Metabolic profiling of frailty, associations with type 2 diabetes and interaction with genetic susceptibility
Authors' conclusion
The increased risk of T2D in individuals with frailty may be mediated through effects on the metabolome, and the influence of such metabolic alterations on diabetes risk may be amplified in individuals with genetic susceptibility to T2D.
Study context
- Population
- Adults with baseline metabolomics data from the UK Biobank
- Participants
- 197,502 adults
- Exposure
- Pre-frailty and frailty vs non-frailty
- Outcome
- Incident T2D
Methodological detailspopulation-based, prospective cohort data, UK Biobank
- Population-based
- Prospective cohort data
- UK Biobank
Main finding
As reported in the abstract
Each group vs non-frailtyHazard ratio (95% CI)
Pre-frailty
1.33(1.26–1.40)
Frailty
1.59(1.46–1.74)
Observational data: associations, not effects.
Further findings
Metabolic signature of frailty (53 metabolites) and T2D risk
- HR per SD increment
- 1.45 (95% CI: 1.42, 1.48)
Proportion of frailty–T2D association mediated by metabolic signature
- Proportion explained
- 31.0% (95% CI: 25.8, 36.8)
Additive interaction between metabolic signature of frailty and polygenic risk score for T2D (PRS-T2D)
- RERI
- 9.43 (95% CI: 6.06, 12.80)
Original publication
Metabolic profiling of frailty, associations with type 2 diabetes and interaction with genetic susceptibility. Cardiovasc Diabetol. Published 24 May 2025. doi:10.
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