Journal of Clinical Endocrinology & Metabolism, Vol 81, 942-947, Copyright © 1996 by Endocrine Society

ARTICLES

Beta-cell dysfunction independent of obesity and glucose intolerance in the polycystic ovary syndrome

A Dunaif and DT Finegood
Department of Medicine, Pennsylvania State University College of Medicine, Hershey 17033, USA.

Several distinct groups of subjects at high risk to develop noninsulin- dependent diabetes mallitus (NIDDM) have been found to have insulin secretory defects when beta-cell function is assessed in the context of peripheral insulin sensitivity. We investigated this with a modified frequently sampled iv glucose tolerance test to determine acute insulin responses to glucose (AIRg) as well as insulin action by minimal model analysis in 28 women with polycystic ovary syndrome (PCOS; 15 obese and 13 nonobese) and 29 age- and weight-matched normal women (14 obese and 15 nonobese). No subject, PCOS or control, had fasting hyperglycemia, but seven PCOS women (six obese and one nonobese) had impaired glucose tolerance or NIDDM. The PCOS women had significantly decreased insulin sensitivity compared to the normal women (P < or = 0.001), and the obese women were less sensitive than the nonobese women (P < or = 0.001). The empiric measure of insulin release, AIRg, was significantly increased by obesity (P < or = 0.01), but not by PCOS. However, the disposition index (insulin sensitivity x AIRg) was significantly decreased by both PCOS (< or = 0.005) and obesity (< or = 0.005), suggesting that AIRg was inadequate for the degree of insulin resistance. When the PCOS women with impaired glucose tolerance or NIDDM were removed from the analysis, all of the reported PCOS-related changes in insulin action and secretion remained significant. We conclude that both obese and nonobese PCOS women have beta-cell dysfunction as well as insulin resistance. However, this was not associated with glucose intolerance in the majority of PCOS women.

This article has been cited by other articles:

				K. Wang, L. Wang, Y. Zhao, Y. Shi, L. Wang, and Z.-J. Chen No association of the Arg51Gln and Leu72Met polymorphisms of the ghrelin gene and polycystic ovary syndrome Hum. Reprod., February 1, 2009; 24(2): 485 - 490. [Abstract] [Full Text] [PDF]

				P. F. Svendsen, L. Nilas, K. Norgaard, J.-E. B. Jensen, and S. Madsbad Obesity, body composition and metabolic disturbances in polycystic ovary syndrome Hum. Reprod., September 1, 2008; 23(9): 2113 - 2121. [Abstract] [Full Text] [PDF]

				K. Elkind-Hirsch, O. Marrioneaux, M. Bhushan, D. Vernor, and R. Bhushan Comparison of Single and Combined Treatment with Exenatide and Metformin on Menstrual Cyclicity in Overweight Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2670 - 2678. [Abstract] [Full Text] [PDF]

				S. C. Kent, C. L. Gnatuk, A. R. Kunselman, L. M. Demers, P. A. Lee, and R. S. Legro Hyperandrogenism and Hyperinsulinism in Children of Women with Polycystic Ovary Syndrome: A Controlled Study J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1662 - 1669. [Abstract] [Full Text] [PDF]

				K. E. S. Salley, E. P. Wickham, K. I. Cheang, P. A. Essah, N. W. Karjane, and J. E. Nestler POSITION STATEMENT: Glucose Intolerance in Polycystic Ovary Syndrome A Position Statement of the Androgen Excess Society J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4546 - 4556. [Abstract] [Full Text] [PDF]

				S. Tan, S. Hahn, S. Benson, T. Dietz, H. Lahner, L. C Moeller, M. Schmidt, S. Elsenbruch, R. Kimmig, K. Mann, et al. Metformin improves polycystic ovary syndrome symptoms irrespective of pre-treatment insulin resistance Eur. J. Endocrinol., November 1, 2007; 157(5): 669 - 676. [Abstract] [Full Text] [PDF]

				R. N. Bergman Orchestration of Glucose Homeostasis: From a Small Acorn to the California Oak Diabetes, June 1, 2007; 56(6): 1489 - 1501. [Full Text] [PDF]

				M. Cnop, J. Vidal, R. L. Hull, K. M. Utzschneider, D. B. Carr, T. Schraw, P. E. Scherer, E. J. Boyko, W. Y. Fujimoto, and S. E. Kahn Progressive Loss of {beta}-Cell Function Leads to Worsening Glucose Tolerance in First-Degree Relatives of Subjects With Type 2 Diabetes Diabetes Care, March 1, 2007; 30(3): 677 - 682. [Abstract] [Full Text] [PDF]

				R. Pasquali and A. Gambineri Insulin-sensitizing agents in polycystic ovary syndrome. Eur. J. Endocrinol., June 1, 2006; 154(6): 763 - 775. [Abstract] [Full Text] [PDF]

				O.C. Pillay, L.F. W. Te Fong, J.C. Crow, E. Benjamin, T. Mould, W. Atiomo, P.A. Menon, A.J. Leonard, and P. Hardiman The association between polycystic ovaries and endometrial cancer Hum. Reprod., April 1, 2006; 21(4): 924 - 929. [Abstract] [Full Text] [PDF]

				A. D. Coviello, R. S. Legro, and A. Dunaif Adolescent Girls with Polycystic Ovary Syndrome Have an Increased Risk of the Metabolic Syndrome Associated with Increasing Androgen Levels Independent of Obesity and Insulin Resistance J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 492 - 497. [Abstract] [Full Text] [PDF]

				G. Gennarelli, V. Rovei, R. F. Novi, J. Holte, F. Bongioanni, A. Revelli, G. Pacini, P. Cavallo-Perin, and M. Massobrio Preserved Insulin Sensitivity and {beta}-Cell Activity, but Decreased Glucose Effectiveness in Normal-Weight Women with the Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3381 - 3386. [Abstract] [Full Text] [PDF]

				R. S. Legro, P. Chiu, A. R. Kunselman, C. M. Bentley, W. C. Dodson, and A. Dunaif Polycystic Ovaries Are Common in Women with Hyperandrogenic Chronic Anovulation but Do Not Predict Metabolic or Reproductive Phenotype J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2571 - 2579. [Abstract] [Full Text] [PDF]

				J. Vrbikova and D. Cibula Combined oral contraceptives in the treatment of polycystic ovary syndrome Hum. Reprod. Update, May 1, 2005; 11(3): 277 - 291. [Abstract] [Full Text] [PDF]

				D. A. Ehrmann Polycystic Ovary Syndrome N. Engl. J. Med., March 24, 2005; 352(12): 1223 - 1236. [Full Text] [PDF]

				D. A. Ehrmann, K. Kasza, R. Azziz, R. S. Legro, M. N. Ghazzi, and for the PCOS/Troglitazone Study Group Effects of Race and Family History of Type 2 Diabetes on Metabolic Status of Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 66 - 71. [Abstract] [Full Text] [PDF]

				M. O. Goodarzi, S. Erickson, S. C. Port, R. I. Jennrich, and S. G. Korenman {beta}-Cell Function: A Key Pathological Determinant in Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 310 - 315. [Abstract] [Full Text] [PDF]

				C. M. Bruns, S. T. Baum, R. J. Colman, J. R. Eisner, J. W. Kemnitz, R. Weindruch, and D. H. Abbott Insulin Resistance and Impaired Insulin Secretion in Prenatally Androgenized Male Rhesus Monkeys J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6218 - 6223. [Abstract] [Full Text] [PDF]

				A. Gambineri, C. Pelusi, E. Manicardi, V. Vicennati, M. Cacciari, A. M. Morselli-Labate, U. Pagotto, and R. Pasquali Glucose Intolerance in a Large Cohort of Mediterranean Women With Polycystic Ovary Syndrome: Phenotype and Associated Factors Diabetes, September 1, 2004; 53(9): 2353 - 2358. [Abstract] [Full Text] [PDF]

				J. VrbIkova, D. Cibula, K. Dvorakova, S. Stanicka, G. Sindelka, M. Hill, M. Fanta, K. Vondra, and J. Skrha Insulin Sensitivity in Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2942 - 2945. [Abstract] [Full Text] [PDF]

				D. Cibula Is insulin resistance an essential component of PCOS?: The influence of confounding factors Hum. Reprod., April 1, 2004; 19(4): 757 - 759. [Abstract] [Full Text] [PDF]

				M. Maliqueo, I. Atwater, R. Lahsen, F. Perez-Bravo, B. Angel, and T. Sir-Petermann Proinsulin serum concentrations in women with polycystic ovary syndrome: a marker of {beta}-cell dysfunction? Hum. Reprod., December 1, 2003; 18(12): 2683 - 2688. [Abstract] [Full Text] [PDF]

				M. E. Silfen, M. R. Denburg, A. M. Manibo, R. A. Lobo, R. Jaffe, M. Ferin, L. S. Levine, and S. E. Oberfield Early Endocrine, Metabolic, and Sonographic Characteristics of Polycystic Ovary Syndrome (PCOS): Comparison between Nonobese and Obese Adolescents J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4682 - 4688. [Abstract] [Full Text] [PDF]

				A. Cagnacci, A. M. Paoletti, A. Renzi, M. Orru, M. Pilloni, G. B. Melis, and A. Volpe Glucose Metabolism and Insulin Resistance in Women with Polycystic Ovary Syndrome during Therapy with Oral Contraceptives Containing Cyproterone Acetate or Desogestrel J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3621 - 3625. [Abstract] [Full Text] [PDF]

				Z. T. Bloomgarden Diabetes Issues in Women and Children: Polycystic ovary syndrome Diabetes Care, August 1, 2003; 26(8): 2457 - 2463. [Full Text] [PDF]

				R. S. Legro Polycystic Ovary Syndrome and Cardiovascular Disease: A Premature Association? Endocr. Rev., June 1, 2003; 24(3): 302 - 312. [Abstract] [Full Text] [PDF]

				B. O. Yildiz, H. Yarali, H. Oguz, and M. Bayraktar Glucose Intolerance, Insulin Resistance, and Hyperandrogenemia in First Degree Relatives of Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2031 - 2036. [Abstract] [Full Text] [PDF]

				A. B. Goldfine, C. Bouche, R. A. Parker, C. Kim, A. Kerivan, J. S. Soeldner, B. C. Martin, J. H. Warram, and C. R. Kahn Insulin resistance is a poor predictor of type 2 diabetes in individuals with no family history of disease PNAS, March 4, 2003; 100(5): 2724 - 2729. [Abstract] [Full Text] [PDF]

				C. Schofl, R. Horn, T. Schill, H. W. Schlosser, M. J. Muller, and G. Brabant Circulating Ghrelin Levels in Patients with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4607 - 4610. [Abstract] [Full Text] [PDF]

				A. Balen and K. Michelmore What is polycystic ovary syndrome?: Are national views important? Hum. Reprod., September 1, 2002; 17(9): 2219 - 2227. [Abstract] [Full Text] [PDF]

				S. B. Seminara and W. F. Crowley Jr. Genetic Approaches to Unraveling Reproductive Disorders: Examples of Bedside to Bench Research in the Genomic Era Endocr. Rev., June 1, 2002; 23(3): 382 - 392. [Abstract] [Full Text] [PDF]

				V. Jayagopal, E. S. Kilpatrick, S. Holding, P. E. Jennings, and S. L. Atkin The Biological Variation of Insulin Resistance in Polycystic Ovarian Syndrome J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1560 - 1562. [Abstract] [Full Text] [PDF]

				A. J.G. Hanley, G. McKeown-Eyssen, S. B. Harris, R. A. Hegele, T. M.S. Wolever, J. Kwan, and B. Zinman Association of Parity With Risk of Type 2 Diabetes and Related Metabolic Disorders Diabetes Care, April 1, 2002; 25(4): 690 - 695. [Abstract] [Full Text] [PDF]

				D. Cibula, M. Fanta, M. Hill, G. Sindelka, J. Skrha, and J. Zivny Insulin sensitivity in non-obese women with polycystic ovary syndrome during treatment with oral contraceptives containing low-androgenic progestin Hum. Reprod., January 1, 2002; 17(1): 76 - 82. [Abstract] [Full Text] [PDF]

				C. G. Solomon, F. B. Hu, A. Dunaif, J. Rich-Edwards, W. C. Willett, D. J. Hunter, G. A. Colditz, F. E. Speizer, and J. E. Manson Long or Highly Irregular Menstrual Cycles as a Marker for Risk of Type 2 Diabetes Mellitus JAMA, November 21, 2001; 286(19): 2421 - 2426. [Abstract] [Full Text] [PDF]

				S. E. Kahn The Importance of {beta}-Cell Failure in the Development and Progression of Type 2 Diabetes J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4047 - 4058. [Full Text] [PDF]

				S. Colilla, N. J. Cox, and D. A. Ehrmann Heritability of Insulin Secretion and Insulin Action in Women with Polycystic Ovary Syndrome and Their First Degree Relatives J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2027 - 2031. [Abstract] [Full Text]

				S. E. Kahn, R. L. Prigeon, R. S. Schwartz, W. Y. Fujimoto, R. H. Knopp, J. D. Brunzell, and D. Porte Jr. Obesity, Body Fat Distribution, Insulin Sensitivity and Islet {{beta}}-Cell Function as Explanations for Metabolic Diversity J. Nutr., February 1, 2001; 131(2): 354S - 360. [Abstract] [Full Text]

				S. A. Arslanian, V. D. Lewy, and K. Danadian Glucose Intolerance in Obese Adolescents with Polycystic Ovary Syndrome: Roles of Insulin Resistance and {beta}-Cell Dysfunction and Risk of Cardiovascular Disease J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 66 - 71. [Abstract] [Full Text]

				L. Ibáñez, J. DiMartino-Nardi, N. Potau, and P. Saenger Premature Adrenarche--Normal Variant or Forerunner of Adult Disease? Endocr. Rev., December 1, 2000; 21(6): 671 - 696. [Abstract] [Full Text]

				C. McDonald, A. Dunaif, and D. T. Finegood Minimal-Model Estimates of Insulin Sensitivity Are Insensitive to Errors in Glucose Effectiveness J. Clin. Endocrinol. Metab., July 1, 2000; 85(7): 2504 - 2508. [Abstract] [Full Text]

				D. Cibula, R. Cifkova, M. Fanta, R. Poledne, J. Zivny, and J. Skibova Increased risk of non-insulin dependent diabetes mellitus, arterial hypertension and coronary artery disease in perimenopausal women with a history of the polycystic ovary syndrome Hum. Reprod., April 1, 2000; 15(4): 785 - 789. [Abstract] [Full Text] [PDF]

				J. R. Eisner, D. A. Dumesic, J. W. Kemnitz, and D. H. Abbott Timing of Prenatal Androgen Excess Determines Differential Impairment in Insulin Secretion and Action in Adult Female Rhesus Monkeys J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1206 - 1210. [Abstract] [Full Text]

				C.-B. Book and A. Dunaif Selective Insulin Resistance in the Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3110 - 3116. [Abstract] [Full Text]

				L. Poretsky, N. A. Cataldo, Z. Rosenwaks, and L. C. Giudice The Insulin-Related Ovarian Regulatory System in Health and Disease Endocr. Rev., August 1, 1999; 20(4): 535 - 582. [Abstract] [Full Text] [PDF]

				R. S. Legro, A. R. Kunselman, W. C. Dodson, and A. Dunaif Prevalence and Predictors of Risk for Type 2 Diabetes Mellitus and Impaired Glucose Tolerance in Polycystic Ovary Syndrome: A Prospective, Controlled Study in 254 Affected Women J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 165 - 169. [Abstract] [Full Text]

				R. S. Legro, D. Finegood, and A. Dunaif A Fasting Glucose to Insulin Ratio Is a Useful Measure of Insulin Sensitivity in Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., August 1, 1998; 83(8): 2694 - 2698. [Abstract] [Full Text]

				N. Moghrabi, I. A. Hughes, A. Dunaif, and S. Andersson Deleterious Missense Mutations and Silent Polymorphism in the Human 17{beta}-Hydroxysteroid Dehydrogenase 3 Gene (HSD17B3) J. Clin. Endocrinol. Metab., August 1, 1998; 83(8): 2855 - 2860. [Abstract] [Full Text]

				N. Mauras, S. Welch, A. Rini, and M. W. Haymond Ovarian Hyperandrogenism Is Associated with Insulin Resistance to Both Peripheral Carbohydrate and Whole-Body Protein Metabolism in Postpubertal Young Females: A Metabolic Study J. Clin. Endocrinol. Metab., June 1, 1998; 83(6): 1900 - 1905. [Abstract] [Full Text]

				J. Holte, G. Gennarelli, L. Wide, H. Lithell, and C. Berne High Prevalence of Polycystic Ovaries and Associated Clinical, Endocrine, and Metabolic Features in Women with Previous Gestational Diabetes Mellitus J. Clin. Endocrinol. Metab., April 1, 1998; 83(4): 1143 - 1150. [Abstract] [Full Text]

				A. Dunaif Insulin Resistance and the Polycystic Ovary Syndrome: Mechanism and Implications for Pathogenesis Endocr. Rev., December 1, 1997; 18(6): 774 - 800. [Abstract] [Full Text]

				D. A. Ehrmann, D. J. Schneider, B. E. Sobel, M. K. Cavaghan, J. Imperial, R. L. Rosenfield, and K. S. Polonsky Troglitazone Improves Defects in Insulin Action, Insulin Secretion, Ovarian Steroidogenesis, and Fibrinolysis in Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2108 - 2116. [Abstract] [Full Text] [PDF]

				D. A. Ehrmann, M. K. Cavaghan, J. Imperial, J. Sturis, R. L. Rosenfield, and K. S. Polonsky Effects of Metformin on Insulin Secretion, Insulin Action, and Ovarian Steroidogenesis in Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., February 1, 1997; 82(2): 524 - 530. [Abstract] [Full Text] [PDF]