Defining prediabetes in polycystic ovarian syndrome

Mark P. Trolice

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DOI: 10.4236/ojog.2011.12008                

Abstract

Objective: The article will review the associations between Prediabetes (PD) and Polycystic Ovarian Syndrome (PCOS) and present factors that decrease the progression of PD into type 2 diabetes mellitus (T2DM).Metformin will also be examined for its role in ovulation induction, pregnancy and ameliorating the metabolic syndrome. Study Design: Medline search. Methods of study: Keyword search: Prediabetes (PD), Polycystic Ovarian Syndrome (PCOS), Metformin, Glucose Tolerance Test (GTT), Type 2 Diabetes Mellitus. Results: As the most common endocrinopathy during the reproductive years, PCOS has a genetic multifactorial inheritance and is associated with a high risk of insulin resistance. The use of metformin has shown mixed results in this patient population as a therapy to improve ovulation function and the metabolic syndrome and showed no definitive reduction in the rate of miscarriage. PCOS patients are significantly predisposed to PD and T2DM. Conclusion: Lifestyle changes such as weight loss and physical activity reduce the progression of PD into T2DM in PCOS patients. The new AACE and ADA guidelines establish simplified methods of screening and treating PD. The role of metformin remains undefined in the infertile PCOS patient.

Keywords

Polycystic Ovarian Syndrome; Prediabetes; Impaired Glucose Tolerance; Impaired Fasting Glucose; Type 2 Diabetes

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Franks, S. (1995) Polycystic ovary syndrome. The New England Journal of Medicine, 333, 853-861. doi:10.1056/NEJM199509283331307
[2]	Blight, L.F., Judd, S.J. and White, G.H. (1989) Relative diagnostic value of serum non-SHBG-bound testosterone, free androgen index and free testosterone in the assessment of mild to moderate hirsutism. Annals of Clinical Biochemistry, 26, 311-316.
[3]	Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group Revised 2003 (2004) Consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertility and Sterility, 81, 19-25. doi:10.1016/j.fertnstert.2003.10.004
[4]	Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group Revised 2003 (2004) Consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Human Reproduction, 19, 41-47. doi:10.1093/humrep/deh098
[5]	Third Report of the National Cholesterol Education Program (NCEP) (2002) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation, 106, 3143-3421.
[6]	Apridonidze, T., Essah, P.A., Iuorno, M.J. and Nestler, J.E. (2005) Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome. The Journal of Clinical Endocrinology & Metabolism, 90, 1929-1935. doi:10.1210/jc.2004-1045
[7]	Palomba, S., Falbo, A., Zullo, F. and Orio, F. (2009) Evidence-based and potential benefits of metformin in the polycystic ovary syndrome: A comprehensive review. Endocrine Review, 30, 1-50. doi:10.1210/er.2008-0030
[8]	Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group (2008) Consensus on infertility treatment related to polycystic ovary syndrome. Fertility and Sterility, 89, 505-522.
[9]	Lord, J.M., Flight, I.H.K. and Norman, R.J. (2003) Metformin in polycystic ovary syndrome: Systematic review and meta-analysis. British Medical Journal, 327, 951-953. doi:10.1136/bmj.327.7421.951
[10]	Creanga, A.A., Bradley, H.M., McCormick, C. and Witkop, C.T. (2008) Use of metformin in polycystic ovary syndrome: A meta-analysis. Obstetrics & Gynecology, 111, 959-968. doi:10.1097/AOG.0b013e31816a4ed4
[11]	Palomba, S., Orio, F., Falbo, A., Manguso, F., Russo, T., Cascella, T., et al. (2005) Prospective paralell randomized double blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first line treatment for ovulation induction in non-obese anovulatory women with polycystic ovary syndrome. The Journal of Clinical Endocrinology & Metabolism, 90, 4068-4074. doi:10.1210/jc.2005-0110
[12]	Tang, T., Lord, J.M., Norman, R.J., Yasmin, E. and Balen, A.H. (2010) Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database of Systematic Reviews, CD003053.
[13]	Legro, R.S., Barnhart, H.X., et al. (2007) Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. New England Journal of Medicine, 356, 551-566. doi:10.1056/NEJMoa063971
[14]	Barbieri, R.L. (2007) Clomiphene versus metformin for ovulation induction in polycystic ovary syndrome: the winner is …. The Journal of Clinical Endocrinology & Metabolism, 92, 3399-3401. doi:10.1210/jc.2007-1393
[15]	He, D., Jiang, F. (2011) Meta-analysis of letrozole versus clomiphene citrate in polycystic ovary syndrome. Reproductive BioMedicine Online, (Epub ahead of print)
[16]	Tredway, D., Schertz, J.C., Bock, D., Hemsey, G. and Diamond, M.P. (2011) Anastrozole vs. clomiphene citrate in infertile women with ovulatory dysfunction: A phase II, randomized, dose-finding study. Fertility and Sterility, 95, 1549-1551. doi:10.1016/j.fertnstert.2010.12.064
[17]	Tang, T., Glanville, J., Hayden, C.J., White, D., Barth, J.H. and Balen, A.H. (2006) Combined lifestyle modification and metformin in obese patients with polycystic ovary syndrome: A randomized, placebo-controlled, double blind multicentre study. Human Reproduction, 21, 80-89. doi:10.1093/humrep/dei311
[18]	Clark, A.M., Thornley, B., Tomlinson, L., Galletley, C. and Norman, R.J. (1998) Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Human Reproduction, 13, 1502-1505. doi:10.1093/humrep/13.6.1502
[19]	Hollmann, M., Runnebaum B. and Gerhard, I. (1996) Effects of weight loss on the hormonal profile in obese, infertile women. Human Reproduction, 11, 1884-1891.
[20]	Huber-Buchholz, M.M., Carey, D.G. and Norman, R.J. (1999) Restoration of reproductive potential by lifestyle modification in obese polycystic ovary syndrome: Role of insulin sensitivity and luteinizing hormone. The Journal of Clinical Endocrinology & Metabolism, 84, 1470-1474. doi:10.1210/jc.84.4.1470
[21]	Balen, A.H., et al. (1993) Miscarriage rates following in vitro fertilization are increased in women with polycystic ovaries and reduced by pituitary desensitization with buserlin. Human Reproduction, 8, 959-964.
[22]	Gray, R.H. and Wu, L.Y. (2000) Subfertility and risk of spontaneous abortion. American Journal Public Health, 90, 1452-1454. doi:10.2105/AJPH.90.9.1452
[23]	Khattab, S., et al. (2006) Metformin reduces abortion in pregnant women with polycystic ovary syndrome. Gynecological Endocrinology, 22, 680-684. doi:10.1080/09513590601010508
[24]	Li, T., et al. (2007) Insulin Resistance Increases the Risk of Spontaneous abortion after Assisted Reproduction Technology Treatment. The Journal of Clinical Endocrinology & Metabolism, 92, 1430-1433. doi:10.1210/jc.2006-1123
[25]	Glueck, C.J., et al. (2001) Continuing metformin throughout pregnancy with polycystic ovary syndrome appears to safely reduce first-trimester spontaneous abortion: A pilot study. Fertility and Sterility, 75, 46-52. doi:10.1016/S0015-0282(00)01666-6
[26]	Jakubowicz, D.J., et al. (2001) Insulin reduction with metformin increases luteal phase serum glycodelin and insulin-like growth factor-binding protein 1 concentrations and enhances uterine vascularity and blood flow in polycystic ovary syndrome. Journal Clinical Endocrinology Metabolism, 86, 1126-1133. doi:10.1210/jc.86.3.1126
[27]	Jakubowicz, D.J., et al. (2004) Reduced serum glycodelin and insulin-like growth factor-binding protein-1 in women with polycystic ovary syndrome during first trimester of pregnancy. Journal Clinical Endocrinology Metabolism, 89, 833-839. doi:10.1210/jc.2003-030975
[28]	Cocksedge1, K.A., Li, T.-C., Saravelos, S.H. and Metwally, M. (2008) A reappraisal of the role of polycystic ovary syndrome in recurrent miscarriage. Reproductive BioMedicine Online, 17, 151-160.
[29]	Palomba, S., Falbo, A., et al. (2009) Effect of preconceptional metformin on abortion risk in polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials. Fertility and Sterility, 92, 1646-1458. doi:10.1016/j.fertnstert.2008.08.087
[30]	LO, T., Costello, M.F., Andriolo, R.B. and Freitas, V. (2009) Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database of Systematic Reviews.
[31]	Burghen, G.A., Givens, J.R. and Kitabchi, A.E. (1980) Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease. The Journal of Clinical Endocrinology & Metabolism, 50, 113-116. doi:10.1210/jcem-50-1-113
[32]	DeUgarte, C.M., Barolucci, A.A. and Azziz, R. (2005) Prevalence of insulin resistance in the polycystic ovary syndrome using the homeostasis model assessment. Fertility and Sterility, 83, 1454-1460. doi:10.1016/j.fertnstert.2004.11.070
[33]	Legro, R.S., Driscoll, D., Strauss 3rd, J.F., Fox, J. and Dunaif, A. (1998) Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proceedings of the National Academy of Sciences, 95, 14956-14960. doi:10.1073/pnas.95.25.14956
[34]	Yildiz, B.O., Yarali, H., Oguz, H. and Bayraktar, M. (2003) Glucose intolerance, insulin resistance, and hyperandrogenemia in first degree relatives of women with polycystic ovary syndrome. The Journal of Clinical Endocrinology & Metabolism, 88, 2031-2036. doi:10.1210/jc.2002-021499
[35]	Yilmaz, M., Bukan, N., Ersoy, R., Karakoc, A., Yetkin, I., Ayvaz, G., Cakir, N. and Arslan, M. (2005) Glucose intolerance, insulin resistance and cardiovascular risk factors in first degree relatives of women with polycystic ovary syndrome. Human Reproduction, 20, 2414-2420. doi:10.1093/humrep/dei070
[36]	Norman, R.J., Masters, S. and Hague, W. (1996) Hyperinsulinemia is common in family members of women with polycystic ovary syndrome. Fertility and Sterility, 66, 942-947.
[37]	Dunaif, A., Segal, K.R., Shelley, D.R., Green, G., Dobrjansky, A. and Licholai, T. (1992) Evidence for distinctive and intrinsic defects in insulin action in polycystic ovary syndrome. Diabetes, 41, 1257-1266. doi:10.2337/diabetes.41.10.1257
[38]	Unwin, N., Shaw, J., Zimmet, P. and Alberti, K.G. (2002) Impaired glucose tolerance and impaired fasting glycaemia: the current status on definition and intervention. Diabetic Medicine, 19, 708-723. doi:10.1046/j.1464-5491.2002.00835.x
[39]	Gupta, S., Metterle, L., Thakkar, P., Surti, N., Chandra, A. and Agarwal, A. (2009) Ovulation induction in polycystic ovarian syndrome. Archives of Medical Science, 5, S132-S142.
[40]	Radon, P.A., McMahon, M.J. and Meyer, W.R. (1999) Impaired glucose tolerance in pregnant women with polycystic ovary syndrome. Obstetrics & Gynecology, 94, 194-197. doi:10.1016/S0029-7844(99)00252-5
[41]	Glueck, C.J., Wang, P., Kobayashi, S., Phillips, H. and Sieve-Smith, L. (2002) Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome. Fertility and Sterility, 77, 20-525. doi:10.1016/S0015-0282(01)03202-2
[42]	Legro, R. (2008) Impact of metformin, oral contraceptives, and lifestyle modification on polycystic ovary syndrome in obese adolescent women: Do we need a new drug? The Journal of Clinical Endocrinology & Metabolism, 93, 4218-4214. doi:10.1210/jc.2008-1994
[43]	Cocksedge, K. (2008) A reappraisal of the role of polycystic ovary syndrome in recurrent miscarriage. Reproductive BioMedicine Online, 17, 151-161. doi:10.1016/S1472-6483(10)60304-5
[44]	Coetzee, E.J. and Jackson, W.P. (1984) Oral hypoglycemics in the first trimester and fetal outcome. South African Medical Journal, 65, 635-637.
[45]	Rouzi, A.A. and Ardawi, M.S. (2006) A randomized controlled trial of the efficacy of rosiglitazone and clomiphene citrate versus metformin and clomiphene citrate in women with clomiphene citrate-resistant polycystic ovary syndrome. Fertility and Sterility, 85, 428-435. doi:10.1016/j.fertnstert.2005.07.1312
[46]	Talbott, E.O., Zborowski, J.V. and Boudreaux, M.Y. (2004) Do women with polycystic ovary syndrome have an increased risk of cardiovascular disease? Review of the evidence. Minerva Ginecologica, 56, 27-39.
[47]	Ehrmann, D.A., Barnes, R.B., Rosenfield, R.L., Cavaghan, M.K. and Imperial, J. (1999) Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care, 22, 141-146. doi:10.2337/diacare.22.1.141
[48]	Legro, R.S., Kunselman, A.R., Dodson, W.C. and Dunaif, A. (1999) 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. The Journal of Clinical Endocrinology & Metabolism, 84, 165-169. doi:10.1210/jc.84.1.165
[49]	CDC (2008) National Diabetes Fact Sheet. http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2007.pdf.
[50]	Aroda, V.R. and Ratner, R. (2008) Approach to the patient with prediabetes. The Journal of Clinical Endocrinology & Metabolism, 93, 3259-3265. doi:10.1210/jc.2008-1091
[51]	American Diabetes Association Position Statement (2010) Diabetes Care, 33, S11-61.
[52]	Diabetes Prevention Program. August 2006 (Cited 2008 October 30). http://diabetes.niddk.nih.gov/dm/pubs/preventionprogram/.
[53]	Deatcher, J.V. (2008) Prediabetes. The American Journal of Nursing, 108, 77-79.
[54]	Sherwin, R.S., et al. (2002) The prevention or delay of type 2 diabetes. Diabetes Care, 25, 742-749. doi:10.2337/diacare.25.4.742
[55]	AACE. (2008) American College of Endocrinology consensus statement on the diagnosis and management of Pre-Diabetes in the continuum of hyperglycemia-When do the risks of diabetes begin? 23 July 2008. http://www.aace.com/meetings/consensus/hyperglycemia/hyperglycemia.pdf.
[56]	Cowie, C.C., et al. (2008) Economic costs of diabetes in the U.S. in 2007. Diabetes Care, 31, 596-615.