Predominant role of obesity/insulin resistance in oxidative stress development.

BACKGROUND: Hyperlipidaemia, hyperglycaemia and hyperinsulinaemia, hallmarks of the postprandial state, have been also associated with increased oxidative stress and lipoprotein oxidation contributing to vascular injury and atherosclerosis. However, the specific links among metabolic disorders, postprandial state, insulin resistance and oxidative stress are still to be clarified. This study aimed at investigating the individual role played by obesity, insulin resistance and type 2 diabetes in the occurrence of fasting and postprandial oxidative stress. DESIGN: Biomarkers of oxidative stress [F2-isoprostanes and circulating oxidized low-density lipoproteins (LDL)], LDL oxidability (conjugated diene kinetic, thiobarbituric acid reactive substances (TBARs) formation and electronegativity increase) and antioxidant vitamins (?-carotene, ?-tocopherol and retinol) were evaluated at fasting and 6 h after a standard fat-rich meal in 10 obese diabetic (ObD), 11 obese and 11 normal-weight control men. Insulin sensitivity was evaluated by euglycaemic hyperinsulinaemic clamp. RESULTS: ObD and obese subjects, characterized by a similar level of adiposity and insulin resistance, showed higher urinary F2-isoprostanes and circulating oxidized LDL, an increased susceptibility to oxidation of plasma LDL (lower lag phase, higher TBARs formation, and higher relative electrophoretic mobility), and lower plasma content of ?-carotene and retinol than control subjects, both at fasting and after the test meal. CONCLUSIONS: Obesity and insulin resistance, more than type 2 diabetes, play the most relevant role in oxidative stress development. The correction of obesity and insulin resistance might be a useful strategy in counteracting systemic oxidative stress.