Eur J Endocrinol
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DOI: 10.1530/EJE-08-0266
European Journal of Endocrinology, Vol 159, Issue 6, 739-746
Copyright © 2008 by European Society of Endocrinology
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CLINICAL STUDY

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

R D Stanworth1,2, D Kapoor1,2, K S Channer3,4 and T H Jones1,2

1 Robert Hague Centre for Diabetes and Endocrinology, Barnsley Hospital NHS Foundation Trust, Gawber Road, Barnsley S75 2EP, South Yorkshire, UK2 Academic Unit of Diabetes, Endocrinology and Metabolism, University of Sheffield, Sheffield, South Yorkshire, UK3 Department of Cardiology, Royal Hallamshire Hospital, Sheffield, UK4 Faculty of Health and Wellbeing, Sheffield Hallam University, Sheffield, UK

(Correspondence should be addressed to T H Jones; Email: hugh.jones{at}nhs.net)

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 negatively with AR sensitivity and positively 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, gonadotropins, and age. AR CAG was also independently associated with total, bioavailable and free testosterone, LH, waist circumference, body mass index, leptin, and systolic blood pressure. There was no association of AR CAG with sex hormone binding globulin, 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.






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