Elevated markers of endothelial dysfunction predict type 2 diabetes mellitus in middle-aged men and women from the general population.
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.


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.
Thorand
Barbara
B
GSF National Research Center for Environment and Health, Institute of Epidemiology, Neuherberg, Germany.
Baumert
Jens
J
Chambless
Lloyd
L
Meisinger
Christa
C
Kolb
Hubert
H
Döring
Angela
A
Löwel
Hannelore
H
Koenig
Wolfgang
W
D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000097:blood* / Q000453:epidemiology*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology* / Q000209:etiology; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D015994:Incidence; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors; D012995:Solubility; D014841:von Willebrand Factor / Q000378:metabolism
D015415:Biomarkers; D019040:E-Selectin; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein