Insulin action and fibrinolysis influenced by vitamin E in obese Type 2 diabetes mellitus.
Increased oxidative stress, hypofibrinolysis and insulin resistance are present in obese Type 2 diabetic patients. It is supposed that treatment with antioxidant alpha-tocopherol (vitamin E) could not only decrease free radical production, but also ameliorate insulin action. We evaluated the effect of 3 months administration of vitamin E (600 mg daily) on insulin action examined by hyperinsulinemic clamp in 11 obese Type 2 diabetic patients. Oxidative stress and fibrinolysis were also determined. The administration of vitamin E caused a decrease of glucose disposal rate (26.6 +/- 9.5 vs 21.3 +/- 7.5 micromol/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 receptor number was observed on erythrocytes after vitamin E (284 +/- 84 vs 171 +/- 59 pmol/l, P < 0.01). Significantly higher plasma malondialdehyde (MDA) concentration documented an increased oxidative stress in diabetic patients as compared with healthy persons (3.13 +/- 0.68 vs 1.89 +/- 0.18 micromol/l, P<0.001). An inverse relationship was found between MDA concentration and insulin sensitivity expressed by glucose disposal rate (r = -0.73). Vitamin E further worsened the hypofibrinolysis documented by a decrease of tissue plasminogen activator (P < 0.01) without changes in its inhibitor PAI-1. In conclusion. our results demonstrate that higher doses of vitamin E may further deteriorate insulin action and fibrinolysis in obese Type 2 diabetic patients.
Skrha
J
J
Department of Internal Medicine 3, Faculty of Medicine 1, Charles University, Prague, Czech Republic.
Sindelka
G
G
Kvasnicka
J
J
Hilgertová
J
J
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects / Q000502:physiology*; D015309:Glucose Clamp Technique; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D009765:Obesity; D018384:Oxidative Stress; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011972:Receptor, Insulin / Q000097:blood; D012016:Reference Values; D010959:Tissue Plasminogen Activator / Q000097:blood; D014810:Vitamin E / Q000627:therapeutic use*
D001786:Blood Glucose; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D014810:Vitamin E; D008315:Malondialdehyde; D011972:Receptor, Insulin; D010959:Tissue Plasminogen Activator