Overweight and obese but not normal weight women with PCOS are at increased risk of type 2 diabetes mellitus-a prospective, population-based cohort study
Open accessAbstract
STUDY QUESTION: What are the respective roles of polycystic ovary syndrome (PCOS), long-term weight gain and obesity for the development of prediabetes or Type 2 diabetes mellitus (T2DM) by age 46 years? SUMMARY ANSWER: The risk of T2DM in women with PCOS is mainly due to overweight and obesity, although these two factors have a synergistic effect on the development of T2DM. WHAT IS KNOWN ALREADY: PCOS is associated with an increased risk of prediabetes and T2DM. However, the respective roles of PCOS per se and BMI for the development of T2DM have remained unclear. STUDY DESIGN, SIZE, DURATION: In a prospective, general population-based follow-up birth cohort 1966 (n = 5889), postal questionnaires were sent at ages 14 (95% answered), 31 (80% answered) and 46 years (72% answered). Questions about oligoamenorrhoea and hirsutism were asked at age 31 years, and a question about PCOS diagnosis at 46 years. Clinical examination and blood sampling were performed at 31 years in 3127 women, and at 46 years in 3280 women. A 2-h oral glucose tolerance test (OGTT) was performed at 46 years of age in 2780 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women reporting both oligoamenorrhoea and hirsutism at age 31 years and/or diagnosis of PCOS by 46 years were considered as women with PCOS (n = 279). Women without any symptoms at 31 years and without PCOS diagnosis by 46 years were considered as controls (n = 1577). The level of glucose metabolism was classified according to the results of the OGTT and previous information of glucose metabolism status from the national drug and hospital discharge registers. MAIN RESULTS AND THE ROLE OF CHANCE: ) women with PCOS when compared to overweight/obese controls (odds ratio: 2.45, 95% CI: 1.28-4.67). Normal weight women with PCOS did not present with an increased risk of prediabetes or T2DM. The increase in weight between ages 14, 31 and 46 years was significantly greater in women with PCOS developing T2DM than in women with PCOS and normal glucose tolerance, with the most significant increase occurring in early adulthood (between 14 and 31 years: median with [25%; 75% quartiles]: 27.25 kg [20.43; 34.78] versus 13.80 kg [8.55; 20.20], P < 0.001). LIMITATIONS, REASONS FOR CAUTION: The diagnosis of PCOS was based on self-reporting, and the questionnaire at 46 years did not distinguish between polycystic ovaries only in ultrasonography and the syndrome. Ovarian ultrasonography was not available to aid the diagnosis of PCOS. WIDER IMPLICATIONS OF THE FINDINGS: These results emphasize weight management already during adolescence and early adulthood to prevent the development of T2DM in women with PCOS, as the period between 14 and 31 years seems to be a crucial time-window during which the women with PCOS who are destined to develop T2DM by 46 years of age experience a dramatic weight gain. Furthermore, our results support the view that, particularly in times of limited sources of healthcare systems, OGTT screening should be targeted to overweight/obese women with PCOS rather than to all women with PCOS. STUDY FUNDING/COMPETING INTERESTS: Finnish Medical Foundation; North Ostrobothnia Regional Fund; Academy of Finland (project grants 104781, 120315, 129269, 1114194, 24300796, Center of Excellence in Complex Disease Genetics and SALVE); Sigrid Juselius Foundation; Biocenter Oulu; University Hospital Oulu and University of Oulu (75617); Medical Research Center Oulu; National Institute for Health Research (UK); National Heart, Lung, and Blood Institute (grant 5R01HL087679-02) through the STAMPEED program (1RL1MH083268-01); National Institute of Health/National Institute of Mental Health (5R01MH63706:02); ENGAGE project and grant agreement HEALTH-F4-2007-201413; EU FP7 EurHEALTHAgeing-277849 European Commission and Medical Research Council, UK (G0500539, G0600705, G1002319, PrevMetSyn/SALVE) and Medical Research Center, Centenary Early Career Award. The authors have no conflicts of interests. TRIAL REGISTRATION NUMBER: N/A.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The improvement in insulin levels and insulin resistance with addition of metformin to COCP is of special interest for women with PCOS with additional risk factors for type 2 diabetes, such as a high BMI.
“This is of special interest for women with PCOS with additional risk factors for type 2 diabetes, such as a high BMI (86, 87).”
From Metformin and Combined Oral Contraceptive Pills in the Management of Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis (2024) · cites this paper as [86]
In a prospective population-based birth-cohort study from Finland, women (aged 46 years) with a history of oligo-/amenorrhea and hirsutism had 2.5 times higher odds of T2DM compared with controls, but no case of T2DM was found in normal weight women with PCOS at this age.
“In a prospective population-based birth-cohort study from Finland, women (aged 46 years) with a history of oligo-/amenorrhea and hirsutism had 2.5 times higher odds of T2DM compared with controls, but no case of T2DM was found in normal weight women with PCOS at this age (Ollila et al., 2017).”
From Type 2 diabetes mellitus in women with polycystic ovary syndrome during a 24-year period: importance of obesity and abdominal fat distribution (2020) · cites this paper as Ollila et al., 2017
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Franks, S. (1995) · New England Journal of Medicine · doi:10.1056/nejm199509283331307 · Cited by 2,463 · see citing works
Self-citationFauser, B. C. J. M., Tarlatzis, B. C., Rebar, R. W., Legro, R. S., Balen, A. H., Lobo, R., Carmina, E., Chang, J., Yildiz, B. O., Laven, J. S. E., et al. (2012) · Fertility and Sterility · doi:10.1016/j.fertnstert.2011.09.024 · Cited by 1,976 · see citing works
Self-citationLegro, R. S., Arslanian, S. A., Ehrmann, D. A., Hoeger, K. M., Murad, M. H., Pasquali, R., & Welt, C. K. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2350 · Cited by 1,919 · see citing works
Legro, R. S. (1999) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.84.1.165 · Cited by 1,743 · see citing works
Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome.
Ehrmann, D. A., Barnes, R. B., Rosenfield, R. L., Cavaghan, M. K., & Imperial, J. (1999) · Diabetes Care · doi:10.2337/diacare.22.1.141 · Cited by 1,257 · cited 4× · see citing works
“Reasons for discrepancy between the results might be the crosssectional design of studies (Ehrmann et al., 1999; Stepto et al., 2013; Joham et al., 2014) and the use of self-reported diagnosis of T2DM in the prospective ones (Elting et al., 2001; Boudreaux et al., 2006).”
ResultInfluentialMoran, L. J., Misso, M. L., Wild, R. A., & Norman, R. J. (2010) · Human Reproduction Update · doi:10.1093/humupd/dmq001 · Cited by 1,108 · see citing works
Wild, R. A., Carmina, E., Diamanti-Kandarakis, E., Dokras, A., Escobar-Morreale, H. F., Futterweit, W., Lobo, R., Norman, R. J., Talbott, E., & Dumesic, D. A. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2724 · Cited by 1,010 · see citing works
Franks, S. (1997) · Archives of Disease in Childhood · doi:10.1136/adc.77.1.89 · Cited by 802 · see citing works
Self-citationStepto, N. K., Cassar, S., Joham, A. E., Hutchison, S. K., Harrison, C. L., Goldstein, R. F., & Teede, H. J. (2013) · Human Reproduction · doi:10.1093/humrep/des463 · Cited by 747 · see citing works
Insulin and hyperandrogenism in women with polycystic ovary syndrome
Baptiste, C. G., Battista, M., Trottier, A., & Baillargeon, J. (2009) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2009.12.010 · Cited by 368 · see citing works
Goodman, N. F., Cobin, R. H., Futterweit, W., Glueck, J. S., Legro, R. S., & Carmina, E. (2015) · Endocrine Practice · doi:10.4158/ep15748.dscpt2 · Cited by 361 · see citing works
Norman, R. J., Masters, L., Milner, C. R., Wang, J. X., & Davies, M. J. (2001) · Human Reproduction · doi:10.1093/humrep/16.9.1995 · Cited by 341 · see citing works
Molecular mechanisms of insulin resistance in polycystic ovary syndrome
Diamanti-Kandarakis, E., & Papavassiliou, A. G. (2006) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2006.05.006 · Cited by 301 · see citing works
Elting, M. W., Korsen, T. J. M., Bezemer, P. D., & Schoemaker, J. (2001) · Human Reproduction · doi:10.1093/humrep/16.3.556 · Cited by 253 · see citing works
Polycystic Ovary Syndrome Is a Risk Factor for Type 2 Diabetes
Gambineri, A., Patton, L., Altieri, P., Pagotto, U., Pizzi, C., Manzoli, L., & Pasquali, R. (2012) · Diabetes · doi:10.2337/db11-1360 · Cited by 226 · see citing works
Prevalence of the Metabolic Syndrome and Its Components
Ilanne‐Parikka, P., Eriksson, J. G., Lindström, J., Hämäläinen, H., Keinanen-Kiukaanniemi, S. M., Laakso, M., Louheranta, A. M., Mannelin, M., Rastas, M., Salminen, V., et al. (2004) · Diabetes Care · doi:10.2337/diacare.27.9.2135 · Cited by 196 · see citing works
Mani, H., Levy, M. J., Davies, M. J., Morris, D. H., Gray, L. J., Bankart, J., Blackledge, H., Khunti, K. K., & Howlett, T. A. (2012) · Clinical Endocrinology · doi:10.1111/cen.12068 · Cited by 192 · see citing works
Taponen, S., Martikainen, H. K., Järvelin, M., Laitinen, J. H., Pouta, A. M., Hartikainen, A., Sovio, U., McCarthy, M. I., Franks, S., & Ruokonen, A. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020982 · Cited by 190 · see citing works
Self-citationOllila, M.-M. E., Piltonen, T., Puukka, K., Ruokonen, A., Järvelin, M.-R., Tapanainen, J. S., Franks, S., & Morin-Papunen, L. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3543 · Cited by 182 · see citing works
Self-citationGestational Diabetes and Type 2 Diabetes in Reproductive-Aged Women With Polycystic Ovary Syndrome
Joham, A. E., Ranasinha, S., Zoungas, S., Moran, L., & Teede, H. J. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2007 · Cited by 150 · see citing works
Polycystic Ovary Syndrome and Risk for Long-Term Diabetes and Dyslipidemia
Wang, E. T., Calderon-Margalit, R., Cedars, M. I., Daviglus, M. L., Merkin, S. S., Schreiner, P. J., Sternfeld, B., Wellons, M., Schwartz, S. M., Lewis, C. E., et al. (2011) · Obstetrics & Gynecology · doi:10.1097/aog.0b013e31820209bb · Cited by 146 · see citing works
Risk of T2DM and impaired fasting glucose among pcos subjects: Results of an 8-year follow-up
Boudreaux, M. Y., Talbott, E. O., Kip, K. E., Brooks, M. M., & Witchel, S. F. (2006) · Current Diabetes Reports · doi:10.1007/s11892-006-0056-1 · Cited by 139 · see citing works
Morgan, C. L., Jenkins-Jones, S., Currie, C. J., & Rees, D. A. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-1690 · Cited by 136 · see citing works
Taponen, S. (2004) · Human Reproduction · doi:10.1093/humrep/deh214 · Cited by 90 · see citing works
Celik, C., Taşdemir, N., Abalı, R., Baştu, E., & Yılmaz, M. (2014) · Fertility and Sterility · doi:10.1016/j.fertnstert.2013.12.050 · Cited by 74 · see citing works
Zhao, X., Zhong, J., Mo, Y., Chen, X., Chen, Y., & Yang, D. (2009) · International Journal of Gynecology & Obstetrics · doi:10.1016/j.ijgo.2009.09.021 · Cited by 61 · see citing works
Hudecova, M., Holte, J., Olovsson, M., Larsson, A. O., Berne, C., & Poromaa, I. S. (2011) · Human Reproduction · doi:10.1093/humrep/der065 · Cited by 53 · see citing works
Livadas, S., Κόλλιας, Α., Panidis, D., & Diamanti‐Kandarakis, E. (2014) · European Journal of Endocrinology · doi:10.1530/eje-13-1007 · Cited by 45 · see citing works
Vaginal misoprostol for second‐trimester pregnancy termination after one previous cesarean delivery
Naguib, A. H., Morsi, H. M., Borg, T. F., et al. (2009) · International Journal of Gynecology & Obstetrics · doi:10.1016/j.ijgo.2009.08.010 · Cited by 27 · see citing works
Espinós, J. J., Corcoy, R., & Calaf, J. (2009) · Gynecological Endocrinology · doi:10.1080/09513590802585597 · Cited by 21 · see citing works
Alberti (1998) · doi:10.1002/(sici)1096-9136(199807)15:7
Flagged first, then by citations
Cited by
Sorted by citations
Long-term cardiometabolic disease risk in women with PCOS: a systematic review and meta-analysis
Wekker, V, van Dammen, L., Koning, A., Heida, K. Y., Painter, R. C., Limpens, J., Laven, J. S. E., Roeters van Lennep, J. E., Roseboom, T. J., & Hoek, A. (2020) · Human Reproduction Update · doi:10.1093/humupd/dmaa029 · Cited by 425 · see citing works
Beyond fertility: polycystic ovary syndrome and long-term health
Cooney, L. G., & Dokras, A. (2018) · Fertility and Sterility · doi:10.1016/j.fertnstert.2018.08.021 · Cited by 270 · see citing works
Rubin, K. H., Glintborg, D., Nybo, M., Abrahamsen, B., & Andersen, M. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-01354 · Cited by 195 · see citing works
Cardiovascular disease in a nationwide population of Danish women with polycystic ovary syndrome
Glintborg, D., Rubin, K. H., Nybo, M., Abrahamsen, B., & Andersen, M. (2018) · Cardiovascular Diabetology · doi:10.1186/s12933-018-0680-5 · Cited by 200 · see citing works
The Impact of Obesity on the Incidence of Type 2 Diabetes Among Women With Polycystic Ovary Syndrome
Kakoly, N. S., Earnest, A., Teede, H. J., Moran, L. J., & Joham, A. E. (2019) · Diabetes Care · doi:10.2337/dc18-1738 · Cited by 174 · see citing works
Zhu, S., Zhang, B., Jiang, X., Li, Z., Zhao, S., Cui, L., & Chen, Z.-J. (2019) · Fertility and Sterility · doi:10.1016/j.fertnstert.2018.09.013 · Cited by 109 · see citing works
Melin, J., Forslund, M., Alesi, S., Piltonen, T., Romualdi, D., Spritzer, P. M., Tay, C. T., Pena, A., Witchel, S. F., Mousa, A., et al. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad465 · Cited by 78 · see citing works
Self-citationIsmayilova, M., & Yaya, S. (2022) · BMC Women's Health · doi:10.1186/s12905-022-01630-3 · Cited by 68 · see citing works
Melin, J., Forslund, M., Alesi, S., Piltonen, T., Romualdi, D., Spritzer, P. M., Tay, C. T., Pena, A., Witchel, S. F., Mousa, A., et al. (2023) · European Journal of Endocrinology · doi:10.1093/ejendo/lvad098 · Cited by 72 · see citing works
Self-citationForslund, M., Landin-Wilhelmsen, K., Trimpou, P., Schmidt, J., Brännström, M., & Dahlgren, E. (2020) · Human Reproduction Open · doi:10.1093/hropen/hoz042 · Cited by 66 · see citing works
AMH as part of the diagnostic PCOS workup in large epidemiological studies
Piltonen, T. T., Komsi, E., Morin-Papunen, L. C., Korhonen, E., Franks, S., Järvelin, M.-R., Arffman, R. K., & Ollila, M.-M. (2023) · European Journal of Endocrinology · doi:10.1093/ejendo/lvad065 · Cited by 58 · see citing works
Self-citationMeng, Y., Zhao, T., Zhang, R., Zhu, X., Ma, C., & Shi, Q. (2025) · Frontiers in Public Health · doi:10.3389/fpubh.2025.1514250 · Cited by 43 · see citing works
The impact of ageing and menopause in women with polycystic ovary syndrome
Helvaci, N., & Yildiz, B. O. (2022) · Clinical Endocrinology · doi:10.1111/cen.14558 · Cited by 32 · see citing works
Medical Treatment and Comorbidity in Polycystic Ovary Syndrome: An Updated Review
Glintborg, D., & Andersen, M. (2020) · Current Opinion in Endocrine and Metabolic Research · doi:10.1016/j.coemr.2020.02.014 · Cited by 20 · see citing works
- Authors
- Ollila, M.-M. E., West, S., Keinänen-Kiukaanniemi, S., Jokelainen, J., Auvinen, J., Puukka, K., Ruokonen, A., Järvelin, M.-R., Tapanainen, J. S., Franks, S., Piltonen, T. T., & Morin-Papunen, L. C.
- Affiliations
- Oulu University Hospital (FI)
- Finnish Institute for Health and Welfare (FI)
- University of Helsinki (FI)
- Hammersmith Hospital (GB)
- Corresponding author
- Morin-Papunen, L.C.
- ORCID
- Venue
- Human Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-12-28
- Volume
- 32
- Issue
- 2
- Pages
- 423-431
- ISSN
- 0268-1161 (ISSN-L)
- 1460-2350
- PMC
- PMC5260860
- OpenAlex
- W2564015027
- Cited by
- 165
- References
- 31
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 7 · 2023: 21 · 2022: 21 · 2021: 27 · 2020: 16 · 2019: 21 · 2018: 20 · 2017: 10
- FWCI
- 22.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Reproduction (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Funders
- Finnish Medical Foundation, North Ostrobothnia Regional Fund, Academy of Finland (104781, 120315, 129269, 1114194, 24300796)
- Sigrid Juselius Foundation, Biocenter Oulu, University Hospital Oulu and University of Oulu (75617)
- Medical Research Center Oulu, National Institute for Health Research (5R01HL087679-02)
- STAMPEED program (1RL1MH083268-01)
- NIH/NIMH (5R01MH63706:02)
- ENGAGE (HEALTH-F4-2007, 201413)
- EU FP7 EurHEALTHAgeing (277849)
- European Commission and Medical Research Council, UK (G0500539, G0600705, G1002319)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Keywords
- polycystic ovary syndrome, type 2 diabetes, prediabetes, obesity, overweight, body mass index, normal-weight women, hirsutism, glucose metabolism, women's health, birth cohort follow-up, synergistic risk factors, oral glucose tolerance test
- MeSH terms
- Adult, Body Weight, Diabetes Mellitus, Type 2, Female, Glucose Tolerance Test, Humans, Middle Aged, Obesity, Polycystic Ovary Syndrome, Prediabetic State, Prospective Studies, Risk Factors, Body Mass Index, Overweight
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
