Insulin action and fibrinolysis influenced by vitamin E in obese Type 2 diabetes mellitus

Increased oxidative stress, hypofibrinolysis and insulin resistance are pre sent in obese Type 2 diabetic patients. It is supposed that treatment with antioxidant alpha-tocopherol (vitamin E) could not only decrease free radic al production. but also ameliorate insulin action. We evaluated the effect of 3 months administration of vitamin E (600 mg daily) on insulin action ex amined by hyperinsulinemic clamp in 11 obese Type 2 diabetic patients. Oxid ative stress and fibrinolysis were also determined. The administration of v itamin E caused a decrease of glucose disposal rate (26.6 +/- 9.5 vs 21.3 /- 7.5 mu mol/kg/min, P < 0.02) and of metabolic clearance rate of glucose (3.7 +/- 1.6 vs 2.9 +/- 0.8 ml/kg/min, P < 0.02). A decrease of insulin rec eptor number was observed on erythrocytes after vitamin E (284 +/- 84 vs 17 1 +/- 59 pmol/l, P < 0.01). Significantly higher plasma malondialdehyde (MD A) concentration documented an increased oxidative stress in diabetic patie nts as compared with healthy persons (3.13 +/- 0.68 vs 1.89 +/- 0.18 mu mol /l, P < 0.001). An inverse relationship was found between MDA concentration and insulin sensitivity expressed by glucose disposal rate (r = - 0.73). V itamin E further worsened the hypofibrinolysis documented by a decrease of tissue plasminogen activator (P < 0.01) without changes in its inhibitor PA I-1. In conclusion, our results demonstrate that higher doses of vitamin E may further deteriorate insulin action and fibrinolysis in obese Type 2 dia betic patients. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.