Exp Clin Endocrinol Diabetes 2007; 115 - P01_125
DOI: 10.1055/s-2007-972381

The impact of testosterone and the androgen receptor (AR) CAG length polymorphism on insulin resistance in men

M Möhlig 1, J Spranger 1, MO Weickert 1, AM Arafat 2, AFH Pfeiffer 1, C Schöfl 2
  • 1German Institute of Human Nutrition Potsdam-Rehbrücke, Clinical Nutrition, Nuthetal, Germany
  • 2Charité University Medicine Berlin, Department of Endocrinology, Diabetes and Nutrition, Berlin, Germany

Objectives: Low testosterone levels in men are assumed to be associated with insulin resistance (IR). The effects of testosterone are mediated by the androgen receptor (AR), whose activity is modified by the AR CAG length polymorphism. We therefore hypothesized that the impact of testosterone on IR could be modified by this polymorphism.

Methods: 204 men with normal glucose tolerance were included. IR was quantified using HOMA %S. Free testosterone (T) was calculated from total testosterone and sexual hormone binding globulin using a web-based calculator (http://www.issam.ch/freetesto.htm). The AR CAG repeat length polymorphism was determined by PCR and gel electrophoresis. The relation between T, the AR CAG length and IR was modelled by multiple linear regression analysis with HOMA%S as the dependent variable (using SPSS software).

Results: BMI was significantly associated with HOMA %S and the regression consisting of BMI and age explained 14% of the variation of HOMA %S. Neither T nor the AR CAG length correlated with HOMA %S and the addition of T or the AR CAG length could not improve the model. However, the inclusion of a multiplicative interaction term between T and the AR CAG length improved the model, which now explained 16.3% of the variation of HOMA %S (p for the interaction term 0.039). To illustrate the impact of the interaction we calculated HOMA %S from this model for different CAG lengths and T concentrations. At a CAG length of 23 T had no impact on HOMA %S. At shorter lengths a rise in T was associated with a decrease in HOMA %S while for longer lengths a rise in T was associated with an increase in HOMA %S.

Conclusion: T and the AR CAG length interact with respect to insulin resistance in men. The impact of this interaction on insulin resistance, however, is small. Nevertheless, it appears necessary to consider this interaction when in men associations of T levels and IR are investigated and the results are interpreted.