Managing Diabetes Risk in Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) affects approximately 10% of women of reproductive age in the United States and has been cited as the most common cause of anovulatory infertility.^1,2 In addition, individuals with PCOS often develop metabolic disorders such as prediabetes and type 2 diabetes (T2D). A 2010 meta-analysis demonstrated an increased prevalence of impaired glucose tolerance (IGT) and T2D in women with PCOS (odds ratio [OR] 2.48; 95% CI, 1.63-3.77 and OR 4.43; 95% CI, 4.06-4.82, respectively) compared with women without PCOS.³

As reported in a recent narrative review published in Hormones, an estimated 60% to 80% of women with PCOS have insulin resistance, which appears to be an intrinsic component of the syndrome and independent of obesity.² “Obesity itself carries an increased risk for insulin resistance, but we believe there is an inherent risk in PCOS for prediabetes and type 2 diabetes,” R. Jeffrey Chang, MD, a reproductive endocrinologist and professor of obstetrics, gynecology, and reproductive sciences at the University of California, San Diego, told Endocrinology Advisor.   

From 40% to 70% of individuals with PCOS are obese, which contributes to impaired glucose metabolism.² Findings from a study described in Current Diabetes Reports in 2006 indicated that individuals with PCOS with obesity were 5 times more likely to develop T2D vs age- and BMI-matched controls,⁴ and numerous studies have demonstrated that obesity is closely associated with increased risk for IGT and T2D in PCOS.^5,6

“Obesity appears to exert a synergistic, independent, adverse effect on glucose metabolism, this accompanied by the added burden of intrinsic IR that characterizes patients with PCOS,” as explained in the narrative review.² “Body composition, including increased ratio of truncal/lower body fat and higher inter- and intramuscular adipose tissue also contribute to the aggravation of IR in this population.”

Additionally, hyperandrogenism may contribute to the development of prediabetes in PCOS, a concept supported by research showing more pronounced insulin resistance in patients with vs without hyperandrogenemia.^7,8 “Patients with nonandrogenic PCOS have far less metabolic comorbidity,” Dr Chang noted.

An elevated risk of insulin resistance and T2D has been reported in individuals with PCOS and a family history of T2D, suggesting that a genetic link may underlie the impaired glucose metabolism in these individuals.⁹ Recent research has also implicated the gut microbiome as well as muscle mitochondrial dysfunction in the development of impaired glucose metabolism and T2D in PCOS.²

Screening and Treatment

The Endocrine Society recommends that all individuals with PCOS undergo an oral glucose tolerance test (OGTT) every 3 to 5 years, with more frequent screening for those who develop symptoms of T2D, significant weight gain, or central adiposity.¹⁰ In guidelines published in 2015 by the American Association of Clinical Endocrinologists, the American College of Endocrinology, and the Androgen Excess and PCOS Society, the authors recommend an annual OGTT for patients with PCOS and IGT, while those with a family history of T2D or a BMI >30 kg/m² should be screened every 1 to 2 years.¹¹

Lifestyle modification is the first-line treatment strategy for at-risk patients, followed by the addition of an insulin sensitizer, if needed, according to Dr Chang. Lifestyle changes have been found to reduce the progression from IGT to T2D in individuals with PCOS, as in the general population.¹⁰ Improved diet quality has been shown to reduce insulin resistance in individuals with PCOS, and exercise may also reduce insulin resistance and visceral fat in this group.²

Diet recommendations include a daily calorie reduction of 500 to 1000 kcal; increased consumption of vegetables, fruits, fiber, whole grains, and mono- and polyunsaturated fats; and reduced intake of saturated fats. There is evidence indicating that a reduced-carbohydrate diet may be especially effective for abdominal fat loss.² For adequate physical activity, a minimum of 30 minutes of moderate-intensity exercise per day is recommended.

Professional guidelines further recommend that metformin be prescribed for individuals of normal weight with PCOS and IGT, as well as for overweight patients who have persistent IGT despite lifestyle modifications.² In various studies, metformin was associated with weight loss and improved insulin resistance in individuals with PCOS (although not to the same extent as lifestyle changes), and some findings suggest that it could prevent the development of IGT or T2D in these individuals.²

Management of individuals with PCOS who develop T2D is similar to that of patients with T2D without PCOS. “Accordingly, metformin and lifestyle changes are the treatment of choice, while any antidiabetic agent can be added in patients who do not achieve glycemic targets despite treatment with metformin,” wrote the authors of the recent review.² “However, only insulin, metformin and glyburide can be safely used in pregnancy and therefore appropriate contraceptive measures should be implemented in patients receiving other antidiabetic agents.”

Researchers should continue to explore causes of the various types of dysregulation observed in PCOS, including the multiple metabolic problems involved in the pathogenesis of the disease, Dr Chang stated.

References

1. US Department of Health and Human Services. Office on Women’s Health. Polycystic ovary syndromehttps://www.womenshealth.gov/a-z-topics/polycystic-ovary-syndrome. Updated May 22, 2018. Accessed May 21, 2018.
2. Lazaridou S, Dinas K, Tziomalos K. Prevalence, pathogenesis and management of prediabetes and type 2 diabetes mellitus in patients with polycystic ovary syndrome. Hormones (Athens). 2017;16(4):373-380. 
3. Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2010;16(4):347-363.
4. 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(1):77-83.
5. 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(1):165-169.
6. Norman RJ, Masters L, Milner CR, Wang JX, Davies MJ. Relative risk of conversion from normoglycaemia to impaired glucose tolerance or non-insulin dependent diabetes mellitus in polycystic ovarian syndrome. Hum Reprod. 2001;16(9):1995-1998.
7. Goverde AJ, van Koert AJB, Eijkemans MJ, et al. Indicators for metabolic disturbances in anovulatory women with polycystic ovary syndrome diagnosed according to the Rotterdam consensus criteria. Hum Reprod. 2009;24(3)710-717.
8. Panidis D, Tziomalos K, Misichronis G, et al. Insulin resistance and endocrine characteristics of the different phenotypes of polycystic ovary syndrome: a prospective study.Hum Reprod. 2012;27(2):541-549.
9. Lerchbaum E, Schwetz V, Giuliani A, Obermayer-Pietsch B. Influence of a positive family history of both type 2 diabetes and PCOS on metabolic and endocrine parameters in a large cohort of PCOS women.Eur J Endocrinol. 2014;170:727-739.
10. Legro RS, Arslanian SA, Erhmann DA, et al. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(12):4565-4592.
11. Goodman NF, Cobin RH, Futterweit W, Glueck JS, Legro RS, Carmina E. American Association of Clinical Endocrinologists, American College of Endocrinology, and Androgen Excess and PCOS Society disease state clinical review: guide to the best practices in the evaluation and treatment of polycystic ovary syndrome – part 2.Endocr Pract. 2015;21(12):1415-1426.