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 macrophagemediated 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 (PϽ0.05) 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 (rϭϪ0.673, PϽ0.05) 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 (rϭ0.872, PϽ0.002) but not in diabetic subjects.In conclusion, compositional alterations in HDL 2 from poorly controlled type 2 diabetic subjects may reduce its antiatherogenic properties.

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This study examined the kinetics of low-density lipoprotein (LDL) oxidation in the fasting and postprandial states of diabetic and control subjects to determine if LDL oxidation may contribute to accelerated atherosclerosis in diabetes. We compared in vitro oxidation of LDL from 12 control and 13 Type 2 diabetic subjects in the fasting and postprandial states. The extent of oxidation was assessed by length of lag phase, formation of conjugated dienes (CD), lipid peroxides, thiobarbituric acid reactive substances (TBARS), and percentage reduction in free amine groups. Diabetic subjects were significantly older and heavier. Comparisons between control and diabetic subjects in the postprandial state showed that the lag phase was significantly shorter in diabetic subjects than controls (P = 0.005), TBARS were significantly higher (P = 0.006), and levels of CD were higher at 60, 65, and 70 min (P < 0.01). In the fasting state, however, these comparisons were not significant. In diabetic subjects, postprandial samples had a significantly shorter lag phase (P = 0.003), higher TBARS (P = 0.006), and higher levels of CD at 60, 65 (P < 0.001), and 70 min (P = 0.0013) compared to fasting samples. Elevated levels of serum triglycerides in diabetic subjects were negatively correlated to lag phase, in fasting (P = 0.06) and postprandial states (P = 0.002). We conclude that accelerated oxidation of LDL seen in postprandial states in diabetes may be a critical contributor to cardiovascular risks. Elevated levels of serum triglycerides may contribute to the rapid oxidation of LDL seen in diabetic subjects.

These studies indicate that the LDL from diabetic subjects are more susceptible to oxidation than LDL from non-diabetic subjects. Supplementation of diabetic subjects with antioxidant vitamins significantly decreases susceptibility of LDL to oxidation by Cu. These studies are consistent with epidemiological and intervention studies suggesting that antioxidant vitamin use significantly decreases risk for coronary heart disease.