Sex Hormone–Binding Globulin and Risk of Clinical Diabetes in American Black, Hispanic, and Asian/Pacific Islander Postmenopausal Women

BACKGROUND: Recent prospective studies have shown a strong inverse association between sex hormone-binding globulin (SHBG) concentrations and risk of clinical diabetes in white individuals. However, it remains unclear whether this relationship extends to other racial/ethnic populations. METHODS: We evaluated the association between baseline concentrations of SHBG and clinical diabetes risk in the Women's Health Initiative Observational Study. Over a median follow-up of 5.9 years, we identified 642 postmenopausal women who developed clinical diabetes (380 blacks, 157 Hispanics, 105 Asians) and 1286 matched controls (777 blacks, 307 Hispanics, 202 Asians). RESULTS: Higher concentrations of SHBG at baseline were associated with a significantly lower risk of clinical diabetes [relative risk (RR), 0.15; 95% CI, 0.09-0.26 for highest vs lowest quartile of SHBG, adjusted for BMI and known diabetes risk factors]. The associations remained consistent within ethnic groups [RR, 0.19 (95% CI, 0.10-0.38) for blacks; RR, 0.17 (95% CI, 0.05-0.57) for Hispanics; and 0.13 (95% CI, 0.03-0.48) for Asians]. Adjustment for potential confounders, such as total testosterone (RR, 0.11; 95% CI, 0.07-0.19) or HOMA-IR (RR, 0.26; 95% CI, 0.14-0.48) did not alter the RR substantially. In addition, SHBG concentrations were significantly associated with risk of clinical diabetes across categories of hormone therapy use (never users: RR(per SD) = 0.42, 95% CI, 0.34-0.51; past users: RR(per SD) = 0.53;, 95% CI, 0.37-0.77; current users: RR(per SD) = 0.57; 95% CI, 0.46-0.69; P-interaction = 0.10). CONCLUSIONS: In this prospective study of postmenopausal women, we observed a robust, inverse relationship between serum concentrations of SHBG and risk of clinical diabetes in American blacks, Hispanics, and Asians/Pacific Islanders. These associations appeared to be independent of sex hormone concentrations, adiposity, or insulin resistance.