LOW-DENSITY-LIPOPROTEIN SIZE, HIGH-DENSITY-LIPOPROTEIN CONCENTRATION,AND ENDOTHELIAL DYSFUNCTION IN NON-INSULIN-DEPENDENT DIABETES

We examined endothelial function (nitric-oxide mediated) in 29 men wit h diet-treated non-insulin-dependent (Type 2) diabetes mellitus (NIDDM ) and 18 male age-matched controls. Forearm blood flow was measured by venous occlusive plethysmography during intra-arterial administration of acetylcholine (ACh, 7.5 and 15 mu g min(-1)) and sodium nitropruss ide (SNP, 3 and 10 mu g min(-1)). LDL particle size was estimated by n on-denaturing gel electrophoresis. Serum lipids, blood pressure, and g lycated haemoglobin were also measured. LDL particle size was smaller (p = 0.048) in the diabetic patients than controls. In the diabetic pa tients, LDL particle size was a significant positive predictor (p = 0. 01) of the area under the dose-response curve for ACh, after adjusting for age, HbA(1c), systolic BP, and cholesterol (R-2 0.20). In stepwis e regression including serum lipid and lipoprotein concentrations and LDL particle size, decreased HDL cholesterol was the best predictor of an impaired vasodilatory response to ACh. Vasodilatory responses to s odium nitroprusside were not significantly correlated with LDL particl e size or serum lipid and lipoprotein concentrations. We conclude that in men with NIDDM, small, dense LDL particle size is associated with abnormal endogenous release of nitric oxide. The contribution of small , dense LDL particles to the development of endothelial dysfunction an d early diabetic vasculopathy may not, however, be as great as decreas ed HDL cholesterol. (C) 1997 by John Wiley & Sons, Ltd.