{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:47:58Z","timestamp":1785757678853,"version":"3.56.0"},"reference-count":53,"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\/"}],"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>Insulin resistance (IR) constitutes a central pathophysiological mechanism underlying a spectrum of chronic metabolic disorders. The Metabolic Score for Insulin Resistance (METS-IR), which integrates fasting blood glucose (FBG), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and body mass index (BMI), serves as a simple, cost-effective surrogate marker for IR. However, its associations with type 2 diabetes mellitus (T2DM), cancer, and all-cause mortality remain to be systematically synthesized. This study aims to systematically evaluate its clinical prognostic value.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically searched PubMed, EMBASE, and Web of Science for prospective or retrospective cohort studies evaluating the associations of baseline METS-IR with incident T2DM, cancer, or all-cause mortality. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using random-effects models, and linear and nonlinear dose-response meta-analyses were performed. Heterogeneity, robustness, and publication bias were additionally assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 23 cohort studies were included. For T2DM (6 studies), the highest METS-IR category was associated with a substantially elevated risk compared with the lowest category (HR\u00a0=\u00a04.03, 95% CI: 2.57\u20136.33), and per 1-standard deviation (1-SD) increment in METS-IR corresponded to a 48% higher risk (HR\u00a0=\u00a01.48, 95% CI: 1.24\u20131.77); dose-response analysis revealed a significant nonlinear increasing relationship (\n                      <jats:italic>P<\/jats:italic>\n                      for nonlinearity&amp;lt; 0.001). For cancer (5 studies), per 1-SD increment in METS-IR was associated with a 21% higher risk of cancer (HR\u00a0=\u00a01.21, 95% CI: 1.10\u20131.34); dose-response analysis indicated a significant nonlinear association (\n                      <jats:italic>P<\/jats:italic>\n                      for nonlinearity = 0.042). For all-cause mortality (13 studies), per 1-SD rise in METS-IR was linked to an 8% increased risk of all-cause death (HR\u00a0=\u00a01.08, 95% CI: 1.03\u20131.14); dose-response analysis demonstrated an overall linear increasing trend (\n                      <jats:italic>P<\/jats:italic>\n                      for linearity = 0.029), with each 20-unit increase in METS-IR associated with an approximately 2.8% higher risk of all-cause mortality (HR\u00a0=\u00a01.028, 95% CI: 1.004\u20131.056).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Elevated METS-IR levels are significantly associated with a nonlinear, progressive increase in the risk of incident T2DM. Its associations with cancer and all-cause mortality are weaker and more complex yet still exhibit consistent directional trends. METS-IR represents a convenient, readily applicable tool for early identification of metabolic risk using routine clinical parameters; however, its prognostic value for cancer and all-cause mortality merits further validation in large-scale, long-term follow-up studies.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>Systematic review registration<\/jats:title>\n                      <jats:p>PROSPERO, identifier CRD420261293948.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1884402","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:19:11Z","timestamp":1785755951000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Associations of metabolic score for insulin resistance with type 2 diabetes, cancer, and all-cause mortality: a meta-analysis of cohort studies"],"prefix":"10.3389","volume":"17","author":[{"given":"Feng","family":"Guo","sequence":"first","affiliation":[{"name":"Faculty of Nursing, Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Liu","sequence":"additional","affiliation":[{"name":"Faculty of Nursing, Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyi","family":"Sun","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajing","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Faculty of Nursing, Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangxue","family":"Feng","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)02750-2","article-title":"Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults","volume":"403","year":"2024","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(24)00150-5","article-title":"National, regional, and global trends in insufficient physical activity among adults from 2000 to 2022: a pooled analysis of 507 population-based surveys with 5.7 million participants","volume":"12","author":"Strain","year":"2024","journal-title":"Lancet Glob Health"},{"key":"B3","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1038\/s41467-025-67268-5","article-title":"Worldwide trends in metabolic syndrome from 2000 to 2023: a systematic review and modelling analysis","volume":"17","author":"Noubiap","year":"2025","journal-title":"Nat Commun"},{"key":"B4","doi-asserted-by":"publisher","first-page":"15","DOI":"10.4093\/dmj.2021.0280","article-title":"Insulin resistance: from mechanisms to therapeutic strategies","volume":"46","author":"Lee","year":"2022","journal-title":"Diabetes Metab J"},{"key":"B5","doi-asserted-by":"publisher","first-page":"998","DOI":"10.3390\/curroncol31020075","article-title":"Insulin resistance: the increased risk of cancers","volume":"31","author":"Szablewski","year":"2024","journal-title":"Curr Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/oby.23503","article-title":"Measuring and estimating insulin resistance in clinical and research settings","volume":"30","author":"Gastaldelli","year":"2022","journal-title":"Obes (Silver Spring)"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/jch.14449","article-title":"Correlation between non-insulin-based insulin resistance indexes and the risk of prehypertension: a cross-sectional study","volume":"24","author":"Zhang","year":"2022","journal-title":"J Clin Hypertens (Greenwich)"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-17-0883","article-title":"METS-IR, a novel score to evaluate insulin sensitivity, is predictive of visceral adiposity and incident type 2 diabetes","volume":"178","author":"Bello-Chavolla","year":"2018","journal-title":"Eur J Endocrinol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0336388","article-title":"Relationship of the metabolic score for insulin resistance and the new-onset hypertension: evidence from CHARLS","volume":"20","author":"Ma","year":"2025","journal-title":"PloS One"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2022.0099","article-title":"The usefulness of metabolic score for insulin resistance for the prediction of incident non-alcoholic fatty liver disease in Korean adults","volume":"28","author":"Lee","year":"2022","journal-title":"Clin Mol Hepatol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1699985","article-title":"Metabolic score for insulin resistance and the incidence of cardiovascular disease: a meta-analysis of cohort studies","volume":"16","author":"He","year":"2025","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1427727","article-title":"Association between different insulin resistance indices and all-cause mortality in patients with diabetic kidney disease: a prospective cohort study","volume":"15","author":"Zhu","year":"2025","journal-title":"Front Endocrinol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1186\/s40170-024-00344-4","article-title":"Glycemic status, insulin resistance, and mortality from lung cancer among individuals with and without diabetes","volume":"12","author":"Cho","year":"2024","journal-title":"Cancer Metab"},{"key":"B14","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1186\/s12943-026-02693-8","article-title":"A sweet danger: the silent link between hyperinsulinemia and gastric cancer","volume":"25","author":"Laurenziello","year":"2026","journal-title":"Mol Cancer"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17233727","article-title":"Inverse association between METS-IR and lung cancer risk: the role of BMI in a nationwide Korean cohort","volume":"17","author":"Shine","year":"2025","journal-title":"Cancers (Basel)"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/eurpub\/ckad234","article-title":"The association between METS-IR, an indirect index for insulin resistance, and lung cancer risk","volume":"34","author":"Wang","year":"2024","journal-title":"Eur J Public Health"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1326436","article-title":"Association of the metabolic score for insulin resistance with cardiovascular diseases, cardiovascular and all-cause mortality in Chinese hypertensive population","volume":"14","author":"Zhang","year":"2024","journal-title":"Front Endocrinol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1479980","article-title":"The association between the metabolic score for insulin resistance and mortality in patients with cardiovascular disease: a national cohort study","volume":"15","author":"Su","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B19","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1093\/aje\/kwr265","article-title":"Meta-analysis for linear and nonlinear dose-response relations: examples, an evaluation of approximations, and software","volume":"175","author":"Orsini","year":"2012","journal-title":"Am J Epidemiol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1177\/0962280218773122","article-title":"One-stage dose-response meta-analysis for aggregated data","volume":"28","author":"Crippa","year":"2019","journal-title":"Stat Methods Med Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2024.102482","article-title":"Dose-response association of diabetic kidney disease with routine clinical parameters in patients with type 2 diabetes mellitus: a systematic review and meta-analysis","volume":"69","author":"Guo","year":"2024","journal-title":"EClinicalMedicine"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2025.104361","article-title":"The prognostic significance of metabolic score for insulin resistance in evaluating all-cause and cardiovascular mortality risk among individuals across stages 1\u20134 of cardiovascular\u2013kidney\u2013metabolic syndrome: a nationwide prospective cohort study","volume":"36","author":"Wang","year":"2026","journal-title":"Nutrition Metab Cardiovasc Dis"},{"key":"B23","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1186\/s13098-025-01732-6","article-title":"The association between new insulin resistance indices and all-cause mortality in elderly patients with diabetes: a prospective cohort study","volume":"17","author":"Yang","year":"2025","journal-title":"Diabetol Metab Syndr"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-024-04037-2","article-title":"Course and trajectories of insulin resistance, incident heart failure and all-cause mortality in nondiabetic people","volume":"87","author":"Xing","year":"2025","journal-title":"Endocrine"},{"key":"B25","doi-asserted-by":"publisher","first-page":"12657","DOI":"10.1038\/s41598-025-86361-9","article-title":"Nonlinear associations between METS-IR and all-cause as well as cardiovascular mortality in adults with osteoporosis and osteopenia: evidence from NHANES 2007-2023","volume":"15","author":"Liu","year":"2025","journal-title":"Sci Rep"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.2139\/ssrn.5278524","article-title":"Association of different insulin resistance surrogates with risk of incident type 2 diabetes mellitus, major adverse cardiovascular events and mortality: evidence from UK biobank cohort study","author":"Hu","year":"2025","journal-title":"SSRN [Preprint]."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1186\/s12986-024-00808-w","article-title":"Association between metabolic score for insulin resistance and clinical outcomes: insights from the Tehran lipid and glucose study","volume":"21","author":"Zadeh","year":"2024","journal-title":"Nutr Metab"},{"key":"B28","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s00432-024-05919-8","article-title":"Association between four insulin resistance surrogates and the risk of esophageal cancer: a prospective cohort study using the UK Biobank","volume":"150","author":"Yang","year":"2024","journal-title":"J Cancer Res Clin Oncol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13061628","article-title":"Association between surrogate markers of insulin resistance and the incidence of colorectal cancer in Korea: a nationwide population-based study","volume":"13","author":"Son","year":"2024","journal-title":"J Clin Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1346158","article-title":"METS-IR and all-cause mortality in Korean over 60 years old: Korean genome and epidemiology study-health examinees (KoGES-HEXA) cohorts","volume":"15","author":"Ryu","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15694","article-title":"Biological aging mediates the associations of metabolic score for insulin resistance with all-cause and cardiovascular disease mortality among US adults: a nationwide cohort study","volume":"26","author":"Li","year":"2024","journal-title":"Diabetes Obes Metab"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1383864","article-title":"Relationship between METS-IR and thyroid cancer incidence in Korea: a nationwide population-based study","volume":"14","author":"Kim","year":"2024","journal-title":"Front Oncol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"14","DOI":"10.2196\/49617","article-title":"Metabolic score for insulin resistance and new-onset type 2 diabetes in a middle-aged and older adult population: nationwide prospective cohort study and implications for primary care","volume":"10","author":"Cheng","year":"2024","journal-title":"JMIR Public Health Surveill"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.895609","article-title":"Association between a novel metabolic score for insulin resistance and mortality in people with diabetes","volume":"9","author":"Wang","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1111\/1753-0407.13161","article-title":"Association of metabolic score for insulin resistance and its 6-year change with incident type 2 diabetes mellitus","volume":"13","author":"Zhang","year":"2021","journal-title":"J Diabetes"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.2147\/ijgm.S336990","article-title":"Associations between the metabolic score for insulin resistance index and the risk of type 2 diabetes mellitus among non-obese adults: insights from a population-based cohort study","volume":"14","author":"Cai","year":"2021","journal-title":"Int J Gen Med"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2026.113093","article-title":"Association between the insulin resistance indices and incident type 2 diabetes across different body mass index states: a cohort study and external validation from two East Asian populations","volume":"232","author":"Huang","year":"2026","journal-title":"Diabetes Res Clin Pract"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1186\/s13098-024-01463-0","article-title":"Metabolic score for insulin resistance as a predictor of mortality in heart failure with preserved ejection fraction: results from a multicenter cohort study","volume":"16","author":"Zhou","year":"2024","journal-title":"Diabetol Metab Syndr"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21176275","article-title":"Pathophysiology of type 2 diabetes mellitus","volume":"21","author":"Galicia-Garcia","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B40","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/s41586-019-1797-8","article-title":"The integrative biology of type 2 diabetes","volume":"576","author":"Roden","year":"2019","journal-title":"Nature"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)61032-X","article-title":"Type 2 diabetes: principles of pathogenesis and therapy","volume":"365","author":"Stumvoll","year":"2005","journal-title":"Lancet"},{"key":"B42","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":"B43","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1186\/s12933-021-01377-5","article-title":"Positive association between the ratio of triglycerides to high-density lipoprotein cholesterol and diabetes incidence in Korean adults","volume":"20","author":"Kim","year":"2021","journal-title":"Cardiovasc Diabetol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1093\/eurjpc\/zwaf523","article-title":"Insulin resistance bio-anthropometric markers predict hypertension control in individuals without diabetes","author":"Landolfo","year":"2025","journal-title":"Eur J Prev Cardiol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s13098-024-01308-w","article-title":"Association between insulin resistance, metabolic syndrome and its components and lung cancer: a systematic review and meta-analysis","volume":"16","author":"Liu","year":"2024","journal-title":"Diabetol Metab Syndr"},{"key":"B46","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.semcancer.2025.06.006","article-title":"Insulin resistance in cancer risk and prognosis","volume":"114","author":"Jacobo-Tovar","year":"2025","journal-title":"Semin Cancer Biol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/j.ccell.2025.03.033","article-title":"Complexity of insulin resistance in early-onset colorectal cancer","volume":"43","author":"Samuel","year":"2025","journal-title":"Cancer Cell"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012415","article-title":"Association of metabolic syndrome and its components with risk of stroke recurrence and mortality: a meta-analysis","volume":"97","author":"Zhang","year":"2021","journal-title":"Neurology"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2024.10.023","article-title":"Ultra-processed food consumption, plasma metabolite profile, and risk of all-cause and cause-specific mortality in a population-based cohort","volume":"43","author":"Du","year":"2024","journal-title":"Clin Nutr"},{"key":"B50","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/s41746-025-02314-6","article-title":"A machine learning-derived polygenic risk score reveals that healthy lifestyle counteracts obesity-related mortality","volume":"9","author":"Xiao","year":"2026","journal-title":"NPJ Digit Med"},{"key":"B51","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1093\/eurjpc\/zwad033","article-title":"Life's essential 8 cardiovascular health with premature cardiovascular disease and all-cause mortality in young adults: the Kailuan prospective cohort study","volume":"30","author":"Xing","year":"2023","journal-title":"Eur J Prev Cardiol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3390\/nu17142310","article-title":"Obesity and pancreatic diseases: from inflammation to oncogenesis and the impact of weight loss interventions","volume":"17","author":"Souto","year":"2025","journal-title":"Nutrients"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1038\/s41598-025-85519-9","article-title":"Severe obesity, high inflammation, insulin resistance with risks of all-cause mortality and all-site cancers, and potential modification by healthy lifestyles","volume":"15","author":"Jin","year":"2025","journal-title":"Sci Rep"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1884402\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:19:12Z","timestamp":1785755952000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1884402\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,3]]},"references-count":53,"alternative-id":["10.3389\/fendo.2026.1884402"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1884402","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,3]]},"article-number":"1884402"}}