Insulin Secretory Defects in Polycystic Ovary Syndrome

The increased prevalence of non-insulin-dependent diabetes mellitus (NIDDM) among women with polycystic ovary syndrome (PCOS) has been ascribed to the insulin resistance characteristic of PCOS. This study was undertaken to determine the role of defects in insulin secretion as well as familial factors to the predisposition to NIDDM seen in PCOS. We studied three groups of women: PCOS with a family history ofNIDDM (PCOS FHx POS; n = 11), PCOS without a family history of NIDDM (PCOS FHx NEG; n = 13), and women without PCOS who have a family history of NIDDM (NON-PCOS FHx POS; n = 8). Beta cell function was evaluated during a frequently sampled intravenous glucose tolerance test, by a low dose graded glucose infusion, and by the ability of the beta cell to be entrained by an oscillatory glucose infusion. PCOS FHx POS women were significantly less likely to demonstrate appropriate beta cell compensation for the degree of insulin resistance. The ability of the beta cell to entrain, as judged by the spectral power for insulin secretion rate, was significantly reduced in PCOS FHx POS subjects. In conclusion, a history of NIDDM in a first-degree relative appears to define a subset of PCOS subjects with a greater prevalence of insulin secretory defects. The risk of developing NIDDM imparted by insulin This study was presented in part at the 76th Annual Meeting of The Endocrine Society in Anaheim, CA on 15-18 June 1994. Address correspondence to David A. Ehrmann, M.D., Department of Medicine, Section of Endocrinology, The University of Chicago Pritzker School of Medicine, 5841 South Maryland Avenue, MC 1027, Chicago, IL 60637. Phone: 312-702-9653; FAX: 312-702-9194; e-mail: [email protected]. Receivedfor publication 21 November 1994 and accepted in revised form 2 March 1995. 1. Abbreviations used in this paper: AIRg, first-phase insulin secretion; ANCOVA, analysis of covariance; AUCinsulin, area under the insulin response curve from 0 to 10 min; AUCinsulin%, AUCinsulin divided by one half the area under the insulin response curve from -20 to 0 min; BMI, body mass index; DHAS, dehydroepiandrosterone sulfate; FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; HbAI, hemoglobin Al; IGT, impaired glucose tolerance; ISR, insulin secretion rate; IVGTT, intravenous glucose tolerance test; LH, luteinizing hormone; NIDDM, non-insulin-dependent diabetes mellitus; NON-PCOS FHx POS, without PCOS and with a family history of NIDDM; OGTT, oral glucose tolerance test; PCOS, polycystic ovary syndrome; PCOS FHx NEG, with PCOS and without a family history of NIDDM; PCOS FHx POS, with PCOS and a family history of NIDDM; SHBG, sex hormone-binding globulin; Si, sensitivity index. resistance in PCOS may be enhanced by these defects in insulin secretion. (J. Clin. Invest. 1995. 96:520-527.)