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*CHOLESTEROL
*COPPER, ELEMENTAL
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*Diabetes
The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 9 3212-3216
Copyright © 1999 by The Endocrine Society

Original Studies

Influence of Low Density Lipoprotein (LDL) Subfraction Profile and LDL Oxidation on Endothelium-Dependent and Independent Vasodilation in Patients with Type 2 Diabetes1

K. C. B. Tan, V. H. G. Ai, W. S. Chow, M. T. Chau, L. Leong and K. S. L. Lam

Department of Medicine, University of Hong Kong, and the Department of Diagnostic Radiology, Queen Mary Hospital (V.H.G.A., M.T.C., L.L.), Hong Kong

Address all correspondence and requests for reprints to: Dr. K. Tan, Department of Medicine, Queen Mary Hospital, Pokfulam Road, Hong Kong.

Recent studies have suggested that hypercholesterolemia is associated with endothelial dysfunction. In patients with type 2 diabetes mellitus, dyslipidemia is mainly characterized by hypertriglyceridemia, low high density lipoprotein, and a preponderance of small dense low density lipoprotein (LDL) particles. We have examined the relationships among LDL subfractions, the susceptibility of LDL to oxidation in vitro, and endothelial function in type 2 diabetes mellitus. LDL subfractions were measured by density gradient ultracentrifugation. The susceptibility of LDL to oxidation was determined by measuring the kinetics of conjugated dienes formation during copper-mediated oxidation of LDL. Endothelium-dependent and independent vasodilation of the brachial artery were assessed by high resolution vascular ultrasound. Diabetic patients had a higher concentration of small dense LDL-III than matched controls (P < 0.01). The lag phase of conjugated dienes formation was shorter in the diabetic patients (P < 0.05), and the rate of LDL oxidation was faster (P < 0.05). Both endothelium-dependent (P < 0.01) and independent dilation of the brachial artery (P < 0.01) were impaired in the diabetic patients. On multivariate analysis, the rate of oxidation and LDL-III concentration accounted for 12% and 6%, respectively, of the variation in endothelium-dependent vasodilation (adjusted r2 = 0.18; P < 0.05), whereas LDL-III concentration and the maximum amount of conjugated dienes formed accounted for 27% and 5%, respectively, of the variation in endothelium-independent vasodilation (adjusted r2 = 0.32; P < 0.01) in the diabetic patients. In conclusion, endothelial and smooth muscle cell dysfunction in type 2 diabetes were related to abnormalities in LDL subfractions and in LDL oxidation.




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