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Androgen receptor CAG repeat polymorphism is associated with serum testosterone levels, obesity and serum leptin in men with type 2 diabetes

R Stanworth, Academic Unit of Diabetes, Endocrinlogy and Metabolism, University of Sheffield, Sheffield, S10 2RX, United Kingdom
D Kapoor, Diabetes & Endocrinology, Barnsley Hospital, Barnsley, United Kingdom
K Channer, Dept of Cardiology M131, Royal Hallamshire Hospital, Sheffield, United Kingdom
T Jones, Diabetes & Endocrinology, Barnsley Hospital, Barnsley, United Kingdom

Correspondence: Roger Stanworth, Email: roger.stanworth{at}nhs.net

Abstract

Objective; To determine the relationships between androgen receptor CAG repeat polymorphism length (AR CAG), sex hormones and clinical variables in men with type 2 diabetes (DM2). Men with DM2 are known to have a high prevalence of low testosterone levels. Studies suggest that testosterone replacement therapy may improve insulin sensitivity and glycaemic control in men with DM2 and reduces central obesity and serum leptin. AR CAG is known to correlate with androgen receptor sensitivity and with body fat, insulin levels and leptin in healthy men.

Design; Cross-sectional study set in a district general hospital diabetes centre.

Methods; Sex hormones, AR CAG and symptoms of hypogonadism were assessed in 233 men with DM2. Associations were sought between these variables and others such as obesity, leptin, glycaemic control and blood pressure.

Results; Testosterone was negatively associated and AR CAG positively associated with obesity and leptin. The associations of AR CAG with leptin and obesity were independent of testosterone, estradiol, gonadotrophins and age. AR CAG was also independently associated with total, bioavailable and free testosterone, luteinising hormone, waist circumference, BMI, leptin and systolic blood pressure. There was no association of AR CAG with SHBG, estradiol, HbA1C or the symptoms of hypogonadism.

Conclusions; The association of longer AR CAG with obesity and leptin suggests that shorter AR CAG may have an influence in maintaining healthy anthropomorphics and metabolism in men with DM2. Testosterone and LH levels are higher in men with longer AR CAG, probably reflecting reduced negative feedback through a less sensitive receptor.