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Insulin Action and Secretion in Polycystic Ovary Syndrome

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Polycystic Ovary Syndrome

Part of the book series: Contemporary Endocrinology ((COE))

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Summary

Polycystic ovary syndrome (PCOS) is a common, heterogeneous disorder comprised of hyperandrogenism and anovulation. Although insulin action and secretion are neither necessary nor sufficient for the definition of PCOS, they are both disordered in this setting. Numerous studies have described hyperinsulinism and insulin resistance in both adults and adolescents. Those findings led to more experiments designed to further define the mechanism on a tissue, cellular, and even molecular level. In a time of obesity epidemic, the metabolic consequences of PCOS cannot be overlooked. The importance of complications and associations such as type 2 diabetes, metabolic syndrome, sleep apnea, fatty liver disease (FLD), and early cardiovascular dysfunction underscores the need for appropriate treatment.

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References

  1. Arslanian S, Witchel SF. Polycystic ovary syndrome in adolescents: is there an epidemic? Curr Opin Endocrinol Diabetes 2002;9:32–42.

    CAS  Google Scholar 

  2. Coviello AD, Legro RS, Dunaif A. 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 2006;91:492–7.

    PubMed  CAS  Google Scholar 

  3. Ehrmann DA, Liljenquist DR, Kasza K, Azziz R, Legro RS, Ghazzi MN. Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006;91:48–53.

    PubMed  CAS  Google Scholar 

  4. Yalow RS, Berson SA. Immunoassay of endogenous plasma insulin in man. J Clin Invest 1960;39:1157–75.

    PubMed  CAS  Google Scholar 

  5. Arslanian SA. Clamp techniques in paediatrics: what have we learned? Horm Res 2005;64 Suppl 3:16–24.

    Google Scholar 

  6. Book CB, Dunaif A. Selective insulin resistance in the polycystic ovary syndrome. J Clin Endocrinol Metab 1999;84:3110–6.

    PubMed  CAS  Google Scholar 

  7. Corbould A, Zhao H, Mirzoeva S, Aird F, Dunaif A. Enhanced mitogenic signaling in skeletal muscle of women with polycystic ovary syndrome. Diabetes 2006;55:751–9.

    PubMed  CAS  Google Scholar 

  8. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997;18:774–800.

    PubMed  CAS  Google Scholar 

  9. Wu XK, Zhou SY, Liu JX, et al. Selective ovary resistance to insulin signaling in women with polycystic ovary syndrome. Fertil Steril 2003;80:954–65.

    PubMed  Google Scholar 

  10. Arslanian SA, Saad R, F. B. Insulin Resistance in Youth: Definition and Methods of Measurement. Nova Science Publishers, Inc. Hauppauge, NY. In: Insulin Resistance children anol Adolescence. Editors: D. Daneman and J. Hamilton pp. 31–56. 2005.

    Google Scholar 

  11. Consensus Development Conference on Insulin Resistance. 5–6 November 1997. American Diabetes Association. Diabetes Care 1998;21:310–4.

    Google Scholar 

  12. Archard M, Thiers M. LeVirilisme Plaire et son association a L’insuffisance glyolytique (diabetes des femmes à barbe). Bull Acad Natl Med 1921;86:51–64.

    Google Scholar 

  13. Burghen GA, Givens JR, Kitabchi AE. Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease. J Clin Endocrinol Metab 1980;50:113–6.

    PubMed  CAS  Google Scholar 

  14. De Leo V, la Marca A, Petraglia F. Insulin-lowering agents in the management of polycystic ovary syndrome. Endocr Rev 2003;24:633–67.

    PubMed  Google Scholar 

  15. Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 1989;38:1165–74.

    PubMed  CAS  Google Scholar 

  16. Legro RS, Finegood D, Dunaif A. A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1998;83:2694–8.

    PubMed  CAS  Google Scholar 

  17. Norman RJ, Masters S, Hague W. Hyperinsulinemia is common in family members of women with polycystic ovary syndrome. Fertil Steril 1996;66:942–7.

    PubMed  CAS  Google Scholar 

  18. Colilla S, Cox NJ, Ehrmann DA. Heritability of insulin secretion and insulin action in women with polycystic ovary syndrome and their first degree relatives. J Clin Endocrinol Metab 2001;86: 2027–31.

    PubMed  CAS  Google Scholar 

  19. Yildiz BO, Yarali H, Oguz H, Bayraktar M. Glucose intolerance, insulin resistance, and hyperandrogenemia in first degree relatives of women with polycystic ovary syndrome. J Clin Endocrinol Metab 2003;88:2031–6.

    PubMed  CAS  Google Scholar 

  20. Nagamani M, Van Dinh T, Kelver ME. Hyperinsulinemia in hyperthecosis of the ovaries. Am J Obstet Gynecol 1986;154:384–9.

    PubMed  CAS  Google Scholar 

  21. Geffner ME, Kaplan SA, Bersch N, Golde DW, Landaw EM, Chang RJ. Persistence of insulin resistance in polycystic ovarian disease after inhibition of ovarian steroid secretion. Fertil Steril 1986;45:327–33.

    PubMed  CAS  Google Scholar 

  22. Pasquali R, Fabbri R, Venturoli S, Paradisi R, Antenucci D, Melchionda N. Effect of weight loss and antiandrogenic therapy on sex hormone blood levels and insulin resistance in obese patients with polycystic ovaries. Am J Obstet Gynecol 1986;154:139–44.

    PubMed  CAS  Google Scholar 

  23. Nestler JE. Insulin regulation of human ovarian androgens. Hum Reprod 1997;12 Suppl 1:53–62.

    PubMed  CAS  Google Scholar 

  24. Nestler JE. Role of hyperinsulinemia in the pathogenesis of the polycystic ovary syndrome, and its clinical implications. Semin Reprod Endocrinol 1997;15:111–22.

    PubMed  CAS  Google Scholar 

  25. Teede HJ, Meyer C, Norman RJ. Insulin-sensitisers in the treatment of polycystic ovary syndrome. Expert Opin Pharmacother 2005;6:2419–27.

    PubMed  CAS  Google Scholar 

  26. Utiger RD. Insulin and the polycystic ovary syndrome. N Engl J Med 1996;335:657–8.

    PubMed  CAS  Google Scholar 

  27. Baillargeon JP. Use of insulin sensitizers in polycystic ovarian syndrome. Curr Opin Investig Drugs 2005;6:1012–22.

    PubMed  CAS  Google Scholar 

  28. Dunaif A, Scott D, Finegood D, Quintana B, Whitcomb R. The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome. J Clin Endocrinol Metab 1996;81:3299–306.

    PubMed  CAS  Google Scholar 

  29. Kiddy DS, Hamilton-Fairley D, Bush A, et al. Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 1992;36:105–11.

    CAS  Google Scholar 

  30. Nestler JE, Barlascini CO, Matt DW, et al. Suppression of serum insulin by diazoxide reduces serum testosterone levels in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 1989;68:1027–32.

    PubMed  CAS  Google Scholar 

  31. Nestler JE, Jakubowicz DJ. Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med 1996;335:617–23.

    PubMed  CAS  Google Scholar 

  32. Nestler JE, Jakubowicz DJ, Evans WS, Pasquali R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med 1998;338:1876–80.

    PubMed  CAS  Google Scholar 

  33. Pasquali R, Gambineri A, Biscotti D, et al. Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. J Clin Endocrinol Metab 2000;85:2767–74.

    PubMed  CAS  Google Scholar 

  34. Yilmaz M, Biri A, Karakoc A, et al. The effects of rosiglitazone and metformin on insulin resistance and serum androgen levels in obese and lean patients with polycystic ovary syndrome. J Endocrinol Invest 2005;28:1003–8.

    PubMed  CAS  Google Scholar 

  35. Baillargeon JP, Diamanti-Kandarakis E, Ostlund RE, Jr., Apridonidze T, Iuorno MJ, Nestler JE. Altered D-chiro-inositol urinary clearance in women with polycystic ovary syndrome. Diabetes Care 2006;29:300–5.

    PubMed  CAS  Google Scholar 

  36. Gerli S, Mignosa M, Di Renzo GC. Effects of inositol on ovarian function and metabolic factors in women with PCOS: a randomized double blind placebo-controlled trial. Eur Rev Med Pharmacol Sci 2003;7:151–9.

    PubMed  CAS  Google Scholar 

  37. Nestler JE, Jakubowicz DJ, Reamer P, Gunn RD, Allan G. Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N Engl J Med 1999;340:1314–20.

    PubMed  CAS  Google Scholar 

  38. Oberfield SE. Metabolic lessons from the study of young adolescents with polycystic ovary syndrome–is insulin, indeed, the culprit? J Clin Endocrinol Metab 2000;85:3520–5.

    PubMed  CAS  Google Scholar 

  39. Rosenfield RL, Barnes RB, Cara JF, Lucky AW. Dysregulation of cytochrome P450c 17 alpha as the cause of polycystic ovarian syndrome. Fertil Steril 1990;53:785–91.

    PubMed  CAS  Google Scholar 

  40. Baillargeon JP, Nestler JE. Commentary: polycystic ovary syndrome: a syndrome of ovarian hypersensitivity to insulin? J Clin Endocrinol Metab 2006;91:22–4.

    PubMed  CAS  Google Scholar 

  41. Yen SS. The polycystic ovary syndrome. Clin Endocrinol (Oxf) 1980;12:177–207.

    CAS  Google Scholar 

  42. Stein I, Leventhal M. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935;29:181–91.

    Google Scholar 

  43. Nobels F, Dewailly D. Puberty and polycystic ovarian syndrome: the insulin/insulin-like growth factor I hypothesis. Fertil Steril 1992;58:655–66.

    PubMed  CAS  Google Scholar 

  44. Apter D, Butzow T, Laughlin GA, Yen SS. Metabolic features of polycystic ovary syndrome are found in adolescent girls with hyperandrogenism. J Clin Endocrinol Metab 1995;80:2966–73.

    PubMed  CAS  Google Scholar 

  45. Ibanez L, Potau N, Georgopoulos N, Prat N, Gussinye M, Carrascosa A. Growth hormone, insulin-like growth factor-I axis, and insulin secretion in hyperandrogenic adolescents. Fertil Steril 1995;64: 1113–9.

    PubMed  CAS  Google Scholar 

  46. Arslanian S. Type 2 diabetes in children: clinical aspects and risk factors. Horm Res 2002;57 Suppl 1:19–28.

    PubMed  CAS  Google Scholar 

  47. Ibanez L, Dimartino-Nardi J, Potau N, Saenger P. Premature adrenarche–normal variant or forerunner of adult disease? Endocr Rev 2000;21:671–96.

    PubMed  CAS  Google Scholar 

  48. Oppenheimer E, Linder B, DiMartino-Nardi J. Decreased insulin sensitivity in prepubertal girls with premature adrenarche and acanthosis nigricans. J Clin Endocrinol Metab 1995;80:614–8.

    PubMed  CAS  Google Scholar 

  49. Vuguin P, Linder B, Rosenfeld RG, Saenger P, DiMartino-Nardi J. The roles of insulin sensitivity, insulin-like growth factor I (IGF-I), and IGF-binding protein-1 and -3 in the hyperandrogenism of African-American and Caribbean Hispanic girls with premature adrenarche. J Clin Endocrinol Metab 1999;84:2037–42.

    PubMed  CAS  Google Scholar 

  50. Ibanez L, Potau N, Zampolli M, Rique S, Saenger P, Carrascosa A. Hyperinsulinemia and decreased insulin-like growth factor-binding protein-1 are common features in prepubertal and pubertal girls with a history of premature pubarche. J Clin Endocrinol Metab 1997;82:2283–8.

    PubMed  CAS  Google Scholar 

  51. Mauras N, Welch S, Rini A, Haymond MW. 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 1998;83:1900–5.

    PubMed  CAS  Google Scholar 

  52. Ibanez L, Potau N, Zampolli M, et al. Hyperinsulinemia in postpubertal girls with a history of premature pubarche and functional ovarian hyperandrogenism. J Clin Endocrinol Metab 1996;81:1237–43.

    PubMed  CAS  Google Scholar 

  53. Silfen ME, Denburg MR, Manibo AM, et al. Early endocrine, metabolic, and sonographic characteristics of polycystic ovary syndrome (PCOS): comparison between nonobese and obese adolescents. J Clin Endocrinol Metab 2003;88:4682–8.

    PubMed  CAS  Google Scholar 

  54. Fernandes AR, de Sa Rosa e Silva AC, Romao GS, Pata MC, dos Reis RM. Insulin resistance in adolescents with menstrual irregularities. J Pediatr Adolesc Gynecol 2005;18:269–74.

    PubMed  Google Scholar 

  55. Lewy VD, Danadian K, Witchel SF, Arslanian S. Early metabolic abnormalities in adolescent girls with polycystic ovarian syndrome. J Pediatr 2001;138:38–44.

    PubMed  CAS  Google Scholar 

  56. Kahn SE, Prigeon RL, McCulloch DK, et al. Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes 1993;42:1663–72.

    PubMed  CAS  Google Scholar 

  57. Kahn SE. Clinical review 135: The importance of beta-cell failure in the development and progression of type 2 diabetes. J Clin Endocrinol Metab 2001;86:4047–58.

    PubMed  CAS  Google Scholar 

  58. Legro RS, Chiu P, Kunselman AR, Bentley CM, Dodson WC, Dunaif A. Polycystic ovaries are common in women with hyperandrogenic chronic anovulation but do not predict metabolic or reproductive phenotype. J Clin Endocrinol Metab 2005;90:2571–9.

    PubMed  CAS  Google Scholar 

  59. Ehrmann DA, Kasza K, Azziz R, Legro RS, Ghazzi MN. Effects of race and family history of type 2 diabetes on metabolic status of women with polycystic ovary syndrome. J Clin Endocrinol Metab 2005;90:66–71.

    PubMed  CAS  Google Scholar 

  60. Gambineri A, Pelusi C, Manicardi E, et al. Glucose intolerance in a large cohort of mediterranean women with polycystic ovary syndrome: phenotype and associated factors. Diabetes 2004;53: 2353–8.

    PubMed  CAS  Google Scholar 

  61. Lin TC, Yen JM, Gong KB, et al. Abnormal glucose tolerance and insulin resistance in polycystic ovary syndrome amongst the Taiwanese population- not correlated with insulin receptor substrate-1 Gly972Arg/Ala513Pro polymorphism. BMC Med Genet 2006;7:36.

    Google Scholar 

  62. Ehrmann DA, Sturis J, Byrne MM, Karrison T, Rosenfield RL, Polonsky KS. Insulin secretory defects in polycystic ovary syndrome. Relationship to insulin sensitivity and family history of non-insulin-dependent diabetes mellitus. J Clin Invest 1995;96:520–7.

    PubMed  CAS  Google Scholar 

  63. Dunaif A, Finegood DT. Beta-cell dysfunction independent of obesity and glucose intolerance in the polycystic ovary syndrome. J Clin Endocrinol Metab 1996;81:942–7.

    PubMed  CAS  Google Scholar 

  64. Arslanian SA, Lewy VD, Danadian K. 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 2001;86:66–71.

    PubMed  CAS  Google Scholar 

  65. Saad R, Gungor N, Arslanian S. Progression from normal glucose tolerance to type 2 diabetes in a young girl: longitudinal changes in insulin sensitivity and secretion assessed by the clamp technique and surrogate estimates. Pediatr Diabetes 2005;6:95–9.

    PubMed  Google Scholar 

  66. Legro RS, Kunselman AR, Dodson WC, Dunaif A. 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 1999;84:165–9.

    PubMed  CAS  Google Scholar 

  67. Dunaif A, Xia J, Book CB, Schenker E, Tang Z. Excessive insulin receptor serine phosphorylation in cultured fibroblasts and in skeletal muscle. A potential mechanism for insulin resistance in the polycystic ovary syndrome. J Clin Invest 1995;96:801–10.

    PubMed  CAS  Google Scholar 

  68. Li M, Youngren JF, Dunaif A, et al. Decreased insulin receptor (IR) autophosphorylation in fibroblasts from patients with PCOS: effects of serine kinase inhibitors and IR activators. J Clin Endocrinol Metab 2002;87:4088–93.

    PubMed  CAS  Google Scholar 

  69. Willis D, Mason H, Gilling-Smith C, Franks S. Modulation by insulin of follicle-stimulating hormone and luteinizing hormone actions in human granulosa cells of normal and polycystic ovaries. J Clin Endocrinol Metab 1996;81:302–9.

    PubMed  CAS  Google Scholar 

  70. Dunaif A. Insulin resistance and ovarian hyperandrogenism. Endocrinologist 1992;2:248–60.

    Google Scholar 

  71. Dunaif A, Givens J, Haseltine F, Merriam Ge. The Polycystic Ovary Syndrome. Cambridge, MA: Blackwell Scientific; 1992.

    Google Scholar 

  72. Nestler JE, Strauss JF, 3rd. Insulin as an effector of human ovarian and adrenal steroid metabolism. Endocrinol Metab Clin North Am 1991;20:807–23.

    PubMed  CAS  Google Scholar 

  73. Poretsky L, Cataldo NA, Rosenwaks Z, Giudice LC. The insulin-related ovarian regulatory system in health and disease. Endocr Rev 1999;20:535–82.

    PubMed  CAS  Google Scholar 

  74. Nestler JE, Jakubowicz DJ, de Vargas AF, Brik C, Quintero N, Medina F. Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system. J Clin Endocrinol Metab 1998;83:2001–5.

    PubMed  CAS  Google Scholar 

  75. Nelson VL, Legro RS, Strauss JF, 3rd, McAllister JM. Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries. Mol Endocrinol 1999;13:946–57.

    PubMed  CAS  Google Scholar 

  76. Willis D, Franks S. Insulin action in human granulosa cells from normal and polycystic ovaries is mediated by the insulin receptor and not the type-I insulin-like growth factor receptor. J Clin Endocrinol Metab 1995;80:3788–90.

    PubMed  CAS  Google Scholar 

  77. Moran C, Huerta R, Conway-Myers BA, Hines GA, Azziz R. Altered autophosphorylation of the insulin receptor in the ovary of a woman with polycystic ovary syndrome. Fertil Steril 2001;75:625–8.

    PubMed  CAS  Google Scholar 

  78. Nestler JE, Singh R, Matt DW, Clore JN, Blackard WG. Suppression of serum insulin level by diazoxide does not alter serum testosterone or sex hormone-binding globulin levels in healthy, nonobese women. Am J Obstet Gynecol 1990;163:1243–6.

    PubMed  CAS  Google Scholar 

  79. Sekar N, Lavoie HA, Veldhuis JD. Concerted regulation of steroidogenic acute regulatory gene expression by luteinizing hormone and insulin (or insulin-like growth factor I) in primary cultures of porcine granulosa-luteal cells. Endocrinology 2000;141:3983–92.

    PubMed  CAS  Google Scholar 

  80. Zhang G, Garmey JC, Veldhuis JD. Interactive stimulation by luteinizing hormone and insulin of the steroidogenic acute regulatory (StAR) protein and 17alpha-hydroxylase/17,20-lyase (CYP17) genes in porcine theca cells. Endocrinology 2000;141:2735–42.

    PubMed  CAS  Google Scholar 

  81. Fedorcsak P, Storeng R, Dale PO, Tanbo T, Abyholm T. Impaired insulin action on granulosa-lutein cells in women with polycystic ovary syndrome and insulin resistance. Gynecol Endocrinol 2000;14:327–36.

    PubMed  CAS  Google Scholar 

  82. Rice S, Christoforidis N, Gadd C, et al. Impaired insulin-dependent glucose metabolism in granulosa-lutein cells from anovulatory women with polycystic ovaries. Hum Reprod 2005;20: 373–81.

    PubMed  CAS  Google Scholar 

  83. Nelson-Degrave VL, Wickenheisser JK, Hendricks KL, et al. Alterations in mitogen-activated protein kinase and extracellular regulated kinase signaling in theca cells contribute to excessive androgen production in polycystic ovary syndrome. Mol Endocrinol 2005;19:379–90.

    PubMed  CAS  Google Scholar 

  84. Corbould A, Kim YB, Youngren JF, et al. Insulin resistance in the skeletal muscle of women with PCOS involves intrinsic and acquired defects in insulin signaling. Am J Physiol Endocrinol Metab 2005;288:E1047–54.

    Google Scholar 

  85. Dunaif A, Segal KR, Shelley DR, Green G, Dobrjansky A, Licholai T. Evidence for distinctive and intrinsic defects in insulin action in polycystic ovary syndrome. Diabetes 1992;41:1257–66.

    PubMed  CAS  Google Scholar 

  86. Carlson CJ, Koterski S, Sciotti RJ, Poccard GB, Rondinone CM. Enhanced basal activation of mitogen-activated protein kinases in adipocytes from type 2 diabetes: potential role of p38 in the downregulation of GLUT4 expression. Diabetes 2003;52:634–41.

    PubMed  CAS  Google Scholar 

  87. Bouzakri K, Roques M, Gual P, et al. Reduced activation of phosphatidylinositol-3 kinase and increased serine 636 phosphorylation of insulin receptor substrate-1 in primary culture of skeletal muscle cells from patients with type 2 diabetes. Diabetes 2003;52:1319–25.

    PubMed  CAS  Google Scholar 

  88. Scherrer U, Randin D, Vollenweider P, Vollenweider L, Nicod P. Nitric oxide release accounts for insulin’s vascular effects in humans. J Clin Invest 1994;94:2511–5.

    PubMed  CAS  Google Scholar 

  89. Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest 1994;94:1172–9.

    PubMed  CAS  Google Scholar 

  90. Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G, Baron AD. Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Invest 1996;97:2601–10.

    PubMed  CAS  Google Scholar 

  91. Montagnani M, Golovchenko I, Kim I, et al. Inhibition of phosphatidylinositol 3-kinase enhances mitogenic actions of insulin in endothelial cells. J Biol Chem 2002;277:1794–9.

    PubMed  CAS  Google Scholar 

  92. Robinson S, Henderson AD, Gelding SV, et al. Dyslipidaemia is associated with insulin resistance in women with polycystic ovaries. Clin Endocrinol (Oxf) 1996;44:277–84.

    CAS  Google Scholar 

  93. Ciaraldi TP, el-Roeiy A, Madar Z, Reichart D, Olefsky JM, Yen SS. Cellular mechanisms of insulin resistance in polycystic ovarian syndrome. J Clin Endocrinol Metab 1992;75:577–83.

    PubMed  CAS  Google Scholar 

  94. Marsden PJ, Murdoch A, Taylor R. Severe impairment of insulin action in adipocytes from amenorrheic subjects with polycystic ovary syndrome. Metabolism 1994;43:1536–42.

    PubMed  CAS  Google Scholar 

  95. Lystedt E, Westergren H, Brynhildsen J, et al. Subcutaneous adipocytes from obese hyperinsulinemic women with polycystic ovary syndrome exhibit normal insulin sensitivity but reduced maximal insulin responsiveness. Eur J Endocrinol 2005;153:831–5.

    PubMed  CAS  Google Scholar 

  96. Ciaraldi TP, Morales AJ, Hickman MG, Odom-Ford R, Olefsky JM, Yen SS. Cellular insulin resistance in adipocytes from obese polycystic ovary syndrome subjects involves adenosine modulation of insulin sensitivity. J Clin Endocrinol Metab 1997;82:1421–5.

    PubMed  CAS  Google Scholar 

  97. Ek I, Arner P, Bergqvist A, Carlstrom K, Wahrenberg H. Impaired adipocyte lipolysis in nonobese women with the polycystic ovary syndrome: a possible link to insulin resistance? J Clin Endocrinol Metab 1997;82:1147–53.

    PubMed  CAS  Google Scholar 

  98. Ek I, Arner P, Ryden M, et al. A unique defect in the regulation of visceral fat cell lipolysis in the polycystic ovary syndrome as an early link to insulin resistance. Diabetes 2002;51:484–92.

    PubMed  CAS  Google Scholar 

  99. Wahrenberg H, Ek I, Reynisdottir S, Carlstrom K, Bergqvist A, Arner P. Divergent effects of weight reduction and oral anticonception treatment on adrenergic lipolysis regulation in obese women with the polycystic ovary syndrome. J Clin Endocrinol Metab 1999;84:2182–7.

    PubMed  CAS  Google Scholar 

  100. Ibanez L, Ong K, de Zegher F, Marcos MV, del Rio L, Dunger DB. Fat distribution in non-obese girls with and without precocious pubarche: central adiposity related to insulinaemia and androgenaemia from prepuberty to postmenarche. Clin Endocrinol (Oxf) 2003;58:372–9.

    Google Scholar 

  101. Legro RS. Detection of insulin resistance and its treatment in adolescents with polycystic ovary syndrome. J Pediatr Endocrinol Metab 2002;15 Suppl 5:1367–78.

    PubMed  CAS  Google Scholar 

  102. Palmert MR, Gordon CM, Kartashov AI, Legro RS, Emans SJ, Dunaif A. Screening for abnormal glucose tolerance in adolescents with polycystic ovary syndrome. J Clin Endocrinol Metab 2002;87:1017–23.

    PubMed  CAS  Google Scholar 

  103. Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK, Imperial J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care 1999;22:141–6.

    PubMed  CAS  Google Scholar 

  104. Kent SC, Legro RS. Polycystic ovary syndrome in adolescents. Adolesc Med 2002;13:73–88, vi.

    PubMed  Google Scholar 

  105. Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999–2002. JAMA 2004;291:2847–50.

    PubMed  CAS  Google Scholar 

  106. Reaven GM, Lithell H, Landsberg L. Hypertension and associated metabolic abnormalities–the role of insulin resistance and the sympathoadrenal system. N Engl J Med 1996;334:374–81.

    PubMed  CAS  Google Scholar 

  107. Grundy SM. Hypertriglyceridemia, insulin resistance, and the metabolic syndrome. Am J Cardiol 1999;83:25F–9F.

    Google Scholar 

  108. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002;287:356–9.

    PubMed  Google Scholar 

  109. Goodarzi MO, Korenman SG. The importance of insulin resistance in polycystic ovary syndrome. Fertil Steril 2003;80:255–8.

    PubMed  Google Scholar 

  110. Glueck CJ, Papanna R, Wang P, Goldenberg N, Sieve-Smith L. Incidence and treatment of metabolic syndrome in newly referred women with confirmed polycystic ovarian syndrome. Metabolism 2003;52:908–15.

    PubMed  CAS  Google Scholar 

  111. Apridonidze T, Essah PA, Iuorno MJ, Nestler JE. Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2005;90:1929–35.

    PubMed  CAS  Google Scholar 

  112. Sam S, Legro RS, Bentley-Lewis R, Dunaif A. Dyslipidemia and metabolic syndrome in the sisters of women with polycystic ovary syndrome. J Clin Endocrinol Metab 2005;90:4797–802.

    PubMed  CAS  Google Scholar 

  113. Goodman E, Daniels SR, Morrison JA, Huang B, Dolan LM. Contrasting prevalence of and demographic disparities in the World Health Organization and National Cholesterol Education Program Adult Treatment Panel III definitions of metabolic syndrome among adolescents. J Pediatr 2004;145:445–51.

    PubMed  Google Scholar 

  114. Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH. Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988–1994. Arch Pediatr Adolesc Med 2003;157:821–7.

    PubMed  Google Scholar 

  115. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation 2002;106: 3143–421.

    Google Scholar 

  116. Vrbikova J, Vondra K, Cibula D, et al. Metabolic syndrome in young Czech women with polycystic ovary syndrome. Hum Reprod 2005;20:3328–32.

    PubMed  CAS  Google Scholar 

  117. Pierpoint T, McKeigue PM, Isaacs AJ, Wild SH, Jacobs HS. Mortality of women with polycystic ovary syndrome at long-term follow-up. J Clin Epidemiol 1998;51:581–6.

    PubMed  CAS  Google Scholar 

  118. Wild S, Pierpoint T, McKeigue P, Jacobs H. Cardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: a retrospective cohort study. Clin Endocrinol (Oxf) 2000;52: 595–600.

    CAS  Google Scholar 

  119. Wild RA, Painter PC, Coulson PB, Carruth KB, Ranney GB. Lipoprotein lipid concentrations and cardiovascular risk in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1985;61: 946–51.

    PubMed  CAS  Google Scholar 

  120. Talbott E, Guzick D, Clerici A, et al. Coronary heart disease risk factors in women with polycystic ovary syndrome. Arterioscler Thromb Vasc Biol 1995;15:821–6.

    PubMed  CAS  Google Scholar 

  121. Talbott E, Clerici A, Berga SL, et al. Adverse lipid and coronary heart disease risk profiles in young women with polycystic ovary syndrome: results of a case-control study. J Clin Epidemiol 1998;51:415–22.

    PubMed  CAS  Google Scholar 

  122. Pasquali R, Casimirri F, Cantobelli S, et al. Insulin and androgen relationships with abdominal body fat distribution in women with and without hyperandrogenism. Horm Res 1993;39:179–87.

    PubMed  CAS  Google Scholar 

  123. Conway GS, Agrawal R, Betteridge DJ, Jacobs HS. Risk factors for coronary artery disease in lean and obese women with the polycystic ovary syndrome. Clin Endocrinol (Oxf) 1992;37:119–25.

    CAS  Google Scholar 

  124. Dahlgren E, Janson PO, Johansson S, Lapidus L, Oden A. Polycystic ovary syndrome and risk for myocardial infarction. Evaluated from a risk factor model based on a prospective population study of women. Acta Obstet Gynecol Scand 1992;71:599–604.

    PubMed  CAS  Google Scholar 

  125. Tarkun I, Arslan BC, Canturk Z, Turemen E, Sahin T, Duman C. Endothelial dysfunction in young women with polycystic ovary syndrome: relationship with insulin resistance and low-grade chronic inflammation. J Clin Endocrinol Metab 2004;89:5592–6.

    PubMed  CAS  Google Scholar 

  126. Diamanti-Kandarakis E, Spina G, Kouli C, Migdalis I. Increased endothelin-1 levels in women with polycystic ovary syndrome and the beneficial effect of metformin therapy. J Clin Endocrinol Metab 2001;86:4666–73.

    PubMed  CAS  Google Scholar 

  127. Lakhani K, Hardiman P, Seifalian AM. Intima-media thickness of elastic and muscular arteries of young women with polycystic ovaries. Atherosclerosis 2004;175:353–9.

    PubMed  CAS  Google Scholar 

  128. Meyer C, McGrath BP, Cameron J, Kotsopoulos D, Teede HJ. Vascular dysfunction and metabolic parameters in polycystic ovary syndrome. J Clin Endocrinol Metab 2005;90:4630–5.

    PubMed  CAS  Google Scholar 

  129. Orio F, Jr., Palomba S, Cascella T, et al. Early impairment of endothelial structure and function in young normal-weight women with polycystic ovary syndrome. J Clin Endocrinol Metab 2004;89:4588–93.

    PubMed  CAS  Google Scholar 

  130. Tarkun I, Canturk Z, Arslan BC, Turemen E, Tarkun P. The plasminogen activator system in young and lean women with polycystic ovary syndrome. Endocr J 2004;51:467–72.

    PubMed  CAS  Google Scholar 

  131. Vryonidou A, Papatheodorou A, Tavridou A, et al. Association of hyperandrogenemic and metabolic phenotype with carotid intima-media thickness in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 2005;90:2740–6.

    PubMed  CAS  Google Scholar 

  132. Topcu S, Caliskan M, Ozcimen EE, et al. Do young women with polycystic ovary syndrome show early evidence of preclinical coronary artery disease? Hum Reprod 2006;21:930–5.

    PubMed  Google Scholar 

  133. Britten MB, Zeiher AM, Schachinger V. Microvascular dysfunction in angiographically normal or mildly diseased coronary arteries predicts adverse cardiovascular long-term outcome. Coron Artery Dis 2004;15:259–64.

    PubMed  Google Scholar 

  134. Christian RC, Dumesic DA, Behrenbeck T, Oberg AL, Sheedy PF, 2nd, Fitzpatrick LA. Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2003;88:2562–8.

    PubMed  CAS  Google Scholar 

  135. Talbott EO, Guzick DS, Sutton-Tyrrell K, et al. Evidence for association between polycystic ovary syndrome and premature carotid atherosclerosis in middle-aged women. Arterioscler Thromb Vasc Biol 2000;20:2414–21.

    PubMed  CAS  Google Scholar 

  136. Paradisi G, Steinberg HO, Hempfling A, et al. Polycystic ovary syndrome is associated with endothelial dysfunction. Circulation 2001;103:1410–5.

    PubMed  CAS  Google Scholar 

  137. O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK, Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 1999;340:14–22.

    PubMed  CAS  Google Scholar 

  138. Vgontzas AN, Legro RS, Bixler EO, Grayev A, Kales A, Chrousos GP. Polycystic ovary syndrome is associated with obstructive sleep apnea and daytime sleepiness: role of insulin resistance. J Clin Endocrinol Metab 2001;86:517–20.

    PubMed  CAS  Google Scholar 

  139. Fogel RB, Malhotra A, Pillar G, Pittman SD, Dunaif A, White DP. Increased prevalence of obstructive sleep apnea syndrome in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 2001;86:1175–80.

    PubMed  CAS  Google Scholar 

  140. Sanders M. Sleep Breathing Disorders. Philadelphia, PA: W.B Saunders Company; 2000.

    Google Scholar 

  141. Ip MS, Lam B, Ng MM, Lam WK, Tsang KW, Lam KS. Obstructive sleep apnea is independently associated with insulin resistance. Am J Respir Crit Care Med 2002;165:670–6.

    PubMed  Google Scholar 

  142. Gopal M, Duntley S, Uhles M, Attarian H. The role of obesity in the increased prevalence of obstructive sleep apnea syndrome in patients with polycystic ovarian syndrome. Sleep Med 2002;3:401–4.

    PubMed  Google Scholar 

  143. Tasali E, Van Cauter E, Ehrmann DA. Relationships between sleep disordered breathing and glucose metabolism in polycystic ovary syndrome. J Clin Endocrinol Metab 2006;91:36–42.

    PubMed  CAS  Google Scholar 

  144. Tassone F, Lanfranco F, Gianotti L, et al. Obstructive sleep apnoea syndrome impairs insulin sensitivity independently of anthropometric variables. Clin Endocrinol (Oxf) 2003;59:374–9.

    Google Scholar 

  145. Vgontzas AN, Papanicolaou DA, Bixler EO, et al. Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Metab 2000;85:1151–8.

    PubMed  CAS  Google Scholar 

  146. Harsch IA, Schahin SP, Bruckner K, et al. The effect of continuous positive airway pressure treatment on insulin sensitivity in patients with obstructive sleep apnoea syndrome and type 2 diabetes. Respiration 2004;71:252–9.

    PubMed  Google Scholar 

  147. Punjabi NM, Shahar E, Redline S, Gottlieb DJ, Givelber R, Resnick HE. Sleep-disordered breathing, glucose intolerance, and insulin resistance: the Sleep Heart Health Study. Am J Epidemiol 2004;160:521–30.

    PubMed  Google Scholar 

  148. Svatikova A, Wolk R, Gami AS, Pohanka M, Somers VK. Interactions between obstructive sleep apnea and the metabolic syndrome. Curr Diab Rep 2005;5:53–8.

    PubMed  Google Scholar 

  149. Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest 1995;96:1897–904.

    PubMed  CAS  Google Scholar 

  150. Clark JM, Brancati FL, Diehl AM. The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol 2003;98:960–7.

    PubMed  CAS  Google Scholar 

  151. Clark JM, Brancati FL, Diehl AM. The prevalence and etiology of elevated aminotransferase levels in the United States. Am Journ Gastro 2003;98:960.

    Google Scholar 

  152. Pagano G, Pacini G, Musso G, et al. Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association. Hepatology 2002;35:367–72.

    PubMed  CAS  Google Scholar 

  153. Marchesini G, Brizi M, Bianchi G, et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 2001;50:1844–50.

    PubMed  CAS  Google Scholar 

  154. Chitturi S, Abeygunasekera S, Farrell GC, et al. NASH and insulin resistance: insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology 2002;35:373–9.

    PubMed  CAS  Google Scholar 

  155. Bugianesi E, Manzini P, D’Antico S, et al. Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver. Hepatology 2004;39:179–87.

    PubMed  CAS  Google Scholar 

  156. Schwimmer JB, Khorram O, Chiu V, Schwimmer WB. Abnormal aminotransferase activity in women with polycystic ovary syndrome. Fertil Steril 2005;83:494–7.

    PubMed  CAS  Google Scholar 

  157. Kinkhabwala S, Futterweit W. Nonalcoholic Fatty Liver Disease in Lean, Overweight, and Obese Women with Polycystic Ovary Syndrome. Poster presentation at 3rd Annual Meeting of the Androgen Excess Society in San Diego, CA (Abstract) 2005.

    Google Scholar 

  158. Setji TL, Holland ND, Sanders LL, Pereira KC, Mae Diehl A, Brown AJ. Nonalcoholic steatohepatitis and nonalcoholic fatty liver disease in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006;91:1741–7.

    PubMed  CAS  Google Scholar 

  159. Clark JM, Brancati FL, Diehl AM. Nonalcoholic fatty liver disease. Gastroenterology 2002;122: 1649–57.

    PubMed  Google Scholar 

  160. Sheth SG, Gordon FD, Chopra S. Nonalcoholic steatohepatitis. Ann Intern Med 1997;126:137–45.

    PubMed  CAS  Google Scholar 

  161. Azziz R, Ehrmann D, Legro RS, et al. Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome: a multicenter, double blind, placebo-controlled trial. J Clin Endocrinol Metab 2001;86:1626–32.

    PubMed  CAS  Google Scholar 

  162. Garmes HM, Tambascia MA, Zantut-Wittmann DE. Endocrine-metabolic effects of the treatment with pioglitazonein obese patients with polycystic ovary syndrome. Gynecol Endocrinol 2005;21:317–23.

    PubMed  CAS  Google Scholar 

  163. Rautio K, Tapanainen JS, Ruokonen A, Morin-Papunen LC. Endocrine and metabolic effects of rosiglitazone in overweight women with PCOS: a randomized placebo-controlled study. Hum Reprod 2006;21:1400–1407.

    PubMed  CAS  Google Scholar 

  164. Diamanti-Kandarakis E, Baillargeon JP, Iuorno MJ, Jakubowicz DJ, Nestler JE. A modern medical quandary: polycystic ovary syndrome, insulin resistance, and oral contraceptive pills. J Clin Endocrinol Metab 2003;88:1927–32.

    PubMed  CAS  Google Scholar 

  165. Arslanian SA, Lewy V, Danadian K, Saad R. Metformin therapy in obese adolescents with polycystic ovary syndrome and impaired glucose tolerance: amelioration of exaggerated adrenal response to adrenocorticotropin with reduction of insulinemia/insulin resistance. J Clin Endocrinol Metab 2002;87:1555–9.

    PubMed  CAS  Google Scholar 

  166. Bridger T, MacDonald S, Baltzer F, Rodd C. Randomized placebo-controlled trial of metformin for adolescents with polycystic ovary syndrome. Arch Pediatr Adolesc Med 2006;160:241–6.

    PubMed  Google Scholar 

  167. Glueck CJ, Wang P, Fontaine R, Tracy T, Sieve-Smith L. Metformin to restore normal menses in oligo-amenorrheic teenage girls with polycystic ovary syndrome (PCOS). J Adolesc Health 2001;29:160–9.

    PubMed  CAS  Google Scholar 

  168. Ibanez L, Valls C, Potau N, Marcos MV, de Zegher F. Sensitization to insulin in adolescent girls to normalize hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism after precocious pubarche. J Clin Endocrinol Metab 2000;85:3526–30.

    PubMed  CAS  Google Scholar 

  169. Ibanez L, Ferrer A, Ong K, Amin R, Dunger D, de Zegher F. Insulin sensitization early after menarche prevents progression from precocious pubarche to polycystic ovary syndrome. J Pediatr 2004;144:23–9.

    PubMed  Google Scholar 

  170. Ibanez L, de Zegher F. Ethinylestradiol-drospirenone, flutamide-metformin, or both for adolescents and women with hyperinsulinemic hyperandrogenism: opposite effects on adipocytokines and body adiposity. J Clin Endocrinol Metab 2004;89:1592–7.

    PubMed  CAS  Google Scholar 

  171. McCartney CR, Prendergast KA, Chhabra S, Eagleson CA, Yoo R, Chang RJ, Foster CM, Marshall JC. The Association of Obesity and Hyperandrogenemia during the Pubertal Transition in Girls: Obesity as a Potential Factor in the Genesis of Postpubertal Hyperandrogenism. J Clin Endocrinol Metab 2006;91:1714–1722.

    PubMed  CAS  Google Scholar 

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Authors
  1. Julia Warren-Ulanch MD
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  2. Silva A. Arslanian MD
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Editor information

Editors and Affiliations

  1. Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University, Chicago, IL

    Andrea Dunaif MD

  2. Department of Reproductive Medicine, University of California, San Diego School of Medicine, La Jolla, CA

    R. Jeffrey Chang MD

  3. Institute of Reproductive and Developmental Biology, Imperial College London, London, UK

    Stephen Franks MD, FMEDSCI

  4. Department of Ob/Gyn, Penn State College of Medicine, Hershey, PA

    Richard S. Legro MD

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Warren-Ulanch, J., Arslanian, S.A. (2008). Insulin Action and Secretion in Polycystic Ovary Syndrome. In: Dunaif, A., Chang, R.J., Franks, S., Legro, R.S. (eds) Polycystic Ovary Syndrome. Contemporary Endocrinology. Humana Press. https://doi.org/10.1007/978-1-59745-108-6_11

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  • DOI: https://doi.org/10.1007/978-1-59745-108-6_11

  • Publisher Name: Humana Press

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