Journal of Diabetes Research
Volume 2017 (2017), Article ID 5250162, 5 pages
Risk of Type 2 Diabetes Mellitus following Gestational Diabetes Pregnancy in Women with Polycystic Ovary Syndrome
Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
Academic Editor: Daniela Foti
Copyright © 2017 Joan C. Lo et al.. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background. This study assesses gestational diabetes mellitus (GDM) in women with polycystic ovary syndrome (PCOS) and the probability of type 2 diabetes mellitus (DM) after GDM pregnancy. Methods. A cohort of 988 pregnant girls with PCOS who delivered during 2002–2005 was examined to find out the incidence and predictors of GDM, together with follow-up through 2010 among those with GDM to gauge the probability of DM. Outcomes. Of the 988 pregnant girls with PCOS, 192 (19 percent) developed GDM. Multivariable predictors of GDM included older age, Asian race, prepregnancy obesity, family history of DM, preconception metformin use, and multiple gestation. Among women with PCOS and GDM pregnancy, the prevalence of DM was 2.8 (95% confidence interval (CI) 1.9–4.2) per 100 person-years and considerably higher for those who received pharmacologic therapy for GDM (6.6 versus 1.5 percent 100 person-years, ). The multivariable adjusted risk of DM was fourfold higher in women who received pharmacologic therapy for GDM (adjusted hazard ratio 4.1, 95% CI 1.8–9.6). The five-year incidence of DM was 13.1% total and higher in the pharmacologic treatment subgroup (27.0 percent versus 7.1 percent, ). Conclusions. The strongest predictors of GDM among girls with PCOS included Asian race and prepregnancy obesity. Pharmacologic therapy of GDM is associated with fourfold higher risk of succeeding DM.
Women with polycystic ovary syndrome (PCOS) are at higher risk for developing gestational diabetes mellitus (GDM) during pregnancy [1–6]. Both PCOS and GDM are also risk factors for type 2 diabetes mellitus [1, two, 7–9]. Women with GDM pregnancy possess a 7-fold higher risk of developing subsequent type 2 diabetes mellitus in comparison with women without GDM , with an annual prevalence of 1.7–2.2 percent [11–13]. In women with PCOS, the danger of diabetes was reported to 8-fold higher in comparison to that in women without PCOS . While fewer studies have examined diabetes risk in women with PCOS, women who experience a GDM pregnancy, impaired glucose metabolism, and glucose intolerance after GDM pregnancy was observed [14, 15]. In this study, we examined a large, community-based inhabitants of women with PCOS and GDM pregnancy to find out the subsequent risk of diabetes and differential risk by GDM severity.
2. Materials and Methods
Kaiser Permanente Northern California (KPNC) is an integrated healthcare delivery system with over 3 million members and over 30,000 births/year. We discovered nondiabetic KPNC girls with PCOS who had a delivered pregnancy during 1 January 2002 to 31 December 2005 and underwent screening for GDM throughout pregnancy. Ladies identified with GDM were followed after maternity delivery to 31 December 2010 for the development of type 2 diabetes mellitus, censoring at diabetes, membership disenrollment, death, or end of follow-up (whichever came first). The research was approved by the KPNC Institutional Review Board, along with also the demand for informed consent was waived as a result of the nature of the study.
As previously described [16, 17], chart review was conducted to verify PCOS diagnosis employing the 2003 ESHRE/ASRM Rotterdam criteria , requiring at least 2 of the 3 criteria: oligo- or amenorrhea, androgen excess, and polycystic ovary morphology by ultrasound. Androgen excess was characterized by acne, hirsutism, and/or elevated androgen levels. Polycystic ovary morphology has been confirmed by imaging, except for 5 percent of the cohort where records were unavailable to verify reproductive endocrine indicators of polycystic-appearing ovaries . Patient characteristics, including preconception body mass index (BMI), metformin, fertility medications or at vitro fertilization [16, 17], family history of diabetes, and pharmacologic management of GDM, have been ascertained by chart review and pharmacy records.
The diagnosis of GDM was predicated on a 3 hr 100 g oral glucose tolerance test (OGTT) with the American Diabetes Association criteria throughout the study interval . We also included women using 1 hr 50 gram screening glucose ≥180 mg/dL (10 mmol/L) that were handled as GDM patients with no 3-hr OGTT (). Subsequent development of type 2 diabetes has been established by laboratory signs of fasting glucose ≥126 mg/dL (7.0 mmol/L), HbA1C ≥6.5 percent, or therapy using a hypoglycemic agent (insulin or glyburide), except during another GDM pregnancy. Metformin therapy in the absence of lab criteria did not meet the requirements for diabetes, given its known use in PCOS administration. When the two fasting glucose and HbA1C criteria were met, the date of diabetes has been determined by fasting glucose criteria.
2.1. Statistical Methods
Differences between subgroups were compared with chi-square, Fisher exact or Student’s t-evaluations. Multivariable logistic regression was utilized to examine independent predictors of GDM. For women with PCOS who underwent a GDM maternity, the subsequent incidence of diabetes has been computed per 100 person-years. The institution of GDM pharmacotherapy and risk of subsequent diabetes mellitus was examined using Cox proportional hazard analyses, adjusted for possible confounders. Analyses were performed with SAS version 9.3 (SAS Institute, Cary, NC) or STATA version 10.2 (College Station, TX); a two-sided value of0.05 was selected as the criterion for statistical significance.
Among 1023 girls with PCOS and delivered maternity, 988 (96.6 percent) underwent GDM screening. The remaining 35 girls not screened for GDM included 17 who delivered extremely preterm (≤29 months of gestation) and 11 that had been handled presumptively as GDM patients. Among the 988 girls screened for GDM, 174 (17.6 percent) met the GDM criteria based on the 3-hour OGTT  and 18 using 1-hour glucose ≥180 mg/dL (10.0 mmol/L) after 50 g oral glucose were handled as GDM patients with no 3-hour OGTT, producing a total of 192 (19.4 percent) pregnant women with PCOS and GDM. Within this subset, 57 (29.7 percent) received pharmacologic therapy for GDM (insulin or glyburide).
As previously described , the cohort has been racially/ethnically diverse, with 41.0 percent White, 25.5% Asian, 26.0% Hispanic, 3.9% Black, and 3.6 percent other race. The mean age was 31.4 ±4.4 decades, and 42.4 percent were overweight. As expected, women with PCOS who had GDM were older and more likely to be more Asian compared to people without GDM (Table 1). They were more likely to be overweight, have a family history of diabetes, receive preconception metformin, undergo fertility therapy, and expertise multiple gestation. In multivariable logistic regression analyses adjusted for these clinical elements, predictors of GDM included older age, Asian race, family history of diabetes, moderate and acute prepregnancy obesity, preconception metformin use, and multiple gestation, together with severe obesity and Asian race since the strongest risk factors (Table 1). Although treatment with fertility drugs or in vitro fertilization for conception may be markers such as PCOS seriousness (and thus metabolic perturbation), fertility therapy was no longer associated with risk of GDM in adjusted analyses.
Table 1: Baseline features in elderly women with polycystic ovary syndrome (PCOS) by gestational diabetes mellitus (GDM) status.
Among the 192 women with PCOS and GDM maternity, 191 (99.5 percent) remained health plan members after delivery. There were five episode cases of type 2 diabetes within the first year, followed by 25 cases during follow-up. Since these five cases might represent preexisting undiagnosed diabetes, the rest of the analyses focus on the 25 episode cases beyond the first year among 186 PCOS GDM girls (total follow-up 951.9 person-years). Individuals who developed diabetes had significantly higher BMI and so are much more likely to have received pharmacologic therapy for GDM, whereas gaps in preconception metformin use and family history of diabetes weren’t significant (Table two).
Table 2: Baseline attributes and incident diabetes mellitus (DM) in women with polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) pregnancy.
Figure 1 indicates the prevalence of diabetes annually of follow-up for the first five years after pregnancy shipping. The overall incidence of diabetes has been 2.8 (CI 1.9–4.2) per 100 person-years during follow-up through 2010. The total prevalence was 4-fold higher if pharmacologic GDM therapy was demanded (6.6 versus 1.5 per 100 person-years, ) in comparison to no pharmacologic therapy for GDM. Among the 122 women with PCOS and GDM who’d complete 5-year follow-up postdelivery, the cumulative 5-year risk of diabetes was 13.1% total and 27.0 percent versus 7.1 percent () for people with and without pharmacologic GDM therapy, respectively. Adjusted for age, race/ethnicity, prepregnancy BMI, family history of diabetes, and preconception metformin use, pharmacologic therapy for GDM was associated with a 4-fold higher rate of incident diabetes (hazard ratio 4.1, CI 1.8–9.6; Table two).
Figure 1: Incidence of diabetes mellitus annually of follow-up after pregnancy delivery among women with PCOS and gestational diabetes mellitus.
Among almost 1000 girls with Rotterdam diagnosis-confirmed PCOS, we found a higher incidence of GDM in 19 percent, 2-3 times higher than the KPNC history rate of 6%–8% . Our incidence of GDM among women with PCOS is higher than anticipated at 14% when PCOS was identified exclusively by coded analysis , without chart review for increased cohort specificity. We found that women with PCOS who had been of Asian race had significantly higher risk of GDM, consistent with previous observations for the general population . For women with PCOS who underwent a GDM pregnancy, the subsequent incidence of diabetes has been 2.8 per 100 person-years total and fourfold higher if pharmacologic therapy for GDM was demanded. In other GDM cohorts not chosen for PCOS, insulin therapy was associated with 3–5-fold higher risk of postdelivery diabetes compared to no insulin therapy [19–21].
It’s estimated that 10%–50 percent of women with GDM develop diabetes throughout the 5-year span after delivery [12, 22]. A possible study that excluded preexisting diabetes based on prepregnancy glycemia dimensions reported a diabetes prevalence rate of 1.8 per 100 person-years among GDM women assessed on average in ten years after their last pregnancy . Diabetes prevalence rates of 1.7–2.2 per 100 person-years have also been reported in other GDM populations not chosen for PCOS standing [12, 13]. Our data suggest the possibility of diabetes among PCOS women with prior GDM is much higher. While racial/ethnic differences in diabetes danger weren’t observed in our study, the numbers within each non-White subgroup were restricted. Others have found differential diabetes risk conferred by GDM pregnancy for White in comparison to Asian girls  and higher risk among African American girls , not considering PCOS status. While Asian race is a predictor of GDM in women with PCOS , among the broader population of women with GDM no matter PCOS standing, Asian race can also be a predictor of subsequent type 2 diabetes .
Our study has some limitations. Although postpartum diabetes surveillance is likely greater for PCOS women, the varying rate of diabetes screening in routine medical care throughout the period of our study (including using fasting glucose and/or hemoglobin A1C rather than that of an oral glucose tolerance test) may contribute to possible underestimation of diabetes prevalence. Additional women diagnosed with diabetes in their first postpartum year weren’t included. We also did not examine relevant postpartum factors such as weight trajectory (or postpartum weight retention), physical action, lactation, or subsequent reproductive care (including metformin) that may have affected diabetes risk. Nonetheless, this is one of the first studies from a large US healthcare delivery program examining GDM and subsequent diabetes risk in women with chart-confirmed PCOS, where receipt of pharmacologic GDM therapy was associated with a 4-fold higher risk of subsequent diabetes. Collectively, these findings emphasize the value of systematic diabetes screening in this high-risk inhabitants  and additional studies examining racial/ethnic differences in the results, the function of androgen excess, weight status, and modifiable risk factors.
Conflicts of Interest
Joan C. Lo has received research funding from Amgen and Sanofi, and Assiamira Ferrara has received research funds from Takeda, unrelated to this particular study. The rest of the authors have nothing to disclose.
The authors thank Drs. Seth Feigenbaum, Grace Lee, and Susan Peng for the physician chart review. This study was financed by the National Institute of Child Health and Human Development, National Institute of Public Health (R01HD052966).
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