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.
Sex-specific differences in disease trajectories following T2D onset were identified, with women exhibiting greater vulnerability to mental health conditions and men showing higher proportions of cardiovascular and renal complications, while both sexes experienced earlier mortality when T2D was combined with a mental health condition.
Key Findings
Results
Women with T2D were more likely than men to be diagnosed with mental health conditions post-T2D onset.
Mental health condition trajectories occurred in 8.1% of women versus 5.3% of men following T2D onset.
The study cohort included 28,720 individuals with incident T2D between 2010 and 2020 from the UK CPRD GOLD database.
Median follow-up was 6.8 years, during which 39% of the cohort moved to another health state.
A competing risk semi-Markov multi-state analysis was applied to investigate transitions to mental health conditions following T2D onset.
The authors note that some observed differences in mental health diagnoses may reflect differences in healthcare-seeking behaviour rather than true differences in underlying prevalence.
Results
Men with T2D were more likely than women to be diagnosed with cardiovascular disease or end-stage renal disease.
CVD/ESRD trajectories occurred in 8.4% of men versus 5.3% of women following T2D onset.
Men constituted 62% of the cohort, with a median age of 54 (IQR 46, 64) at T2D onset.
Women were typically older at T2D diagnosis (mean = 56, IQR = 45, 67) compared to men.
Men also had higher proportions of hypertension trajectories than women (21.1% versus 20.2%).
Men experienced earlier onset of most events compared to women across trajectories.
Results
Both women and men who had a combination of T2D and a mental health condition experienced premature mortality compared to other disease trajectories.
This finding applied across both sexes in the cohort.
The analysis used competing risk semi-Markov multi-state modelling to capture transitions including death as a competing outcome.
The cohort included incident T2D cases diagnosed between 2010 and 2020 from linked primary and secondary electronic health records.
Premature mortality was observed specifically in the trajectory combining T2D with mental health conditions, distinguishing it from other trajectories such as CVD/ESRD or hypertension alone.
Results
Hypertension was the most frequent event following T2D onset across all age groups and sexes.
Hypertension trajectories were recorded in 21.1% of men and 20.2% of women.
This pattern was consistent across different age groups within the cohort.
The finding was identified using multi-state analysis of transitions from T2D onset.
The cohort spanned incident T2D diagnoses from 2010 to 2020 with a median follow-up of 6.8 years.
Results
Women with T2D showed higher average health service utilisation and long-term prescribing than men.
This difference in service utilisation was observed across the study cohort of 28,720 individuals.
Data were drawn from linked primary and secondary electronic health records in the UK CPRD GOLD.
Higher utilisation in women occurred despite women being less likely to develop CVD/ESRD trajectories.
The finding suggests that differences in care-seeking behaviour may influence observed sex differences in diagnosed conditions, particularly mental health.
Results
Women experienced a later onset of events following T2D diagnosis compared to men.
Women were typically older at T2D diagnosis (mean = 56, IQR = 45, 67) versus men (median = 54, IQR = 46, 64).
Despite later event onset, women showed higher proportions of mental health condition trajectories.
Men showed earlier onset of most events across the disease trajectories studied.
This temporal difference was identified through competing risk semi-Markov multi-state analysis over a median follow-up of 6.8 years.
Conclusions
The study identified that current UK medical guidelines lack sex-specific prevention strategies and management approaches for T2D and its comorbidities, especially mental health conditions.
This observation was made in the context of significant sex-specific differences in disease trajectories found in the study.
The authors emphasise the need for stratified healthcare interventions based on sex and age.
The findings highlight the complex interplay of physical and mental health in T2D care that current guidelines do not adequately address.
The cohort studied 28,720 individuals across a 10-year period using linked EHR data from the UK CPRD GOLD.
What This Means
This research followed nearly 29,000 people in the UK who were newly diagnosed with type 2 diabetes between 2010 and 2020, tracking what health conditions they developed over time. The study used a sophisticated statistical method called multi-state analysis to map out the different 'trajectories' — or pathways — that people followed after their diabetes diagnosis, including development of heart disease, kidney failure, high blood pressure, depression, and anxiety. The researchers found important differences between women and men in which complications they were most likely to develop and when those complications appeared.
The key findings show that after a diabetes diagnosis, women were more likely to develop mental health conditions such as depression or anxiety (8.1% of women versus 5.3% of men), while men were more likely to develop cardiovascular disease or end-stage kidney disease (8.4% versus 5.3%). High blood pressure was the most common complication for both sexes. Critically, both women and men who developed a mental health condition alongside their diabetes experienced earlier death compared to those who followed other disease pathways — highlighting mental health as a particularly serious concern in diabetes care. Women also used health services more frequently and received more long-term prescriptions than men.
This research suggests that one-size-fits-all approaches to managing type 2 diabetes may be missing important differences between how the disease progresses in women versus men. The findings point to a potential gap in UK medical guidelines, which currently do not include sex-specific strategies for preventing or managing diabetes complications, particularly mental health conditions. This research suggests that healthcare for people with type 2 diabetes could be improved by tailoring monitoring and support based on a person's sex, age, and the combination of physical and mental health needs they face.
Eto F, Samuel M, Stow D, Henkin R, Angdembe A, Barnes M, 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 medicine. https://doi.org/10.1371/journal.pmed.1005196