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Progression of glucose intolerance and cardiometabolic risk factors over a decade in Chinese women with polycystic ovary syndrome: A case-control study.

ABSTRACT: BACKGROUND:Polycystic ovary syndrome (PCOS) is associated with increased metabolic risk, though data on long-term follow-up of cardiometabolic traits are limited. We postulated that Chinese women with PCOS would have higher risk of incident diabetes and cardiometabolic abnormalities than those without PCOS during long-term follow-up. METHODS AND FINDINGS:One hundred ninety-nine Chinese women with PCOS diagnosed by the Rotterdam criteria and with a mean age of 41.2 years (SD = 6.4) completed a follow-up evaluation after an average of 10.6 ± 1.3 years. Two hundred twenty-five women without PCOS (mean age: 54.1 ± 6.7 years) who underwent baseline and follow-up evaluation over the same period were used for comparison. Progression of glycaemic status of women both with and without PCOS was assessed by using 75-g oral glucose tolerance test (OGTT) screening with the adoption of 2009 American Diabetes Association diagnostic criteria. The frequency of impaired glucose regulation, hypertension, and hyperlipidaemia of women with PCOS at follow-up has increased from 31.7% (95% CI 25.2%-38.1%) to 47.2% (95% CI 40.3%-54.2%), 16.1% (95% CI 11.0%-21.2%) to 34.7% (95% CI 28.1%-41.3%), and 52.3% (95% CI 45.3%-59.2%) to 64.3% (95% CI 57.7%-71.0%), respectively. The cumulative incidence of diabetes mellitus (DM) in follow-up women with PCOS is 26.1% (95% CI 20.0%-32.2%), almost double that in the cohort of women without PCOS (p < 0.001). Age-standardised incidence of diabetes among women with PCOS was 22.12 per 1,000 person-years (95% CI 10.86-33.37) compared with the local female population incidence rate of 8.76 per 1,000 person-years (95% CI 8.72-8.80) and 10.09 per 1,000 person-years (95% CI 4.92-15.26, p < 0.001) for women without PCOS in our study. Incidence rate for women with PCOS aged 30-39 years was 20.56 per 1,000 person-years (95% CI 12.57-31.87), which is approximately 10-fold higher than that of the age-matched general female population in Hong Kong (1.88 per 1,000 person-years, [95% CI 1.85-1.92]). The incidence rate of type 2 DM (T2DM) of both normal-weight and overweight women with PCOS was around double that of corresponding control groups (normal weight: 8.96 [95% CI 3.92-17.72] versus 4.86 per 1,000 person-years [95% CI 2.13-9.62], p > 0.05; overweight/obese: 28.64 [95% CI 19.55-40.60] versus 14.1 per 1,000 person-years [95% CI 8.20-22.76], p < 0.05). Logistic regression analysis identified that baseline waist-to-hip ratio (odds ratio [OR] = 1.71 [95% CI 1.08-2.69], p < 0.05) and elevated triglyceride (OR = 6.63 [95% CI 1.23-35.69], p < 0.05) are associated with the progression to T2DM in PCOS. Limitations of this study include moderate sample size with limited number of incident diabetes during follow-up period and potential selection bias. CONCLUSIONS:High risk of diabetes and increased cardiovascular disease risk factors among Chinese women with PCOS are highlighted in this long-term follow-up study. Diabetes onset was, on average, 10 years earlier among women with PCOS than in women without PCOS.

SUBMITTER: Ng NYH

PROVIDER: S-EPMC6814217 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Progression of glucose intolerance and cardiometabolic risk factors over a decade in Chinese women with polycystic ovary syndrome: A case-control study.

Ng Noel Yat Hey NYH Jiang Guozhi G Cheung Lai Ping LP Zhang Yuying Y Tam Claudia Ha Ting CHT Luk Andrea On Yan AOY Quan Jianchao J Lau Eric Siu Him ESH Yau Tiffany Tse Ling TTL Chan Michael Ho Ming MHM Ho Chung Shun CS Lim Cadmon King Poo CKP Ozaki Risa R Huang Jin J Liu Kin Hung KH Tam Wing Hung WH Sahota Daljit Singh DS Chu Winnie Chiu Wing WCW Goggins William W Woo Jean J Li Tin Chiu TC Chow Chun Chung CC Chan Juliana Chung Ngor JCN Ma Ronald Ching Wan RCW

PLoS medicine 20191025 10

<h4>Background</h4>Polycystic ovary syndrome (PCOS) is associated with increased metabolic risk, though data on long-term follow-up of cardiometabolic traits are limited. We postulated that Chinese women with PCOS would have higher risk of incident diabetes and cardiometabolic abnormalities than those without PCOS during long-term follow-up.<h4>Methods and findings</h4>One hundred ninety-nine Chinese women with PCOS diagnosed by the Rotterdam criteria and with a mean age of 41.2 years (SD = 6.4) ...[more]

PMID: 31652273

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Project description:To determine insulin resistance and response in patients with polycystic ovary syndrome (PCOS) and normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance, and combined glucose intolerance (CGI).In this cross-sectional study, 143 patients with PCOS (diagnosed on the basis of National Institutes of Health criteria) underwent oral glucose tolerance testing (OGTT), and 68 patients also had frequently sampled intravenous glucose tolerance tests. Changes in plasma glucose, insulin, cardiovascular risk factors, and androgens were measured.Compared with patients with NGT, those with both IFG and CGI were significantly insulin resistant (homeostasis model assessment 3.3 +/- 0.2 vs. 6.1 +/- 0.9 and 6.4 +/- 0.5, P < 0.0001) and hyperinsulinemic (insulin area under the curve for 120 min 973 +/- 69 vs. 1,470 +/- 197 and 1,461 +/- 172 pmol/l, P < 0.0001). Insulin response was delayed in patients with CGI but not in those with IFG (2-h OGTT, insulin 1,001 +/- 40 vs. 583 +/- 45 pmol/l, P < 0.0001). Compared with the NGT group, the CGI group had a lower disposition index (1,615 +/- 236 vs. 987 +/- 296, P < 0.0234) and adiponectin level (11.1 +/- 1.1 vs. 6.2 +/- 0.8 ng/ml, P < 0.0096). Compared with the insulin-resistant tertile of the NGT group, those with IFG had a reduced insulinogenic index (421 +/- 130 vs. 268 +/- 68, P < 0.05). Compared with the insulin-sensitive tertile of the NGT group, the resistant tertile had higher triglyceride and high-sensitivity C-reactive protein (hs-CRP) and lower HDL cholesterol and sex hormone-binding globulin (SHBG). In the entire population, insulin resistance correlated directly with triglyceride, hs-CRP, and the free androgen index and inversely with SHBG.Patients with PCOS develop IFG and CGI despite having significant hyperinsulinemia. Patients with IFG and CGI exhibit similar insulin resistance but very different insulin response patterns. Increases in cardiac risk factors and free androgen level precede overt glucose intolerance.

Project description:Are PCOS risk variants identified in women of Han Chinese ethnicity also associated with risk of PCOS or the phenotypic features of PCOS in European women?One variant, rs2268361-T, in the intron of FSHR was associated with PCOS and lower FSH levels, while another variant rs705702-G near the RAB5B and SUOX genes was associated with insulin and glucose levels after oral glucose testing in women with PCOS of European ethnicity.Three of the eleven variants associated with PCOS in the Han Chinese genome-wide association studies were also associated with PCOS in at least one European population when corrected for multiple testing (DENND1A, THADA and YAP1). However, additional replication is needed to establish the importance of these variants in European women and to determine the relationship to PCOS phenotypic traits.The study was a case-control examination in a discovery cohort of women with PCOS (n = 485) and controls (n = 407) from Boston (Boston 1). Replication was performed in women from Greece (cases n = 884 and controls n = 311) and an additional cohort from Boston (Boston electronic medical record (EMR); n = 350 cases and n = 1258 controls).Women had PCOS defined by the National Institutes of Health criteria in Boston 1 and Greece (n = 783), with additional subjects fulfilling the Rotterdam criteria (hyperandrogenism, polycystic ovary morphology and regular menses) in Greece (n = 101). Controls in Boston and Greece had regular menstrual cycles and no hyperandrogenism. The second cohort from Boston was defined using the EMR and natural language processing. Allele frequencies for variants associated with PCOS in Han Chinese women were examined in PCOS cases and controls, along with the relationship to quantitative traits.A variant rs2268361-T in an intron of FSHR was associated with PCOS (0.84 [0.76-0.93], OR [95% CI]; P = 0.002). The rs2268361-T was associated with lower FSH levels (-0.15 ± 0.05; P = 0.0029). A variant rs705702-G near RAB5B and SUOX was associated with insulin (-0.16 ± 0.05, P = 0.0029) and glucose levels (-0.20 ± 0.05, P = 0.0002) 120 min after an oral glucose test.The study was large and contained replication cohorts, but was limited by a small number of controls in the Greek cohort and a small number of cases in the second Boston cohort. The second Boston group was identified using electronic medical record review, but was validated for the cardinal features of PCOS.This study demonstrates a cross-ethnic PCOS risk locus in FSHR in women of European ancestry with PCOS. The variant may influence FSH receptor responsiveness as suggested by the associated change in FSH levels. The relationship between a variant near RAB5B and SUOX and glucose stimulated insulin and glucose levels suggests an influence of one of these genes on glucose tolerance, but the absence of a relationship with PCOS points to potential differences in the international PCOS patient populations.The project was supported by Award Number R01HD065029 from the Eunice Kennedy Shriver National Institute Of Child Health & Human Development, Award Number 1 UL1 RR025758, Harvard Clinical and Translational Science Center, from the National Center for Research Resources, award 1-10-CT-57 from the American Diabetes Association and the Partners Healthcare Center for Personalized Genetics Project Grant. C.K.W. is a consultant for Takeda Pharmaceuticals.NCT00166569.

Dataset Information

Progression of glucose intolerance and cardiometabolic risk factors over a decade in Chinese women with polycystic ovary syndrome: A case-control study.

Publications

Progression of glucose intolerance and cardiometabolic risk factors over a decade in Chinese women with polycystic ovary syndrome: A case-control study.

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