ArticleFrontiers in endocrinology2026
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.
Article in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Insulin resistance (IR) plays a critical role in the development and prognosis of metabolic dysfunction-associated steatotic liver disease (MASLD). However, evidence regarding associations between novel triglyceride glucose (TyG) and adiposity-related composite indices, serving as simple IR surrogates, and the risk of incident MASLD remains limited. This study aimed to evaluate associations between six novel TyG-related composite indices and MASLD risk, as well as the potential mediating role of biological aging. Methods: This prospective cohort study included 426,831 participants from the UK Biobank, who were free of MASLD at baseline. Six novel TyG and adiposity-related composite indices [e.g., TyG-body mass index (BMI), TyG-waist circumference (WC), TyG-waist-to-height ratio (WHtR), TyG-body roundness index (BRI), TyG-a body shape index (ABSI), and TyG-weight-adjusted-waist index (WWI)] were calculated. Kaplan-Meier curves, Cox proportional hazards models, and restricted cubic splines (RCS) analyses were applied to evaluate associations between novel TyG-related indices and MASLD risk. Predictive performance was evaluated using Harrell's C-index, net reclassification index (NRI), and integrated discrimination improvement index (IDI). Mediation analyses were performed to explore the potential role of biological aging. Additionally, MRI-measured proton density fat fraction (PDFF) was used to defined MASLD and investigate its association with TyG-related indices. Results: Over a median follow-up of 13.72 years, 6,308 new-onset MASLD cases were recorded. All six TyG-related composite indices were significantly associated with an increased risk of incident MASLD. Compared with the lowest quartile, hazard ratios (HRs) and 95% confidence intervals (CIs) for the highest quartile were 6.28 (5.62-7.02) for TyG-BMI, 8.27 (7.34-9.30) for TyG-WC, 8.18 (7.24-9.23) for TyG-WHtR, 7.79 (6.91-8.78) for TyG-BRI, 3.86 (3.49-4.26) for TyG-ABSI, and 6.06 (5.42-6.78) for TyG-WWI. RCS analyses revealed nonlinear relationships of all TyG-related indices and MASLD risk (all Conclusion: Six novel TyG and adiposity-related composite indices were independently associated with the risk of incident MASLD. These indices, particularly TyG-WHtR and TyG-WC, may server as simple and effective predictors for MASLD. Biological aging partially mediated these associations, offering novel insights into the pathways from IR to MASLD development.
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