---
title: "PCOS and Risk of Progression to Pre‑Diabetes and Diabetes: A Multistate Modeling Analysis"
id: "pubmed-42659541"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42659541"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42659541/"
doi: "10.1002/edm2.70322"
published_at: "2026-09-01T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# PCOS and Risk of Progression to Pre‑Diabetes and Diabetes: A Multistate Modeling Analysis
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42659541
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42659541/)
- **DOI:** [10.1002/edm2.70322](https://doi.org/10.1002%2Fedm2.70322)
- **Published At:** 2026-09-01T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This population-based cohort analysis used data from the Tehran Lipid and Glucose Study to assess how **polycystic ovary syndrome (PCOS)** affects transitions between glycemic states over time using a **multistate Markov model**. - Women aged >20 years without pre‑diabetes (pre‑DM) or diabetes mellitus (DM) at baseline (1999–2000) and with known PCOS status were included; assessments occurred approximately every 3 years for a total of six follow-ups. - Three discrete states were defined: **Normoglycemia**, **Pre‑DM**, and **DM**, with three possible transitions: (I) Normoglycemia → Pre‑DM, (II) Normoglycemia → DM, and (III) Pre‑DM → DM. - The analytic cohort comprised 1,587 women. At study end, 782 (49.3%) remained free of pre‑DM and DM. - The most common progression observed was transition I (Normoglycemia → Pre‑DM), affecting 46.6% of participants. - Women with PCOS had a statistically significant 23% higher hazard of transition I compared with women without PCOS [HR 1.23, 95% CI 1.01–1.49; p = 0.034]. - PCOS status was not associated with a statistically significant change in hazard for transitions II (direct Normoglycemia → DM) or III (Pre‑DM → DM) in this analysis. - The authors conclude PCOS meaningfully influences the dynamic progression from normoglycemia to **pre‑diabetes**, and they recommend further longitudinal work to confirm and extend these findings. - Conflict of interest: the authors declared no conflicts. - Data and results reported here derive from the published article; additional methodological or subgroup details were not reported in the source abstract.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 Reproductive Endocrinology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. * 2 Endocrine Research Center, Research Institute for Endocrine Disorders, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. * 3 Foundation for Research & Education Excellence, Vestavia Hills, Alabama, USA. * PMID: **42659541** * PMCID: [ PMC13521517 ](https://pmc.ncbi.nlm.nih.gov/articles/PMC13521517/) * DOI: [ 10.1002/edm2.70322 ](https://doi.org/10.1002/edm2.70322) Item in Clipboard # The Effect of Polycystic Ovarian Syndrome on Development of Diabetes Mellitus by a Multistate Modelling Approach Maryam Mousavi et al. Endocrinol Diabetes Metab. 2026 Sep. Show details Display options Display options Format Abstract PubMed PMID Endocrinol Diabetes Metab Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Endocrinol+Diabetes+Metab%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Endocrinol+Diabetes+Metab%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42659541/) . 2026 Sep;9(5):e70322. doi: 10.1002/edm2.70322. ### Authors [Maryam Mousavi](https://pubmed.ncbi.nlm.nih.gov/?term=Mousavi+M&cauthor_id=42659541)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42659541/#short-view-affiliation-1 "Reproductive Endocrinology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran."), [Marzieh Saei Ghare Naz](https://pubmed.ncbi.nlm.nih.gov/?term=Saei+Ghare+Naz+M&cauthor_id=42659541)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42659541/#short-view-affiliation-1 "Reproductive Endocrinology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran."), [Mahsa Noroozzadeh](https://pubmed.ncbi.nlm.nih.gov/?term=Noroozzadeh+M&cauthor_id=42659541)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42659541/#short-view-affiliation-1 "Reproductive Endocrinology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran."), [Fereidoun Azizi](https://pubmed.ncbi.nlm.nih.gov/?term=Azizi+F&cauthor_id=42659541)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42659541/#short-view-affiliation-2 "Endocrine Research Center, Research Institute for Endocrine Disorders, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran."), [Fahimeh Ramezani Tehrani](https://pubmed.ncbi.nlm.nih.gov/?term=Ramezani+Tehrani+F&cauthor_id=42659541)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42659541/#short-view-affiliation-1 "Reproductive Endocrinology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42659541/#short-view-affiliation-3 "Foundation for Research & Education Excellence, Vestavia Hills, Alabama, USA.") ### Affiliations * 1 Reproductive Endocrinology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. * 2 Endocrine Research Center, Research Institute for Endocrine Disorders, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. * 3 Foundation for Research & Education Excellence, Vestavia Hills, Alabama, USA. * PMID: **42659541** * PMCID: [ PMC13521517 ](https://pmc.ncbi.nlm.nih.gov/articles/PMC13521517/) * DOI: [ 10.1002/edm2.70322 ](https://doi.org/10.1002/edm2.70322) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background:** Women with polycystic ovary syndrome (PCOS) are more susceptible to metabolic dysfunction, especially glucose impairment. Previous studies have considered prediabetes (pre-DM) and diabetes mellitus (DM) as single-point outcomes without accounting for the transition states. This study aimed to explore the transition between different blood glucose states using a multistate Markov model among women with and without PCOS. **Methods:** This study employed a dataset from the population-based study of the Tehran Lipid and Glucose Study. Women, aged over 20 years, without pre-DM and DM at baseline (1999-2000) and with documented PCOS status, were included; subsequent follow-ups were conducted every 3 years, totaling six follow-up assessments. Three states of 'Normoglycemia', 'Pre-DM', and 'DM' and three possible transitions of (I) normoglycemia to pre-DM, (II) normoglycemia to DM, and (III) pre-DM to DM were defined. The multi-state Markov models were applied to examine the predictive effect of PCOS on the transition rates throughout the progression of DM. **Results:** Out of 1587 participated women, 782 (49.3%) remained free of pre-DM and DM at the end of the study. Transition from normoglycemia to pre-DM was the most frequent progression observed, affecting 46.6% of the study participants. Women with PCOS significantly had 23% higher hazard of transition I [HR (95% CI): 1.23 (1.01-1.49); p = 0.034] compared to those without PCOS. While being PCOS did not significantly affect the risk of other transitions. **Conclusions:** This study underscores the significant impact of PCOS on the dynamic progression from normoglycemia to pre-DM. Future longitudinal studies are essential to support our findings. **Keywords:** diabetes; multistate model; polycystic ovarian syndrome; pre‐diabetes. © 2026 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement The authors declare no conflicts of interest. ## Figures [ ![FIGURE 1](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed9b/13521517/fd2e54248fea/EDM2-9-e70322-g004.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed9b/13521517/2c1d91cb7c81/EDM2-9-e70322-g004.webp) ** FIGURE 1 ** Theoretical states and transitions in… ** FIGURE 1 ** Theoretical states and transitions in the progression of glucose dysregulation. DM, diabetes; pre‐DM,… **FIGURE 1** Theoretical states and transitions in the progression of glucose dysregulation. DM, diabetes; pre‐DM, pre‐diabetes. [ ![FIGURE 2](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed9b/13521517/683962e7b0a4/EDM2-9-e70322-g002.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed9b/13521517/a006ea00ee02/EDM2-9-e70322-g002.webp) ** FIGURE 2 ** The study flowchart. ** FIGURE 2 ** The study flowchart. **FIGURE 2** The study flowchart. [ ![FIGURE 3](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed9b/13521517/48252ed3f353/EDM2-9-e70322-g003.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed9b/13521517/22a79dff6b88/EDM2-9-e70322-g003.webp) ** FIGURE 3 ** Distribution of individuals with PCOS… ** FIGURE 3 ** Distribution of individuals with PCOS categorized by their most recent diabetes status. **FIGURE 3** Distribution of individuals with PCOS categorized by their most recent diabetes status. [ ![FIGURE 4](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed9b/13521517/9f0a084740b5/EDM2-9-e70322-g001.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed9b/13521517/1e6560520df9/EDM2-9-e70322-g001.webp) ** FIGURE 4 ** Cumulative hazard functions for different… ** FIGURE 4 ** Cumulative hazard functions for different transitions of glucose impairments in a multistate model.… **FIGURE 4** Cumulative hazard functions for different transitions of glucose impairments in a multistate model. I: Normoglycemia → pre‐DM, II: Normoglycemia → DM, and III: Pre‐DM to DM. [See this image and copyright information in PMC](https://pubmed.ncbi.nlm.nih.gov/42659541/) ## Similar articles * [ 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. ](https://pubmed.ncbi.nlm.nih.gov/28031324/) Ollila MM, West S, Keinänen-Kiukaanniemi S, Jokelainen J, Auvinen J, Puukka K, Ruokonen A, Järvelin MR, Tapanainen JS, Franks S, Piltonen TT, Morin-Papunen LC.Ollila MM, et al.Hum Reprod. 2017 Feb;32(2):423-431. doi: 10.1093/humrep/dew329. Epub 2016 Dec 28.Hum Reprod. 2017.PMID: 28031324Free PMC article. * [ PM2.5 constituents and transitions from glycemic states to stroke: Multistate and accelerated failure time analyses of a large cohort. ](https://pubmed.ncbi.nlm.nih.gov/41485618/) Wei S, Lin W, Fang Y, Jian Y, Zhou Q, Liu H, Chen G, Wang M, Rao M, Zhuang Z, Ai Z, Zhang C, Zhang Z, Lin H.Wei S, et al.Int J Cardiol. 2026 Mar 15;447:134143. doi: 10.1016/j.ijcard.2025.134143. Epub 2026 Jan 2.Int J Cardiol. 2026.PMID: 41485618 * [ Assessment of glucose metabolism in polycystic ovary syndrome: HbA1c or fasting glucose compared with the oral glucose tolerance test as a screening method. ](https://pubmed.ncbi.nlm.nih.gov/23756702/) Lerchbaum E, Schwetz V, Giuliani A, Obermayer-Pietsch B.Lerchbaum E, et al.Hum Reprod. 2013 Sep;28(9):2537-44. doi: 10.1093/humrep/det255. Epub 2013 Jun 11.Hum Reprod. 2013.PMID: 23756702 * [ AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ANDROGEN EXCESS AND PCOS SOCIETY DISEASE STATE CLINICAL REVIEW: GUIDE TO THE BEST PRACTICES IN THE EVALUATION AND TREATMENT OF POLYCYSTIC OVARY SYNDROME - PART 2. ](https://pubmed.ncbi.nlm.nih.gov/26642102/) Goodman NF, Cobin RH, Futterweit W, Glueck JS, Legro RS, Carmina E; American Association of Clinical Endocrinologists (AACE); American College of Endocrinology (ACE); Androgen Excess and PCOS Society.Goodman NF, et al.Endocr Pract. 2015 Dec;21(12):1415-26. doi: 10.4158/EP15748.DSCPT2.Endocr Pract. 2015.PMID: 26642102Review. * [ Polycystic ovary syndrome as an independent risk factor for gestational diabetes and hypertensive disorders of pregnancy: a population-based study on 9.1 million pregnancies. ](https://pubmed.ncbi.nlm.nih.gov/32535629/) Mills G, Badeghiesh A, Suarthana E, Baghlaf H, Dahan MH.Mills G, et al.Hum Reprod. 2020 Jul 1;35(7):1666-1674. doi: 10.1093/humrep/deaa099.Hum Reprod. 2020.PMID: 32535629 [ See all similar articles ](https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed&from_uid=42659541) ## References 1. 1. Deswal R., Narwal V., Dang A., and Pundir C. S., “The Prevalence of Polycystic Ovary Syndrome: A Brief Systematic Review,” Journal of Human Reproductive Sciences 13, no. 4 (2020): 261–271. - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC7879843/) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/33627974/) 2. 1. Palomba S., Santagni S., Falbo A., and La Sala G. B., “Complications and Challenges Associated With Polycystic Ovary Syndrome: Current Perspectives,” International Journal of W
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