Associations of different insulin resistance-related indices with the incidence and progression trajectory of cardiometabolic multimorbidity: a prospective cohort study from UK biobank
Authors' conclusion
Our findings highlight the critical role of IR-related indices, particularly TyG-WHtR and TyG-WC, in the incidence, progression, and prevention of CMM. The mediation effects of biomarkers indicate the potential for targeted interventions to reduce CMM risk in high-IR individuals.
Study context
- Population
- Individuals from the UK Biobank free of cardiometabolic diseases (T2D, coronary heart disease (CHD), stroke) at baseline
- Participants
- 374,274 individuals
- Exposure
- Insulin resistance (IR)-related indices, per 1-SD increase
- Outcome
- Incident cardiometabolic multimorbidity (CMM): two or more of T2D, CHD and stroke
- Follow-up
- Mean 13.7 years
Methodological detailsUK Biobank, multi-state models, mediation analyses
- UK Biobank
- Multi-state models
- Mediation analyses
Main finding
As reported in the abstract
Incident CMM, HR per 1-SD increase
- Triglyceride-glucose (TyG) index, HR
- 1.30 (1.26-1.34) (95% CI)
- TyG-body mass index (TyG-BMI), HR
- 1.42 (1.39-1.46) (95% CI)
- TyG-waist circumference (TyG-WC), HR
- 1.54 (1.49-1.59) (95% CI)
- TyG-waist-height ratio (TyG-WHtR), HR
- 1.52 (1.48-1.57) (95% CI)
- TG/HDL-C ratio, HR
- 1.19 (1.17-1.21) (95% CI)
- Developed cardiometabolic multimorbidity (CMM)
- 5048 (1.3%)
Observational data: associations, not effects.
Further findings
Predictive performance (net reclassification index (NRI), IDI)
- TyG-WHtR and TyG-WC had significantly higher NRI and IDI, indicating superior predictive performance for CMM risk
Transitions from free of cardiometabolic diseases (CMDs) to single CMDs
- Indices had the strongest impact on T2D
- all P < 0.001
Progression from initial CHD to CMM
- More likely to progress to CMM with higher IR-related indices
- all P < 0.001
- Effect sizes for TyG-WC and TyG-WHtR greater than other indices across all transitions
Mediation by biomarkers
- Liver function, renal function and inflammation biomarkers collectively mediated approximately one-third of associations of TyG-WHtR and TyG-WC with incident CMM
Original publication
Associations of different insulin resistance-related indices with the incidence and progression trajectory of cardiometabolic multimorbidity: a prospective cohort study from UK biobank. Cardiovasc Diabetol. Published 18 June 2025. doi:10.
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