© 1999 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Decreased Protection by HDL From Poorly Controlled Type 2 Diabetic Subjects Against LDL Oxidation May Be Due to the Abnormal Composition of HDL
From the Metabolic Research Group, Veterans Affairs Medical Center and Department of Internal Medicine (M.S.G., J.W.A., S.R.B.), and the Department of Internal Medicine (D.R.V.d.W.), College of Medicine, University of Kentucky, Lexington.
Correspondence to James W. Anderson, MD, Endocrine Section, Room 402B, VAMC, Cooper Drive Division, 2250 Leestown Rd 111C, Lexington, KY 40511. E-mail jwandersmd{at}aol.com
Abstract—High plasma triglyceride concentrations in diabetic subjects increase their risk for developing coronary heart disease. Numerous studies have shown that the high density lipoprotein (HDL) composition is abnormal in type 2 diabetic subjects. One study has shown that HDL (lipoprotein A-I) isolated from subjects with non–insulin-dependent diabetes mellitus exhibits a decreased capacity to induce cholesterol efflux. The current study examined the effect of HDL2 and HDL3 subfractions from poorly controlled type 2 diabetic and control subjects on THP-1 macrophage–mediated low density lipoprotein (LDL) oxidation. The composition and protective effects of HDL2, but not of HDL3, differed significantly between control and diabetic subjects. HDL2 from diabetics were triglyceride enriched and cholesterol depleted compared with those from controls. Control HDL2 inhibited LDL oxidation, as assessed by lipid peroxides and electrophoretic mobility, significantly (P<0.05) more than did diabetic HDL2 in both the fasting and postprandial state. In addition, HDL2 from diabetics did not protect against apolipoprotein B-100 fragmentation in LDL. Cross-linking in apolipoprotein A-I, oxidized in the presence of LDL, was extensive in HDL2 from diabetics compared with that from controls. Serum triglyceride concentrations were negatively correlated with protection by HDL2 (r=-0.673, P<0.05) in diabetic but not in control subjects. HDL2-associated platelet-activating factor acetylhydrolase activity was positively correlated with protection by HDL2 in control (r=0.872, P<0.002) but not in diabetic subjects. In conclusion, compositional alterations in HDL2 from poorly controlled type 2 diabetic subjects may reduce its antiatherogenic properties.
Key Words: diabetes • hypertriglyceridemia • atherosclerosis • oxidized LDL • HDL
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