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SYMPOSIUM |
From the Medical College of Georgia, Augusta, Georgia.
Address for reprints: L. Michael Prisant, MD, 1120 Fifteenth Street, BI-5082, Hypertension and Clinical Pharmacology, Medical College of Georgia, Augusta, GA 30912.
Why focus on diabetes mellitus? The reason is the future of our health care system may be in jeopardy. What is the basis for this concern?
The incidence and prevalence of diabetes is increasing.1,2 From 1959 to 1993, the prevalence of diabetes increased by a factor of 5.3 Beyond the 7.8 million diagnosed patients with diabetes, there are an additional 7 million persons who are undiagnosed based on an oral glucose tolerance test. The prevalence of a fasting glucose 110 g/dL or higher among persons 65 years or older is 27.8%, 37.6%, and 25.5% among African American, Mexican American, and Caucasian men.4 The corresponding rate is 26.3%, 25.3%, and 16.7% among African American, Mexican American, and Caucasian women. Furthermore, those patients with impaired glucose tolerance, which account for 11% of the population, are at increased risk of developing diabetes. In addition, this group of individuals is at risk for morbid events.5-7
How could this jeopardize our health care system? The cost of treatment is the main reason. All diabetics will require polypharmacy for control of glucose, blood pressure, lipids, and the procoagulant state. However, the cost of intense pharmacological control is trivial compared to the cost of disability, ambulatory medical care, coronary revascularization, heart failure, stroke, recurrent dialysis, focal photocoagulation, lower extremity foot ulcers and revascularization, and long-term nursing care. For instance, diabetes mellitus is the most common reason for end-stage renal disease requiring dialysis. The economic implication of a doubling of patients on dialysis over 10 years from 2000 to 2010 is staggering. As reported by Winer and Sowers in this issue,8 consider the future repercussions of the projection of 29 million diabetics by 2050 on our health care delivery system.1
How can we prevent the complications of diabetes? For the patients who have diabetes, implementing national guidelines is critical.
The treatment of hypertension has been a highly effective risk-reducing strategy for diabetic persons.9-11 However, only 16% of general practitioners and 14% of physicians of diabetes outpatient clinics targeted a blood pressure goal below 130/85 mmHg.12 Finally, the American Diabetes Association,13 the National Kidney Foundation,14 and the Joint National Committee Report 715 are concordant with a blood pressure treatment goal of less than 130/80 mmHg. Thiazide diuretics, beta-blockers, converting enzyme inhibitors, angiotensin receptor blockers, and calcium antagonists are effective in reducing cardiovascular events among diabetics.15 Both converting enzyme inhibitors and angiotensin receptor blockers reduce proteinuria and the progression of diabetic nephropathy. Only angiotensin receptor blockers have been tested prospectively and proven to reduce the rate of end-stage renal disease in type II diabetes. The best global protective outcomes have been documented with ramipril16 and losartan.17,18 Abbot, Basta, and Bakris19 highlight the fact that only 11% of people being treated for hypertension with diabetic kidney disease achieve the blood pressure goal of less than 130 mmHg. To achieve these treatment goals in diabetic patients with or without chronic renal insufficiency, combination drug therapy is required.
Diabetic dyslipidemia is characterized by an increase in triglyceride levels, low high-density lipoprotein (HDL) cholesterol concentrations, and small, dense low-density lipoprotein (LDL) particles. Therefore, one might predict that triglyceride-lowering and HDL-raising treatments by fibrates would have a positive effect on outcome. However, there are limited trial data for fibrates compared to statins among diabetic subjects.20 In the largest trial to date, the Heart Protection Study used simvastatin 40 mg per day and reduced vascular events, regardless of whether these diabetic participants had coronary heart disease.21 The beneficial effect was seen regardless of baseline glycosylated hemoglobin or obesity. In 2005, the results of the Fenofibrate Intervention and Event Lowering in Diabetics (FIELD) trial should answer the effectiveness of fibrates on outcome. However, to achieve the composite goal of an LDL cholesterol less than 100 mg/dL, triglycerides less than 150 mg/dL, and HDL cholesterol greater than 45 mg/dL in men and 55 mg/dL in women will require a combination of hypolipidemic drugs.22 Although it is safe to combine ezetimibe or a bile acid sequestrant with a statin to achieve LDL cholesterol goals, most clinicians are hesitant to combine niacin or fibrates with statins to reach either HDL cholesterol or triglyceride goals for fear of precipitating rhabdomyolysis or hepatotoxicity. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial should answer whether it is safe to combine fenofibrate with a statin.
Although elevated glucose is associated with both macrovascular and microvascular events, the hypoglycemic benefits are best documented for microvascular events.23 Mudaliar23 also reviews the potential cardiovascular hazards of the hypoglycemic agents. The current treatment goal is an average preprandial plasma glucose between 90 and 130 mg/dL and a bedtime plasma glucose between 110 to 150 mg/dL.13 Hemoglobin A1c should be targeted to be less than 7%. The ACCORD trial will answer questions about the level of intensity of glucose control and the potential beneficial effects of insulin sensitizers.
Aspirin is appropriate therapy for adult diabetics with or without vascular disease. Although clopidogrel is recommended for aspirin-intolerant patients,24 there are no data to support that clopidogrel is superior to aspirin25,26 or additive to aspirin in diabetic patients.27-29
What can we do to prevent diabetes from developing? Winer and Sowers8 attribute the diabetes epidemic to increased caloric intake, decreased leisure time activity, and a genetic predisposition. Lifestyle changes show the greatest risk reduction for preventing diabetes in subjects with impaired fasting glucose.30 It is interesting that hypoglycemic, hypolipidemic, hypotensive, hormone replacement, and weight-reducing measures are effective also. The downstream cost of prevention is likely to yield the greatest saving for our overburdened health care system.
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FOOTNOTES |
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REFERENCES |
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30. Prisant LM: Preventing type II diabetes mellitus. J Clin Pharmacol 2004;44: 406-416.
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