ACCELERATED CHOLESTERYL ESTER TRANSFER AND ALTERED LIPOPROTEIN COMPOSITION IN DIABETIC CYNOMOLGUS MONKEYS

To determine whether nonhuman primates demonstrate the same alteration s in transport of cholesteryl ester (CE) in plasma observed in diabeti c humans, cholesteryl ester transfer (CET) was measured in cynomolgus monkeys with chronic spontaneous diabetes mellitus (glycated hemoglobi n: diabetics 10.7 +/- 4.1%; controls 3.8 +/- 0.8%, P < 0.005). Among t he plasma lipids, only triglycerides were significantly increased in d iabetic monkeys (diabetics 303 +/- 294 mg/dl; controls 85 +/- 34 mg/dl ; P < 0.05); total plasma, LDL, HDL(2), and HDL(3) cholesterol concent rations did not differ significantly from those of control animals. Si milar to human beings with insulin-dependent and non-insulin-dependent diabetes mellitus, CET estimated both as the mass of cholesteryl este r transferred from HDL to the apoB-containing lipoproteins (VLDL + LDL ) and as the loss of radiolabeled cholesteryl ester from HDL was signi ficantly greater (P < 0.001) in diabetic compared to control monkeys. Glycated hemoglobin levels in the combined control and diabetic groups correlated directly with both the mass of cholesteryl ester transferr ed at 2 h (r = 0.75; P < 0.001) and the isotopic transfer (k) (r = 0.6 4; P < 0.005). The mass of cholesteryl ester transfer protein (CETP) t ended to be higher in the diabetic animals (diabetic 4.06 +/- 0.73 mu g/ml versus control 3.05 +/- 0.93; P < 0.1). Consistent with CET being enhanced in vivo in the diabetic animals, compositional studies revea led that the triglyceride:cholesteryl ester core lipid ratio of their VLDL tended to be lower and LDL and HDL(2) significantly higher than i n controls (P < 0.001); and like human beings with non-insulin-depende nt diabetes mellitus, the free cholesterol:lecithin ratio was reduced in their HDL(2) (P < 0.05). Moreover, the sphingomyelin:lecithin ratio was significantly reduced in the diabetic monkeys' VLDL and LDL (P < 0.05 and P < 0.005, respectively), indicating that a disturbance also was present in lipoprotein surface phospholipid composition. Thus, dia betic cynomolgus monkeys have abnormalities in CET and disturbances in lipoprotein composition that resemble those in human beings with diab etes mellitus. Cynomolgus monkeys may be useful models for studying th e mechanism(s) that underlie the acceleration of CET and altered lipop rotein composition in diabetic patients.