Korean Diabetes J.  2008 Feb;32(1):1-6. 10.4093/kdj.2008.32.1.1.

Insulin Resistance in Polycystic Ovary Syndrome

• Sung YA

• KMID: 2298103
• DOI: http://doi.org/10.4093/kdj.2008.32.1.1

Abstract

Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women of reproductive age and now recognized as an important metabolic and reproductive disorder. The majority of women with PCOS have insulin resistance and this is regarded to have a central etiological role in PCOS. Insulin resistance and concomitant hyperinsulinemia modifies reproductive function by driving androgen production, suppression of sex hormone-binding globulin (SHBG) and disruption of insulin signaling pathways in the central nervous system. Insulin resistance, together with defects in insulin secretion, confers markedly increased risk for type 2 diabetes mellitus and metabolic syndrome. There are post-binding defects in insulin receptor signaling, with selective resistance to insulin's metabolic actions and preserved other actions. Genetic and environmental abnormalities interact to produce peripheral insulin resistance in PCOS. The numerous in vivo and in vitro data supporting the central role of insulin resistance in the pathogenesis of PCOS have led a new therapy for PCOS with insulin-sensitizing agents.

Keyword

Polycystic ovary syndrome; Insulin resistance

MeSH Terms

Central Nervous System
Diabetes Mellitus, Type 2
Female
Humans
Hyperinsulinism
Insulin
Insulin Resistance
Polycystic Ovary Syndrome
Receptor, Insulin
Sex Hormone-Binding Globulin
Insulin
Receptor, Insulin
Sex Hormone-Binding Globulin

Reference

1. Diamanti-Kandarakis E, Kouli CR, Bergiele AT, Filandra FA, Tsianateli TC, Spina GG, Zapanti ED, Bartzis MI. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab. 1999. 84:4006–4011.

2. Asunción M, Calvo RM, San Millán JL, Sancho J, Avila S, Escobar-Morreale HF. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab. 2000. 85:2434–2438.

3. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004. 89:2745–2749.

5. Legro RS. Polycystic ovary syndrome: the new millenium. Mol Cell Endocrinol. 2002. 186:219–225.

6. Doi SA, Al-Zaid M, Towers PA, Scott CJ, Al-Shoumer KA. Ovarian steroids modulate neuroendocrine dysfunction in polycystic ovary syndrome. J Endocrinol Invest. 2005. 28:882–892.

7. Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes. 1989. 38:1165–1174.

8. O'Meara NM, Blackman JD, Ehrmann DA, Barnes RB, Jaspan JB, Rosenfield RL, Polonsky KS. Defects in β-cell function in functional ovarian hyperandrogenism. J Clin Endocrinol Metab. 1993. 76:1241–1247.

9. Legro RS, Gnatuk CL, Kunselman AR, Dunaif A. Changes in glucose tolerance over time in women with polycystic ovary syndrome: a controlled study. J Clin Endocrinol Metab. 2005. 90:3236–3242.

10. Gambineri A, Pelusi C, Manicardi E, Vicennati V, Cacciari M, Morselli-Labate AM, Pagotto U, Pasquali R. Glucose intolerance in a large cohort of mediterranean women with polycystic ovary syndrome: phenotype and associated factors. Diabetes. 2004. 53:2353–2358.

11. Dahlgren E, Janson PO, Johansson S, Lapidus L, Odn 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.

12. 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.

13. Diamanti-Kandarakis E. Insulin resistance in PCOS. Endocrine. 2006. 30:13–17.

14. Nestler JE, Jakubowicz DJ. Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17 alpha activity and serum androgens. J Clin Endocrinol Metab. 1997. 82:4075–4079.

15. Vrbíková J, Cibula D, Dvorákov K, Stanicka S, Sindelká G, Hill M, Fanta M, Vondra K, Skrha J. Insulin sensitivity in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2004. 89:2942–2945.

16. Legro RS, Castracane VD, Kauffman RP. Detecting insulin resistance in polycystic ovary syndrome. Obstet Gynecol Surv. 2004. 59:141–154.

17. Ehrmann DA, Kasza K, Azziz R, Legro RS. Ghazzi MN 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. 2005. 90:66–71.

18. The Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004. 19:41–47.

19. Goodarzi MO, Azziz R. Diagnosis, epidemiology, and genetics of the polycystic ovary syndrome. Best Pract Res Clin Endocrinol Metab. 2006. 20:193–205.

20. Palomba S. Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005. 90:4068–4074.

21. Ciampelli M, Leoni F, Cucinelli F, Mancuso S, Panunzi S, De Gaetano A, Lanzone A. Assessment of insulin sensitivity from measurements in the fasting state and during an oral glucose tolerance test in polycystic ovary syndrome and menopausal patients. J Clin Endocrinol Metab. 2005. 90:1398–1406.

22. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF. Criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an androgen excess society guideline. J Clin Endocrinol Metab. 2006. 91:4237–4245.

23. 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. 83:2694–2860.

24. Carmina EE, Lobo RA. Use of fasting blood to assess the prevalence of insulin resistance in women with polycystic ovary syndrome. Fertil Steril. 2004. 82:661–665.

25. Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound insulin resistance independent of obesity in polycystic ovary syndrome. Diabetes. 1989. 38:1165–1171.

26. DeUgarte CM, Bartolucci AA, Azziz R. Prevalence of insulin resistance in the polycystic ovary syndrome using the homeostasis model assessment. Fertil Steril. 2005. 83:1454–1460.

27. Sam S, Sung YA, Legro RS, Dunaif A. Evidence for pancreatic β-cell dysfunction in brothers of women with polycystic ovary syndrome. Metabolism Clinical and Experimental. 2008. 57:84–89.

28. Diamanti-Kandarakis E, Papavassiliou AG. Molecular mechanisms of insulin resistance in polycystic ovary syndrome. Trends Mol Med. 2006. 12:324–332.

29. Legro RS, Barnhart HX, Schlaff WD. Cooperative Multicenter Reproductive Medicine Network. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007. 356:551–566.

30. Xita N, Tsatsoulis A. Fetal programming of polycystic ovary syndrome by androgen excess: evidence from experimental, clinical, and genetic association studies. J Clin Endocrinol Metab. 2006. 91:1660–1666.

31. 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. 82:1421–1425.

32. Chu YL, Sun YY, Qiu HY, Li HF. Tyrosine phosphorylation and protein expression of insulin receptor substrate-1 in the patients with polycystic ovary syndrome. Zhonghua Fu Chan Ke Za Zhi. 2004. 39:176–179.

33. Wang ZC, Gu XF, Yang DZ, Kuang JQ. Expression of insulin receptor substrate 1 and phosphorylation of tyrosine in adipose tissue of polycystic ovary syndrome. Zhonghua Fu Chan Ke Za Zhi. 2005. 40:120–123.

34. Qiu HY, Chu YL, Li M, Sun YY, Li HF. Tyrosine phosphorylation and protein expression of insulin receptor substrate-2 in the adipose tissue from patients with polycystic ovary syndrome. Zhonghua Fu Chan Ke Za Zhi. 2005. 40:116–119.

35. Højlund K, Glintborg D, Andersen NR, Birk JB, Treebak JT, Frøsig C, Beck-Nielsen H, Wojtaszewski JF. Impaired insulin-stimulated phosphorylation of Akt and AS160 in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment. Diabetes. 2008. 57:357–366.

36. Dunaif A, Wu X, Lee A, Diamanti-Kandarakis E. Defects in insulin receptor signaling in vivo in the polycystic ovary syndrome (PCOS). Am J Physiol Endocrinol Metab. 2001. 281:E392–E399.

37. Corbould A, Kim YB, Youngren JF, Pender C, Kahn BB, Lee A, Dunaif A. 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–E1054.

38. Boudreaux MY, Talbott EO, Kip KE, Brooks MM, Witchel SF. Risk of T2DM and impaired fasting glucose among PCOS subjects: results of an 8 year follow-up. Curr Diab Rep. 2006. 6:77–83.

39. Legro RS, Kunselman AR, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose. J Clin Endocrinol Metab. 1999. 84:165–169.

40. Dahlgren E, Johansson S, Lindstedt G, Knutsson F, Odén A, Janson PO, Mattson LA, Crona N, Lundberg PA. Women with polycystic ovary syndrome wedge resected in 1956 to 1965: a long-term follow-up focusing on natural history and circulating hormones. Fertil Steril. 1992. 57:505–513.

41. De Leo V. Insulin-lowering agents in the management of polycystic ovary syndrome. Endocr Rev. 2003. 24:633–667.

42. Park HR, Choi Y, Lee HJ, Oh JY, Hong YS, Sung YA. The metabolic syndrome in young Korean women with polycystic ovary syndrome. Diab Res Clin Prcact. 2007. 77:suppl1. s243–s246.