end-products in the arterial wall, alterations in endothelial function and coagulation ... Winocour PH, Durrington PN, Ishola M et al:Lipoprotein abnormalities in ...
I Atheroscierosis Upda te Canadian Atherosclerosis Society/Societe canadienne d'atherosclerose
Atherosclerosis and diabetes mellitu David C.W. Lau, MD, PhD, FRCPC
A mong North Americans with diabetes mellitus, either insulin-dependent (IDDM) or non-insulin-dependent (NIDDM), atherosclerotic cardiovascular disease is two to six times more prevalent than among age- and sex-matched people without diabetes and is a principal cause of premature death.' Furthermore, diabetic women lose the protection against coronary artery disease that their sex usually confers. Several risk factors for atherosclerotic cardiovascular disease are often present in people with diabetes. Apart from the known factors - smoking, hypertension and obesity - hyperglycemia, hyperinsulinemia and dyslipoproteinemias may account for the accelerated atherogenesis.2 Hyperglycemia is thought to mediate macrovascular diabetic complications by several mechanisms: accelerated formation of advanced nonenzymatic glycosylation end-products in the arterial wall, alterations in endothelial function and coagulation cascade.2 The results of recent epidemiologic and experimental studies suggest that hyperinsulinemia2 and possibly insulin resistance3 accelerate the development of atherosclerosis. Dyslipoproteinemias are common in the diabetic patient and, depending on the prevailing metabolic abnormalities, can present as hypertriglyceridemia, combined hypertriglyceridemia and hypercholesterolemia, or hypercholesterolemia alone. Hypertriglyceridemia, the most common, may result from decreased clearance of very-lowdensity lipoproteins and apolipoprotein B or increased hepatic synthesis. Changes in composition of lipoproteins may be more important than changes in level in predisposing diabetic patients to increased atherogenesis.4 Finally, levels of highdensity lipoprotein cholesterol are not infrequently depressed in NIDDM.1,2 Increased platelet aggregability and decreased plasminogen-activator activity in the hyperglycemic state may predispose to thrombus formation in Dr. Lau is an associate professor with the Department of Medicine and the Julia McFarlane Diabetes Research Centre at the University of Calgary, Calgary, Alta.
Reprint requests to: Dr. David C. W. Lau, Rm. 2953, Health Sciences Centre, 3330 Hospital Dr. NW, Calgazy, Alta. T2N 4N1
1466
CMAJ, VOL. 140, JUNE 15, 1989
diseased vessels.2 Abnormal endothelial functions in both IDDM and NIDDM indude increased synthesis of von Willebrand factor, which enhances platelet adhesion, and decreased production of prostacyclin, a vasodilator and inhibitor of platelet aggregation.2 Hyperinsulinemia increases cholesterol synthesis in and proliferation of arterial wall smooth muscle cells.2 Treatment is aimed at reducing the risks of cardiovascular disease by adopting a healthy lifestyle. The cornerstone of therapy consists of a nutritious, well-balanced diabetic diet with low levels of cholesterol and fat, designed to achieve or maintain a desirable body weight, along with a regular exercise program. Good glycemic control, with fasting and postpraendial blood glucose levels not exceeding 7.8 and 11.1 mmol/L (140 and 200 mg/dl) respectively, is recommended. For IDDM patients requiring medical therapy, hyperinsulinemia should be avoided by the use of multiple insulin injections to mimic a more physiologic pattern. In NIDDM a second-generation sulfonylurea or biguanide oral hypoglycemic agent, or both, is preferred to minimize nocturnal and fasting hyperinsulinemia and to improve insulin resistance. Judicious choice of antihypertensive medications that do not adversely alter the lipid profile, such as angiotensin-converting enzyme inhibitors and calcium-channel blockers, is also important. Accelerated atherosclerosis is often multifactorial, and many of the risk factors are reversible. In caring for diabetic patients we must broaden our focus beyond glycemic control and aim to prevent coronary, cerebral and peripheral vascular disease. Lipid levels and ophthalmologic, renal and cardiac status must be assessed annually. References 1. Kannel WB: Lipids, diabetes, and coronary heart disease: insights from the Framingham study. Am Heart J 1985; 110:
1100-1106 2. Stolar M: Atherosclerosis in diabetes: the role of hyperinsulinemia. Metabolism 1988; 37 (suppl): 1-8 3. Reaven G: Banting Lecture 1988: Role of insulin resistance in human disease. Diabetes 1988; 37: 1595-1607 4. Winocour PH, Durrington PN, Ishola M et al: Lipoprotein abnormalities in insulin-dependent diabetes mellitus. Lancet 1986; 1: 1176-1178
