HYPERLIPIDEMIA AND ATHEROSCLEROSIS IN EXPERIMENTAL INSULINOPENIC DIABETIC MONKEYS

Chronic insulinopenic diabetes was induced by i.v. streptozotocin in the non-human primate Macaca fuscata. Five diabetic monkeys were kept for 8-19 months and nine for 24-48 months without any insulin treatment. Hyperglycemia (241 +/- 22 mg/dl, M +/- SE less-than-or-equal-to 1 year) progressed to 376 +/- 34 mg/dl (> 2 years) and ketosis to 3.5 mM (> 2 years) during the course of diabetes; this was roughly inversely proportional to hypoinsulinemia (3.4-mu-U/ml, 2 years). Serum cholesterol increased from 184 +/- 11 (less-than-or-equal-to 1 year) to 328 +/- 66 mg/dl (> 2 years) with the major increase in LDL-cholesterol (2.7-fold over control, > 2 years). HDL-cholesterol did not change at all throughout the experimental period. TG increased from 144 +/- 25 (less-than-or-equal-to 1 year) to 676 +/- 116 (> 2 years) with a major increase in the VLDL fraction (15-fold over control, > 2 years). Serum levels of apo B increased to 141 +/- 16 (less-than-or-equal-to 2 years) and 223 +/- 8 mg/dl (> 2 years) in contrast to control, 73 +/- 2. Morphologically, lipid deposition in the intima and fatty streaks have been observed in the abdominal aorta of all the diabetic monkeys with duration of more than 2 years. In six of the diabetic monkeys atheromatous changes such as intimal and medial thickening with smooth muscle cell proliferation were observed with foam cell formation. Similar atherosclerotic lesions were observed in renal and coronary arteries in at least six of these monkeys. In diabetic monkeys with duration of less than 2 years, mild atherosclerotic lesions were observed in two out of five. The results indicate that long standing insulinopenia leads to metabolic derangements characterized by hyperglycemia, ketonemia and hyperlipidemia. Elevation of LDL-cholesterol and VLDL TG with an increase of apo B is a characteristic of lipoprotein disorder. Morphologically, early to moderately advanced lesions of atherosclerosis were observed in aorta, renal and coronary arteries as a result of metabolic derangement due to insulin deficiency.