{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T04:31:58Z","timestamp":1786422718525,"version":"build-2736575974"},"reference-count":52,"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. Med."],"abstract":"<jats:p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is common, yet early disease often remains unrecognized. The triglyceride\u2013glucose (TyG) index, calculated from fasting triglyceride and glucose concentrations, has emerged as an accessible surrogate marker of metabolic dysfunction. This review examines the clinical interpretation, biological context, and current limitations of the TyG index and its anthropometric and inflammatory derivatives in MASLD. Current evidence links higher TyG-related measures to prevalent steatosis, fibrosis markers, and selected extrahepatic outcomes. Indices incorporating body mass index, waist circumference, or waist-to-height ratio may improve risk discrimination in some settings, particularly when body-fat distribution is informative. However, their performance varies according to population characteristics, disease definition, reference standard, and clinical purpose. TyG is not a direct measure of hepatic or peripheral insulin resistance, liver inflammation, or fibrosis. It should therefore be considered a metabolic risk marker rather than a stand-alone diagnostic test for MASLD or MASH. Important limitations include the predominance of cross-sectional evidence, heterogeneity among NAFLD, MAFLD, and MASLD definitions, variable cutoff values, and component overlap between TyG-derived indices and cardiometabolic diagnostic criteria. Evidence for liver-specific hard outcomes remains limited. Future studies should directly compare TyG-related markers with established metabolic and liver-directed tests in diverse prospective cohorts, using standardized repeated measurements and outcomes including progressive fibrosis, cirrhosis, hepatocellular carcinoma, and liver-related death. At present, TyG-related measures may complement, but cannot replace, liver-specific assessment.<\/jats:p>","DOI":"10.3389\/fmed.2026.1857612","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T04:21:49Z","timestamp":1786422109000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Interpreting the triglyceride\u2013glucose index and its derived indices in metabolic dysfunction-associated steatotic liver disease: clinical utility and evidence gaps"],"prefix":"10.3389","volume":"13","author":[{"given":"Longzhou","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Cardiology, Suining Central Hospital","place":["Suining, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucai","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Suining Central Hospital","place":["Suining, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Suining Central Hospital","place":["Suining, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencai","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Suining Central Hospital","place":["Suining, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejun","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Suining Central Hospital","place":["Suining, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.tem.2024.02.007","article-title":"Current status and future trends of the global burden of MASLD","volume":"35","author":"Miao","year":"2024","journal-title":"Trends Endocrinol Metab"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"972","DOI":"10.14218\/jcth.2021.00201","article-title":"Epidemiology and clinical outcomes of metabolic (dysfunction)-associated fatty liver disease","volume":"9","author":"Lin","year":"2021","journal-title":"J Clin Transl Hepatol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1097\/hep.0000000000000323","article-title":"AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease","volume":"77","author":"Rinella","year":"2023","journal-title":"Hepatology"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1542","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":"ref5","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1007\/s11154-020-09621-1","article-title":"Lean NAFLD: an underrecognized and challenging disorder in medicine","volume":"22","author":"Maier","year":"2021","journal-title":"Rev Endocr Metab Disord"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"111315","DOI":"10.1016\/j.biopha.2021.111315","article-title":"Adipose tissue and insulin resistance in obese","volume":"137","author":"Ahmed","year":"2021","journal-title":"Biomed Pharmacother"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"2133","DOI":"10.1152\/physrev.00063.2017","article-title":"Mechanisms of insulin action and insulin resistance","volume":"98","author":"Petersen","year":"2018","journal-title":"Physiol Rev"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1089\/met.2008.0034","article-title":"The product of fasting glucose and triglycerides as surrogate for identifying insulin resistance in apparently healthy subjects","volume":"6","author":"Simental-Mend\u00eda","year":"2008","journal-title":"Metab Syndr Relat Disord"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"3347","DOI":"10.1210\/jc.2010-0288","article-title":"The product of triglycerides and glucose, a simple measure of insulin sensitivity. Comparison with the euglycemic-hyperinsulinemic clamp","volume":"95","author":"Guerrero-Romero","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"ref10","first-page":"15","article-title":"The triglyceride and glucose index (TyG) is an effective biomarker to identify nonalcoholic fatty liver disease","volume-title":"Lipids Health Dis","author":"Zhang","year":"2017"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1186\/s12944-018-0913-3","article-title":"A longitudinal epidemiological study on the triglyceride and glucose index and the incident nonalcoholic fatty liver disease","volume":"17","author":"Zheng","year":"2018","journal-title":"Lipids Health Dis"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1043169","DOI":"10.3389\/fendo.2022.1043169","article-title":"The triglyceride and glucose index and risk of nonalcoholic fatty liver disease: a dose-response meta-analysis","volume":"13","author":"Ling","year":"2023","journal-title":"Front Endocrinol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1186\/s12902-022-01172-7","article-title":"Association between triglyceride-glucose index and nonalcoholic fatty liver disease in type 2 diabetes mellitus","volume":"22","author":"Li","year":"2022","journal-title":"BMC Endocr Disord"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s12933-022-01511-x","article-title":"Triglyceride-glucose index as a marker in cardiovascular diseases: landscape and limitations","volume":"21","author":"Tao","year":"2022","journal-title":"Cardiovasc Diabetol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1186\/s12933-024-02263-6","article-title":"Lipid-based insulin-resistance markers predict cardiovascular events in metabolic dysfunction associated steatotic liver disease","volume":"23","author":"Colantoni","year":"2024","journal-title":"Cardiovasc Diabetol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"102122","DOI":"10.1016\/j.aohep.2025.102122","article-title":"Diagnosis of metabolic dysfunction-associated steatotic liver disease by triglyceride glucose-body mass index: a systematic review and meta-analysis","volume":"31","author":"Du","year":"2026","journal-title":"Ann Hepatol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e0324483","DOI":"10.1371\/journal.pone.0324483","article-title":"Association of triglyceride glucose-body mass index (TyG-BMI) with metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis","volume":"20","author":"Boushehri","year":"2025","journal-title":"PLoS One"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1186\/s12876-025-03915-x","article-title":"Modified triglyceride-glucose indices as novel predictors of metabolic dysfunction-associated fatty liver disease in US adolescents: a nationally representative study from NHANES 2017-2020","volume":"25","author":"Zou","year":"2025","journal-title":"BMC Gastroenterol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"951689","DOI":"10.3389\/fendo.2022.951689","article-title":"Potential screening indicators for early diagnosis of NAFLD\/MAFLD and liver fibrosis: triglyceride glucose index-related parameters","volume":"13","author":"Xue","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1321922","DOI":"10.3389\/fendo.2024.1321922","article-title":"Association between TyG index trajectory and new-onset lean NAFLD: a longitudinal study","volume":"15","author":"Liu","year":"2024","journal-title":"Front Endocrinol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1186\/s12876-025-04301-3","article-title":"The effect of longitudinal trajectories of triglyceride-glucose index on the incident metabolic dysfunction-associated steatotic liver disease","volume":"25","author":"Wu","year":"2025","journal-title":"BMC Gastroenterol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1186\/s12876-025-03870-7","article-title":"Correlation between hs-CRP-triglyceride glucose index and NAFLD and liver fibrosis","volume":"25","author":"Zhou","year":"2025","journal-title":"BMC Gastroenterol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s12933-026-03119-x","article-title":"Association of the C-reactive protein-triglyceride-glucose index with metabolic dysfunction-associated steatotic liver disease and long-term all-cause and cardiovascular mortality: evidence from two nationwide prospective cohort studies","volume":"25","author":"Jin","year":"2026","journal-title":"Cardiovasc Diabetol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s12933-024-02572-w","article-title":"Association between triglyceride-glucose (TyG) related indices and cardiovascular diseases and mortality among individuals with metabolic dysfunction-associated steatotic liver disease: a cohort study of UK biobank","volume":"24","author":"Qiao","year":"2025","journal-title":"Cardiovasc Diabetol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e240115","DOI":"10.1530\/JOE-24-0115","article-title":"The role of adipose tissue dysfunction in hepatic insulin resistance and T2D","volume":"262","author":"Sancar","year":"2024","journal-title":"J Endocrinol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1097\/mol.0000000000000297","article-title":"Role of lipoprotein lipase in lipid metabolism","volume":"27","author":"Olivecrona","year":"2016","journal-title":"Curr Opin Lipidol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"101185","DOI":"10.1016\/j.jhepr.2024.101185","article-title":"Lipid metabolism in MASLD and MASH: from mechanism to the clinic","volume":"6","author":"Carli","year":"2024","journal-title":"JHEP Rep"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"964","DOI":"10.4093\/dmj.2025.0644","article-title":"Hepatic insulin resistance and steatosis in metabolic dysfunction-associated Steatotic liver disease: new insights into mechanisms and clinical implications","volume":"49","author":"Truong","year":"2025","journal-title":"Diabetes Metab J"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"119053","DOI":"10.1016\/j.atherosclerosis.2024.119053","article-title":"Lipotoxicity-driven metabolic dysfunction-associated steatotic liver disease (MASLD)","volume":"400","author":"Iturbe-Rey","year":"2025","journal-title":"Atherosclerosis"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1400961","DOI":"10.3389\/fendo.2024.1400961","article-title":"Therapeutic implications for sphingolipid metabolism in metabolic dysfunction-associated steatohepatitis","volume":"15","author":"Ramos-Molina","year":"2024","journal-title":"Front Endocrinol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"101774","DOI":"10.1016\/j.aohep.2024.101774","article-title":"Mechanisms and therapeutic targets of mitochondria in the progression of metabolic dysfunction-associated steatotic liver disease","volume":"30","author":"Mu","year":"2025","journal-title":"Ann Hepatol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"908","DOI":"10.3390\/antiox14080908","article-title":"Targeting Lipophagy in liver diseases: impact on oxidative stress and steatohepatitis","volume":"14","author":"Hwang","year":"2025","journal-title":"Antioxidants"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"138760","DOI":"10.1016\/j.ijbiomac.2024.138760","article-title":"The role of ALDHs in lipid peroxidation-related diseases","volume":"288","author":"Wang","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1038\/s41419-019-1678-y","article-title":"Hepatic ferroptosis plays an important role as the trigger for initiating inflammation in nonalcoholic steatohepatitis","volume":"10","author":"Tsurusaki","year":"2019","journal-title":"Cell Death Dis"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.freeradbiomed.2025.05.413","article-title":"CDKN1A and EGR1 are key genes for endoplasmic reticulum stress-induced ferroptosis in MASH","volume":"236","author":"Xu","year":"2025","journal-title":"Free Radic Biol Med"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"101414","DOI":"10.1016\/j.jhepr.2025.101414","article-title":"Inflammation in MASLD progression and cancer","volume":"7","author":"Kim","year":"2025","journal-title":"JHEP Rep."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s13679-025-00657-5","article-title":"The intriguing roles of cytokines in metabolic dysfunction-associated Steatotic liver disease: a narrative review","volume":"14","author":"Vachliotis","year":"2025","journal-title":"Curr Obes Rep"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"114020","DOI":"10.1016\/j.intimp.2025.114020","article-title":"SFAs facilitates ceramide's de novo synthesis via TLR4 and intensifies hepatocyte lipotoxicity","volume":"147","author":"Zou","year":"2025","journal-title":"Int Immunopharmacol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3390\/livers5020017","article-title":"The intestinal thread of fate: how the microbiota shapes the story of liver disease","volume":"5","author":"Acierno","year":"2025","journal-title":"Liver"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"101777","DOI":"10.1016\/j.aohep.2025.101777","article-title":"From gut to liver: exploring the crosstalk between gut-liver axis and oxidative stress in metabolic dysfunction-associated steatotic liver disease","volume":"30","author":"Zhou","year":"2025","journal-title":"Ann Hepatol"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00204-024-03889-x","article-title":"Metabolic dysfunction-associated steatotic liver disease-induced changes in the antioxidant system: a review","volume":"99","author":"Svobodov\u00e1","year":"2025","journal-title":"Arch Toxicol"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/s41575-020-00372-7","article-title":"Molecular and cellular mechanisms of liver fibrosis and its regression","volume":"18","author":"Kisseleva","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"C1637","DOI":"10.1152\/ajpcell.00951.2024","article-title":"Pathophysiological underpinnings of metabolic dysfunction-associated steatotic liver disease","volume":"328","author":"Kuchay","year":"2025","journal-title":"Am J Physiol Cell Physiol"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.7150\/thno.106597","article-title":"Metabolism of hepatic stellate cells in chronic liver diseases: emerging molecular and therapeutic interventions","volume":"15","author":"Yan","year":"2025","journal-title":"Theranostics"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1016\/j.jhep.2024.10.044","article-title":"Multi-modal analysis of human hepatic stellate cells identifies novel therapeutic targets for metabolic dysfunction-associated steatotic liver disease","volume":"82","author":"Kim","year":"2025","journal-title":"J Hepatol"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.3390\/life13112213","article-title":"Adiponectin: a promising target for the treatment of diabetes and its complications","volume":"13","author":"Begum","year":"2023","journal-title":"Life"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1007\/s11739-023-03374-w","article-title":"Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review","volume":"19","author":"Di Vincenzo","year":"2024","journal-title":"Intern Emerg Med"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"150292","DOI":"10.1016\/j.gene.2026.150292","article-title":"Hierarchical analysis of metabolic phenotype reveals distinct microbiota and circulatory transcriptome in metabolic dysfunction-associated steatotic liver disease","volume":"1009","author":"Tung","year":"2026","journal-title":"Gene"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1097\/js9.0000000000003576","article-title":"Decoding the triglyceride-glucose index in metabolic dysfunction-associated steatotic liver disease: integrative insights from Mendelian randomization, cross-tissue transcriptomics, and spatial multi-omics","volume":"112","author":"Wei","year":"2026","journal-title":"Int J Surg"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1097\/meg.0000000000003033","article-title":"Triglyceride glucose index as a causal risk factor for metabolic dysfunction-associated fatty liver disease: evidence from the National Health and 5 nutrition examination survey 2017-2020 and Mendelian randomization","volume":"37","author":"Su","year":"2025","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"100423","DOI":"10.1016\/j.metop.2025.100423","article-title":"Association between triglyceride glucose-body mass index and MASH, cardiovascular disease in MASLD patients: a cross-sectional study and machine learning analysis","volume":"28","author":"Tang","year":"2025","journal-title":"Metabol Open"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1186\/s12876-025-03877-0","article-title":"Associations between non-insulin-based insulin resistance surrogate markers and liver-related outcomes in metabolic dysfunction-associated steatotic liver disease: a nationwide cohort study in South Korea","volume":"25","author":"Moon","year":"2025","journal-title":"BMC Gastroenterol"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1857612\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T04:21:50Z","timestamp":1786422110000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1857612\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,11]]},"references-count":52,"alternative-id":["10.3389\/fmed.2026.1857612"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1857612","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,11]]},"article-number":"1857612"}}