Total testosterone levels are lower than normal in men with type 2 diabetes even when controlling for body mass index (2,61-63). Much of this difference may result from lower SHBG, because the calculated value for free testosterone was not different from controls (2), although another study found lower levels of free testosterone using an analog assay (63). Several prospective studies found that low SHBG levels predict the development of type 2 diabetes (64-66). This finding follows logically from the inverse correlation between SHBG and obesity (25) and insulin resistance (50) and the propensity for obese and insulin-resistant individuals to develop type 2 diabetes. In the Massachusetts Male Aging Study (66), not only total but also free-testosterone levels were 17% lower in men who developed type 2 diabetes 7-10 yr later than in those with no diabetes. Free-testosterone levels that were 10% lower at baseline were also found in men in the Multiple Risk Factor Intervention Trials (MRFIT) who developed diabetes at follow-up 5 yr later (65).
Testosterone levels in men with type 1 diabetes mellitus have been alternatively reported to be normal or reduced and are partly influenced by the disruption of GnRH secretion that occurs in illness (67,68). In one study of adult men with type 1 diabetes mellitus, total testosterone and SHBG were higher, whereas the calculated free testosterone was lower than in healthy controls (69), but in a study of adolescents with type 1 diabetes mellitus, SHBG levels were normal (70).
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