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Diabetes 54:3554-3559, 2005
© 2005 by the American Diabetes Association, Inc.

Plasma Cholesteryl Ester Transfer Is a Determinant of Intima-Media Thickness in Type 2 Diabetic and Nondiabetic Subjects

Role of CETP and Triglycerides

Rindert de Vries1, Frank G. Perton1, Geesje M. Dallinga-Thie2, Arie M. van Roon3, Bruce H.R. Wolffenbuttel1, Arie van Tol1,4, and Robin P.F. Dullaart1

1 Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
2 Laboratory of Vascular Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
3 Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
4 Department of Cell Biology and Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands

We tested whether carotid artery intima-media thickness (IMT) is associated with plasma cholesteryl ester transfer (CET) and/or the plasma cholesteryl ester transfer protein (CETP) concentration in type 2 diabetic and control subjects. In 87 male and female subjects with type 2 diabetes (nonsmokers, no insulin or lipid-lowering drug treatment) and 82 control subjects, IMT, plasma CET, CETP mass, and lipids were determined. HDL cholesterol was lower, whereas IMT, pulse pressure, plasma triglycerides, and plasma CET and CETP concentration were higher in diabetic patients versus control subjects. In diabetic patients, plasma CET was positively determined by triglycerides (P < 0.001), non-HDL cholesterol (P < 0.001), CETP (P = 0.002), and the interaction between CETP and triglycerides (P = 0.004). In control subjects, plasma CET was positively related to triglycerides (P < 0.001) and non-HDL cholesterol (P < 0.001). HDL cholesterol was inversely related to plasma CET in each group (P < 0.01 for both). IMT was positively associated with plasma CET in diabetic (P = 0.05) and control (P < 0.05) subjects after adjustment for age, sex, and pulse pressure. No independent relationship with plasma CETP mass was found. Plasma CET is a positive determinant of IMT. Plasma CETP mass, in turn, is a determinant of CET with an increasing effect at higher triglycerides. These data, therefore, provide a rationale to evaluate the effects of CETP inhibitor treatment on plasma CET and on cardiovascular risk in diabetes-associated hypertriglyceridemia.

Address correspondence and reprint requests to Robin P.F. Dullaart, MD, PhD, University Medical Center Groningen, Department of Endocrinology, P.O. Box 30001, 9700 RB, Hanzeplein 1, Groningen, 9713 GZ Netherlands. E-mail: r.p.f.dullaart{at}int.umcg.nl

Abbreviations: apo, apolipoprotein; CET, cholesteryl ester transfer; CETP, CET protein; IMT, intima-media thickness


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