Sex differences in disease trajectories after type 2 diabetes: women face earlier mental health burden, men earlier cardio-renal decline
核心洞察
A UK cohort study of 28,720 people with type 2 diabetes (搜索) found that 39% experienced at least one significant health event over a median 6.8 years of follow-up.
Women were more likely to develop mental health conditions post-diagnosis (8.1% vs 5.3%), while men showed higher rates of cardiovascular disease (搜索)/end-stage renal disease (搜索) (8.4% vs 5.3%) and hypertension (搜索).
Both sexes with a mental health condition following type 2 diabetes (搜索) experienced premature mortality, with men dying on average 9 years younger than women in the same trajectory.
In the years following a type 2 diabetes (搜索) (T2D) diagnosis, women are more likely to develop mental health conditions, while men are more likely to develop cardiovascular and renal complications, according to a study published August 25th in the open access journal PLOS Medicine by Fabiola Eto from Queen Mary University of London, UK, and colleagues.
The observational cohort study, using anonymised linked primary and secondary electronic health record data from the UK Clinical Practice Research Datalink (搜索) (CPRD) GOLD, examined 28,720 men and women who developed T2D between 2010 and 2020. 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). During a median follow-up of 6.8 years, 39% of the cohort moved to another health state.
Divergent trajectories by sex
The researchers applied competing risk semi-Markov multi-state analysis to track the order, timing, and combination of conditions each person developed after their T2D diagnosis. 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 cardiovascular disease (搜索) or end-stage renal disease (搜索) (CVD/ESRD) (8.4% versus 5.3%) and hypertension (搜索) (21.1% versus 20.2%).
Hypertension (搜索) was the most frequent event following T2D onset across all age groups and sexes. Both women and men who had hypertension after T2D onset were more likely to have a CVD/ESRD diagnosis as the next condition (10.6% and 13.6%, respectively). However, compared to men, women had 1.75 times the probability of having a mental health condition after hypertension (8.6% versus 4.9%).
Timing and premature mortality
Women generally experienced a later onset of events after T2D diagnosis than men, with median time between health states ranging from 1 to 4 years for women and 1 to 5 years for men. Anxiety (搜索), depression (搜索), or somatoform disorders occurred at the earliest age for both sexes (50 and 51 years old, respectively). Men had an earlier onset of CVD/ESRD following T2D onset compared to women, with men's earliest median age for CVD/ESRD at 60 years old versus 66 years old for women.
A striking finding was that both women and men who had a combination of T2D and a mental health condition experienced premature mortality compared to other trajectories. Notably, men in the trajectory T2D followed by a mental health condition and then death died on average 9 years younger than women following the same sequence (61 versus 70 years of age), despite using healthcare services considerably less.
Healthcare utilisation patterns
Women showed higher average health service utilisation and long-term prescribing than men. On average, women had more primary care consultations (average of 92 versus 32) and hospitalisations (average of 3 versus 1) than men over the 2010–2020 period. The researchers noted that this may contribute to the increased diagnoses observed among women, and that some of the observed differences in mental health diagnoses may reflect differences in healthcare-seeking behaviour rather than true differences in the underlying proportions of these conditions.
Implications for clinical practice
Current UK medical guidelines lack sex-specific prevention strategies and management for T2D and comorbidities, especially mental health conditions. The authors emphasise 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.
"One of the clearest signals in our data was the sex difference. Younger women with type 2 diabetes (搜索) were showing mental health complications earlier and more often than we expected, which suggests routine psychological screening should be incorporated into standard diabetes care. For men, the pattern looked different: cardiovascular and kidney risks tended to emerge earlier, pointing to a need for earlier monitoring and stronger strategies to support men's engagement with their treatment over time," the authors write.
The study has several limitations. Its descriptive design cannot establish causation, and future causal studies are needed to confirm whether observed trajectories reflect true causal relationships. The researchers could not examine causes of death separately, and ethnicity could not be analysed due to small numbers of individuals in each trajectory. Additionally, the analysis did not incorporate biomarkers or clinical measurements such as HbA1c, blood pressure, or eGFR, nor did it account for treatment exposures.