Evidence for pancreatic β-cell dysfunction in brothers of women with polycystic ovary syndrome

Hyperandrogenemia and insulin resistance are heritable traits in sisters of women with polycystic ovary syndrome (PCOS). Hyperandrogenemia also appears to be the male reproductive phenotype; however, it is less clear whether male relatives are at risk for the metabolic disorders associated with PCOS. In this study, we tested the hypothesis that brothers of women with PCOS have defects in insulin action and/or secretion. Twenty-three non-Hispanic white brothers of women with PCOS and 23 non-Hispanic white control men of comparable age matched for body mass index underwent a modified frequently sampled intravenous glucose tolerance test. Parameters of insulin sensitivity and secretion were determined using minimal-model Bergman protocol. Disposition index was significantly decreased (2540 [1080, 3172] vs 2901 [2096, 4487], P = .009) independent of a family history of diabetes mellitus, and glucose effectiveness was significantly increased (2.4 [1.9, 2.7] vs 2.0 [1.8, 2.2], P = .02) in brothers compared with control men. We conclude that brothers of women with PCOS have evidence for pancreatic β-cell dysfunction and may be at increased risk for type 2 diabetes mellitus.