Baoyin Li, Tao Liu, Zhijian Zhu, Bing Wang, Zhigang Lu, Yesheng Pan
{"title":"Association of hepatic biomarkers with incident diabetes: a mediation analysis of the triglyceride-glucose index in a large Chinese cohort.","authors":"Baoyin Li, Tao Liu, Zhijian Zhu, Bing Wang, Zhigang Lu, Yesheng Pan","doi":"10.1186/s12944-025-02661-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Diabetes disproportionately impacts low- and middle-income populations, exacerbating existing health disparities. The role of hepatic biomarkers, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the ALT/AST ratio, in predicting diabetes onset remains insufficiently elucidated. This research assessed how these biomarkers relate to diabetes risk, as well as assessed the mediating effect of the triglyceride-glucose (TyG) index.</p><p><strong>Methods: </strong>The secondary analysis utilized data from the Dryad public database, encompassing a cohort of 211,833 Chinese adults aged ≥ 20 years who underwent health examinations between 2010 and 2016. After applying rigorous exclusion criteria, 50,463 participants were included. Cox proportional hazards models were applied to examine how hepatic biomarkers and the TyG index influenced diabetes incidence. The mediation analysis was conducted to assess the TyG index's contribution to the hepatic biomarker-diabetes relationship.</p><p><strong>Results: </strong>Throughout the observational phase (mean 3.08 years), 1309 participants (2.59%) established diabetes. Increased levels of ALT, AST, and the ALT/AST ratio were all significantly related to a heightened diabetes risk, with the most significant correlation noted for the ALT/AST ratio (adjusted HR per unit increase: 1.04; 95% CI: 1.02-1.05; P < 0.001). Participants in the highest quartile of the ALT/AST ratio had nearly three times the risk of diabetes than the lowest quartile (HR: 2.94; 95% CI: 2.42-3.57; P < 0.001). Joint analysis revealed synergistic effects between elevated hepatic biomarkers and the TyG index, with the combination of high ALT/AST ratio and elevated TyG index yielding the greatest risk (HR: 5.23; 95% CI: 4.42-6.18; P < 0.001). The mediation analysis showed that the TyG index significantly mediated the associations, accounting for 40.25%, 36.45%, and 76.97% of the effects of ALT, AST, and the ALT/AST ratio, respectively, on diabetes risk.</p><p><strong>Conclusion: </strong>Hepatic biomarkers, particularly the ALT/AST ratio, robustly predict diabetes risk in this large cohort, with the TyG index explaining most of this association. These insights reinforce the importance of integrating hepatic and metabolic assessment in preventive strategies to address the growing diabetes epidemic.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"246"},"PeriodicalIF":3.9000,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278604/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lipids in Health and Disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12944-025-02661-z","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Diabetes disproportionately impacts low- and middle-income populations, exacerbating existing health disparities. The role of hepatic biomarkers, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the ALT/AST ratio, in predicting diabetes onset remains insufficiently elucidated. This research assessed how these biomarkers relate to diabetes risk, as well as assessed the mediating effect of the triglyceride-glucose (TyG) index.
Methods: The secondary analysis utilized data from the Dryad public database, encompassing a cohort of 211,833 Chinese adults aged ≥ 20 years who underwent health examinations between 2010 and 2016. After applying rigorous exclusion criteria, 50,463 participants were included. Cox proportional hazards models were applied to examine how hepatic biomarkers and the TyG index influenced diabetes incidence. The mediation analysis was conducted to assess the TyG index's contribution to the hepatic biomarker-diabetes relationship.
Results: Throughout the observational phase (mean 3.08 years), 1309 participants (2.59%) established diabetes. Increased levels of ALT, AST, and the ALT/AST ratio were all significantly related to a heightened diabetes risk, with the most significant correlation noted for the ALT/AST ratio (adjusted HR per unit increase: 1.04; 95% CI: 1.02-1.05; P < 0.001). Participants in the highest quartile of the ALT/AST ratio had nearly three times the risk of diabetes than the lowest quartile (HR: 2.94; 95% CI: 2.42-3.57; P < 0.001). Joint analysis revealed synergistic effects between elevated hepatic biomarkers and the TyG index, with the combination of high ALT/AST ratio and elevated TyG index yielding the greatest risk (HR: 5.23; 95% CI: 4.42-6.18; P < 0.001). The mediation analysis showed that the TyG index significantly mediated the associations, accounting for 40.25%, 36.45%, and 76.97% of the effects of ALT, AST, and the ALT/AST ratio, respectively, on diabetes risk.
Conclusion: Hepatic biomarkers, particularly the ALT/AST ratio, robustly predict diabetes risk in this large cohort, with the TyG index explaining most of this association. These insights reinforce the importance of integrating hepatic and metabolic assessment in preventive strategies to address the growing diabetes epidemic.
期刊介绍:
Lipids in Health and Disease is an open access, peer-reviewed, journal that publishes articles on all aspects of lipids: their biochemistry, pharmacology, toxicology, role in health and disease, and the synthesis of new lipid compounds.
Lipids in Health and Disease is aimed at all scientists, health professionals and physicians interested in the area of lipids. Lipids are defined here in their broadest sense, to include: cholesterol, essential fatty acids, saturated fatty acids, phospholipids, inositol lipids, second messenger lipids, enzymes and synthetic machinery that is involved in the metabolism of various lipids in the cells and tissues, and also various aspects of lipid transport, etc. In addition, the journal also publishes research that investigates and defines the role of lipids in various physiological processes, pathology and disease. In particular, the journal aims to bridge the gap between the bench and the clinic by publishing articles that are particularly relevant to human diseases and the role of lipids in the management of various diseases.