{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T14:42:18Z","timestamp":1793371338514,"version":"4.5.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"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>Insulin resistance (IR) is a key metabolic determinant of cardiovascular risk. Ceramides, a class of bioactive lipids, have been linked to IR; however, their clinical associations in patients with established coronary artery disease (CAD) are incompletely characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a prospective, multicenter observational cohort of adults with established CAD (n=987), we quantified plasma ceramide species (Cer16:0, Cer18:0, Cer24:0, Cer24:1) and surrogate IR indices (triglyceride\u2013glucose index (TyG), metabolic score for insulin resistance (METS-IR), and triglyceride\u2013to\u2013high-density lipoprotein cholesterol ratio (TG\/HDL-C)). Mixed graphical models (MGM) were used to estimate conditional associations within a multivariable network. Double machine learning (DML) with causal-forest estimators provided covariate-adjusted association estimates and probed robustness values (RV) to unmeasured confounding. Exposures were standardized per standard deviation. We also developed a ceramide-augmented model to classify clinical IR, prespecified as TyG \u2265 9, and quantified discrimination by the area under the receiver operating characteristic curve (ROC\u2013AUC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Ceramides correlated with IR indices. In MGM analyses, Cer24:0 showed a direct conditional association with TyG (partial r=0.23; 95% CI, 0.17\u20130.29), independent of other variables in the network. In DML analyses, per 1-unit increase in ln (Cer24:0) was associated with higher TyG (estimate, 0.459; 95% CI, 0.252\u20130.665; P = 0.001); These estimates demonstrated moderate RV to unmeasured confounding, with an RV (\n                      <jats:italic>theta<\/jats:italic>\n                      ) of 0.223. A ceramide-augmented model classified clinical IR with an ROC\u2013AUC of 0.770 (95% CI, 0.741\u20130.799).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Across complementary analytic frameworks, Cer24:0 consistently exhibited positive associations with lipid-centric IR metrics among adults with established CAD. Although observational, these findings suggest that circulating ceramide profiling\u2014particularly Cer24:0\u2014may refine metabolic risk stratification beyond conventional indices in cardiology practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1777380","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T05:29:54Z","timestamp":1772083794000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Plasma ceramide Cer24:0 and insulin resistance: associations with TyG and TG\/HDL-C in a multicenter study of coronary artery disease cohorts"],"prefix":"10.3389","volume":"17","author":[{"given":"Shuanli","family":"Xin","sequence":"first","affiliation":[{"name":"Department of Cardiology, Handan First Hospital","place":["Handan, Hebei, 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Beijing Anzhen Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Beijing Anzhen Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengdan","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Handan First Hospital","place":["Handan, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guidong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Handan First Hospital","place":["Handan, Hebei, 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