Observational studyFrontiers in endocrinology2026
Plasma ceramide Cer24:0 and insulin resistance: associations with TyG and TG/HDL-C in a multicenter study of coronary artery disease cohorts.
Observational study in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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13 authors.
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Abstract
Background: 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. Methods: 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-glucose index (TyG), metabolic score for insulin resistance (METS-IR), and triglyceride-to-high-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 ≥ 9, and quantified discrimination by the area under the receiver operating characteristic curve (ROC-AUC). Results: Ceramides correlated with IR indices. In MGM analyses, Cer24:0 showed a direct conditional association with TyG (partial r=0.23; 95% CI, 0.17-0.29), 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, 0.252-0.665; P = 0.001); These estimates demonstrated moderate RV to unmeasured confounding, with an RV ( Conclusions: 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-particularly Cer24:0-may refine metabolic risk stratification beyond conventional indices in cardiology practice.
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