Low levels of sex hormone-binding globulin and testosterone predict the development of non-insulin-dependent diabetes mellitus in men

Few prospective data are available regarding the association of sex hormone-binding globulin (SHBG), testosterone, and the risk of developing diabetes. Stored fasting serum samples from participants enrolled in the Multiple Risk Factor Intervention Trial (MRFIT) at 22 different centers throughout the United States from December 1973 through February 1976 were used to perform a nested case-control study. For 176 initially nondiabetic men who developed diabetes during 5 years of fellow-up, two controls were selected, one matched only for randomization date, treatment group, and clinic (''loose controls'') and the other matched additionally for fasting glucose and body mass index (''tight controls''). When cases were compared with loose controls, higher levels of fasting insulin and lower levels of total and free testosterone and SHBG were significantly associated with increased development of diabetes. However, when cases were compared with tightly matched controls, these associations weakened considerably. Low SHBG and testosterone may constitute part of the prediabetic state in men along with previously reported variables, such as higher glucose and insulin levels and obesity.