The Major Impact of Obesity on the Development of Type 2 Diabetes (T2D) in Women With PCOS: A Systematic Review and Meta-Analysis of Observational Studies

Background/Aims: Polycystic ovary syndrome (PCOS) is associated with disordered carbohydrate metabolism and an increased risk for T2D. However, there are limited data on the magnitude of this risk. Furthermore, 50-80% of women with PCOS are obese and obesity is known to have a synergistic deleterious effect on glucose tolerance in affected women. We systematically reviewed the literature regarding the association between PCOS, obesity and T2D risk. Methods: A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases. Data are expressed as relative risk (RR) with 95% confidence intervals (CI). The I(2) index was employed for heterogeneity. The available data, did not allow us to analyze the impact of weight status as normal, overweight and obese and as a consequence the studied subjects were stratified as obese (BMI>30 kg/m(2)) and non-obese (BMI<30kg/m(2)). Results: Twelve studies fulfilled eligibility criteria, yielding a total of 224,284 participants (45,361 PCOS and 5,717 T2DM cases). Women with PCOS had a higher risk of T2D compared with to unaffected women (RR 3.13, 95% CI, 2.83-3.47, p<0.001; I(2) 40.1%). When women with PCOS were stratified according to the presence or absence of obesity, the RR for developing T2D in obese compared with non-obese women with PCOS was 4.20 (95% CI 1.97-9.10; p<0.001). Moreover, compared to control women, the RR for developing T2D was significantly increased only in obese PCOS, RR 4.06 (95% CI 2.75-5.98; p<0.001). There was a trend toward significantly increased risk in non-obese PCOS women [RR 2.68 (95% CI 0.97-7.49; p=0.06). Conclusion: Women with PCOS have a >3-fold increased risk of T2D compared to women without PCOS, but this risk is substantially increased by the presence of obesity. Accordingly, weight reduction should be pursued in these women. References: 1. Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes. 1989;38(9):1165-1174.2. 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):165-169.3. 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(1):141-146.4. Rubin KH, Glintborg D, Nybo M, Abrahamsen B, Andersen M. Development and risk factors of type 2 diabetes in a nationwide population of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2017;102(10):3848-3857.