title: The influences of obesity and glycemic control on endothelial activation in patients with type 2 diabetes.
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 A1c 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 A1c 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.
authors.affiliation: Department of Medicine, University of Auckland, 1000 Auckland, New Zealand. w.bagg@auckland.ac.nz
authors.forename: W
authors.initials: W
authors.lastname: Bagg
authors.forename: C
authors.initials: C
authors.lastname: Ferri
authors.forename: G
authors.initials: G
authors.lastname: Desideri
authors.forename: G
authors.initials: G
authors.lastname: Gamble
authors.forename: P
authors.initials: P
authors.lastname: Ockelford
authors.forename: G D
authors.initials: GD
authors.lastname: Braatvedt
mesh_terms: D015415:Biomarkers; D001786:Blood Glucose / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D004562:Electrocardiography; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D012044:Regression Analysis
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D015815:Cell Adhesion Molecules; D019332:Endothelin-1; D007004:Hypoglycemic Agents; D009569:Nitric Oxide