Fig. 1

Study design There were 3 steps to the design of this study. Phase 1: Patients with CAD, a total of 1465 individuals from three centers, were stratified into discovery and validation groups based on different enrollment times. widely metabolomics was used to detect plasma metabolites and lipids. Phase 2: Using multivariate logistic regression, 22 characteristic metabolites (CMs) were identified that were associated with CAD-T2TM (vs. CAD-ONLY). Relationships between these CMs and fasting blood glucose, HbA1c and all-cause mortality were established. Phase 3: At the cellular level, three CMs significantly negatively correlated with T2DM were validated. Only pipecolic acid and L-pipecolic acid induced changes in cellular energy metabolism. Finally, transcriptional data provided insight into potential targets and pathways affected by these two metabolites