on December 1, 2005
Published online before print December 1, 2005, doi: 10.1161/01.ATV.0000198392.05307.aa
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Submitted on August 23, 2005
Accepted on November 17, 2005
Elevated Markers of Endothelial Dysfunction Predict Type 2 Diabetes Mellitus in Middle-Aged Men and Women From the General Population
Barbara Thorand ;
From the GSF National Research Center for Environment and Health (B.T., J.B., C.M., A.D., H.L.), Institute of Epidemiology, Neuherberg, Germany; University of North Carolina at Chapel Hill (L.C.), Chapel Hill, NC; German Diabetes Center (H.K.), University of Düsseldorf, Düsseldorf, Germany; and Department of Internal Medicine II-Cardiology (W.K.), University of Ulm Medical Center, Ulm, Germany.
* To whom correspondence should be addressed. E-mail: wolfgang.koenig{at}medizin.uni-ulm.de.
Objective--Using the Monitoring of Trends and Determinants in Cardiovascular Disease/Cooperative Research in the Region of Augsburg database, we investigated prospectively whether increased levels of soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule 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 soluble intercellular adhesion molecule 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 1: men, 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.
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