Showing papers by "Scott M. Grundy published in 1977"

Effects of diabetes mellitus on cholesterol metabolism in man.

Abstract: 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 less than 0.05), fecal bile acid excretion (415 versus 261 mg per day, P less than 0.05), bile acid pool size (3150 versus 1950 mg, P less than 0.05), fasting plasma cholesterol (193 versus 160 mg per deciliter, P less than 0.05) and plasma triglycerides (251 versus 150 mg per deciliter, P less than 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 less than 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.

Failure of Complete Bile Diversion and Oral Bile Acid Therapy in the Treatment of Homozygous Familial Hypercholesterolemia

Abstract: Two patients with homozygous familial hypercholesterolemia, refractory to medical therapy, underwent complete bile diversion by common-duct ligation and Cholecystotomy, in an attempt to arrest the progression of their xanthomatosis and atherosclerosis by depletion of body cholesterol. Clofibrate was given after operation to one patient, and cholic acid to both, in an effort to enhance further the negative sterol balance. Bile diversion produced an increase of six to eight times in gastrointestinal sterol output, which was not increased further by either clofibrate or cholic acid therapy. Despite a calculated sterol loss of 560 g over 14 months in one patient and 400 g over 10 months in the other, neither plasma cholesterol nor xanthoma size decreased. Continuity of the biliary tree was therefore restored. The data suggest that patients with homozygous familial hypercholesterolemia respond to even massive gastrointestinal sterol depletion with equal increases in sterol synthesis. (N Engl J Med 296...