{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T06:28:00Z","timestamp":1786429680131,"version":"build-2736575974"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2019s 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>P<\/jats:italic>\n                      for non-linearity &amp;lt;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 \u22655%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1915819","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T05:36:58Z","timestamp":1786426618000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"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"],"prefix":"10.3389","volume":"17","author":[{"given":"Kun","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Science and Education, Wuxi Maternity and Child Health Care Hospital, Affiliated Women\u2019s Hospital of Jiangnan University","place":["Wuxi, 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiadi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Women' Health, Wuxi Maternity and Child Health Care Hospital, Affiliated Women\u2019s Hospital of Jiangnan University","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.06.003","article-title":"A multisociety Delphi consensus statement on new fatty liver disease nomenclature","volume":"79","author":"Rinella","year":"2023","journal-title":"J Hepatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1136\/gutjnl-2023-330595","article-title":"MASLD: a systemic metabolic disorder with cardiovascular and Malignant 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