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.

Lipoprotein oxidation may contribute to development of atherosclerosis, and supplementation with antioxidants may reduce risk for atherosclerotic events. Genistein, a major isoflavone from soy protein, and catechins from green tea have important antioxidant properties. This study compared the effects of various diets containing antioxidant-rich foods or supplements on serum lipids and lipoprotein oxidation of male Sprague-Dawley rats. The control diet used was devoid of vitamin E. Test diets included these ingredients: green tea powder, 20 g/kg; beta-carotene, 250 mg/kg; a low isoflavone soy protein isolate; a genistein-rich soy protein isolate; and vitamin E, 4000 mg/kg. Ten-week-old rats were acclimatized for 1 week on a special custom diet without vitamin E. Following randomization and allocation to different diet groups, rats were fed the test diets for 3 weeks. Blood was drawn by cardiac puncture, and the plasma was separated by centrifugation. The VLDL-LDL fraction was isolated by ultracentrifugation. Oxidation kinetics of the VLDL-LDL fraction were determined by measuring the lag phase and formation of conjugated dienes, lipid peroxides, and TBARS. The vitamin E diet (P < 0.001) and high-genistein diet profoundly decreased all parameters of lipoprotein oxidation. The following alterations were noted with the high-genistein diet compared to the control diet: the lag phase was 49% longer (P=0.002); conjugated diene formation was decreased by 28% (P=0.01); lipid peroxide formation was decreased 31% (P=0.0059); and TBARS production was 35% lower (P=0.019). The low-isoflavone diet increased the lag phase by 43% (P=0.0019) but did not significantly alter other measures of oxidation. Green tea increased only the lag phase by 33% (P=0.012) compared to the control diet. Beta-Carotene had no significant effect on the oxidation of lipoproteins. The effect of genistein-rich soy protein isolates on lipoprotein oxidation in vitro suggests that either soy isoflavones or other antioxidants derived from soy protein, like vitamin E, may be transported in these lipoproteins. The minimal effects of the isoflavone-poor soy protein isolate suggests that either the small amount of isoflavones present have a potent effect or other components of soy protein are exerting these effects. Further studies are required to examine these results.