The relationship between testosterone and diabetes in men is an important issue, given that one third of U.S. men aged 65 yr or older have diabetes, with a similar percentage having low testosterone levels. The medical literature from 1970 to March 2011 was reviewed for key articles. In population-based studies, low testosterone is commonly associated with type 2 diabetes and the metabolic syndrome, and it identifies men with an adverse metabolic profile. The difference in testosterone levels between men with diabetes compared to men without diabetes is moderate and comparable in magnitude to the effects of other chronic diseases, suggesting that low testosterone may be a marker of poor health. Although the inverse association of testosterone with diabetes is partially mediated by SHBG, low testosterone is linked to diabetes via a bidirectional relationship with visceral fat, muscle, and possibly bone. There is consistent evidence from randomized trials that testosterone therapy alters body composition in a metabolically favorable manner, but changes are modest and have not consistently translated into reductions in insulin resistance or improvements in glucose metabolism. The key response to the aging, overweight man with type 2 diabetes and subnormal testosterone levels should be implementation of lifestyle measures such as weight loss and exercise, which, if successful, raise testosterone and provide multiple health benefits. Although approved therapy for diabetes should be used, testosterone therapy should not be given to such men until benefits and risks are clarified by adequately powered clinical trials.
