The Role of Type 2 Diabetes in Shaping Multimorbidity Progression: Evidence from the UK Biobank Cohort

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Aims/hypothesis Type 2 diabetes (T2D) frequently cooccurs with other chronic conditions and has been suggested as a key driver of multimorbidity development. However, the temporal dynamics of how T2D influences multimorbidity progression are not well understood. We aimed to investigate how T2D influences the rate of multimorbidity progression. Methods We analyzed data from the UK Biobank, a prospective population-based cohort study (n=502,368, median age 58 years [range 37-73 years], 46% male at baseline) with a median follow-up of 15.3 year. 8.7% of participants were diagnosed with T2D over the follow-up period. We counted the current number of morbidities (among 80 long-term chronic conditions) identified through hospital admission records using ICD-10 diagnosis codes. We modeled the age-specific transition rates between multimorbidity states using multistate models tailored for time-split data (i.e., 2 to 3 morbidities, T2D (with 1 morbidity) to T2D (with 2 morbidities), etc.). Age was modeled using natural splines with an interaction term with T2D, adjusting for sex, education, ethnicity, smoking, and body mass index. Results The total follow-up time was 7.5 million person-years (PY), of which 0.33 million PY was in T2D. Individuals with T2D consistently experienced higher transition rates between morbidity transition states. For example, the transition rate from 2 to 3 morbidities was 7.94 per 100 PY without the presence of T2D, compared to 18.35 per 100 PY with T2D (rate ratio=2.31, 95% CI: 2.28-2.34). The excess in transition rates was most pronounced from states with few comorbidities. Further, the transition rates were consistently influenced by T2D status and age, with younger individuals with T2D showing the most accelerated progression. Conclusion/interpretation Our study suggests that T2D is associated with accelerated development of subsequent multimorbidity, highlighting T2D as a critical contributor of chronic disease accumulation. The progression of disease accumulation is more pronounced in younger age groups, which suggests different underlying mechanisms of multimorbidity progression across age, warranting further investigation. The findings indicate the need for early intervention among younger people with T2D to slow multimorbidity progression.