title: Decreased protection by HDL from poorly controlled type 2 diabetic subjects against LDL oxidation may Be due to the abnormal composition of HDL.
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 HDL(2) and HDL(3) 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 HDL(2), but not of HDL(3), differed significantly between control and diabetic subjects. HDL(2) from diabetics were triglyceride enriched and cholesterol depleted compared with those from controls. Control HDL(2) inhibited LDL oxidation, as assessed by lipid peroxides and electrophoretic mobility, significantly (P<0.05) more than did diabetic HDL(2) in both the fasting and postprandial state. In addition, HDL(2) 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 HDL(2) from diabetics compared with that from controls. Serum triglyceride concentrations were negatively correlated with protection by HDL(2) (r=-0.673, P<0.05) in diabetic but not in control subjects. HDL(2)-associated platelet-activating factor acetylhydrolase activity was positively correlated with protection by HDL(2) in control (r=0.872, P<0.002) but not in diabetic subjects. In conclusion, compositional alterations in HDL(2) from poorly controlled type 2 diabetic subjects may reduce its antiatherogenic properties.
authors.affiliation: Metabolic Research Group, Veterans Affairs Medical Center and Department of Internal Medicine, College of Medicine, University of Kentucky, Lexington, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Gowri
authors.forename: D R
authors.initials: DR
authors.lastname: Van der Westhuyzen
authors.forename: S R
authors.initials: SR
authors.lastname: Bridges
authors.forename: J W
authors.initials: JW
authors.lastname: Anderson
mesh_terms: D002460:Cell Line; D008076:Cholesterol, HDL / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000097:blood*; D008264:Macrophages / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D012016:Reference Values; D012044:Regression Analysis; D014280:Triglycerides / Q000032:analysis
chemical_list: D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; C099252:oxidized low density lipoprotein