Decreased protection by HDL from poorly controlled type 2 diabetic subjects against LDL oxidation may be due to the abnormal composition of HDL

High plasma triglyceride concentration in diabetic subjects increase their risk for developing coronary heart disease. Numerous studies have shown tha t the high density lipoprotein (HDL) composition is abnormal in type 2 diab etic 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 effe ct of HDL2 and HDL3 subfractions from poorly controlled type 2 diabetic and control subjects on THP-I macrophage-mediated low density lipoprotein (LDL ) oxidation. The composition and protective effects of HDL2, but not of HDL 3, 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 t han did diabetic HDL2 in both the fasting and postprandial state, In additi on, HDL2 from diabetics did not protect against apolipoprotein B-100 fragme ntation in LDL. Cross-linking in apolipoprotein A-I, oxidized in the presen ce of LDL, was extensive in HDL2 from diabetics compared with that from con trols. Serum triglyceride concentrations were negatively correlated with pr otection by HDL2 (r= -0.673, P<0.05) in diabetic but not in control subject s. 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 antiath erogenic properties.