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

Susan Sam, Yeon Ah Sung, Richard S. Legro, Andrea Dunaif

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43 Scopus citations


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.

Original languageEnglish
Pages (from-to)84-89
Number of pages6
JournalMetabolism: Clinical and Experimental
Issue number1
StatePublished - Jan 2008

Bibliographical note

Funding Information:
The authors wish to thank the women with PCOS and their brothers for participating in this study; Barbara Scheetz and Jennifer Schlinder for coordinating the study; and the staff of the General Clinical Research Centers at the Pennsylvania State University College of Medicine, Brigham and Women's Hospital, and Northwestern University's Feinberg School of Medicine for their care of the study participants. This study was supported by National Institutes of Health grants U54 HD34449, DK40605, M01 RR00048, M01 RR10732, K12 RR017707, M01 RR02635, and C06 RR016499.


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