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Long term exercise training decreases IL-6 serum levels in subjects with impaired glucose tolerance: effect of the -174G/C variant in interleukin-6 gene

A Oberbach, Department of Medicine, University of Leipzig, Leipzig, Germany
S Lehmann, Department of Medicine, University of Leipzig, Leipzig, Germany
K Kirsch, Department of Medicine, University of Leipzig, Leipzig, Germany
J Krist, Department of Medicine, University of Leipzig, Leipzig, Germany
M Sonnabend, Internal Medicine/Cardiology, University of Leipzig, Leipzig, Germany
A Linke, Internal Medicine/Cardiology, University of Leipzig, Leipzig, Germany
A Toenjes, Coordination Centre for Clinical Trials, University of Leipzig, Leipzig, Germany
M Stumvoll, Department of Medicine, University of Leipzig, Leipzig, Germany
M Bluher, Medical Department III, University of Leipzig, Leipzig, Germany
P Kovacs, Interdisciplinary Centre for Clinical Research, Medical Faculty, University of Leipzig, Leipzig, Germany

Correspondence: Peter Kovacs, Email: peter.kovacs{at}medizin.uni-leipzig.de

Abstract

Objective: Exercise training has been shown to have anti-inflammatory effects in patients with type 2 diabetes (T2D). Changes in interleukin-6 (IL-6) serum concentrations in response to training could contribute to these beneficial effects. However, there are heterogeneous data on whether circulating IL-6 is altered by exercise training. We therefore hypothesize that genetic factors modify the individual changes in IL-6 levels after long term training.

Research design and methods: The -174G/C variant in the IL-6 gene was genotyped in sixty subjects with impaired glucose tolerance (IGT). For a 12 months interventional study, patients were randomized into three groups: A control group (n=16) was compared to one group, which underwent a standardized training program (n=24) and another group, which was treated with rosiglitazone 4mg once daily (n=20). At baseline, after 1, 6, and 12 months, we measured anthropometric parameters and serum concentration of IL-6, and at baseline and after 12 months we determined glucose tolerance and fitness level.

Results: Only in subjects carrying the SNP -174C allele, long term exercise training resulted in significantly reduced IL-6 serum concentrations. Multivariate linear regression analysis identified the IL-6 genotype as significant predictor of changes in IL-6 serum concentrations independently of age, gender, and improvement in BMI, HbA1c, and fitness level in response to training.

Conclusions: Genetic variants in the IL-6 significantly modify changes in IL-6 serum concentrations in response to long term exercise training programs. Our data suggest that genetic factors are important determinants for the individual response to anti-inflammatory effects of exercise training.