Six novel triglyceride glucose and adiposity-related composite indices were independently associated with the risk of incident MASLD, with biological aging partially mediating these associations and accounting for 3%–12% of the effect.
All six TyG-related composite indices were significantly associated with increased risk of incident MASLD over a median follow-up of 13.72 years.
TyG-WC showed the strongest association with MASLD risk, with a hazard ratio of 8.27 for the highest versus lowest quartile.
Restricted cubic spline analyses revealed nonlinear relationships between all six TyG-related indices and MASLD risk.
Incorporating novel TyG-related indices significantly improved predictive performance for MASLD, with the greatest gains observed for TyG-WHtR and TyG-WC.
Biological aging, assessed by KDM biological age (KDM-BA) and PhenoAge, partially mediated the associations between TyG-related indices and MASLD risk.
Results were consistent when MASLD was defined using MRI-measured proton density fat fraction (PDFF) ≥5%.
Six TyG and adiposity-related composite indices were identified as the exposure variables: TyG-BMI, TyG-WC, TyG-WHtR, TyG-BRI, TyG-ABSI, and TyG-WWI.
This research suggests that six combined measures of blood fat levels and body fat distribution — each pairing a triglyceride-glucose (TyG) index with a different measure of body size or shape — are strongly linked to the future development of metabolic dysfunction-associated steatotic liver disease (MASLD), commonly known as fatty liver disease. The study followed over 426,000 adults from the UK Biobank for nearly 14 years, during which more than 6,300 people developed MASLD. People in the highest quarter of these combined indices had risks of developing MASLD that were 4 to 8 times higher than those in the lowest quarter, with waist-circumference-based combinations showing the strongest associations. The study also found that all six indices improved doctors' ability to predict who would go on to develop MASLD, with the combinations using waist circumference and waist-to-height ratio performing best. Additionally, the research identified that accelerated biological aging — meaning the body's internal aging processes running faster than expected based on chronological age — partly explains how insulin resistance leads to fatty liver disease, accounting for roughly 3% to 12% of the link between these indices and MASLD risk. This research suggests that these simple, calculable indices — requiring only standard clinical measurements like triglycerides, glucose, and waist circumference — could be useful tools for identifying people at higher risk of developing fatty liver disease before it occurs. The finding that biological aging acts as a partial mediator also points to new potential pathways connecting metabolic dysfunction to liver disease, which could inform future prevention strategies.
Wang K, Han R, Huang Y, Cai J, Wu X. (2026). Associations between novel triglyceride glucose and adiposity-related indices and risk of metabolic dysfunction-associated steatotic liver disease: the mediating role of biological aging and evidence from the UK Biobank.. Frontiers in endocrinology. https://doi.org/10.3389/fendo.2026.1915819