| Title: | 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 |
| Journal: | Frontiers in Endocrinology |
| Published: | 11 Aug 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42643580/ |
| DOI: | https://doi.org/10.3389/fendo.2026.1915819 |
| URL: | https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2026.1915819/pdf |
Publication 21182
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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.</p>
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.</p>
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 P for non-linearity <0.001). Incorporating novel TyG-related indices significantly improved predictive performance, with the greatest gains observed for TyG-WHtR and TyG-WC. Mediation analyses indicated that biological aging, assessed by KDM-BA and PhenoAge, accounted for 3%-12% of these associations. Results were consistent across subgroup and sensitivity analyses and when MASLD was defined as PDFF ≥5%.</p>
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.</p>
17 Keywords
- Adiposity
- Aged
- Aging
- Biological Specimen Banks
- Blood Glucose
- Body Mass Index
- Fatty Liver
- Female
- Humans
- Insulin Resistance
- Male
- Middle Aged
- Prospective Studies
- Risk Factors
- Triglycerides
- UK Biobank
- United Kingdom
5 Authors
- Kun Wang
- Renfang Han
- Yueqing Huang
- Jingfen Cai
- Xiadi Wu
1 Application
| Application ID | Title |
|---|---|
| 104283 | Identification of shared risk factors and gene-environment interactions for cardiometabolic diseases and cardiometabolic multimorbidity |
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