{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T19:40:41Z","timestamp":1783021241234,"version":"3.54.6"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Metabolism Res"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Heart failure (HF) is a major cardiovascular complication of type 2 diabetes mellitus (T2DM), yet reliable biomarkers for early risk stratification remain limited. We investigated the prospective association between plasma angiopoietin\u2010like protein 7 (ANGPTL7) and incident HF, and examined the extent to which this relationship is mediated by insulin resistance (IR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>This study included 2871 participants with T2DM and no baseline HF from the UK Biobank. Plasma ANGPTL7 was quantified using the Olink Proximity Extension Assay. Incident HF was ascertained via hospital and death records over a median follow\u2010up of 13.5\u00a0years. Multivariable Cox proportional hazards models and restricted cubic splines (RCS) were employed to estimate hazard ratios (HRs) and evaluate dose\u2010response relationships. Predictive performance was assessed using time\u2010dependent receiver operating characteristic (ROC) curves. Furthermore, we conducted stratified analyses by HF polygenic risk score (PRS) and performed causal mediation analysis to quantify the contributions of IR indices.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Elevated ANGPTL7 levels were robustly associated with an increased risk of incident HF. Patients in the highest tertile had a 1.90\u2010fold higher risk compared to the lowest (HR 1.90, 95% CI 1.47\u20132.45,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). This positive association was linear (\n                      <jats:italic>p<\/jats:italic>\n                      for nonlinearity\u00a0=\u00a00.988). Time\u2010dependent ROC analysis showed that the AUCs for ANGPTL7 in predicting 5\u2010, 10\u2010, and 15\u2010year incident HF were 0.651, 0.666, and 0.670, respectively. Significant risk elevations for ANGPTL7 T3 versus T1 were consistent in both low\u2010PRS (HR 3.20, 95% CI 1.91\u20135.36) and high\u2010PRS groups (HR 1.75, 95% CI 1.14\u20132.69). Mechanistically, IR significantly mediated this association, with TyG\u2010WC and METS\u2010IR accounting for 19.4% and 9.0% of the total effect, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In T2DM patients, elevated plasma ANGPTL7 is an independent risk factor for future HF, showing a linear dose\u2010response relationship partially mediated by IR. ANGPTL7 may represent a promising biomarker and a potential therapeutic target warranting further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/dmrr.70153","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T10:35:08Z","timestamp":1773138908000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma ANGPTL7 Links Insulin Resistance to Heart Failure: Unveiling a Novel Fibro\u2010Metabolic Axis in Type 2 Diabetes"],"prefix":"10.1002","volume":"42","author":[{"given":"Yanjun","family":"Song","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease  Beijing China"},{"name":"Cardiometabolic Medicine Center, Department of Cardiology, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Fuwai Hospital  Beijing China"},{"name":"Coronary Heart Disease Center, Department of Cardiology, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Fuwai Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease  Beijing China"},{"name":"Cardiometabolic Medicine Center, Department of Cardiology, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Fuwai Hospital  Beijing China"},{"name":"Coronary Heart Disease Center, Department of Cardiology, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Fuwai Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen'ge","family":"Chang","sequence":"additional","affiliation":[{"name":"Cardiometabolic Medicine Center, Department of Cardiology, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Fuwai Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyue","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease  Beijing China"},{"name":"Cardiometabolic Medicine Center, Department of Cardiology, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Fuwai Hospital  Beijing China"},{"name":"Coronary Heart Disease Center, Department of Cardiology, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Fuwai Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihao","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease  Beijing China"},{"name":"Cardiometabolic Medicine Center, Department of Cardiology, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Fuwai Hospital  Beijing China"},{"name":"Coronary Heart Disease Center, Department of Cardiology, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Fuwai Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangyu","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease  Beijing China"},{"name":"Cardiometabolic Medicine Center, Department of Cardiology, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Fuwai Hospital  Beijing China"},{"name":"Coronary Heart Disease Center, Department of Cardiology, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Fuwai Hospital  Beijing 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