{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T04:46:14Z","timestamp":1785732374889,"version":"3.56.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFC3506305"],"award-info":[{"award-number":["2024YFC3506305"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"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>The triglyceride-glucose (TyG) index is an established surrogate marker of insulin resistance. However, most evidence has relied on a single baseline measurement and may not fully capture long-term metabolic exposure. This study examined whether longitudinal TyG trajectories are independently associated with subsequent incident type 2 diabetes mellitus (T2DM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective longitudinal cohort study used repeated health examination data from adults without diabetes at baseline between 2011 and 2025. TyG trajectories were identified using latent class mixed models based on repeated TyG measurements. Follow-up for incident T2DM began after the third eligible TyG measurement to preserve temporal ordering between exposure assessment and outcome occurrence. Multivariable Cox proportional hazards models with multiple imputation were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic splines and time-dependent area under the curve (AUC) analyses were used for dose-response and predictive performance assessments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 16, 751 participants included in trajectory modeling, three TyG trajectory groups were identified and ordered by mean TyG level: low-ascending (G1), moderate-ascending (G2), and high-persistent (G3). A total of 10, 163 participants contributed follow-up after the third-visit landmark, among whom 430 incident T2DM events were recorded. Incidence rates were 2.90, 13.47, and 37.25 per 1, 000 person-years in G1, G2, and G3, respectively. In the main adjusted model, compared with G1, both G2 (HR\u00a0=\u00a02.27, 95% CI: 1.64-3.14) and G3 (HR\u00a0=\u00a05.40, 95% CI: 3.87-7.53) were associated with higher risks of incident T2DM (both P &amp;lt; 0.001). A graded association was observed across trajectory levels (HR per level increase = 2.34, 95% CI: 2.01-2.72; P &amp;lt; 0.001). Adding TyG information provided modest incremental discrimination beyond the base clinical model, with limited additional improvement over baseline TyG alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Longitudinal TyG trajectories identified distinct diabetes risk strata among adults undergoing repeated health examinations. A high-persistent TyG trajectory was associated with increased risk of incident T2DM after the landmark time point, supporting the potential value of monitoring TyG dynamics for early risk stratification in routine care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1895734","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T04:26:14Z","timestamp":1785731174000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal trajectories of the triglyceride-glucose index and risk of incident type 2 diabetes in adults undergoing repeated health examinations"],"prefix":"10.3389","volume":"17","author":[{"given":"Nanping","family":"Mao","sequence":"first","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoli","family":"Wang","sequence":"additional","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingna","family":"Jin","sequence":"additional","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]},{"name":"Health Management Center, Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyun","family":"He","sequence":"additional","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Wu","sequence":"additional","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]},{"name":"Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/obr.13593","article-title":"The burden of type 2 diabetes mellitus in states of the european union and United Kingdom at the national and subnational levels: A systematic review","volume":"24","author":"Soares Andrade","year":"2023","journal-title":"Obes Rev Off J Int Assoc Study Obes"},{"key":"B2","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/s41572-026-00687-w","article-title":"Type 2 diabetes mellitus","volume":"12","author":"Davies","year":"2026","journal-title":"Nat Rev Dis Primer"},{"key":"B3","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/S2213-8587(19)30147-0","article-title":"Insulin resistance underlying type 2 diabetes","volume":"7","author":"Lima","year":"2019","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-025-01114-y","article-title":"Insulin resistance in type 2 diabetes mellitus","volume":"21","author":"Accili","year":"2025","journal-title":"Nat Rev Endocrinol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2020.154263","article-title":"Multi-year reproducibility of hyperinsulinemic euglycemic clamp-derived insulin sensitivity in free-living adults: Association with incident prediabetes in the POP-ABC study","volume":"109","author":"James","year":"2020","journal-title":"Metabolism"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2021.109042","article-title":"The triglyceride-glucose index is a more powerful surrogate marker for predicting the prevalence and incidence of type 2 diabetes mellitus than the homeostatic model assessment of insulin resistance","volume":"180","author":"Park","year":"2021","journal-title":"Diabetes Res Clin Pract"},{"key":"B7","doi-asserted-by":"publisher","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":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2018.06.006","article-title":"The role of triglyceride glucose index in development of type 2 diabetes mellitus","volume":"143","author":"Low","year":"2018","journal-title":"Diabetes Res Clin Pract"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpc.2025.100996","article-title":"Prognostic value of triglyceride-glucose index on predicting major adverse cardiovascular events in hypertensive patients: A systematic review and meta-analysis","volume":"22","author":"Dakota","year":"2025","journal-title":"Am J Prev Cardiol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s12933-025-02585-z","article-title":"Does diabetes modify the triglyceride-glucose index associated with cardiovascular events and mortality? A meta-analysis of 50 cohorts involving 7,239,790 participants","volume":"24","author":"Zhang","year":"2025","journal-title":"Cardiovasc Diabetol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13516","article-title":"Long-term insulin resistance is associated with frailty, frailty progression, and cardiovascular disease","volume":"15","author":"Ke","year":"2024","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.145","article-title":"The impact of insulin resistance on the kidney and vasculature","volume":"12","author":"Artunc","year":"2016","journal-title":"Nat Rev Nephrol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s12933-021-01319-1","article-title":"Triglyceride-glucose index in the development of peripheral artery disease: Findings from the atherosclerosis risk in communities (ARIC) study","volume":"20","author":"Gao","year":"2021","journal-title":"Cardiovasc Diabetol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3803\/EnM.2024.2271","article-title":"The triglyceride-glucose index and risk of end-stage renal disease across different durations of type 2 diabetes mellitus: A longitudinal cohort study","volume":"40","author":"Kim","year":"2025","journal-title":"Endocrinol Metab"},{"key":"B15","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1186\/s12933-023-02002-3","article-title":"Association of triglyceride-glucose index trajectory and frailty in urban older residents: Evidence from the 10-year follow-up in a cohort study","volume":"22","author":"Yuan","year":"2023","journal-title":"Cardiovasc Diabetol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1186\/s12933-025-02693-w","article-title":"Association between triglyceride glucose-body mass index and the trajectory of cardio-renal-metabolic multimorbidity: Insights from multi-state modelling","volume":"24","author":"Tang","year":"2025","journal-title":"Cardiovasc Diabetol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1186\/s12933-022-01577-7","article-title":"Triglyceride-glucose index trajectory and stroke incidence in patients with hypertension: A prospective cohort study","volume":"21","author":"Huang","year":"2022","journal-title":"Cardiovasc Diabetol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s12944-021-01532-7","article-title":"Triglyceride glucose-body mass index and the risk of diabetes: A general population-based cohort study","volume":"20","author":"Wang","year":"2021","journal-title":"Lipids Health Dis"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-7568(22)00247-1","article-title":"Association of the triglyceride glucose index as a measure of insulin resistance with mortality and cardiovascular disease in populations from five continents (PURE study): A prospective cohort study","volume":"4","author":"Lopez-Jaramillo","year":"2023","journal-title":"Lancet Healthy Longev"},{"key":"B20","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.ejim.2024.08.026","article-title":"Triglyceride glucose (TyG) index: A promising biomarker for diagnosis and treatment of different diseases","volume":"131","author":"Sun","year":"2025","journal-title":"Eur J Intern Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2012.04.010","article-title":"Classifying developmental trajectories over time should be done with great caution: A comparison between methods","volume":"65","author":"Twisk","year":"2012","journal-title":"J Clin Epidemiol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1186\/s12944-020-01403-7","article-title":"Association between triglyceride-glucose index and risk of incident diabetes: a secondary analysis based on a Chinese cohort study: TyG index and incident diabetes","volume":"19","author":"Li","year":"2020","journal-title":"Lipids Health Dis"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1054741","article-title":"Visit-to-visit variability in triglyceride-glucose index and diabetes: A 9-year prospective study in the Kailuan Study","volume":"13","author":"Wang","year":"2022","journal-title":"Front Endocrinol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1295641","article-title":"Non-linear association of triglyceride-glucose index with prevalence of prediabetes and diabetes: a cross-sectional study","volume":"14","author":"Zhang","year":"2023","journal-title":"Front Endocrinol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1259062","article-title":"Impact of the baseline insulin resistance surrogates and their longitudinal trajectories on cardiovascular disease (coronary heart disease and stroke): A prospective cohort study in rural China","volume":"14","author":"Wang","year":"2023","journal-title":"Front Endocrinol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1042\/BST0360348","article-title":"Fatty acids and glucolipotoxicity in the pathogenesis of Type 2 diabetes","volume":"36","author":"Cnop","year":"2008","journal-title":"Biochem Soc Trans"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/apt.17930","article-title":"Pathogenesis of MASLD and MASH - role of insulin resistance and lipotoxicity","author":"Bansal","year":"2024","journal-title":"Aliment Pharmacol Ther"},{"key":"B28","doi-asserted-by":"publisher","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 Biomedecine Pharmacother"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-008-0032-z","article-title":"Ectopic fat and insulin resistance","volume":"8","author":"Lettner","year":"2008","journal-title":"Curr Diabetes Rep"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2022.109159","article-title":"Adipose extracellular matrix deposition is an indicator of obesity and metabolic disorders","volume":"111","author":"Chen","year":"2023","journal-title":"J Nutr Biochem"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.034","article-title":"Endoplasmic reticulum stress and the inflammatory basis of metabolic disease","volume":"140","author":"Hotamisligil","year":"2010","journal-title":"Cell"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1210\/er.2007-0023","article-title":"Glucolipotoxicity: fuel excess and beta-cell dysfunction","volume":"29","author":"Poitout","year":"2008","journal-title":"Endocr Rev"},{"key":"B33","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.ahj.2022.02.014","article-title":"Distinct triglyceride-glucose trajectories are associated with different risks of incident cardiovascular disease in normal-weight adults","volume":"248","author":"Tian","year":"2022","journal-title":"Am Heart J"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.2007.s119","article-title":"Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes","author":"Robertson","year":"2004","journal-title":"Diabetes"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1895734\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T04:26:15Z","timestamp":1785731175000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1895734\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,3]]},"references-count":34,"alternative-id":["10.3389\/fendo.2026.1895734"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1895734","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,3]]},"article-number":"1895734"}}