , Raise FO to Mate FO enough times Raise F1s to Mate F1 siblings Clone cell , sexual maturity , to produce enough F1 sexualmaturity , to make Implant, Gestate 2 years generation carrying 2 years homozygous KO , 9 months , birth edited allele to mate 9 months of FO with each other Generation Primary Fibroblasts ? ? ? Time, years FIG .
    [Show full text]
  • Beyond Type 1 and Type 2 Diabetes; Why Correct Diabetes Classification Is Important Gabriel I. Uwaifo, MD Dept of Endocrinology
    Beyond Type 1 and Type 2 Diabetes; Why Correct Diabetes Classification is Important Gabriel I. Uwaifo, MD, FACP, FTOS, FACE. Dept of Endocrinology, Diabetes, Metabolism and Weight Management, Ochsner Medical Center Objectives To highlight various classification methods of diabetes To highlight the importance and consequences of appropriate diabetes classification To provide suggested processes for diabetes classification in primary care settings and indices for specialty referral Presentation outline 1. Case presentations 2. Diabetes classification; past present and future 3. Diabetes classification; why is it important? 4. Suggested schemas for diabetes classification 5. Case presentation conclusions 6. Summary points and conclusions 3 Demonstrative cases Patient DL is a 56 yr old AA gentleman with a BMI of 24 referred for management of his “type 2 diabetes”. He is on basal bolus insulin with current HBA1c of 8.3. His greatest concern is on account of recent onset progressive neurologic symptoms and gaite unsteadiness Patient CY is a 21 yr old Caucasian lady with BMI of 28 and strong family history of diabetes referred for management of her “type 2 diabetes”. She is unsure if she even has diabetes as she indicates most of the SMBGs are under 160 and her current HBA1 is 6.4 on low dose metformin. Patient DR is a 54 yr old Asian lady with BMI of 36 and long standing “type 2 diabetes”. She has been referred because of poor diabetes control on multiple oral antidiabetics and persistent severe hypertriglyceridemia. Questions; Do all
    [Show full text]