Differential metabolic biomarkers between coronary heart disease and diabetes mellitus

BackgroundCoronary heart disease (CHD), the leading cause of death globally, is a complex disease often association with metabolic disorders, particularly when co-occurring with diabetes mellitus (DM). However, the mechanisms underlying the interaction between these two chronic conditions remain poorly understood. MethodsIn this study, we enrolled 320 participants, including 103 healthy controls (HC), 62 individuals with CHD, 44 with DM, and 47 with both CHD and DM (CHDDM)) in the training set, along with 64 participants (20 HC, 18 CHD, 12 DM, and 14 CHDDM) in the test set. Plasma metabolomic profiling was performed using gas chromatograph-mass spectrometry (GC-MS) and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS)-based multi-platform untargeted metabolomics. ResultsUsing multi-platform metabolomics, we identified 453 distinct metabolites. Through multivariate statistical analysis, we assigned 63, 27, and 56 disease-associated metabolic biomarkers for CHD, DM, and CHDDM, respectively, followed by pathway enrichment analysis. Using an area under the receiver operating characteristic (ROC) curve (AUC) cutoff value > 0.77, we identified 10, 4, and 8 disease-specific biomarkers for CHD, DM, and CHDDM, respectively. Notably, N-Formyl-L-methionine, N-Acetyl-L-methionine, PE 36:1p (18:0p/18:1), PE 36:2p (18:0p/18:2), and PE 34:2p (16:0p/18:2) were predominant in CHD, glycerophosphocholine and turanose were distinctive to DM, and xanthine and PE 38:5p (18:1p/20:4) were unique to CHDDM. These disease-specific metabolites showed superior diagnostic performance in their respective conditions. Additionally, 23 metabolites were identified as potential biomarkers for assessing the risk of CHD in DM patients. ConclusionThis comparative metabolomics approach provided new insights into disease-specific markers and pathogenic pathways, offering potential for improved diagnosis and management of CHD and DM.