{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T19:36:09Z","timestamp":1781292969714,"version":"3.54.1"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"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>Objective<\/jats:title>\n                    <jats:p>Despite the AST\/ALT ratio emerging as a promising diabetes predictor, current research lacks comprehensive understanding of population-specific patterns and underlying mechanisms. This study aims to investigate the AST\/ALT-diabetes risk relationship in Chinese and Japanese populations, specifically examining non-linear relationships, population-specific thresholds, and BMI\u2019s potential mediating role to address existing knowledge gaps.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a retrospective cohort analysis using data from the China Rich Healthcare Group (n=84,281) and Japanese NAGALA database (n=15,291). AST\/ALT ratio was calculated by dividing AST concentration by ALT concentration. Diabetes was defined by fasting plasma glucose \u22657.00mmol\/L or self-reported diagnosis. We employed Cox proportional hazards models, including restricted cubic splines to explore non-linear relationships, two-piecewise regression for identifying population-specific thresholds, and mediation analysis to quantify BMI\u2019s mediating effect on the AST\/ALT-diabetes risk association.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In a cohort of 99,572 participants with 1,403 new diabetes cases, AST\/ALT showed a significant negative association with diabetes risk across Chinese and Japanese populations (HR per unit increase: Chinese: 0.417, 95% CI: 0.341-0.510; Japanese: 0.631, 95% CI: 0.416-0.956). Country-specific variations were evident, with distinct non-linear relationships: Chinese participants exhibited risk reduction until AST\/ALT reached 0.912, while Japanese participants showed an inflection point at 0.882. BMI\u2019s mediating effect differed markedly between populations, with a higher proportion in Japanese participants (32.22%), suggesting nuanced pathophysiological mechanisms underlying the AST\/ALT-diabetes relationship.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study unveils significant ethnic variations in the AST\/ALT-diabetes interaction, highlighting population-specific diagnostic thresholds and mediation mechanisms. These insights advocate for customized screening approaches and suggest that AST\/ALT and BMI-targeted interventions may yield differential outcomes across East Asian populations, emphasizing the critical need for precision-based medical strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1704211","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T06:55:42Z","timestamp":1768892142000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Association between the ratio of aspartate aminotransferase to alanine aminotransferase and risk of diabetes and the mediating effect of BMI: a comparative analysis in Chinese and Japanese populations"],"prefix":"10.3389","volume":"16","author":[{"given":"Mengyao","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Shenzhen University","place":["Shenzhen, Guangdong, China"]},{"name":"Department of Laboratory Medicine, Shenzhen Second People\u2019s Hospital","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Shenzhen University","place":["Shenzhen, Guangdong, China"]},{"name":"Department of Laboratory Medicine, Shenzhen Second People\u2019s Hospital","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuheng","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of Shenzhen University","place":["Shenzhen, Guangdong, China"]},{"name":"Department of Nephrology, Shenzhen Second People\u2019s Hospital","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haofei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of Shenzhen University","place":["Shenzhen, Guangdong, China"]},{"name":"Department of Nephrology, Shenzhen Second People\u2019s Hospital","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayong","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Shenzhen Key Laboratory of Medical Laboratory and Molecular Diagnostics, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People\u2019s Hospital, Medical Innovation Technology Transformation Center of Shenzhen Second People\u2019s Hospital, Shenzhen University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3554","DOI":"10.3390\/ijms24043554","article-title":"Peripheral neuropathy in diabetes mellitus: pathogenetic mechanisms and diagnostic options","volume":"24","author":"Galiero","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B2","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1146\/annurev.pathol.4.110807.092150","article-title":"A glimpse of various pathogenetic mechanisms of diabetic nephropathy","volume":"6","author":"Kanwar","year":"2011","journal-title":"Annu Rev Pathol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(25)00299-2","article-title":"11th edition of the IDF Diabetes Atlas: global, regional, and national diabetes prevalence estimates for 2024 and projections for 2050","author":"Genitsaridi","year":"2025","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1186\/s12967-023-04006-9","article-title":"J-shape relationship between normal fasting plasma glucose and risk of type 2 diabetes in the general population: results from two cohort studies","volume":"21","author":"He","year":"2023","journal-title":"J Transl Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2011.72","article-title":"Nonalcoholic fatty liver disease and diabetes mellitus: pathogenesis and treatment","volume":"7","author":"Smith","year":"2011","journal-title":"Nat Rev Endocrinol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1016\/j.cgh.2024.03.006","article-title":"The global epidemiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among patients with type 2 diabetes","volume":"22","author":"Younossi","year":"2024","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2016.01.001","article-title":"Non-alcoholic fatty liver disease and diabetes","volume":"65","author":"Hazlehurst","year":"2016","journal-title":"Metabolism"},{"key":"B8","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/j.jhep.2019.06.021","article-title":"The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis","volume":"71","author":"Younossi","year":"2019","journal-title":"J Hepatol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13264","article-title":"Nonalcoholic fatty liver disease is associated with an almost twofold increased risk\u00a0of\u00a0incident type 2 diabetes and metabolic syndrome. Evidence from a systematic review and meta-analysis","volume":"31","author":"Ballestri","year":"2016","journal-title":"J Gastroenterol Hepatol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1017448","article-title":"AST-to-ALT ratio in the first trimester and the risk of gestational diabetes mellitus","volume":"13","author":"An","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B11","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/1475-2840-11-117","article-title":"Alanine aminotransferase\/aspartate aminotransferase ratio is the best surrogate marker for insulin resistance in non-obese Japanese adults","volume":"11","author":"Kawamoto","year":"2012","journal-title":"Cardiovasc Diabetol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000173404.37692.9b","article-title":"Elevated serum aminotransferase level as a predictor of intracerebral hemorrhage: Korea medical insurance corporation study","volume":"36","author":"Kim","year":"2005","journal-title":"Stroke"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50229","article-title":"Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values","volume":"37","author":"Mofrad","year":"2003","journal-title":"Hepatology"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2013.10.002","article-title":"Aspartate aminotransferase: an old dog teaches new tricks","volume":"544","author":"Toney","year":"2014","journal-title":"Arch Biochem Biophys"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2020.0069","article-title":"Macro-aspartate aminotransferase in a healthy woman","volume":"26","author":"Lorubbio","year":"2020","journal-title":"Clin Mol Hepatol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.21.5.732","article-title":"Prospective study of serum gamma-glutamyltransferase and risk of NIDDM","volume":"21","author":"Perry","year":"1998","journal-title":"Diabetes Care"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.28.7.1757","article-title":"Liver enzymes, the metabolic syndrome, and incident diabetes: the Mexico City diabetes study","volume":"28","author":"Nannipieri","year":"2005","journal-title":"Diabetes Care"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.6.1889","article-title":"High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes","volume":"51","author":"Vozarova","year":"2002","journal-title":"Diabetes"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2007.218","article-title":"Liver enzymes as a predictor for incident diabetes in a Japanese population: the Hisayama study","volume":"15","author":"Doi","year":"2007","journal-title":"Obes (Silver Spring)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.2337\/dc07-2184","article-title":"Liver enzymes compared with alcohol consumption in predicting the risk of type 2 diabetes: the Kansai Healthcare Study","volume":"31","author":"Sato","year":"2008","journal-title":"Diabetes Care"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kws469","article-title":"Liver aminotransferases and risk of incident type 2 diabetes: a systematic review and meta-analysis","volume":"178","author":"Kunutsor","year":"2013","journal-title":"Am J Epidemiol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1016\/j.cgh.2016.03.034","article-title":"Development and validation of the framingham steatosis index to identify persons with hepatic steatosis","volume":"14","author":"Long","year":"2016","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1186\/s12944-020-01419-z","article-title":"Association between the alanine aminotransferase\/aspartate aminotransferase ratio and new-onset non-alcoholic fatty liver disease in a nonobese Chinese population: a population-based longitudinal study","volume":"19","author":"Zou","year":"2020","journal-title":"Lipids Health Dis"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e0161304","DOI":"10.1371\/journal.pone.0161304","article-title":"Incremental predictive value of serum AST-to-ALT ratio for incident metabolic syndrome: the ARIRANG study","volume":"11","author":"Yadav","year":"2016","journal-title":"PloS One"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1177\/00033197211004410","article-title":"AST\/ALT ratio and peripheral artery disease in a chinese hypertensive population: A cross-sectional study","volume":"72","author":"Liu","year":"2021","journal-title":"Angiology"},{"key":"B26","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1186\/s12882-020-02144-6","article-title":"Elevated alanine aminotransferase and low aspartate aminotransferase\/alanine aminotransferase ratio are associated with chronic kidney disease among middle-aged women: a cross-sectional study","volume":"21","author":"Ochiai","year":"2020","journal-title":"BMC Nephrol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0000000000000811","article-title":"Insulin resistance is associated with elevated transaminases and low aspartate aminotransferase\/alanine aminotransferase ratio in young adults with normal weight","volume":"29","author":"Simental-Mend\u00eda","year":"2017","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1055\/a-0752-0217","article-title":"A high alanine aminotransferase\/aspartate aminotransferase ratio determines insulin resistance and metabolically healthy\/unhealthy obesity in a general adult population in korea: the korean national health and nutritional examination survey 2007-2010","volume":"127","author":"Kwon","year":"2019","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"B29","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s12986-017-0219-x","article-title":"Serum alanine aminotransferase\/aspartate aminotransferase ratio is one of the best markers of insulin resistance in the Chinese population","volume":"14","author":"Zhao","year":"2017","journal-title":"Nutr Metab (Lond)"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i24.7478","article-title":"Increased liver markers are associated with higher risk of type 2 diabetes","volume":"21","author":"Ko","year":"2015","journal-title":"World J Gastroenterol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"e3553","DOI":"10.1002\/dmrr.3553","article-title":"Low aspartate aminotransferase\/alanine aminotransferase ratio is a predictor of diabetes incidence in Japanese people: Population-based Panasonic cohort study 5","volume":"38","author":"Nakajima","year":"2022","journal-title":"Diabetes Metab Res Rev"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S337416","article-title":"Association between aspartate aminotransferase to alanine aminotransferase ratio and incidence of type 2 diabetes mellitus in the Japanese population: A secondary analysis of a retrospective cohort study","volume":"14","author":"Chen","year":"2021","journal-title":"Diabetes Metab Syndr Obes"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2022.1049804","article-title":"Low aspartate aminotransferase\/alanine aminotransferase (DeRitis) ratio assists in predicting diabetes in Chinese population","volume":"10","author":"Xie","year":"2022","journal-title":"Front Public Health"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1041616","article-title":"Nonlinear relationship between aspartate aminotransferase to alanine aminotransferase ratio and the risk of prediabetes: A retrospective study based on chinese adults","volume":"13","author":"Cao","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B35","doi-asserted-by":"publisher","first-page":"7853","DOI":"10.1038\/s41598-023-35001-1","article-title":"Associations of alanine aminotransferase\/aspartate aminotransferase with insulin resistance and \u03b2-cell function in women","volume":"13","author":"Minato-Inokawa","year":"2023","journal-title":"Sci Rep"},{"key":"B36","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1016\/S2213-8587(19)30318-3","article-title":"Diabetes clusters and risk of diabetes-associated diseases","volume":"7","author":"Liu","year":"2019","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)62154-6","article-title":"Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future","volume":"383","author":"Kahn","year":"2014","journal-title":"Lancet"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2025.1584626","article-title":"A study on predicting impaired fasting glucose risk in Chinese adults based on individual characteristics","volume":"12","author":"Lin","year":"2025","journal-title":"Front Med (Lausanne)"},{"key":"B39","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1186\/s12876-021-01809-2","article-title":"Clinical characteristics and longitudinal changes of patients with non-alcoholic fatty liver disease in 2 decades: the NAGALA study","volume":"21","author":"Okamura","year":"2021","journal-title":"BMC Gastroenterol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e021768","DOI":"10.1136\/bmjopen-2018-021768","article-title":"Association of body mass index and age with incident diabetes in Chinese adults: a population-based cohort study","volume":"8","author":"Chen","year":"2018","journal-title":"BMJ Open"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/s41366-018-0076-3","article-title":"Ectopic\u00a0fat obesity presents the greatest risk for incident type 2 diabetes: a population-based longitudinal study","volume":"43","author":"Okamura","year":"2019","journal-title":"Int J Obes (Lond)"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2012410","article-title":"Observational study of hydroxychloroquine in hospitalized patients with covid-19","volume":"382","author":"Geleris","year":"2020","journal-title":"N Engl J Med"},{"key":"B43","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1007\/s00508-019-1450-4","article-title":"Diabetes mellitus-Definition, classification, diagnosis, screening and prevention (Update 2019)","volume":"131","author":"Harreiter","year":"2019","journal-title":"Wien Klin Wochenschr"},{"key":"B44","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s12933-025-02605-y","article-title":"Association between the atherogenic index of plasma and long-term risk of type 2 diabetes: a 12-year cohort study based on the Japanese population","volume":"24","author":"Zhou","year":"2025","journal-title":"Cardiovasc Diabetol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s12944-020-01213-x","article-title":"Association of Triglyceride to high-density lipoprotein cholesterol ratio and incident of diabetes mellitus: a secondary retrospective analysis based on a Chinese cohort study","volume":"19","author":"Chen","year":"2020","journal-title":"Lipids Health Dis"},{"key":"B46","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s12902-024-01594-5","article-title":"Lipids as potential mediators linking body mass index to diabetes: evidence from a mediation analysis based on the NAGALA cohort","volume":"24","author":"Lu","year":"2024","journal-title":"BMC Endocr Disord"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.110977","article-title":"Missing covariate data in clinical research: when and when not to use the missing-indicator method for analysis","volume":"184","author":"Groenwold","year":"2012","journal-title":"Cmaj"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4067","article-title":"Multiple imputation using chained equations: Issues and guidance for practice","volume":"30","author":"White","year":"2011","journal-title":"Stat Med"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780111003","article-title":"Collinearity diagnosis for a relative risk regression analysis: an application to assessment of diet-cancer relationship in epidemiological studies","volume":"11","author":"Wax","year":"1992","journal-title":"Stat Med"},{"key":"B50","doi-asserted-by":"publisher","first-page":"e26590","DOI":"10.1097\/MD.0000000000026590","article-title":"Personality as a predictor of HbA1c level in patients with type 2 diabetes mellitus","volume":"100","author":"Lee","year":"2021","journal-title":"Med (Baltimore)"},{"key":"B51","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/pedi.12787","article-title":"Does obesity cause type 2 diabetes mellitus (T2DM)? Or is it the opposite","volume":"20","author":"Malone","year":"2019","journal-title":"Pediatr Diabetes"},{"key":"B52","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1186\/s12967-019-02156-3","article-title":"Triglyceride is an independent predictor of type 2 diabetes among middle-aged and older adults: a prospective study with 8-year follow-ups in two cohorts","volume":"17","author":"Zhao","year":"2019","journal-title":"J Transl Med"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1080\/17470218.2015.1115884","article-title":"Explanation in causal inference: Methods for mediation and interaction","volume":"69","author":"B\u00f6hnke","year":"2016","journal-title":"Q J Exp Psychol (Hove)"},{"key":"B54","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1146\/annurev-publhealth-032315-021402","article-title":"Mediation analysis: A practitioner\u2019s guide","volume":"37","author":"VanderWeele","year":"2016","journal-title":"Annu Rev Public Health"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyt127","article-title":"Mediation analysis in epidemiology: methods, interpretation and bias","volume":"42","author":"Richiardi","year":"2013","journal-title":"Int J Epidemiol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1037\/a0020761","article-title":"A general approach to causal mediation analysis","volume":"15","author":"Imai","year":"2010","journal-title":"Psychol Methods"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.726","article-title":"Diabetes in Asia: epidemiology, risk factors, and pathophysiology","volume":"301","author":"Chan","year":"2009","journal-title":"Jama"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.2010.29512","article-title":"Rice intake and type 2 diabetes in Japanese men and women: the Japan Public Health Center-based Prospective Study","volume":"92","author":"Nanri","year":"2010","journal-title":"Am J Clin Nutr"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-0132","article-title":"Psychosocial stress at work doubles the risk of type 2 diabetes in middle-aged women: evidence from the Whitehall II study","volume":"32","author":"Heraclides","year":"2009","journal-title":"Diabetes Care"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1038\/ng.660","article-title":"A genome-wide association study in the Japanese population identifies susceptibility loci for type 2 diabetes at UBE2E2 and C2CD4A-C2CD4B","volume":"42","author":"Yamauchi","year":"2010","journal-title":"Nat Genet"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.5551\/jat.22913","article-title":"Utility of the triglyceride level for predicting incident diabetes mellitus according to the fasting status and body mass index category: the Ibaraki Prefectural Health Study","volume":"21","author":"Fujihara","year":"2014","journal-title":"J Atheroscler Thromb"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2009.08.002","article-title":"Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease","volume":"42","author":"Lee","year":"2010","journal-title":"Dig Liver Dis"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-00306","article-title":"Changes over time in hepatic markers predict changes in insulin sensitivity, \u03b2-cell function, and glycemia","volume":"103","author":"Pinnaduwage","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"B64","doi-asserted-by":"publisher","first-page":"16227","DOI":"10.1038\/s41598-020-73263-1","article-title":"ALDH2 genotype modulates the association between alcohol consumption and AST\/ALT ratio among middle-aged Japanese men: a genome-wide G\u2009\u00d7\u2009E interaction analysis","volume":"10","author":"Sutoh","year":"2020","journal-title":"Sci Rep"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-0495(99)90145-2","article-title":"Association of beta3-adrenergic receptor gene polymorphism with insulin resistance in Japanese-American men","volume":"48","author":"Kawamura","year":"1999","journal-title":"Metabolism"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2024.1472451","article-title":"Burden of diet-related chronic diseases in Chinese and Japanese adults attributable to dietary risk factors from 1990 to 2021: a systematic analysis of the Global Burden of Disease Study 2021","volume":"11","author":"Wang","year":"2024","journal-title":"Front Nutr"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-2667(22)00207-9","article-title":"Challenges in screening and general health checks in China","volume":"7","author":"Gong","year":"2022","journal-title":"Lancet Public Health"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2007.01281.x","article-title":"Japan\u2019s universal long-term care system reform of 2005: containing costs and realizing a vision","volume":"55","author":"Tsutsui","year":"2007","journal-title":"J Am Geriatr Soc"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0000000000002215","article-title":"Association between aspartate aminotransferase-to-alanine aminotransferase ratio and insulin resistance among US adults","volume":"34","author":"Visaria","year":"2022","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2018.0014","article-title":"Development and validation of the korean diabetes risk score: A 10-year national cohort study","volume":"42","author":"Ha","year":"2018","journal-title":"Diabetes Metab J"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(03)00611-8","article-title":"Role of endothelial dysfunction in insulin resistance","volume":"92","author":"Hsueh","year":"2003","journal-title":"Am J Cardiol"},{"key":"B72","doi-asserted-by":"publisher","first-page":"270","DOI":"10.3390\/antiox10020270","article-title":"Mechanisms of non-alcoholic fatty liver disease in the metabolic syndrome. A narrative review","volume":"10","author":"Rinaldi","year":"2021","journal-title":"Antioxid (Basel)"},{"key":"B73","doi-asserted-by":"publisher","first-page":"287","DOI":"10.37349\/emed.2020.00019","article-title":"Nonalcoholic fatty liver disease and type 2 diabetes: pathophysiological mechanisms shared between the two faces of the same coin","volume":"1","author":"Acierno","year":"2020","journal-title":"Explor Med"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.241984","article-title":"Insulin resistance: metabolic mechanisms and consequences in the heart","volume":"32","author":"Abel","year":"2012","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B75","doi-asserted-by":"publisher","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":"B76","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1186\/s12933-023-01876-7","article-title":"Normal-weight visceral obesity promotes a higher 10-year atherosclerotic cardiovascular disease risk in patients with type 2 diabetes mellitus-a multicenter study in China","volume":"22","author":"Zheng","year":"2023","journal-title":"Cardiovasc Diabetol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.192644","article-title":"Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity","volume":"120","author":"Alberti","year":"2009","journal-title":"Circulation"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1704211\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T07:38:22Z","timestamp":1771918702000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1704211\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,20]]},"references-count":77,"alternative-id":["10.3389\/fendo.2025.1704211"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1704211","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,20]]},"article-number":"1704211"}}