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Submitted on February 9, 2004
Accepted on October 18, 2004
Dept. of Medicine and Dept. of Health Studies, The University of Chicago Medical Center, Chicago, IL; Dept. of Obstetrics and Gynecology, The University of Alabama at Birmingham, Birmingham, AL; Dept. of Obstetrics and Gynecology, The Pennsylvania State University, Hershey, PA; Pfizer Pharmaceuticals, Ann Arbor, MI
* To whom correspondence should be addressed.
David A. Ehrmann, E-mail: dehrmann{at}medicine.bsd.uchicago.edu
Background: Racial origin and family history of type 2 diabetes impact upon the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes, both of which are common in women with polycystic ovary syndrome (PCOS). We sought to examine the effects of race and family history of type 2 diabetes on the risk of IGT and type 2 diabetes in a large cohort of women with PCOS.
Methods: Data obtained at baseline were analyzed from 408 premenopausal women with PCOS. Multivariate linear regression models were used to assess the impact of race (White, Black, and Other) and family history of type 2 diabetes on body mass index (BMI), waist circumference, and waist-to-hip ratio (WHR); glycemic measures (glucose and insulin levels obtained during a standard 75 g oral glucose tolerance test (OGTT), fasting glucose to insulin ratio (GIR) and homeostasis model assessment model of insulin resistance (HOMA-IR) derived from fasting levels of glucose and insulin), hemoglobin A1C; and sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS) levels.
Results: Sixteen (4%) of the 408 patients had type 2 diabetes, 94 (23%) had IGT, and the remaining 298 (73%) had normal glucose tolerance. A history of type 2 diabetes in either parent (FHxPOS) was present in 7 (44%) of the 16 diabetic women with PCOS, 37 (39%) of the 94 women with IGT, and 62 (21%) of those with normal glucose tolerance (P < 0.01 by Chi square). The prevalence of IGT and type 2 diabetes were significantly higher in FHxPOS PCOS women compared with FHxNEG PCOS women, with IGT evident in 37 (35%) FHxPOS compared with 57 (19%) FHxNEG women and type 2 diabetes in 7 (7%) FHxPOS compared with 9 (3%) FHxNEG women.
Among the 392 nondiabetic subjects, after adjustment for the effects of race, FHxPOS differed significantly from FHxNEG patients in having a higher mean WHR, hemoglobin A1C level, 2 h glucose level, fasting glucose and insulin levels, GIR, HOMA-IR, and area under the glucose and insulin curves during the OGTT.
Conclusions: A family history of type 2 diabetes is present with a significantly greater frequency among women with PCOS who have IGT or type 2 diabetes when compared with those with normal glucose tolerance. Conversely, a family history of type 2 diabetes in a first-degree relative is associated with a significantly higher risk for IGT or type 2 diabetes in women with PCOS. Even among nondiabetic women with PCOS, a positive family history of type 2 diabetes was strongly associated with metabolic characteristics associated with an increased risk for type 2 diabetes. Finally, the fasting glucose concentration was poorly associated with 2 h glucose concentrations among PCOS women with IGT, suggesting that the fasting glucose concentration is inadequate to predict the presence of IGT in PCOS.
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