Lipid-Lowering Therapy and Macrovascular Disease in Diabetes Mellitus

Patients with diabetes mellitus are at increased risk of morbidity and mortality from macrovascular disease manifesting as coronary heart disease, cerebrovascular accidents, and peripheral vascular disease. Increased frequency of dyslipidemia, hyperglycemia, obesity, hypertension, and associated nephropathy may contribute to accelerated atherogenesis in diabetic patients. Therefore, besides intensive control of hyperglycemia, management of dyslipidemia, hypertension, and obesity should also be emphasized in diabetic patients. Those who smoke should be strongly encouraged to quit smoking. Besides attempts to achieve normal levels of plasma lipoproteins, consideration also should be given to normalization of compositional abnormalities of various lipoproteins in patients with diabetes mellitus. The therapeutic goals for cholesterol reduction should be lower in diabetic patients than nondiabetic subjects. The first step is to achieve good metabolic control of diabetes mellitus by diet, exercise, and weight reduction and, if needed, with sulfonylureas or insulin therapy. Because most of the patients with insulin-dependent diabetes mellitus achieve normal levels of plasma lipoproteins with intensive insulin therapy, lipid-lowering medications are rarely needed. In patients with non-insulin-dependent diabetes mellitus, however, dyslipidemia often persists despite good glycemic control. Lipid-lowering medications should be considered in such patients. Because nicotinic acid can cause marked deterioration in glycemic control, and bile acid-binding resins may accentuate hypertriglyceridemia, these agents are less desirable for use by diabetic patients. Inhibitors of hydroxymethylglutaryl coenzyme A reductase may be preferred in patients with elevated LDL cholesterol and mild hypertriglyceridemia. For diabetic patients with marked hypertriglyceridemia, however, fibric acid derivatives should be the drug of choice.