Early pregnancy metabolic factors associated with gestational diabetes mellitus in normal-weight women with polycystic ovary syndrome: a two-phase cohort study

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Abstract

Background

Polycystic ovary syndrome (PCOS) has been consistently associated with subsequent gestational diabetes mellitus (GDM). Women with PCOS showed a high prevalence of obesity, which raises the question regarding the role of obesity or PCOS pe ser in development of GDM. In this study we conducted a 2-phase study to compare the risk of GDM and its associated early pregnancy metabolic factors in women with and without PCOS, stratified by pre-pregnancy body mass index (BMI).

Methods

A 2-phase design was used in this study. The initial phase of the study included 566 age- and pre-pregnancy BMI-matched singleton pregnant women (242 with and 324 without PCOS). Risk of GDM and associated early-pregnancy risk factors were explored between women with and without PCOS, after stratification by pre-pregnancy BMI. Stratified analysis was conducted in normal weight (pre-pregnancy BMI < 25 kg/m ²) and overweight/obese (pre-pregnancy BMI ≥ 25 kg/m ²) groups. Subsequently, the findings was confirmed in a separate cohort study with 18,106 participants (877 with and 17,229 without PCOS).

Results

Overall, prevalence of GDM is higher in women with PCOS. Results from the initial study showed that in normal-weight subjects, there is a significant increase in GDM prevalence in PCOS women than non-PCOS women (26.5% vs. 16.2%, p = 0.02). Additionally, normal-weight PCOS women showed higher triglycerides levels (1.51 ± 0.84 mmol/L vs. 1.30 ± 0.75 mmol/L, p = 0.02), lower SHBG levels (277.8 ± 110.2 nmol/L vs. 330.5 ± 180.4 nmol/L, p = 0.001) and a possible trend towards higher insulin resistance (LogHoMA-IR 0.70 ± 0.55 vs. 0.57 ± 0.57, p = 0.05) during early pregnancy. However, in overweight/obese group, no difference in risk of GDM was observed between PCOS and non-PCOS subjects (p = 0.7). Results from the independent cohort confirmed the risk for GDM associated with PCOS in normal weight women (p < 0.0001).

Conclusion

Consistent findings from the 2-phase study showed an increased risk of GDM in normal-weight, but not overweight/obese PCOS women. Analysis of early-pregnancy risk factors of GDM suggested that the pathogenesis of GDM in normal weight and overweight/obese women with PCOS may be different.

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Most cited references 20

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A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome.

C Boomsma, M. Eijkemans, E Hughes … (2015)

Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with many characteristic features, including hyperandrogenaemia, insulin resistance and obesity which may have significant implications for pregnancy outcomes and long-term health of the woman. This meta-analysis was conducted to evaluate the risk of pregnancy and neonatal complications in women with PCOS. Electronic databases were searched for the following MeSH headings: PCOS, hyperandrogenism, pregnancy outcome, pregnancy complications, diabetes mellitus, type II. A handsearch of human reproduction and fertility and sterility was also conducted. Studies in which pregnancy outcomes in women with PCOS were compared with controls were considered for inclusion in this meta-analysis. Fifteen of 525 identified studies were included, involving 720 women presenting with PCOS and 4505 controls. Women with PCOS demonstrated a significantly higher risk of developing gestational diabetes [odds ratio (OR) 2.94; 95% confidence interval (CI): 1.70-5.08], pregnancy-induced hypertension (OR 3.67; 95% CI: 1.98-6.81), pre-eclampsia (OR 3.47; 95% CI: 1.95-6.17) and preterm birth (OR 1.75; 95% CI: 1.16-2.62). Their babies had a significantly higher risk of admission to a neonatal intensive care unit (OR 2.31; 95% CI: 1.25-4.26) and a higher perinatal mortality (OR 3.07; 95% CI: 1.03-9.21), unrelated to multiple births. In conclusion, women with PCOS are at increased risk of pregnancy and neonatal complications. Pre-pregnancy, antenatal and intrapartum care should be aimed at reducing these risks.

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PCOS according to the Rotterdam consensus criteria: Change in prevalence among WHO-II anovulation and association with metabolic factors.

F Broekmans, Marinus Eijkemans, Erik Knauff … (2006)

The current report aims to compare the prevalence of polycystic ovary syndrome (PCOS) diagnosed according to the new Rotterdam criteria (Rott-PCOS) versus the previous criteria as formulated by the National Institutes of Health (NIH) (NIH-PCOS) in women with normogonadotropic (WHO-II) anovulation and assess the frequency of obesity and related factors determined in these women. Cohort study based on large anovulation screening database. Two large tertiary referral centres for reproductive medicine. WHO-II normogonadotropic, anovulatory, infertility cases. WHO-II cases were extracted from the screening database and classified according to both the Rotterdam and NIH criteria for PCOS. Within these two classes, the prevalence of obesity, hyperglycaemia and insulin resistance was assessed and compared and their relation to the difference in diagnostic criteria applied was analysed. Prevalence of diagnosis PCOS in the WHO-II anovulation group. Prevalence of obesity, hyperglycaemia and insulin resistance in the two diagnostic classes. The Rott-PCOS group appeared to be more than 1.5 times larger than the group classified as NIH-PCOS (91 versus 55% of the WHO-II cohort). Especially, women with ovarian dysfunction and polycystic ovaries at ultrasound scan, but without hyperandrogenism, were added to the PCOS diagnostic group. The Rott-PCOS exhibited a lower frequency of obesity, hyperglycaemia and insulin resistance compared with the NIH-PCOS group. Obese women in the Rott-PCOS group without androgen excess had a different metabolic profile compared with obese women in the NIH-PCOS group, with lower rates of hyperglycaemia and hyperinsulinism, despite comparable distributions of body weight. The present findings indicate that with the new Rotterdam consensus criteria, oligo/anovulatory women with less severe metabolic derangement will be added to the heterogeneous group of women with PCOS.

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Polycystic ovary syndrome throughout a woman’s life

José Bellver, Luis Rodriguez-Tabernero, Ana B Robles … (2018)

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged women and the main cause of infertility due to anovulation. However, this syndrome spans the lives of women affecting them from in-utero life until death, leading to several health risks that can impair quality of life and increase morbidity and mortality rates. Fetal programming may represent the beginning of the condition characterized by hyperandrogenism and insulin resistance which leads to a series of medical consequences in adolescence, adulthood, and old age. Menstrual and fertility problems evolve into metabolic complications as age advances. An early and precise diagnosis is important for an adequate management of PCOS, especially at the extreme ends of the reproductive lifespan. However, many different phenotypes are included under the same condition, being important to look at these different phenotypes separately, as they may require different treatments and have different consequences. In this way, PCOS exhibits a great metabolic complexity and its diagnosis needs to be revised once again and adapted to recent data obtained by new technologies. According to the current medical literature, lifestyle therapy constitutes the first step in the management, especially when excess body weight is associated. Pharmacotherapy is frequently used to treat the most predominant manifestations in each age group, such as irregular menses and hirsutism in adolescence, fertility problems in adulthood, and metabolic problems and risk of cancer in old age. Close surveillance is mandatory in each stage of life to avoid health risks which may also affect the offspring, since fetal and post-natal complications seem to be increased in PCOS women.

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Author and article information

Contributors

Guanghui Li:

ORCID: http://orcid.org/0000-0001-6828-8774

+86-010-52273110 , liguanghui2007@163.com

Journal

Journal ID (nlm-ta): Diabetol Metab Syndr

Journal ID (iso-abbrev): Diabetol Metab Syndr

Title: Diabetology & Metabolic Syndrome

Publisher: BioMed Central (London )

ISSN (Electronic): 1758-5996

Publication date (Electronic): 23 August 2019

Publication date PMC-release: 23 August 2019

Publication date Collection: 2019

Volume: 11

Electronic Location Identifier: 71

Affiliations

[1 ]ISNI 0000 0004 0369 153X, GRID grid.24696.3f, Division of Endocrinology and Metabolism, Department of Obstetrics, Beijing Obstetrics and Gynecology Hospital, , Capital Medical University, ; No 251, Yaojiayuan Road, Chaoyang District, Beijing, 100026 China

[2 ]ISNI 0000 0001 2299 3507, GRID grid.16753.36, Division of Endocrinology, Metabolism and Molecular Medicine, , Northwestern University Feinberg School of Medicine, ; Chicago, IL 60611 USA

Author information

Guanghui Li http://orcid.org/0000-0001-6828-8774

Article

Publisher ID: 462

DOI: 10.1186/s13098-019-0462-6

PMC ID: 6708128

PubMed ID: 31462934

SO-VID: 98889a71-9faf-4925-8790-fe9fba33ef69

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 23 June 2019

Date accepted : 13 August 2019

Funding

Funded by: Beijing Natural Science Foundation Program

Award ID: 7184210

Award ID: S160001

Award Recipient : Wei Zheng Guanghui Li

Funded by: ‘Capital Clinical Characteristic Research’ from Beijing Science Committee

Award ID: Z161100000516160

Award Recipient : Guanghui Li

Funded by: National key research and development program

Award ID: 2016YFC1000304

Award Recipient : Guanghui Li

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ScienceOpen disciplines: Nutrition & Dietetics

Keywords: polycystic ovary syndrome,metabolic indicators,gestational diabetes,insulin resistance,body mass index

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ScienceOpen disciplines: Nutrition & Dietetics

Keywords: polycystic ovary syndrome, metabolic indicators, gestational diabetes, insulin resistance, body mass index

Early pregnancy metabolic factors associated with gestational diabetes mellitus in normal-weight women with polycystic ovary syndrome: a two-phase cohort study

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Karger: Nutrition and Dietetics

Most cited references 20

A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome.

PCOS according to the Rotterdam consensus criteria: Change in prevalence among WHO-II anovulation and association with metabolic factors.

Polycystic ovary syndrome throughout a woman’s life

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