Estrogens and testosterone predicted diabetes risk in men but not in women. Diabetes risk was directly associated with estrone (HR, 1.101; 95% CI, 1.059–1.145), estrone sulfate (HR, 1.003; 95% CI, 1.001–1.005), and estradiol (HR, 1.130 95 % CI, 10.45–1.221). SHBG and its polymorphisms did not predict risk in men or women. Diabetes risk is more potently determined by obesity and glycemia than by sex hormones. The gene discussed is SHBG; the disease is obesity due to melanocortin 4 receptor deficiency.