This Article Full Text Full Text (PDF) All Versions of this Article: 26/2/398    most recent 01.ATV.0000198392.05307.aav1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thorand, B. Search for Related Content PubMed PubMed Citation Articles by Thorand, B.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:398.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

Barbara Thorand; Jens Baumert; Lloyd Chambless; Christa Meisinger; Hubert Kolb; Angela Döring; Hannelore Löwel; Wolfgang Koenig for the MONICA/KORA Study Group

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.

Correspondence to Wolfgang Koenig, Department of Internal Medicine II–Cardiology, University of Ulm Medical Center, Robert Koch Str. 8, D-89081 Ulm, Germany. E-mail wolfgang.koenig{at}medizin.uni-ulm.de

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 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.

Using a case–cohort design, markers of endothelial dysfunction (soluble E-selectin and soluble intercellular adhesion molecule-1) predicted incident type 2 diabetes mellitus in a large population–based sample of middle-aged men and women. These data support a role for endothelial dysfunction in the etiology of type 2 diabetes.

Key Words: endothelial dysfunction • type 2 diabetes • adhesion molecules • von Willebrand factor

This article has been cited by other articles:

				S. G. Wannamethee, N. Sattar, A. Rumley, P. H. Whincup, L. Lennon, and G. D.O. Lowe Tissue Plasminogen Activator, von Willebrand Factor, and Risk of Type 2 Diabetes in Older Men Diabetes Care, May 1, 2008; 31(5): 995 - 1000. [Abstract] [Full Text] [PDF]

				W. Koenig and C. Meisinger Uric Acid, Type 2 Diabetes, and Cardiovascular Diseases: Fueling the Common Soil Hypothesis? Clin. Chem., February 1, 2008; 54(2): 231 - 233. [Full Text] [PDF]

				F. Perticone, R. Maio, A. Sciacqua, F. Andreozzi, G. Iemma, M. Perticone, C. Zoccali, and G. Sesti Endothelial Dysfunction and C-Reactive Protein Are Risk Factors for Diabetes in Essential Hypertension Diabetes, January 1, 2008; 57(1): 167 - 171. [Abstract] [Full Text] [PDF]

				A. Zirlik, S. M. Abdullah, N. Gerdes, L. MacFarlane, U. Schonbeck, A. Khera, D. K. McGuire, G. L. Vega, S. Grundy, P. Libby, et al. Interleukin-18, the Metabolic Syndrome, and Subclinical Atherosclerosis: Results From the Dallas Heart Study Arterioscler. Thromb. Vasc. Biol., September 1, 2007; 27(9): 2043 - 2049. [Abstract] [Full Text] [PDF]

				Y. Song, J. E. Manson, L. Tinker, N. Rifai, N. R. Cook, F. B. Hu, G. S. Hotamisligil, P. M. Ridker, B. L. Rodriguez, K. L. Margolis, et al. Circulating Levels of Endothelial Adhesion Molecules and Risk of Diabetes in an Ethnically Diverse Cohort of Women Diabetes, July 1, 2007; 56(7): 1898 - 1904. [Abstract] [Full Text] [PDF]

				B. Thorand, J. Baumert, H. Kolb, C. Meisinger, L. Chambless, W. Koenig, and C. Herder Sex Differences in the Prediction of Type 2 Diabetes by Inflammatory Markers: Results from the MONICA/KORA Augsburg case-cohort study, 1984-2002 Diabetes Care, April 1, 2007; 30(4): 854 - 860. [Abstract] [Full Text] [PDF]