---
title: "Sex-specific trajectories to cardio-renal and mental health outcomes after type 2 diabetes onset"
id: "plos-medicine-1-sex-differences-in-trajectories-to-cardio-renal-and-mental-health-outcomes"
canonical_url: "https://medichelpline.com/clinical-feed/plos-medicine-1-sex-differences-in-trajectories-to-cardio-renal-and-mental-health-outcomes"
content_type: "clinical_feed_article"
specialty: "Endocrinology"
source_name: "PLOS Medicine"
source_url: "https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005196"
published_at: "2026-08-25T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Sex-specific trajectories to cardio-renal and mental health outcomes after type 2 diabetes onset
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-medicine-1-sex-differences-in-trajectories-to-cardio-renal-and-mental-health-outcomes
- **Specialty:** [Endocrinology](https://medichelpline.com/clinical-feed/endocrinology.md)
- **Primary Source:** PLOS Medicine
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005196)
- **Published At:** 2026-08-25T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This observational cohort study used linked UK primary and secondary electronic health records (Clinical Practice Research Datalink GOLD) to follow 28,720 people with incident **type 2 diabetes** diagnosed between 2010 and 2020. Median follow-up was 6.8 years. - Men made up 62% of the cohort and had a median age at diagnosis of 54 years (IQR 46–64); women had a median age of 56 years (IQR 45–67). - The investigators applied competing-risk semi-Markov multi-state modelling to characterise transitions from T2D onset to hypertension, **cardiovascular disease** (CVD), **end-stage renal disease** (ESRD), and mental health diagnoses (anxiety, depression, somatoform disorder), and to death. - During follow-up 39% of participants transitioned to at least one other defined health state. **Hypertension** was the most frequent first event across all age groups and in both sexes. - Sex differences in trajectories were evident: women were more likely to be diagnosed with a **mental health** condition after T2D onset (8.1% versus 5.3%), while men were more likely to be diagnosed with CVD/ESRD (8.4% versus 5.3%) and with hypertension (21.1% versus 20.2%). - Women had higher average health service use and more long-term prescribing than men, and events tended to occur later in women than in men. - Both men and women who experienced a combination of T2D and a mental health condition had earlier mortality than other trajectories; men in that group died on average 9 years younger than women following the same sequence. - The authors highlight potential implications for stratified care: routine mental health screening in T2D (especially for younger women), earlier cardiovascular and renal monitoring for men, and integrated physical–mental health pathways for those with combined conditions. - Limitations noted by the authors include the descriptive design that cannot infer causation, inability to examine causes of death separately, limited ethnicity analyses, and potential bias from sex differences in healthcare-seeking affecting mental health diagnosis rates. - Data access restrictions and supporting code repositories are reported; study funding and competing interests are detailed in the source.
## Clinical Analysis & Structured Key Points
[ Skip to main content ](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005196#main-content) Advertisement * [plos.org](https://plos.org/) * [Create account](https://community.plos.org/registration/new) * [Sign in](https://journals.plos.org/user/secure/login?page=%2Fplosmedicine%2Farticle%3Fid%3D10.1371%2Fjournal.pmed.1005196) * * About * Browse * Publish * [](https://journals.plos.org/plosmedicine/ "PLOS Medicine") * Search [advanced search](https://journals.plos.org/plosmedicine/search) * 0 [Save](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1005196#savedHeader) [Total Mendeley and Citeulike bookmarks.](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1005196#savedHeader) * 0 [Citation](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1005196#citedHeader) [Paper's citation count computed by Dimensions.](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1005196#citedHeader) * 101 [View](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1005196#viewedHeader) [PLOS views and downloads.](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1005196#viewedHeader) * 0 [Share](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1005196#discussedHeader) [Sum of Facebook, Twitter, Reddit and Wikipedia activity.](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1005196#discussedHeader) Open Access Peer-reviewed Research Article # Sex differences in trajectories to cardio-renal and mental health outcomes following the onset of type 2 diabetes: An observational cohort study using multi-state analysis in the UK Clinical Practice Research Datalink * Fabiola Eto , Roles Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing – original draft, Writing – review & editing * E-mail: f.eto@qmul.ac.uk Affiliation Wolfson Institute of Population Health, Queen Mary University of London, London, United Kingdom [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0002-0203-8649 ](https://orcid.org/0000-0002-0203-8649 "ORCID Registry") ⨯ * Miriam Samuel, Roles Conceptualization, Data curation, Investigation, Writing – review & editing Affiliation Wolfson Institute of Population Health, Queen Mary University of London, London, United Kingdom [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0003-1258-435X ](https://orcid.org/0000-0003-1258-435X "ORCID Registry") ⨯ * Daniel Stow, Roles Conceptualization, Data curation, Writing – review & editing Affiliation Wolfson Institute of Population Health, Queen Mary University of London, London, United Kingdom [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0002-9534-4521 ](https://orcid.org/0000-0002-9534-4521 "ORCID Registry") ⨯ * Rafael Henkin, Roles Data curation, Software, Writing – review & editing Affiliation William Harvey Research Institute, Queen Mary University of London, London, United Kingdom [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0002-5511-5230 ](https://orcid.org/0000-0002-5511-5230 "ORCID Registry") ⨯ * Alisha Angdembe, Roles Data curation, Writing – review & editing Affiliation William Harvey Research Institute, Queen Mary University of London, London, United Kingdom [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0009-0002-4495-3324 ](https://orcid.org/0009-0002-4495-3324 "ORCID Registry") ⨯ * Michael R. Barnes, Roles Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Writing – review & editing Affiliation William Harvey Research Institute, Queen Mary University of London, London, United Kingdom [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0001-9097-7381 ](https://orcid.org/0000-0001-9097-7381 "ORCID Registry") ⨯ * Sarah Finer , Contributed equally to this work with: Sarah Finer, Rohini Mathur Roles Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing Affiliation Wolfson Institute of Population Health, Queen Mary University of London, London, United Kingdom [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0002-2684-4653 ](https://orcid.org/0000-0002-2684-4653 "ORCID Registry") ⨯ * Rohini Mathur Contributed equally to this work with: Sarah Finer, Rohini Mathur Roles Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing Affiliation Wolfson Institute of Population Health, Queen Mary University of London, London, United Kingdom [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0002-3817-8790 ](https://orcid.org/0000-0002-3817-8790 "ORCID Registry") ⨯ # Sex differences in trajectories to cardio-renal and mental health outcomes following the onset of type 2 diabetes: An observational cohort study using multi-state analysis in the UK Clinical Practice Research Datalink * Fabiola Eto, * Miriam Samuel, * Daniel Stow, * Rafael Henkin, * Alisha Angdembe, * Michael R. Barnes, * Sarah Finer, * Rohini Mathur ![PLOS](https://journals.plos.org/resource/img/logo-plos-full-color.svg) x * Published: August 25, 2026 * * [Article](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005196) * [Authors](https://journals.plos.org/plosmedicine/article/authors?id=10.1371/journal.pmed.1005196) * [Metrics](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1005196) * [Comments](https://journals.plos.org/plosmedicine/article/comments?id=10.1371/journal.pmed.1005196) * [Media Coverage](http://plos.altmetric.com/details/doi/10.1371/journal.pmed.1005196) * [Abstract](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005196#abstract0) * [Author summary](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005196#abstract1) * [Introduction](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005196#sec007) * [Methods](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005196#sec008) * [Results](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005196#sec015) * [Discussion](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005196#sec022) * [Supporting information](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005196#sec024) * [Acknowledgments](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005196#ack) * [References](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005196#references) * [Reader Comments](https://journals.plos.org/plosmedicine/article/comments?id=10.1371/journal.pmed.1005196) * [Figures](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005196) ## Abstract ### Background Type 2 diabetes (T2D) presents a significant global health challenge, and its prevalence is expected to rise. T2D is associated with diverse complications, including cardiovascular diseases (CVD), end-stage renal disease (ESRD), and mental health disorders like depression and anxiety. Previous research has demonstrated sex differences in the metabolic risk profile, clinical characteristics, and care related to T2D and its complications, including mental health conditions. In this study, we aimed to describe the trajectories of hypertension, cardiovascular diseases, ESRD and mental health conditions in women and men from different age groups with T2D. ### Methods and findings Using individual-level anonymised linked primary and secondary electronic health record (EHR) data from the United Kingdom (UK) Clinical Practice Research Datalink (CPRD) GOLD, we carried out an observational cohort study of 28,720 individuals with incident T2D between 2010 and 2020. We applied competing risk semi-Markov multi-state analysis to investigate and understand the different transitions to cardiovascular disease, ESRD, and mental health conditions following the onset of T2D in women and men. During a median follow-up of 6.8 years, 39% of the cohort moved to another health state. Men constituted 62% of the cohort, with a median age of 54 (IQR 46, 64) at T2D onset, while women were typically older at diagnosis (mean = 56, IQR = 45, 67). Disease trajectories differed significantly by sex: women were more likely than men to be diagnosed with mental health conditions post-T2D, (8.1% versus 5.3%), while men were more likely to be diagnosed with CVD/ESRD (8.4% versus 5.3%) and hypertension (21.1% versus 20.2%) trajectories than women. Women showed higher average of health service utilisation and long-term prescribing than men. Women experienced a later onset of events compared to men. Both women and men who had a combination of T2D and a mental health condition experienced premature mortality compared to other trajectories. Hypertension was the most frequent event following T2D onset across all age groups and sexes. As a study limitation, some of the observed differences in mental health diagnoses between women and men may reflect differences in healthcare-seeking behaviour rather than true differences in the underlying proportions of these conditions. ### Conclusions Our study highlights sex-specific differences in disease trajectories following T2D onset, emphasising the need for stratified healthcare interventions. Women exhibited greater vulnerability to mental health conditions post-T2D, while men showed higher proportion of cardiovascular and renal complications, and had earlier onset of most events compared to women. Both sexes experienced earlier mortality when T2D was combined with a mental health condition. Current UK medical guidelines lack sex-specific prevention strategies and management for T2D and comorbidities, especially mental health conditions. Our findings draw attention to the importance of tailored management strategies that consider sex, age, and the complex interplay of physical and mental health in T2D care. ## Author summary ### Why was this study done? * T2D affects over 4 million people in the UK and is known to increase the risk of heart disease, kidney failure, and mental health conditions, such as depression and anxiety, but previous research has mostly examined these complications in isolation, rather than tracking the order and timing in which they tend to appear overtime. Anticipating the order and timing of comorbidities following T2D represents a valuable window of opportunity for early intervention, and may have meaningful implications for how clinicians respond, even if these population-level patterns will not apply uniformly to every individual. * Women and men are known to experience T2D differently, yet no large population-based study had previously mapped the full sequence of conditions that develop after a T2D diagnosis separately for each sex and across different age groups. ### What did the researchers do and find? * We followed nearly 29,000 people newly diagnosed with T2D between 2010 and 2020 using routinely collected UK primary and secondary care records, applying a statistical method called multi-state modelling to track the order, timing, and combination of conditions each person developed after their diagnosis of T2D. * Women were more likely than men to have a mental health condition diagnosed (anxiety, depression, or somatoform disorder) after T2D onset (8.1% versus 5.3%), while men were more likely to receive a diagnosis of cardiovascular disease or kidney failure (8.4% versus 5.3%); hypertension was the most common complication in both sexes across all age groups. * Both women and men who had a mental health condition after T2D died earlier than those in any other disease trajectory; notably, men in this group died on average 9 years younger than women following the same sequence of conditions, despite using healthcare services considerably less. ### What do these findings mean? * These findings indicate that knowing a complication is likely to occur is not enough; knowing when complications tend to occur and in what order may help translate population-level evidence into more targeted clinical action. * Routine mental health screening should be incorporated in T2D care practice—particularly for younger women—while earlier cardiovascular and kidney disease monitoring and stronger healthcare engagement strategies are needed for men. * Our results raise the hypothesis that the combination of T2D and mental health conditions may represent a high-risk group associated with premature death and high healthcare use, pointing to an urgent need for integrated physical and mental healthcare pathways. * This study has some important limitations to consider: its descriptive design cannot establish causation, requiring future causal studies to confirm whether observed trajectories reflect true causal relationships. We could not examine causes of death separately. Ethnicity could not be analysed due to the small numbers of individuals in each trajectory. We cannot rule out that some of the observed differences in mental health diagnoses between women and men may reflect differences in healthcare-seeking behaviour rather than true differences in the underlying proportions of these conditions. ## Figures ![Fig 5](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1005196.g005) ![Fig 6](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1005196.g006) ![Fig 7](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1005196.g007) ![Fig 1](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1005196.g001) ![Fig 2](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1005196.g002) ![Table 1](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1005196.t001) ![Fig 3](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1005196.g003) ![Table 2](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1005196.t002) ![Table 3](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1005196.t003) ![Table 4](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1005196.t004) ![Table 5](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1005196.t005) ![Fig 4](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1005196.g004) ![Fig 5](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1005196.g005) ![Fig 6](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1005196.g006) ![Fig 7](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1005196.g007) ![Fig 1](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1005196.g001) ![Fig 2](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1005196.g002) ![Table 1](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1005196.t001) **Citation:** Eto F, Samuel M, Stow D, Henkin R, Angdembe A, Barnes MR, et al. (2026) Sex differences in trajectories to cardio-renal and mental health outcomes following the onset of type 2 diabetes: An observational cohort study using multi-state analysis in the UK Clinical Practice Research Datalink. PLoS Med 23(8): e1005196. https://doi.org/10.1371/journal.pmed.1005196 **Academic Editor:** David Flood, Wuqu’ Kawoq | Maya Health Alliance, GUATEMALA **Received:** July 19, 2025; **Accepted:** July 17, 2026; **Published:** August 25, 2026 **Copyright:** © 2026 Eto et al. This is an open access article distributed under the terms of the [Creative Commons Attribution License](http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. **Data Availability:** Data used in this project cannot be publicly shared due to the terms of our license preclude us from sharing individual patient level data with third parties. Clinical Practice Research Datalink (CPRD) Aurum data used in this study was provided from the CPRD under a licence from UK Medicine and Healthcare products Regulatory Agency. Data from CPRD at the UK Medicine and Healthcare products Regulatory Agency is available subject to ethical approval, and can be requested using CPRD’s Research Data Governance process ( , all enquiries should be sent to: enquires@cprd.com). The code used to produce the analyses, and the minimal dataset are available at: . Please cite as follows: Fabiola Eto. (2026). Fabiola-Eto/multi-state-T2D-trajectories: Version 1.0 (Version v1.0) [Computer software]. Zenodo. . The codelists used to identify health conditions in the Electronic Health Records are available at . Please cite as follows: Fabiola Eto, Miriam Samuel& finersarah. (2023). f-eto/MULTIPLY-Initiative: Version 1.1 (Version v1.1) [Computer software]. Zenodo. . **Funding:** This work (and salary costs to SF, RM, and FE) was supported by MRC (MR/S027297/1). “Multimorbidity clusters, trajectories and genetic risk in British south Asians, 2020-2023”. Link: . Additional support for this and related work (SF, MRB, RH, AA, MS, DS, and FE) is from NIHR 31672 AI-MULTIPLY, 2022-2025, and NIHR 202635 (SF, MRB). MRB is also funded by NIHR Newcastle Patient Safety Research Collaborative (NIHR204291). RM is also supported by Barts Charity (MGU0504). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. **Competing interests:** I have read the journal’s policy and the authors of this manuscript have the following competing interests: SF has received grants from the NIHR (NIHR 31672, NIHR 202635) and MRC (MR/W014416/1, MR/V004905/1, MR/S027297/1. She is Co-Lead of the Genes & Health programme, which is part-funded (including salary contributions) by a Life Sciences Consortium comprising Astra Zeneca PLC, Bristol-Myers Squibb Company, GlaxoSmithKline Research and Development Limited, Maze Therapeutics Inc, Merck Sharp & Dohme LLC, Novo Nordisk A/S, Pfizer Inc, Takeda Development Centre Americas Inc. The remaining authors have declared that no competing interests exist. **Abbreviations:** BNF, British National Formulary; CPRD, Clinical Practice Research Datalink; EHR, electronic health record; ESRD, end-stage renal disease; GDPR, General Data Protection Regulation; GP, general practice; IMD, Index of Multiple Deprivation; ONS, Office for National Stati
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