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The Influences of Obesity and Glycemic Control on Endothelial Activation in Patients with Type 2 Diabetes

Department of Medicine (W.B., G.G., P.O., G.D.B.), University of Auckland, 1000 Auckland, New Zealand; and Department of Internal Medicine and Public Health, University of L’Aquila (C.F., G.D.), 67100 L’Aquila, Italy

Address all correspondence and requests for reprints to: Dr. W. Bagg, Department of Medicine, 4th Floor, Auckland Hospital, Park Road, Grafton, 1000 Auckland, New Zealand. E-mail: w.bagg{at}auckland.ac.nz

Abstract

The aims of this study were to elucidate the factors that contribute to endothelial activation and fibrinolytic abnormalities in patients with poorly controlled type 2 diabetes and to determine whether improved glycemic control reduces endothelial activation. Adhesion molecules [E-selectin, intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1], von Willebrand factor, total nitric oxide (NO), endothelin-1, tissue plasminogen 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 diabetic patients had significant endothelial activation and abnormal fibrinolysis compared with control subjects. Body mass index in the diabetic patients 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 adhesion molecule-1, plasminogen activator inhibitor-1, or tissue plasminogen activator (all P > 0.05). Type 2 diabetic patients with a body mass index of 28 kg/m² or less had concentrations of E-selectin, ICAM-1, endothelin-1, and NO similar to those in healthy controls. After 20 wk, hemoglobin A_1c was significantly lower in IC vs. UC (IC, 8.02 ± 0.25%; UC, 10.23 ± 0.23%; P < 0.0001), but there were no significant changes in markers of endothelial activation or indexes of fibrinolysis.

Obesity appears to be the most important predictor of endothelial activation in patients with type 2 diabetes. Short-term improvement in glycemic control does not appear to reduce endothelial activation.

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