PREVENTING DIABETES-RELATED MORBIDITY and MORTALITY in the PRIMA1RY CARE SETTING* Samuel Dagogo-Jack, MD, FRCP Memphis, TN

PREVENTING DIABETES-RELATED MORBIDITY AND MORTALITY IN THE PRIMA1RY CARE SETTING* Samuel Dagogo-Jack, MD, FRCP Memphis, TN

Diabetes is the leading cause of blindness, end-stage renal failure, non-traumatic limb amputations, and cardiovascular morbidity and mortality. The vast majority of patients with diabetes receive routine care from primary care providers who are not endocrinologists. Primary care providers, including internists, family practice physicians, and physician extenders with advanced skills, face the important task of implementing standards of care recommendations for persons with diabetes. These recommendations draw upon an emerging body of compelling evidence regarding the prevention and management diabetes and its complications. The challenge of diabetes must be tackled on three fronts: Primary prevention, secondary prevention (of diabetes complications), and tertiary prevention (of morbidity and mortality from established complications). There is now abundant evidence that type 2 diabetes, which accounts for greater than 90% of diabetes world-wide, is preventable. Moreover, the complications of diabetes are preventable by a policy of tight glycemic control and comprehensive risk reduction. Even after complications have set in, intensive glucose control dramatically reduces the risk of progression of complications. The challenge, therefore, is the identification of strategies that enable transla- tion of existing scientific data to pragmatic benefits. This article proposes 10 strategies for preventing or reducing diabetes-related morbidity and mortality at the primary care level. These strategies include provider education; patient empowerment through promotion of lifestyle and self-care practices; surveillance for microvascular complications; cardiovascular risk reduction; efficient use of medications; goal setting; and stratification of patients and triaging of those with poor glycemic control for more intensive management. (J Natl Med Assoc. 2002;94: 549-560.)

INTRODUCTION Diabetes mellitus, which currently affects more © 2002. Professor of Medicine, Division of Endocrinology, Diabetes & than 16 million Americans, continues to be a Metabolism, University of Tennessee College of Medicine, Memphis, TN major clinical challenge, both in terms of the Address for correspondence: Samuel Dagogo-Jack, MD, University undiagnosed disease burden and the obstacles to of Tennessee College of Medicine, 951 Court Avenue, Room 335M, optimal glycemic control.-3 Diabetes is a public Memphis, TN 38163. Tel.: 901-448-5802 Fax: 901-448-5332 E- health problem, accounting for the majority of mail: [email protected] patients with adult-onset blindness, end-stage re- Dr. Dagogo-Jack is supported in part by NIH Clinical Research Center Grant MO 1 RR002 1 1 nal failure, and non-traumatic limb amputations. *Presented in part at the Southern Medical Association 95th Scien- Furthermore, diabetes is the leading underlying tific Assembly, Nashville, TN, November 8-10, 2001 cause of coronary heart disease, stroke and pe-

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ripheral vascular disease.2-5 In fact, a diabetic pa- than that incurred by patients without diabetes. tient without a prior history of myocardial infarc- In specific terms, the differences can be stag- tion has a greater risk of suffering a heart attack gering. For example, the annual per capita cost than a nondiabetic subject with a prior myocar- of health care in Tennessee in 1997 was dial infarction.6 $13,000 for persons with diabetes compared Both the incidence and prevalence of diabe- with $2,700 for persons without diabetes.'2 Na- tes are increasing worldwide. In the United tionally, the quality of diabetes care is deemed States, there was a 33% increase in the preva- to be very poor (hemoglobin {Hb}Alc >9%) in lence of diabetes between 1990 and 1998.7 Be- -25% of patients, poor (HbAlc 8-9%) in sides the human toll, the economic burden of -15%, and suboptimal (HbAlc 7-8%) in diabetes is staggering. The total annual health -20% of the remainder.'3 Thus, only about care costs attributable to diabetes in the U.S. is 40% of patients are in good metabolic control. in excess of $105 billion.8'9 The increasing prev- The patients with the poorest state of glycemic alence of diabetes is particularly marked in the control,-25% of the diabetes population, gen- southeastern region of the U.S., which appears erate exponentially greater health care costs to be the epicenter of the diabetes epidemic.7 than those with better control.'4 Unquestion- For instance, in the author's state of residence, ably, these poorly controlled patients present Tennessee, approximately 206,042 adults an opportunity for the application of focused, (5.1% of the population) had a diagnosis of innovative, cost-containment strategies that are diabetes in 1997, and an additional 1,750, 245 mediated through optimization of glycemic persons were at risk for development of diabe- control and reduction of diabetes complica- tes because of demographic and other predis- tions. posing factors.1-'12 Statewide health statistics analyzed in 1997 indicated a considerable bur- FOCUS ON ETHNIC MINORITIES den of diabetes-related complications in Ten- Measures of health care delivery, health care nessee: There were 74,616 diabetes-related hos- outcomes, and vital statistics indicate an emerg- pitalizations (including 23,583 admissions for ing, if not fully established, health care crisis in cardiovascular disease), 315 new cases of blind- urban America.'1 Urban America is inhabited ness, 654 new cases of end-stage renal failure, by a disproportionate number of ethnic minor- and 1,441 lower extremity amputations. Fur- ities as well as economically disadvantaged cit- thermore, diabetes contributed to 4,054 deaths izens from all ethnic and racial groups. From and accounted for a total health care expendi- the 2000 census figures, ethnic minorities con- ture of 2.7 billion in the state of Tennessee.10-'2 stitute approximately 25% of the overall U.S. Remarkably, one year later, the 1998 data from population. The population of these minority the Centers for Disease Control showed that groups has been increasing at a faster rate than the prevalence of diabetes in Tennessee had the national average. risen to 6.6%, making Tennessee the gth lead- There are many reasons why special atten- ing state in the hierarchy of diabetes preva- tion ought to be focused on ethnic minority lence (8). These disturbing trends in diabetes- populations in relation to diabetes. First, these related statistics are representative of the populations suffer disproportionately from picture across the entire United States.24-9'2 type 2 diabetes: Compared with caucasians, the There is a direct relationship between the prevalence of type 2 diabetes is 2-10 times higher degree of poor diabetic control and the devel- in African Americans, Hispanic Americans, Asian opment of long-term complications and the Americans, and Native Americans.16 In fact, type resultant prohibitive rise in health care costs. 2 diabetes is being diagnosed at alarming rates Nationally, the per capita health care cost in among ethnic minority subjects, including chil- patients with diabetes is considerably higher dren and adolescents.'7,18

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Table 1. Schedule of surveillance for diabetic complications Complications Method Frequency Goal Hyperglycemia Hemoglobin Al c 2-4/yr <7% Retinopathy Dilated funduscopy Yearly Normal retina Nephropathy Microalbuminuria* Yearly <30 mg/g creatinine Neuropathy Light touch sensation (Monofilament) Every'visit Intact sensation Hypertension Sphygmomanometry Every visit <1 30/80mmHg Dyslipidemia Fasting lipid profile Yearly Normal lipids Heart disease Electrocardiogram** Yearly No ischemic changes Diabetic foot Clinical examination Every visit No ulceration *24-hour urine (normal < 300 mg microalbumin per day) or spot urine (microalbumin:creatinine ratio). **Stress cardiac testing is warranted in symptomatic patients and those with additional risk factors.

Second, virtually all of the long-term compli- study24 showed a nearly 60%-80% reduction of cations of diabetes, including premature the risks for microvascular complications (reti- death,'9 occur several-fold more frequently nopathy, neuropathy, nephropathy) in patients among minorities compared with non-His- whose HbAlc was maintained at -7%. The panic whites. Acute diabetic complications oc- DCCT23 and the United Kingdom Prospective cur with varying frequencies in the different Diabetes Study (UKPDS)25 found that every 1% ethnic groups, but there are suggestions that absolute decrease in HbAlc yields 35% - 45% the rate of hospitalization for diabetic ketoaci- reduction in the risk of development or pro- dosis and nonketotic coma may be higher gression of microvascular complications. among certain minority groups, such as African In the UKPDS, a 0.9% reduction in median Americans.20 HbAlc (7% in intensive group vs. 7.9% in con- Third, there are indications of disparities in trols) resulted in 74% reduction in the risk of access to care and quality of metabolic control doubling of serum creatinine levels (among among diabetic patients, as a function of their other benefits), which could considerably delay demographic and socioeconomic characteris- the progression to end-stage renal failure. Fur- tics.21'22 Finally, the demography of the south- thermore, blood pressure control to 144/82 ern states, the epicenter of the diabetes epi- mmHg (vs. 154/87 mmHg in the comparison demic, is consistent with under-served patients group) reduced the risks of development of from the African American and other minority any diabetes-related endpoint by 24%, diabe- populations bearing the brunt of the dis- tes-related death (32%), stroke (44%), micro- ease.7,17,18 vascular complications (37%), and heart failure (56%).26 STANDARDS OF CARE GUIDELINES Based on these compelling data, the Ameri- There is now compelling evidence that in- can Diabetes Association has reiterated existing tensive treatment to control blood glucose lev- guidelines that the goal of diabetes manage- els in patients with type 1 and type 2 diabetes ment should be the attainment and mainte- can dramatically reduce the risk of develop- nance of an HbAlc level of <7%28 numerous ment of diabetes-related complications.23-25 other tasks are called for in these guidelines Concurrent management of co-morbid condi- (Table 1), including monitoring of HbAlc; tions (e.g., dyslipidemia, hypertension) re- methods and frequency of surveillance for reduces morbidity and mortality in patients with nal, retinal, neuropathic, cardiac, and circula- diabetes.26'27 The Diabetes Control and Com- tory complications of diabetes; optimal blood plications Trial (DCCT)23 and the Kumamoto pressure control; implementation of self-man-

JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL. 94, NO. 7, JULY 2002 551 DIABETES PRIORITIES IN PRIMARY CARE agement and lifestyle recommendations, tional subcutaneous route, are completed in among others. The HbAlc goal of <7% is a the near future. minimal target, because updated data from the With regard to oral antidiabetic agents (Ta- UKPDS indicate that the adjusted incidence of ble 2), there are now six chemically distinct myocardial infarction decreased from -25/1000 classes (compared with only one or two up to a person-years to -15/1000 person-years when few years ago), and several others are under HbAlc was lowered further from 7% to 6%.29 In development. Each class has its unique proper- the same cohort, the incidence of microvascular ties conferred by chemical structure, mecha- complications decreased from 10/1000 to nism of action, efficacy, adverse effect profile, 5/1000 person-years with further reduction of and other pharmacokinetic and pharmacody- HbAlc from 7% to 6%.29 namic properties. As many as seven individual Thus, the preferred policy of diabetes man- members may be found within a single oral agement is maintenance of blood glucose as antidiabetic drug class; oftentimes individual close to the normal range as possible without drugs within the same class may have unique dosing and toxicological considerations. In ad- intolerable hypoglycemia. The reason so many dition to developments in pharmacotherapy, diabetic patients are poorly controlled can be numerous medical devices are being intro- attributed, at least in part, to the fact that dia- duced to the diabetes care market at a brisk betes care involves a series of specialized tasks rate. Currently, more than 20 different brands that are difficult to implement satisfactorily in of meters are on the market for home blood the generalist setting. Ironically, the states with glucose monitoring: A new, bloodless device the highest prevalence rates of diabetes also for transcutaneous monitoring ofglucose levels have the lowest quality indicators of diabetes is at an advanced stage of development and care, such as HbAlc test ordering, annual eye deployment. Increasingly, insulin-requiring di- examinations, and screening for dyslipide- abetes patients are being treated with alterna- mia.30 tive delivery devices, such as insulin pens, pumps, andjet-injectors, as opposed to the tra- INCREASING COMPLEXITY OF DIABETES ditional needles and syringes. PRACTICE In keeping with enhanced awareness of the Current limitations need to reduce the burden of diabetes and its Because of a variety of reasons (including complications, the pharmaceutical industry has shortage of endocrinologists), most diabetic patients receive routine care from primary care been introducing new agents for the manage- providers. These primary care providers, in- ment of diabetes at an escalating rate since the cluding internists, family practice physicians, mid-1990's. As a result, there are now different and physician extenders with advanced skills, types of natural and recombinant human insu- are constrained to fit diabetes into a generalist lins with varying pharmacokinetic profiles, ad- practice that includes patients with a broad ministered by traditional methods or via insu- array of medical conditions, all competing for lin pens, jet injectors, or pumps. The natural priority attention. Yet, today's internists and forms of insulin, which are extracted and puri- family physicians are expected to demonstrate fied from animal pancreata, are no longer fairly specialized skills and competencies across available in the United States but are still in use a more demanding spectrum of diabetes care in other countries. The complexity in the field tasks than was the case only a few years ago. of insulin delivery will escalate after ongoing Clearly, the burden of diabetes and the range clinical trials of nasal, oral and other novel of clinical tasks mandated by the existing stan- forms of insulin, designed to bypass the tradi- dards of care recommendations constitute a

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Table 2. Oral antidiabetic agents Drug Classes Mechanism of Action HbAlc Fire Power* Unique Features Sulfonylureas 1-2% Many generic forms; Relatively inexpensive First generation Insulin secretion Tolbutamide Acetohexamide Tolazamide Chlorpropamide Second generation Insulin secretion Glyburide Glipizide Glimepiride Meglitinide 1-2% Repaglinide Insulin secretion Targets postprandial hyperglycemia Amino acid derivative -1% Nateglinide Insulin secretion Targets postprandial hyperglycemia Biguanide 1-2% Metformin Hepatic glucose output No weight gain Alpha-glucosidase Carbohydrate absorption -0.5% Target postprandial hyperglycemia inhibitors Acarbose Miglitol Thiazolidinediones Insulin sensitivity 1-2% Ancillary benefits on Syndrome X Rosiglitazone Pioglitazone *"Fire power" refers to the expected decrease in HbAlc in full-dose monotherapy. Values are approximate and vary according to individual patient characteristics, clinical trial design, and other factors.

major clinical challenge in primary care. In- measures among relatives of their patients with deed, surveys indicate inadequate compliance diabetes. Once diabetes has developed, how- with such recommendations in primary care ever, the priority shifts to secondary preven- practice settings.31,32 tion, namely, avoidance of microvascular and macrovascular diabetic complications. The best ROLE OF PRIMARY CARE PHYSICIANS prophylaxis against microvascular complica- The challenge of diabetes must be tackled tions is tight glycemic control 23-25. The best on three fronts: Primary prevention, secondary prophylaxis against macrovascular complica- prevention (of diabetes complications), and tions is a policy of comprehensive risk reduc- tertiary prevention (of morbidity and mortality tion (glycemic, lipid, blood pressure, smoking from established complications). Primary pre- cessation, etc). Even after myocardial infarc- vention of type 2 diabetes can be accomplished tion has occurred, careful attention to blood in high-risk individuals with impaired glucose glucose control reduces acute and chronic tolerance through lifestyle modification. Mod- post-infarct mortality.35What is needed, there- est reduction (500-700 kcal/day) in caloric fore, is a more efficient model of integrated consumption together with regular physical ac- diabetes care delivery that achieves outstanding tivity (e.g., walking for 30 minutes five times glycemic control, maintains updated fund of per week) exerts a remarkably potent prophy- knowledge for providers, motivates self-man- lactic effect against development of type 2 dia- agement behaviors in patients, utilizes special- betes.33'34 Primary care physicians should vigor- ist referrals efficiently, and prevents morbidity ously promote these primary preventive and mortality from complications of diabetes.

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The following are some suggestions toward at- venient way of assessing average blood glu- tainment of these protean goals. cose over periods of 2-3 months is by mea- suring the HbAlc. Patients unable to grasp 1. Diabetes updates: The primary care physi- the full name of this test can be encour- cian now, more than ever before, needs aged to remember it merely as the "Alc frequent updates of diabetes-specific test." Every diabetic patient needs to know knowledge base. Attendance at national or that keeping the HbAlc level below 7% regional conferences is an effective mecha- (i.e, close to the upper normal range of nism for continuing education. Numerous 6%) is the best insurance against develop- dinner programs, sponsored by industry, ment of long-term complications. Finally, are also available, to supplement learning the good news from the DCCT data that opportunities. Although these latter pro- every 1% absolute decrease in HbAlc level grams are conceptually "promotional," they (e.g. from 9% to 8%) translates to a 45% often provide quality diabetes education by reduction in the risk of retinopathy and outstanding experts in the field. Other av- other microvascular complications must be enues for updating fund of knowledge in- shared at every opportunity, as a motiva- clude journal subscription, affiliation with tional tool for patients with diabetes. diabetes faculty, and involvement in con- 3. Diabetes Education and Nutrition: The tinuing medical education programs at lo- core message to get across to patients is that cal tertiary care institutions. Clearly, there control of blood sugar matters. A patient is need for innovative thinking in the de- with average blood glucose levels of 200- sign of training mechanisms in this area. 250 mg/dl will have at least two-fold greater One idea involves development of "mini- risk of developing retinopathy, neuropathy, fellowships" that enable the generalist to and nephropathy than a patient with aver- perform at advanced levels in selected dis- age glucose levels of 150-160 mg/dl, over ease states (e.g., diabetes, dyslipidemia, hy- the course of several years. cEffective inter- pertension) after completion of a series of nalization of this cardinal message requires brief, in-depth supervised experiences. that patients understand the identity and 2. HbAlc: The testing frequency for HbAlc is significance of the HbAlc test (as already suboptimal, nationally.30 As the "gold stan- elaborated in the preceding passage), and dard" measure of diabetes control that has appreciate the role of self-monitoring of been linked to outcome, there is no excuse blood glucose (discussed later) as a valu- for not ordering the HbAlc test at the rec- able tool for optimization of care. These ommended frequency. The recommended and other pertinent self-management tasks testing frequency is 1- 4 times/year, de- in diabetes education can be accomplished pending on state of glycemic control. The through referral to a certified diabetes ed- minimal goal for prevention of long-term ucator. However, the primary care physi- complications is <7%. From the updated cian must remain engaged and must peri- UKPDS data, significant additional micro- odically monitor the efficacy of these vascular and macrovascular benefits ac- referrals by assessing the patient's grasp of crued when HbAlc was lowered from 7% the aforementioned key concepts. Caloric to 6%.29 It is therefore of utmost priority restriction, avoidance of over-eating, and for patients and their physicians to develop adoption of wholesome eating habits are an interest in setting and reaching HbAlc other aspect of diabetes education that re- targets. Patients need to be told that, since quire emphasis and periodic reinforce- blood glucose levels fluctuate markedly in ment (through dietitian referrals). any given day, and from day to day, a con- 4. Lifestyle intervention: Advice on diet and

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Figure 1. Sample prescription for exercise. An exercise prescription should be specific, gradually upgradable, and based on a clearly defined rationale. In previously sedentary patients, it may be prudent to progress more gradually, say, weekly increments of five minutes.

exercise should be delivered with the same of increasing physical activity should be conviction that accompanies prescription considered if adherence and efficacy are medicine. Referral to a dietitian often dem- suboptimal. A small investment in inexpen- onstrates such seriousness of purpose. Un- sive home exercise equipment (e.g., sta- til Clinical Exercise Physiologists become tionary bike) may be necessary, if outdoor routinely available, primary care physicians opportunities for exercise are limited or should undertake to actually issue written precarious. Of course, noninvasive cardiac prescriptions for exercise. A good exercise screening before exercise is always prudent prescription (Fig. 1) should have three el- in patients who have not been physically ements: 1) a clear rationale - this can be active. established by briefly discussing the meta- 5. Self-monitoring: Self-monitoring of blood bolic benefits of moderate exercise; 2) glucose (SMBG) predicts adherence to specificity - "walk for 10 min every Monday, other medical recommendations and is as- Wednesday, Friday" is a better script than sociated with superior glycemic control. Pa- "exercise regularly", and 3) scalability - the tients who do not perform SMBG tend also exercise prescription should gradually be to ignore other aspects of self-manage- scaled up: For example, "Increase walks to ment. Thus, successful initiation of SMBG 20 min on Monday, Wednesday, Friday af- in any patient is a step toward better glyce- ter one week". A clear plan should be es- mic control. The standard recommenda- tablished for evaluation of adherence and tion for patients with typeldiabetes is to efficacy of the program. Alternative modes perform self-testing of blood glucose three

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to four times daily. The optimal frequency agents) until a fasting blood glucose level of self-testing for type 2 diabetes patients of 130 mg/dl is achieved.3 Once that target has not been determined, and can be ne- is achieved, a more stringent goal for fast- gotiated with patients. Primary care physi- ing blood glucose (e.g., 110 mg/dl) can be cians should encourage patients to perform pursued. Eventually, many patients will re- and record SMBG results, and should re- quire multiple injections of short- and long- view the home record with interest during er-acting insulin preparations for optimal office visits. It is especially important that control. Large daily doses of insulin (100 patients be made to realize that the num- U/day) usually are required to maintain bers are actually used to make changes in optimal glycemic control in patients with the treatment plan. type 2 diabetes. 6. Efficient use of medications: The rational 7. Goal setting: Goals are the therapeutic approach to type 1 diabetes is an optimized road maps that direct and concentrate all insulin replacement regimen that includes efforts. Without a clearly defined goal, the basal and bolus elements. Because of the doctor and patient "are lost at sea." Achiev- pathophysiology of type 2 diabetes (com- able goals should be set, and strategies and bined insulin resistance, beta-cell insulin tactics marshaled toward attainment of secretory defect, and excessive hepatic glu- those goals. A typical goal in a patient with cose production) and its progressive na- initial HbAlc of 11% could be to reduce ture, achievement of optimal glycemic con- that number by 1% by the time of follow-up trol often requires the use of more than visit in 2 months. The applicable strategies one agent. As much as possible, drug com- include review of current medication and binations should be selected for their ther- adherence to lifestyle recommendations. apeutic "fire power," complementary The specific tactics include maximizing mechanisms of action, ancillary benefits current drug doses, substitution or addi- (especially on cardiovascular risk factors), tion of an agent working by a differrent safety, and tolerability (Table 2). Triple mechanism, formal referral to dietitian for therapy with oral antidiabetic agents (e.g, reinforcement, and reinforcement of phys- sulfonylurea + biguanide + thiazolidinedi- ical activity plan, including a written pre- one) is effective and may be an option in scription for exercise (Fig. 1). selected patients. Thus various combina- 8. Cardiovascular risk factors: A comprehen- tions of the available oral agents are now sive approach to modification of cardiovas- conceivable, which should ensure adequate cular risk factors is mandatory. Targets in- glycemic control in virtually every type 2 clude smoking cessation, lipids (LDL- diabetes patient. Combination therapy will cholesterol goal in diabetes is <100 mg/ be most effective if initiated as part of a dl), blood pressure (goal <130/80), asprin comprehensive diabetes care plan that in- prophylaxis, etc. Macrovascular disease ac- cludes lifestyle interventions. The decision counts for the majority of deaths in diabe- to continue a combination regimen should tes. Coronary artery disease and myocardial be based on evidence of continuing effi- infarction present in atypical ways in diabe- cacy, safety, and tolerability. There should tes, so symptoms are unreliable. A high in- be no reservation in adding insulin to the dex of suspicion and a low threshold for regimen, if glycemic control on oral agents ordering stress cardiac testing is appropri- remains suboptimal. Insulin can be started ate in diabetes patients. Intensive glucose as bedtime NPH or glargine at a low initial control in patients with acute myocardial dose (-10 units) and increased by 2-4 infarction has been demonstrated to re- units every few days (while continuing oral duce short-term and long-term mortality in

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diabetic patients.35 Thus, intensification of to diabetic kidney disease should focus glycemic control in the peri-infarct period on prevention. Persons who have had and beyond should be standard practice in type 1 diabetes for 5 years or longer and diabetic patients with acute myocardial in- all persons with type 2 diabetes are farction. screened annually for microalbumin- 9. Surveillance for microvascular complica- uria. The screening test consists of either tions (see Table 1): The microvascular a timed urine collection or a random complications (retinopathy, nephropathy, spot urine for measurement of mi- and neuropathy) develop after several years croalbumin-to-creatinine ratio. In pa- of uncontrolled diabetes. The usually grad- tients with microalbuminuria treated ual time course of these complications af- with ACE inhibitors, follow-up urine test fords an opportunity for early detection should be obtained and the dose of ACE and tertiary prevention (i.e., prevention of inhibitor adjusted for maximum ne- morbidity and mortality from progression phroprotective effect. of diabetic complications). b. Zero tolerance for amputations: Diabe- a. Preemptive strike at kidney disease. tes accounts for 50% of cases of non Both microalbuminuria, the earliest traumatic lower extremity amputations (and reversible) stage of kidney disease, in the U.S. There should be zero toler- and gross proteinuria precede end-stage ance for limb loss in modern diabetes renal failure by variable but lengthy in- practice. The risk factors for lower ex- tervals. The limited availability of organs tremity amputation in persons with dia- for transplantation means that thou- betes include peripheral neuropathy, sands of patients spend several years on peripheral vascular disease, deformities, dialysis without a chance of receiving trauma and deep tissue infections. With kidney transplants. Thus the emphasis the possible exception of trauma, most should be on prevention of kidney dis- of these risk factors are impacted by the ease, since cure cannot be offered to all state of metabolic control. Poor control affected persons. The initial observation of blood glucose is associated with in- that microalbuminuria precedes more creased risk of infections, impaired advanced stages of kidney disease by sev- wound healing, and development of eral years is important information. This long-term diabetic complications, such knowledge creates a window of opportu- as neuropathy and peripheral vascular nity to intervene and prevent further de- disease. Additional risk factors for pe- cline in renal function. The decline in ripheral vascular disease include hyper- kidney function can be slowed down tension, cigarette smoking and elevated considerably if blood pressure is con- blood cholesterol levels. Strategies for trolled (130/80 or lower) in persons limb preservation include: 1) tight con- who have both diabetes and hyperten- trol of blood glucose (and of blood pres- sion. It has now been established that sure), 2) smoking cessation (patients angiotensin converting enzyme (ACE) should be given every assistance, includ- inhibitors36 and angiotensin receptor ing special counseling and prescription blockers (ARB)37,38 are effective in pre- for bupriopion), 3) daily foot inspection serving renal function in diabetes pa- by patients, 4) appropriate foot wear, tients with microalbuminuria and with and 5) regular physical examinations by more advanced forms of nephropathy. physician, including an assessment of ar- ACE inhibitors are well tolerated by nor- terial pulses and skin sensation (using a motensive patients. Thus the approach 5.07/10 gm monofilament). Referral for

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Table 3. Strengths of the Clinical Trials Model CONCLUSION 1. Common Protocol and Manual of Operations Effective diabetes management entails a 2. Goal setting/Incentives multi-modality approach that utilizes lifestyle 3. Frequent contacts with patients and pharmacological interventions. The mne- 4. Close monitoring of endpoints 5. Team approach among multi-professionals monic MEDEM (Monitoring, Education, Diet, 6. Shared responsibility with enrolled patients Exercise, Medications) can be used to recall 7. Accountability to higher authority the key modalities of care. Genuine commit- 8. Case manager and patients feel peer pressure to ment to the patient's overall well being pro- excel motes adherence to the multiple behavioral 9. Willingness of staff to go beyond the call of duty and self-care tasks expected of the diabetic patient. Excellence in diabetes care requires fre- routine podiatric evaluation before the quent patient contacts, especially during the development of limb threatening lesions "down time" between office visits. These con- has been demonstrated to reduce ampu- tacts may be accomplished by means of tele- tation rates. Clinics can obtain the pop- phone, facsimile, or via the Internet. Such con- ular "Feet Can Last A Lifetime" kit from tacts enable the diabetes care team to respond the NIH by calling 1-800-GET-LEVEL. promptly to laboratory test results, review self- 10. Practice-Within-a-Practice: The primary monitored blood glucose data, adjust medica- and assess adherence to and care role in mor- tions, lifestyle physician's preventing pharmacological interventions. These interac- and from diabetes re- bidity mortality tions also have a heuristic impact on patients, quires a paradigm shift from the existing build trust between the patient and caregivers, clinical traditions. Diabetes care needs and may help modify behavior.3940 Patients to be isolated as a "Practice-Within-a- with chronically poorly controlled diabetes Practice", using methods that enable (HbAlc > 8%) will benefit from joint evalua- ready identification of affected patients tion and care by a specialist. Referral to an (e.g., color-coded charts, special chart endocrinologist should have clear goals and stickers, electronic medical record iden- reasonable time course (or number of visits) tifiers, etc.). Once so isolated as a Prac- for attaining such goals. A reduction in HbAlc tice-Within-a-Practice, it should be feasible of approximately 1-2% from baseline within 2 to categorize diabetes patients by quar- visits should be set as the minimal justification tiles of HbAlc (<7%, 7-7.9%, 8-8.9%, for the specialist endocrinologist's interven- >9%) and to triage those in the top 2 tion. Subjective symptoms suggestive of hypo- quartiles for more intensive, focused at- glycemia occur frequently when patients with tention and joint management with en- poorly controlled diabetes experience im- docrinologists. A "Clinical Trials Model" proved glycemic control. These symptoms oc- wherein poorly controlled patients are cur at blood glucose levels that are usually identified and tracked closely by a nurse, within the physiological range or even higher, nurse practitioner, or other appointed and are attributable to altered glycemic thresh- "Case Manager" within the practice is old for release of counterregulatory hor- strongly proposed. This adaptation of mones.41 No specific treatment other than re- the Clinical Trials Model can be an effi- assurance is indicated for patients with such cient mechanism for achieving excel- episodes of "pseudohypoglycemia." Referrals to lence in diabetes management in the pri- other specialists (cardiac, podiatry, ophthal- mary care setting, because of the inherent mology, etc.) should be implemented as neces- strengths of such a model. (Table 3). sary.

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type 2 diabetes and nephropathy. N EnglJ Med 2001;345:861- 869. We Welcome Your 38. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotec- tive effect of the angiotensin-receptor antagonist irbesartan in Comments patients with nephropathy due to type 2 diabetes. N EnglJ Med 2001;345:851-860. Journal of the National Medical Association 39. Lawler FH, Viaviani N. Patient and physician perspec- welcomes your Letters to the Editor about tives regarding treatment of diabetes: compliance with practice guidelines. J Fam Pract 1997;44:369-373. articles that appear in the JNMA or issues 40. Lorenz RA, Bubb J, Davis D, et al. Changing behavior. relevant to minority health care. Practical lessons from the diabetes control and complications Address correspondence to Editor-in-Chief, trial. Diabetes Care 1996;19:648-652. ]NMA, 1012 Tenth St, NW, Washington, DC 41. Boyle PJ, Schwartz NS, Shah SD, Clutter WE, Cryer PE. Plasma glucose concentrations at the onset of hypoglycemic 20001; fax (202) 371-1162; or symptoms in patients with poorly controlled diabetes and in [email protected]. nondiabetics. N EnglJ Med 1988; 318:1487-1492.

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