Type 2 diabetes (T2D) increases the risk of cardiovascular disease, kidney failure and mental health disorders, and the order and timing of these complications after diagnosis may inform prevention and care. The authors set out to map trajectories from T2D onset to major cardio-renal and mental health outcomes separately in women and men and across age groups using linked UK electronic health records.
The study used anonymised individual-level linked primary and secondary care records from the UK Clinical Practice Research Datalink (CPRD) GOLD. The analytic cohort comprised 28,720 people with incident T2D diagnosed between 2010 and 2020. Median follow-up was 6.8 years. Men comprised 62% of the cohort and had a median age at diagnosis of 54 years (IQR 46–64); women had a median age at diagnosis of 56 years (IQR 45–67).
To characterise the sequence and timing of events after T2D onset the investigators applied a competing-risk semi-Markov multi-state modelling framework. This approach allowed estimation of transitions from the initial T2D state to subsequent states including hypertension, cardiovascular disease/end-stage renal disease (CVD/ESRD), and mental health diagnoses (anxiety, depression, somatoform disorder), and ultimately to death, while accounting for competing events.
Primary outcomes tracked after T2D onset were recorded diagnoses of hypertension, CVD or ESRD, and mental health conditions (specifically anxiety, depression, or somatoform disorder) as captured in routine primary and secondary care records. Death was included as an absorbing state. The authors also described health service utilisation and long-term prescribing across trajectories.
Overall, 39% of the cohort transitioned to at least one additional health state during follow-up. Hypertension was the most frequent event following T2D onset across all age groups and in both sexes.
Notable sex differences included:
Women demonstrated greater average healthcare utilisation and more long-term prescribing than men. Events generally occurred later in women compared with men.
Participants with a mental health condition following T2D experienced earlier mortality than those following other trajectories. The authors report that men in the T2D-plus-mental-health group died, on average, 9 years younger than women following the same sequence. The combination of T2D and mental health diagnoses is highlighted as a potentially high-risk trajectory associated with premature death and high healthcare use.
Hypertension occurred most frequently after T2D across all examined age groups. The study also found that men tended to experience progression events earlier than women, while women typically had later onset of events but used healthcare services more. Detailed age-stratified transition rates and timing metrics were estimated using the multi-state model in the original analysis.
Women had higher mean healthcare utilisation and were prescribed more long-term medications compared with men in this cohort. By contrast men had lower reported engagement with services despite a higher proportion progressing to cardio-renal outcomes and experiencing earlier event onset.
The authors note several limitations from the study data and design. The analysis is descriptive and cannot establish causation. Causes of death were not examined separately. Ethnicity could not be meaningfully analysed for trajectories due to small subgroup sizes. The authors also caution that observed sex differences in recorded mental health diagnoses may partly reflect differences in healthcare-seeking behaviour rather than true underlying prevalence differences. Access to individual-level data is restricted by the CPRD licence.
The study highlights sex-specific patterns after T2D onset that may inform targeted clinical practice. Key implications reported by the authors include:
The authors also point out that current UK guidelines lack sex-specific prevention and management strategies for T2D and its comorbidities, especially for mental health conditions, underlining the need for tailored approaches that consider sex, age and combined physical–mental health needs.
Data used in the study are not publicly shareable due to the CPRD licence; access can be requested through CPRD’s governance process. The analysis code and a minimal dataset are available at the authors’ GitHub repository as reported in the source. The work was funded by the MRC and supported by NIHR grants; specific funding references and competing interests are described in the original article.