Effects of Diabetes Mellitus on Cholesterol Metabolism in Man

In view of the reported excess prevalence of atherosclerosis and cholelithiasis in diabetes, we investigated several aspects of cholesterol metabolism under metabolic ward conditions in six Pima Indians with maturity-onset diabetes mellitus. Cholesterol balance (13.5 versus 11.0 mg per kilogram per day, P<0.05), fecal bile acid excretion (415 versus 261 mg per day, P<0.05), bile acid pool size (3150 versus 1950 mg, P<0.05), fasting plasma cholesterol (193 versus 160 mg per deciliter, P<0.05) and plasma triglycerides (251 versus 150 mg per deciliter, P<0.05) were higher during uncontrolled hyperglycemia than during relative euglycemia on insulin. The increased plasma lipid levels and total cholesterol synthesis during hyperglycemia may contribute to the acceleration of atherosclerosis in diabetes mellitus. Gallbladder bile was significantly more saturated with cholesterol (181 per cent versus 114 per cent, P<0.05) during insulin treatment than during uncontrolled hyperglycemia. Bile lipid composition was thus more favorable to cholesterol precipitation and gallstone formation during insulin treatment than in the untreated diabetic state. (N Engl J Med 296:1365–1371, 1977) The higher rate of atherosclerosis suffered by patients with diabetes mellitus^{1 2 3 4} and their alleged increase in cholesterol gallstones^{5 6 7 8} suggested that cholesterol metabolism may be altered in this disease. Although some aspects of lipid metabolism have been examined extensively in diabetes, the metabolism of cholesterol has not. Animal studies of the effects of experimental diabetes on cholesterol metabolism have yielded conflicting results, and human data are few. Consequently, we have studied several aspects of cholesterol metabolism in diabetic patients before and during treatment with insulin. Studies of the metabolic consequences of diabetes in man have been complicated by heterogeneity in the.