Vitamin E/Lipid Peroxide Ratio and Susceptibility of LDL to Oxidative Modification in Non–Insulin-Dependent Diabetes Mellitus

Abstract

Abstract The presence of conventional risk factors cannot sufficiently account for the excess risk of atherosclerosis in patients with non–insulin-dependent diabetes mellitus (NIDDM). Oxidative modification of LDL has been implicated in the pathogenesis of coronary atherosclerosis. Thirty-five patients with NIDDM, 20 nondiabetic, hypertriglyceridemic subjects (HTG-control), and 21 diabetic, normotriglyceridemic subjects (NTG-control) were enrolled in this study. Oxidative susceptibility of LDL was determined by monitoring formation of conjugated dienes. Mean lag time of LDL oxidation and vitamin E/lipid peroxide of LDL was lower in patients with NIDDM (43.2±3.9 minutes and 1.6±1.3) than in HTG-control (48.8±3.2 minutes and 2.3±1.2, respectively) and NTG-control subjects (54.2±6.1 minutes and 3.0±1.8, respectively). Mean LDL particle size in patients with NIDDM and HTG-control subjects (24.4±0.9 and 24.7±0.7 nm, respectively) was smaller than in NTG-control subjects (25.9±1.0 nm). Multiple stepwise regression analyses ascertained that the vitamin E/lipid peroxide of LDL is a major determinant of LDL oxidation lag time. These results suggest that LDL in patients with NIDDM is more susceptible to oxidative modification primarily because of a reduced level of vitamin E/lipid peroxide of LDL. The enhanced susceptibility of LDL to oxidation may be a pivotal factor underlying the increased incidence of vascular disease in patients with NIDDM.