The association of sex hormone-binding globulin with mortality is mediated by age and testosterone in men with type 2 diabetes.

Abstract

Serum sex hormone-binding globulin levels have been associated with mortality in adult men with type 2 diabetes (T2DM). To confirm the association of serum sex hormone-binding globulin with mortality and then determine whether this association is mediated by age and total testosterone concentration. We studied 364 men (median age: 66years) with T2DM over a median follow-up of 4.3years using the Cox regression to study associations between sex hormone-binding globulin, age, total testosterone, and mortality. Mortality was significantly and independently associated with sex hormone-binding globulin, age, and total testosterone. In pairwise combinations of age and sex hormone-binding globulin dichotomized by median values, the association of sex hormone-binding globulin with mortality was age-dependent. Relative to the combination of age >66years/SHBG >35nmol/L (mortality 22.5%), the other combinations were associated with significantly less mortality (mortality in men ≤66years/SHBG≤35nmol/L was 3.23%). In men >66years, SHBG≤35nmol/L was associated with decreased mortality (HR: 0.41, p=0.037) compared with SHBG>35nmol/L. In men ≤66years, there was no significant difference between those with sex hormone-binding globulin above or below the median (HR: 1.73, p=0.56, reference: SHBG≤35nmol/L). TT<12nmol/L was associated with increased mortality in both age categories. Men >66years with the reference combination of SHBG>35nmol/L and TT<12nmol/L (36.84%) nmol/L had significantly higher mortality than those with SHBG>35nmol/L and TT≥12 (18.06%) and those with SHBG≤35nmol/L and TT<12nmol/L (13.79%). Our data suggest sex hormone-binding globulin and total testosterone have particular impact on mortality in men aged over 66years. Further, in older men, the combination of high sex hormone-binding globulin levels and low total testosterone is associated with greater risk than either high sex hormone-binding globulin or low total testosterone individually. Our findings are compatible with data suggesting the importance of sex hormone-binding globulin lies in mediating free testosterone levels.