{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:13:53Z","timestamp":1783660433659,"version":"3.55.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"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>Background<\/jats:title>\n                    <jats:p>Colorectal cancer (CRC) remains a persistent global health challenge, with a rising incidence strongly linked to metabolic dysfunction. Insulin resistance (IR), a hallmark of metabolic dysregulation, is a well-established driver of tumorigenesis and cancer progression. However, the relative predictive value of distinct non-insulin-based surrogate markers of IR for CRC risk assessment remains poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This prospective study analyzed data from 385,206 participants in the UK Biobank. Non-insulin-based surrogate markers evaluated included the TyG index, TyG-BMI, the TG\/HDL-C ratio, and METS-IR. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CRC. Restricted cubic splines (RCS) assessed dose-response relationships. Incremental predictive value and clinical utility were evaluated via C-index increments and decision curve analysis (DCA). Robustness was verified through extensive subgroup and sensitivity analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Over a median follow-up of 13.8 years, 5,175 incident CRC cases were documented. All four IR surrogates were independently and positively associated with CRC risk (all\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001). In the fully adjusted model, comparing extreme quartiles (Q4 vs. Q1), the HRs (95% CIs) were 1.16 (1.07-1.26) for the TyG index, 1.20 (1.11-1.31) for TyG-BMI, 1.09 (1.01-1.19) for the TG\/HDL-C ratio, and 1.21 (1.11-1.32) for METS-IR. RCS revealed significant non-linear relationships for the TyG index and METS-IR, whereas linear trends were observed for the remaining markers in the fully adjusted model. Notably, adding METS-IR and TyG-BMI to the base model yielded the most significant improvements in discrimination (both C-index increments = 0.0015;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001). Furthermore, DCA confirmed sustained net clinical benefits across practical thresholds. Subgroup analyses revealed significant interactions between the IR surrogate markers and age, sex, and smoking status (\n                      <jats:italic>P<\/jats:italic>\n                      -interaction \u2264 0.05). Multiple sensitivity analyses, including excluding cases diagnosed within the first two years, confirmed the findings\u2019 robustness.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Elevated non-insulin-based IR surrogates are robust predictors of CRC risk. The BMI-integrated indices, METS-IR and TyG-BMI, demonstrated superior risk stratification performance. These low-cost, readily available tools may facilitate the early identification of high-risk individuals and inform evidence-based primary prevention strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1848724","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T04:25:29Z","timestamp":1783657529000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of four non-insulin-based insulin resistance surrogate markers with colorectal cancer risk: a large-scale prospective cohort study using the UK Biobank"],"prefix":"10.3389","volume":"17","author":[{"given":"Ye","family":"Ding","sequence":"first","affiliation":[{"name":"School of Nursing, Nanjing University of Chinese Medicine","place":["Nanjing, China"]},{"name":"Department of Nursing, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese 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