Lipids & metabolic liver disease
The role of insulin resistance in the longitudinal progression from non-alcoholic fatty liver disease (NAFLD) to cardiovascular-kidney-metabolic disease
Authors' conclusion
Insulin resistance independently accelerated the progression from NAFLD to CKM diseases, particularly ischemic stroke. Healthy sleep and regular physical activity failed to offset this detrimental impact.
Study context
- Population
- UK Biobank participants free of NAFLD and cardiovascular-kidney-metabolic (CKM) diseases (ischemic stroke (IS), ischemic heart disease (IHD), T2D, chronic kidney disease (CKD)) at baseline; median age 57 years4,949 developed NAFLD
- Participants
- 377,757 participants
- Exposure
- Elevated vs lower TyG index
- Outcome
- Transitions from NAFLD to first-onset, double and triple CKM disease
- Follow-up
- Median 13.6 years
Methodological detailsUK Biobank, Markov multi-state models
- UK Biobank
- Markov multi-state models
Main finding
As reported in the abstract
Transitions from NAFLD to CKM disease with elevated TyG
NAFLD to first-onset CKM disease, HR
1.25
95% CI 1.05–1.49
NAFLD to double CKM disease, HR
1.46
95% CI 1.19–1.80
NAFLD to triple CKM disease, HR
1.81
95% CI 1.28–2.55
Observational data: associations, not effects.
Further findings
Progression from NAFLD among NAFLD cases
- Progressed to T2D
- 12.65%
- Progressed to IHD
- 9.11%
- Progressed to CKD
- 8.63%
- Progressed to IS
- 4.61%
Individual CKM components with elevated TyG
- T2D, HR
- 1.41 (95% CI 1.11-1.78)
- CKD, HR
- 1.37 (95% CI 1.08-1.75)
- IS, HR
- 1.70 (95% CI 1.27-2.27)
Dose-response and lifestyle
- J-shaped dose-response relationship
- Transition risk remained pronounced with healthy sleep and regular physical activity
Original publication
The role of insulin resistance in the longitudinal progression from NAFLD to cardiovascular-kidney-metabolic disease. Cardiovasc Diabetol. Published 15 October 2025. doi:10.
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