Journal of Lipid Research, Vol 36, 759-766, Copyright © 1995 by Lipid Research, Inc.
Accelerated cholesteryl ester transfer and altered lipoprotein composition in diabetic cynomolgus monkeys
JD Bagdade, JD Wagner, LL Rudel and TB Clarkson
Department of Medicine, Rush Medical College, Chicago, IL 60612-3864, USA.
To determine whether nonhuman primates demonstrate the same alterations in
transport of cholesteryl ester (CE) in plasma observed in diabetic humans,
cholesteryl ester transfer (CET) was measured in cynomolgus monkeys with
chronic spontaneous diabetes mellitus (glycated hemoglobin: diabetics 10.7
+/- 4.1%; controls 3.8 +/- 0.8%, P < 0.005). Among the plasma lipids,
only triglycerides were significantly increased in diabetic monkeys
(diabetics 303 +/- 294 mg/dl; controls 85 +/- 34 mg/dl; P < 0.05); total
plasma, LDL, HDL2, and HDL3 cholesterol concentrations did not differ
significantly from those of control animals. Similar to human beings with
insulin-dependent and non-insulin- dependent diabetes mellitus, CET
estimated both as the mass of cholesteryl ester transferred from HDL to the
apoB-containing lipoproteins (VLDL + LDL) and as the loss of radiolabeled
cholesteryl ester from HDL was significantly 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 transferred at 2 h (r = 0.75; P < 0.001) and the
isotopic transfer (k) (r = 0.64; P < 0.005). The mass of cholesteryl
ester transfer protein (CETP) tended to be higher in the diabetic animals
(diabetic 4.06 +/- 0.73 microgram/ml versus control 3.05 +/- 0.93; P <
0.1).(ABSTRACT TRUNCATED AT 250 WORDS)