Influence of low density lipoprotein (LDL) subfraction profile and LDL oxidation on endothelium-dependent and independent vasodilation in patients with type 2 diabetes

Recent studies have suggested that hypercholesterolemia is associated with endothelial dysfunction. In patients with type 2 diabetes mellitus, dyslipi demia is mainly characterized by hypertriglyceridemia, low high density lip oprotein, and a preponderance of small dense low density lipoprotein (LDL) particles. We have examined the relationships among LDL subfractions, the s usceptibility of LDL to oxidation in vitro, and endothelial function in typ e 2 diabetes mellitus. LDL subfractions were measured by density gradient u ltracentrifugation. The susceptibility of LDL to oxidation was determined b y measuring the kinetics of conjugated dienes formation during copper-media ted 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 ma tched 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 independe nt dilation of the brachial artery (P < 0.01)were impaired in the diabetic patients. On multivariate analysis, the rate of oxidation and LDL-III conce ntration accounted for 12% and 6%, respectively, of the variation in endoth elium-dependent vasodilation (adjusted r(2) = 0.15; P < 0.05), whereas LDL- III concentration and the maximum amount of conjugated dienes formed accoun ted for 27% and 5%, respectively, of the variation in endothelium-independe nt vasodilation (adjusted r(2) = 0.32; P < 0.01)in the diabetic patients. I n conclusion, endothelial and smooth muscle cell dysfunction in type 2 diab etes were related to abnormalities in LDL subfractions and in LDL oxidation .