| Title: | Cardiorespiratory fitness and type 2 diabetes risk: A prospective cohort study with mediation analysis of biological aging in the UK Biobank |
| Journal: | Diabetes Obesity and Metabolism |
| Published: | 3 Nov 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41178744/ |
| DOI: | https://doi.org/10.1111/dom.70261 |
| URL: | https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dom.70261 |
Publication 19069
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
AIMS: Higher cardiorespiratory fitness is associated with reduced type 2 diabetes mellitus (T2D) risk, but the underlying mechanisms remain incompletely understood. We investigated whether biological aging mediates the association between maximal oxygen uptake (VO2max) and incident T2D risk.</p>
MATERIALS AND METHODS: This prospective cohort study included 54 418 UK Biobank participants aged 39-70 years without baseline diabetes. VO2max was estimated using a validated algorithm incorporating resting heart rate, physical activity, age, sex and body mass index. Biological age (BA) and phenotypic age (PhenoAge) were calculated from clinical biomarkers. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for sociodemographic, lifestyle and clinical factors. Linear regression analyses assessed cross-sectional associations between VO2max and standardised glycaemic and lipid biomarkers. Mediation analysis quantified the proportion of association explained by biological aging measures.</p>
RESULTS: During 694 986 person-years of follow-up, 2628 participants developed T2D (incidence rate: 3.78 per 1000 person-years). Compared to the lowest VO2max quartile, participants in the highest quartile had a 56% lower T2D risk (HR 0.44, 95% CI = 0.39-0.50). Each standard deviation increase in VO2max was associated with a 28% lower risk (HR 0.72, 95% CI = 0.68-0.76). BA acceleration mediated 8.2% (95% CI = 6.1%-10.8%) and PhenoAge acceleration mediated 9.1% (95% CI = 6.8%-12.1%) of the VO2max-T2D association. Protective associations were consistent across sex, age, ethnicity and genetic risk subgroups. VO2max showed strong inverse correlations with glucose (β = -0.32), glycated haemoglobin (β = -0.28), triglycerides (β = -0.31) and a positive correlation with high-density lipoprotein (HDL) cholesterol (β = 0.29).</p>
CONCLUSIONS: Higher cardiorespiratory fitness demonstrates robust protective associations against T2D incidence, with biological aging mechanisms partially mediating this relationship.</p>
8 Authors
- Xiangliang Liu
- Xinqiao Chen
- Wang Yang
- Guanran Ding
- Yixin Zhao
- Yuguang Li
- Naifei Chen
- Jiuwei Cui
Enabling scientific discoveries that improve human health