Cardiorespiratory fitness and type 2 diabetes risk: A prospective cohort study with mediation analysis of biological aging in the UK Biobank
Authors' conclusion
Higher cardiorespiratory fitness demonstrates robust protective associations against T2D incidence, with biological aging mechanisms partially mediating this relationship.
Study context
- Population
- UK Biobank participants aged 39–70 years without baseline diabetes; VO2max estimated by validated algorithm
- Participants
- 54,418 participants
- Exposure
- Highest vs lowest VO2max quartile
- Outcome
- Incident T2D
Methodological detailsmediation analysis
- Mediation analysis
Main finding
As reported in the abstract
Hazard ratio (95% CI)
Highest VO2max quartilevs Lowest VO2max quartile56% lower T2D risk
0.44(0.39–0.50)
Per SD increase in VO2max28% lower risk
0.72(0.68–0.76)
- Incident T2D over 694 986 person-years
- 2628 (3.78 per 1000 person-years)
Observational data: associations, not effects.
Further findings
Mediation of VO2max-T2D association by biological aging
- Proportion mediated by biological age (BA) acceleration
- 8.2% (95% CI 6.1%-10.8%)
- Proportion mediated by phenotypic age (PhenoAge) acceleration
- 9.1% (95% CI 6.8%-12.1%)
Subgroups
- Protective associations consistent across sex, age, ethnicity and genetic risk subgroups
Cross-sectional associations of VO2max with biomarkers
- Glucose β
- −0.32
- HbA1c β
- −0.28
- TG β
- −0.31
- HDL-C β
- 0.29
Original publication
Cardiorespiratory fitness and type 2 diabetes risk: A prospective cohort study with mediation analysis of biological aging in the UK Biobank. Diabetes Obes Metab. Published 3 November 2025. doi:10.
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