The influences of obesity and glycemic control on endothelial activation in patients with type 2 diabetes

The aims of this study were to elucidate the factors that contribute to end othelial activation and fibrinolytic abnormalities in patients with poorly controlled type 2 diabetes and to determine whether improved glycemic contr ol reduces endothelial activation. Adhesion molecules [E-selectin, intracel lular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1], von Willebrand factor, total nitric oxide (NO), endothelin-1, tissue plasm inogen activator, and plasminogen activator inhibitor-1 were measured in 43 type 2 diabetic subjects with hemoglobin A(1c) of 9.0% or more at baseline (compared with 21 healthy controls) who after 20 wk had been randomized to either improved (IC) or usual (UC) glycemic control. At baseline, type 2 d iabetic patients had significant endothelial activation and abnormal fibrin olysis compared with control subjects. Body mass index in the diabetic pati ents was the only independent predictor of E-selectin (P = 0.007), ICAM-1 ( P = 0.01), and NO (P = 0.008) concentrations, but not vascular cell adhesio n molecule-1, plasminogen activator inhibitor-1, or tissue plasminogen acti vator (all P > 0.05). Type 2 diabetic patients with a body mass index of 28 kg/m(2) or less had concentrations of E-selectin, ICAM-1, endothelin-1, an d NO similar to those in healthy controls. After 20 wk, hemoglobin Ai, was significantly lower in IC us. UC (IC, 8.02 +/- 0.25%; UC, 10.23 +/- 0.23%; P < 0.0001), but there were no significant changes in markers of endothelia l activation or indexes of fibrinolysis. Obesity appears to be the most important predictor of endothelial activatio n in patients with type 2 diabetes. Shortterm improvement in glycemic contr ol does not appear to reduce endothelial activation.