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• Preventive Management of Diabetes Mellitus (UAB Insight, Winter 2001)

ABSTRACT: The basic goal for the management of diabetes mellitus are control of hyperglycemia and screening for and prevention of complications.
CME OBJECTIVE: Readers will be familiar with new screening guidelines for diabetes and with the best means to screen for and prevent macrovascular and microvascular complications. Richard Rosenthal, MD, honoraria Pfizer, Bristol-Myers Squibb Co.
Diabetes mellitus ranks as the sixth leading cause of death by disease in the United States. Yet, of the 16 million Americans - approximately 90% of whom have type 2 diabetes - only half are diagnosed. Diabetes is nearing epidemic proportions, cites the American Diabetes Association (ADA), due to an aging population and increasing prevalence of obesity and sedentary lifestyles. "Conclusive data confirm that serious complications of diabetes begin earlier than previously thought," reveals UAB endocrinologist Richard S. Rosenthal, MD. "Because type 2 diabetes is often asymptomatic in its early stages, most people are diagnosed only after the classic signs and symptoms appear. Unfortunately, polyuria, polydipsia, polyphagia, unexplained weight loss, and fatigue typically do not appear until 7 to 10 years after disease onset. By then, irreversible vascular and end-organ damage may have occurred, setting the stage for microvascular (neuropathy, nephropathy, retinopathy) and macrovascular (heart disease, stroke, peripheral vascular disease) complications," he cautions.The diagnosis of diabetes requires either 2 fasting plasma glucose readings >=126 mg/dL or 2 nonfasting plasma glucose values >=200 mg/dL (if diabetic symptoms are present).Oral glucose tolerance testing is no longer recommended,
and hemoglobin A1C (HbA1c) is not recommended as a screening test. Rosenthal advises that patients with a random plasma glucose level >=200 mg/dL, but without symptoms, should have their fasting blood glucose measured. Patients with impaired glucose homeostasis have an increased risk of developing diabetes and should receive counseling regarding weight control, exercise, and future screening.	Classical signs and symptoms of diabetes typically do not appear until 7 to 10 years after disease onset.
Treatment of Diabetic Complications The Diabetes Control and Complications Trial confirmed that intensive treatment to lower blood glucose and maintain it within as normal a range as possible delayed the onset and progression of microvascular complications in type 1 diabetes. Similarly, the United Kingdom Prospective Diabetes Study indicates that intensive treatment to control glucose levels in people with type 2 diabetes reduces the risk of complications. "The underlying pathophysiology of type 2 diabetes is impaired beta-cell function, but insulin resistance may be the primary cause of the beta-cell failure," Rosenthal reveals. Insulin resistance also contributes to obesity associated with type 2 diabetes, and obesity worsens insulin resistance. Conversely, weight loss improves insulin resistance, blood glucose control, lipid levels, and blood pressure. More than 75% of patients with newly diagnosed type 2 diabetes are obese. Macrovascular Complications Diabetes is an independent major risk factor for atherosclerotic cardiovascular disease (CVD); ischemic heart disease occurs at a younger age in people with diabetes, he counsels. "Evidence of CVD, such as angina, claudication, decreased pulses, vascular bruits, and ECG abnormalities, mandates efforts to correct other CVD risk factors (eg, obesity, smoking, hypertension, sedentary lifestyle, dyslipidemia), in addition to specific treatment of the cardiovascular problem and diabetes." According to Rosenthal, recommendations for risk factor modification are: Check blood pressure at every visit. Data confirm that blood pressure control reduces progression of diabetic nephropathy and the incidence of hypertensive nephropathy, cerebrovascular disease, and CVD. In people with diabetes, blood pressure should be maintained below 125/75 mmHg, initially by recommending weight loss, low sodium intake (<2 g/d), regular exercise, and decreased alcohol intake. Antihypertensive medications of choice are angiotensin converting-enzyme (ACE) inhibitors, calcium channel blockers, and alpha-1 blockers, as these medications do not adversely affect glucose levels or lipid profiles. Obtain a fasting lipid profile annually. LDL cholesterol should be <=100 mg/dL and HDL cholesterol >45 mg/dL in men and >55 mg/dL in women. "The cornerstones for management of lipid disorders include a diet designed to lower glucose levels and alter lipid patterns and regular physical activity," Rosenthal notes. Lipid-lowering medication should be started immediately (along with lifestyle measures) in diabetic patients with known CVD, cerebrovascular disease, and elevated LDL-cholesterol levels. "Otherwise, patients should be evaluated at 6-week intervals to assess the effectiveness of lifestyle modifications. If after 3 to 6 months, LDL-cholesterol levels remain above 100 mg/dL and/or triglycerides exceed 200 mg/dL, lipid-lowering drugs are needed," he counsels. Drugs from the hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor class - the so-called "statin" drugs, including atorvastatin (LipitorT), cerivastatin (BaycolT), fluvastatin (Lescol®), lovastatin (Mevacor®), pravastatin (Pravachol®), and simvastatin (Zocor®) - are the first choice to lower LDL cholesterol. Two fibrates, gemfibrozil (Lopid®) and fenofibrate (TricorT), can lower triglycerides by 50% and should be considered when triglyceride levels remain elevated despite adequate glycemic controls. Microvascular Complications Diabetic Retinopathy: "Up to 21% of patients with type 2 diabetes have retinopathy at the time of diagn osis; 5% to 10% become blind," reports Rosenthal. "Annual evaluation by means of dilated funduscopic examination is a valuable strategy to identify patients with asymptomatic macular edema and proliferative retinopathy. Timely intervention with laser photocoagulation can prevent visual loss." Diabetic Nephropathy: Persistent albuminuria in the range of 30 mg to 300 mg/24 h (microalbuminuria) reflects the earliest stage of diabetic nephropathy and is a significant risk marker for CVD, he notes. "In hypertensive patients with either type 1 or type 2 diabetes who have microalbuminuria or clinical albuminuria, ACE inhibitors delay progression from microalbuminuria to clinical albuminuria and slow declines in glomerular filtration rates." Because of the high proportion of patients who progress from microalbuminuria to overt nephropathy, and subsequently to end-stage renal failure, ACE inhibitors are recommended for all type 1 patients with microalbuminuria, even for those who are normotensive. Periodic creatinine clearances and albumin-to-creatinine ratios document the effect of treatment on albumin excretion and detect the rare instance when drug therapy worsens renal function. Fostering Meaningful Change "Regardless of the treatment goal and of choices about the intensity of glycemic control, patients face considerable barriers in implementing recommendations to modify diet and other personal lifestyle habits and comply with glucose monitoring, medication schedules, home-care instructions; and follow-up visits. Physicians should work with patients to identify and design solutions for remediable barriers and should utilize recommended techniques for patient education and counseling to give patients the factual information and motivational encouragement they need for meaningful change," Rosenthal stresses. The ADA has established standards for screening for management of diabetes and for prevention and treatment of complications (Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, ADA Clinical Practice Recommendations. Diabetes Care, Vol 23(Suppl.1):2000). Rosenthal advises "with these new strategies, primary care providers will be better equipped to help patients manage this chronic disease." For more information: Dr. Richard Rosenthal 1-800-UAB-MIST mist@uabmc.edu ADA Testing Recommendations The ADA recommends that physicians test all adults for diabetes at age 45, and, if normal, repeat the tests at 3-year intervals. Also, physicians should recommend earlier testing for patients at higher risk of diabetes: Obese individuals >= 20% over desired body weight or body mass index (BMI >=25 kg/m 2 ); People with a first-degree relative who has diabetes; Members of a high-risk ethnic group (African American, Hispanic, Native American, Asian, Pacific Islander) People with hypertension (>=140/90 mm Hg); Those with a HDL level <=35 mg/dL (0.90 mmol/l) and/or a triglyceride level >=250 mg/dL (2.82 mmol/L); Women whose babies weighed more than 9 pounds at birth, or who were diagnosed with gestational diabetes mellitus; Anyone with abnormal results on earlier impaired fasting glucose or impaired glucose tolerance. UAB Insight, Winter 2001 UAB INSIGHT is produced by the UABHS Office of Medical Publications, in conjunction with UAB physicians and other health-care professionals. The materials are copyrighted and may be downloaded and/or reprinted for personal use only. 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