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Departments of Clinical Nutrition (M.M., J.S., M.O., M.R., A.F.H.P.) and Epidemiology (H.B., A.K., E.F., M.M.B., K.H.), German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany; and Department of Endocrinology (M.M., J.S., M.O., M.R., A.F.H.P.), Diabetes and Nutrition, Charité-University Medicine Berlin, Campus Benjamin Franklin, 12200 Berlin, Germany; and Research Institute of Child Nutrition (A.K.), D-44225 Dortmund, Germany
Address all correspondence and requests for reprints to: Matthias Möhlig, M.D., Department of Clinical Nutrition, German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, 14558 Bergholz-Rehbrücke, Germany. E-mail: mmoehlig{at}mail.dife.de.
Increased levels of IL-6 add further risk to the impact of obesity in respect to the development of type 2 diabetes mellitus (T2DM). A C-174G polymorphism within the IL-6 promoter region was shown to influence transcription rate of IL-6. We made use of a nested case-control study within the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort of 27,548 individuals, selecting 188 T2DM cases and 376 controls to investigate this polymorphism in respect to development of T2DM. This polymorphism was found to modify the correlation between body mass index (BMI) and IL-6 by showing a much stronger increase of IL-6 at increased BMI for CC genotypes compared with GG genotypes. Interestingly, C-174G polymorphism was found to be an effect modifier for the impact of BMI regarding T2DM. Whereas BMI greater than or equal to 28 kg/m2 increased the risk of T2DM 3.44-fold [95% confidence interval (CI), 1.34- to 8.24-fold] for GG genotypes and 2.94-fold (95% CI, 1.56- to 5.56-fold) for GC genotypes, we found a 17.68-fold (95% CI, 3.57- to 87.66-fold) increase in risk for CC genotypes. In conclusion, obese individuals with BMI greater than or equal to 28 kg/m2 carrying the CC genotype showed a more than 5-fold increased risk of developing T2DM compared with the remaining genotypes and, hence, might profit most from weight reduction.
This work was supported by a grant from the Gottfried-Wilhelm-Leibnitz-Gesellschaft. Further grants to the authors were from the German Diabetes Association (to M.M., J.S., and M.R.), the Fritz-Thyssen-Stiftung (Grant 10.01.2.102 to M.R.), the Deutsche Forschungsgemeinschaft (Grant RI 1076/1-1 to M.R.), the Eli Lilly International Foundation (to J.S. and A.F.H.P.), the European Union (Grant SOC 95 201408 OSF02), and the Deutsche Krebshilfe (Grant 70-2488-HAI to A.K.).
M.M., H.B., and J.S. contributed equally to this article.
Abbreviations: ACE, Angiotensin-converting enzyme; BMI, body mass index; CI, confidence interval; EPIC, European Prospective Investigation into Cancer and Nutrition; HbA1c, hemoglobin A1c; T2DM, type 2 diabetes mellitus.
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