Elevated Markers of Endothelial Dysfunction Predict Type 2 Diabetes Mellitus in Middle-Aged Men and Women From the General Population

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 26; no. 2; pp. 398 - 405
• Main Authors: Thorand, Barbara, Baumert, Jens, Chambless, Lloyd, Meisinger, Christa, Kolb, Hubert, Döring, Angela, Löwel, Hannelore, Koenig, Wolfgang
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.02.2006; Hagerstown, MD Lippincott
• Subjects: Adult; Aged; Associated diseases and complications; Atherosclerosis (general aspects, experimental research); Atherosclerosis - blood; Atherosclerosis - epidemiology; Biological and medical sciences; Biomarkers - blood; Blood and lymphatic vessels; C-Reactive Protein - metabolism; Cardiology. Vascular system; Cohort Studies; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - etiology; Diabetes. Impaired glucose tolerance; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; E-Selectin - blood; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelium, Vascular - physiopathology; Female; Humans; Incidence; Intercellular Adhesion Molecule-1 - blood; Male; Management. Various non-drug treatments. Langerhans islet grafts; Medical sciences; Middle Aged; Predictive Value of Tests; Risk Factors; Solubility; von Willebrand Factor - metabolism; Endocrinopathy; Vascular disease; Type 2 diabetes; Human; adhesion molecules; von Willebrand factor; Atherosclerosis; Endothelial dysfunction; Metabolic diseases; Cardiovascular disease; Willebrand factor
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.ATV.0000198392.05307.aa

OBJECTIVE—Using the Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA)/Cooperative Research in the Region of Augsburg (KORA) database, we investigated prospectively whether increased levels of soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule 1 (sICAM-1), and von Willebrand factor (vWF), all considered to be sensitive markers of endothelial dysfunction, are associated with an increased risk of incident type 2 diabetes mellitus. METHODS AND RESULTS—In a case–cohort study, concentrations of adhesion molecules were measured in stored samples of 532 case subjects and 1712 noncase subjects. VWF was measured in a subsample with available plasma samples (n=191 case and 580 noncase subjects). Men and women with elevated levels of sE-selectin had a significantly increased risk of type 2 diabetes after multivariable adjustment. Hazard ratios (95% CIs) comparing tertile extremes of sE-selectin were 2.63 (1.79 to 3.88) and 1.71 (1.07 to 2.75) for men and women, respectively. Elevated levels of sICAM-1 were also associated with an increased risk of type 2 diabetes; however, the association was not independent of other diabetes risk factors including E-selectin [hazard ratio (95% CI) for tertile 3 versus tertile 1men, 1.32 (0.89 to 1.96); women, 1.03 (0.64 to 1.67)]. In this study, vWF was not associated with risk of type 2 diabetes. CONCLUSIONS—These data support a role of endothelial dysfunction in the etiology of type 2 diabetes.