Metabolism of Cholesterol and Plasma Triglycerides in Nonketotic Diabetes Mellitus

The metabolism of cholesterol and plasma triglycerides (TG) was studied in 14 diabetic men: these patients did not have marked obesity nor did they develop ketoacidosis without insulin. Before insulin therapy, measurements were made of (1) plasma lipoproteins, (2) postheparin lipolytic enzymes, (3) turnover to TG in very-low-density lipoproteins (VLDL) and chylomicrons, (4) cholesterol balance, and (5) biliary lipids. After baseline measurements, the patients were treated with enough long-acting insulin to maintain their fasting plasma glucose in the range of 100–125 mg/dl. When plasma glucose and lipid levels reached a new steady state, all of the above measurements were repeated. Before insulin, most patients had fasting hypertriglyceridemia. This was due mainly to overproduction of VLDL-TG. Insulin therapy lowered both synthesis and concentrations of VLDLTG to near normal. Also, patients with normotriglyceridemia, both before and during insulin therapy, had essentially normal clearance of chylomicrons. Those with high fasting TG had delayed clearance of chylomicrons, but clearance returned to normal in most with insulin therapy. Postheparin lipolytic enzymes were not decreased. Before insulin, synthesis rates of cholesterol and bile acids usually were greater than normal, and bile commonly was supersaturated with cholesterol. During insulin therapy, synthesis of both cholesterol and bile acids remained elevated, possibly because of imperfect control of hyperglycemia. Furthermore, saturation of bile with cholesterol was accentuated by insulin therapy.