Evidence for a relationship between oxidative stress and insulin action in non-insulin-dependent (type II) diabetic...

Ten healthy subjects and 30 non-insulin-dependent (type II) diabetic patients matched for age, gender ratio, body mass index, lean body mass (LBM), waist to hip ratio, and arterial blood pressure volunteered for the study. In all subjects, fasting plasma free radical (O2-) levels and basal membrane lipid fluidity (MLF) and protein mobility (MPM) were determined. The whole group of subjects underwent a euglycemic hyperinsulinemic glucose clamp with simultaneous indirect calorimetry for substrate oxidation determination. Diabetic patients versus controls displayed higher fasting plasma glucose (8.3 +/- 0.4 v 5.1 +/- 0.4 mmol/L, P +/- .001), O2- (0.48 +/- 0.02 v 0.16 +/- 0.02 mumol/L x min), and hemoglobin A1c ([HbA1C] 7.9% +/- 0.4% v 5.7% +/- 0.3%, P < .03) levels and a stronger reduction in basal MLF (0.243 +/- 0.006 v 0.318 +/- 0.009, P < .003) and basal MPM (0.348 +/- 0.003 v 0.518 +/- 0.010, P < .002). Whole-body glucose disposal (WBGD) and oxidative and nonoxidative glucose metabolism were also significantly lower in diabetics than in controls. In diabetic patients (n = 30), plasma O2- levels correlated with basal MLF (r = -.59, P < .005), basal MPM (r = -.84, P < .001), fasting plasma insulin level (r = .51, P < .004), WBGD (r = -.53, P < .002), and nonoxidative (r = -.45, P < .01) glucose metabolism. In conclusion, our results demonstrate that a relationship between plasma O2- levels and insulin action occurs in non-insulin-dependent diabetics.