© 1997 American Heart Association, Inc.
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Vitamin E/Lipid Peroxide Ratio and Susceptibility of LDL to Oxidative Modification in Non–Insulin-Dependent Diabetes Mellitus
From the First Department of Internal Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan.
Correspondence to Hiroshi Yoshida, MD. From June 1, 1996, through April 30, 1998: c/o Daniel Steinberg, MD, PhD, Room 1080, Department 0682, Basic Science Bldg, Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0682; after May 1, 1998: First Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359, Japan.
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.
Key Words: oxidative susceptibility • LDL • lipid peroxide • vitamin E • non–insulin-dependent diabetes mellitus
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