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Diabetes Care 29:368-371, 2006
DOI: 10.2337/diacare.29.02.06.dc05-1474
© 2006 by the American Diabetes Association
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Cardiovascular and Metabolic Risk
Original Article

Association of Systemic Concentrations of Macrophage Migration Inhibitory Factor With Impaired Glucose Tolerance and Type 2 Diabetes

Results from the Cooperative Health Research in the Region of Augsburg, Survey 4 (KORA S4)

Christian Herder, PHD1, Hubert Kolb, PHD1, Wolfgang Koenig, MD2, Burkhard Haastert, PHD3, Sylvia Müller-Scholze, PHD1, Wolfgang Rathmann, MD, MSPH3, Rolf Holle, PHD4, Barbara Thorand, PHD, MPH5 and H.-Erich Wichmann, MD, PHD5

1 German Diabetes Clinic, German Diabetes Center, Leibniz Center at Heinrich Heine University, Düsseldorf, Germany
2 Department of Internal Medicine II–Cardiology, University of Ulm Medical Center, Ulm, Germany
3 Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center at Heinrich Heine University, Düsseldorf, Germany
4 Institute of Health Economics and Health Care Management, GSF–National Research Center for Environment and Health, Neuherberg, Germany
5 Institute of Epidemiology, GSF–National Research Center for Environment and Health, Neuherberg, Germany

Address correspondence and reprint requests to Dr. Christian Herder, German Diabetes Clinic, German Diabetes Center, Leibniz Center at Heinrich Heine University, Auf’m Hennekamp 65, 40225 Düsseldorf, Germany. E-mail: christian.herder{at}ddz.uni-duesseldorf.de

OBJECTIVE—Macrophage migration inhibitory factor (MIF) is a central cytokine in innate immunity. MIF expression can be regulated by glucose and insulin, but data on the association with type 2 diabetes are sparse. The aim of this study was to test whether MIF is associated with impaired glucose tolerance (IGT) and type 2 diabetes and whether these associations are independent of metabolic and immunological risk factors and to compare the associations of MIF and IGT/type 2 diabetes with those of C-reactive protein (CRP) and interleukin-6 (IL-6) with IGT/type 2 diabetes.

RESEARCH DESIGN AND METHODS—The Cooperative Health Research in the Region of Augsburg/Kooperative Gesundheitsforschung im Raum Augsburg, Survey 4 (KORA S4) is a population-based survey performed in Southern Germany (1999–2001). Of 1,653 participants aged 55–74 years, 236 patients with type 2 diabetes, 242 subjects with IGT, and 244 normoglycemic control subjects matched for age and sex were included in this cross-sectional study. Serum concentrations of MIF were measured by enzyme-linked immunosorbent assay.

RESULTS—Serum MIF concentrations are highly increased in individuals with IGT and type 2 diabetes. The associations of MIF with IGT and type 2 diabetes were independent of classical risk factors and of CRP and IL-6 and were much stronger before and after multivariate adjustment than the associations of CRP and IL-6 with IGT and type 2 diabetes.

CONCLUSIONS—Our data suggest that elevations of systemic MIF concentrations precede the onset of type 2 diabetes. This finding may be relevant because MIF has been reported to contribute to the development of type 2 diabetes–related diseases such as atherosclerosis and cancer.

Abbreviations: CRP, C-reactive protein • IGT, impaired glucose tolerance • IL-6, interleukin-6 • KORA, Cooperative Health Research in the Region of Augsburg • MIF, macrophage migration inhibitory factor • OGTT, oral glucose tolerance test


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