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).
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.


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.
Herder
Christian
C
German Diabetes Clinic, German Diabetes Center, Leibniz Center at Heinrich Heine University, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany. christian.herder@ddz.uni-duesseldorf.de
Kolb
Hubert
H
Koenig
Wolfgang
W
Haastert
Burkhard
B
Müller-Scholze
Sylvia
S
Rathmann
Wolfgang
W
Holle
Rolf
R
Thorand
Barbara
B
Wichmann
H-Erich
HE
D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000276:immunology; D005260:Female; D005858:Germany; D018149:Glucose Intolerance / Q000097:blood* / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood*; D008875:Middle Aged; D016011:Normal Distribution; D012016:Reference Values; D012307:Risk Factors
D015850:Interleukin-6; D008263:Macrophage Migration-Inhibitory Factors; D002097:C-Reactive Protein