Insulin resistance-related indices, genetic risk, and the risk of cardiovascular disease in individuals with preclinical or clinical obesity: a large prospective cohort study in the UK biobank
Authors' conclusion
Elevated IR-related indices, particularly TyG-WC, were associated with increased total CVD and CAD risks in preclinical or clinical obesity. Additive effects of TyG-WC and genetic risk on CVD were revealed, with mediating biomarkers suggesting potential targeted interventions for CVD risk reduction.
Study context
- Population
- UK Biobank participants with preclinical or clinical obesity
- Participants
- 112,866 participants
- Exposure
- Highest vs lowest quartile of insulin resistance (IR)-related indices
- Outcome
- Total CVD incidence
- Follow-up
- Median 13.45 years
Methodological detailsUK Biobank
- UK Biobank
Main finding
As reported in the abstract
Total CVD · median 13.45 years
Estimate (95% CI)
Q4vs Q1
HR (TyG-BMI) 1.33(1.28–1.39)
Q4vs Q1
HR (TyG-WC) 1.41(1.34–1.48)
Q4vs Q1
HR (TyG-WHtR) 1.25(1.20–1.31)
- Events: total cardiovascular disease (CVD) cases
- 21,601
Observational data: associations, not effects.
Further findings
Coronary artery disease (CAD)
- CAD cases
- 11,942
- All IR-related indices significantly associated with CAD
Stroke
- Stroke cases
- 3347
- Borderline significant associations with stroke
Dose-response and genetic risk
- TyG-body mass index (TyG-BMI) and TyG-waist-to-height ratio (TyG-WHtR) nonlinear, TyG-waist circumference (TyG-WC) linear association with total CVD
- CVD risk highest with high genetic risk and high IR indices; additive interaction between TyG-WC and genetic risk
Incremental prediction (net reclassification index (NRI), IDI)
- Significantly higher NRI and IDI for TyG-WC, TyG-BMI and TyG-WHtR; TyG-WC highest performance
Mediation
- Inflammation, liver and renal biomarkers might partially mediate the relationship
Original publication
Insulin resistance-related indices, genetic risk, and the risk of cardiovascular disease in individuals with preclinical or clinical obesity: a large prospective cohort study in the UK biobank. Cardiovasc Diabetol. Published 25 October 2025. doi:10.
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