Sex Hormone–Binding Globulin and Risk of Type 2 Diabetes in Women and Men

Circulating sex hormone-binding globulin levels are inversely associated with insulin resistance, but whether these levels can predict the risk of developing type 2 diabetes is uncertain.

We performed a nested case-control study of postmenopausal women in the Women's Health Study who were not using hormone therapy (359 with newly diagnosed type 2 diabetes and 359 controls). Plasma levels of sex hormone-binding globulin were measured; two polymorphisms of the gene encoding sex hormone-binding globulin, SHBG, that were robustly associated with the protein levels were genotyped and applied in mendelian randomization analyses. We then conducted a replication study in an independent cohort of men from the Physicians' Health Study II (170 with newly diagnosed type 2 diabetes and 170 controls).