LIPID METABOLISM IN DIABETES AND THE EFFECTS OF THERAPY

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The increased VLDL and decreased HDL commonly associated with non-insulin dependent diabetes are of concern because of their possible role in the etiology of the greatly increased cardiovascular disease in this disorder. This study compares VLDL and LDL metabolism in non-insulin dependent diabetics and in age and weight-matched nondiabetics. Studies were conducted in diabetics before and after therapy with sulfonylureas; also diabetics were compared on high and low fat diets. The data suggest that diabetics have abnormal VLDL and that diabetes influences VLDL-TG production independent of that of apoB. LDL concentrations in diabetes are influenced by two opposing changes - increase in direct removal of VLDL, but decrease in FCR for VLDL. Improvement of glycemic control with oral hypoglycemic therapy is followed by significant falls in VLDL-TG and LDL cholesterol and reversal of abnormalities of VLDL composition, VLDL triglyceride productions, lipase activities, and HDL subfractions. Transfer of the diabetics to a high carbohydrate, low saturated fat diet is associated with decreases in LDL, no change in HDL, and no change in VLDL in most diabetics. Metabolic studies on the two diets indicate that VLDL decreases upon removal of dietary saturated fat are due to increased clearance. The larger triglyceride rich VLDL in diabetics on a low fat, high carbohydrate diet are less efficiently converted to LDL, but clearance of both VLDL apoB and VLDL triglyceride are lower. The results indicate that high carbohydrate low fat diets can result in less atherogenic lipoproteins in most subjects with non-insulin dependent diabetes.