Comprehensive understanding of plasma metabotype of diabetes mellitus
(DM), coronary heart disease (CHD), and especially diabetes mellitus
with coronary heart disease (CHDDM) is still lacking. In this work, the
plasma metabolic differences and links of DM, CHD, and CHDDM patients
were investigated by the strategy of comparative metabolomics based on 1H
NMR spectroscopy combined with network analysis for revealing their
metabolic differences. A total of 17 metabolites are related to three
diseases, among which valine, alanine, leucine, isoleucine, and N-acetyl-glycoprotein
are positively correlated with CHD and CHDDM (odds ratios (OR) > 1).
The trimethylamine oxide, glycerol, lactose, indoleacetate, and scyllo-inositol
are closely related to the development of DM to CHDDM (OR > 1), and
indoleactate (OR: 1.06, 95% confidence interval (CI): 1.01–1.12) and
lactose (OR: 2.46, 95% CI: 1.67–3.25) are particularly prominent in
CHDDM. We identified three multi-biomarkers types that were
significantly associated with glycosylated hemoglobin (HbA1C) at
baseline. All diseases demonstrated dysregulated
glycolysis/gluconeogenesis and amino acid biosynthesis pathway. In
addition, enrichment in tryptophan metabolism observed in CHDDM,
enrichment in inositol phosphate metabolism observed in DM, and the
metabolites related to microbiota metabolism were dysregulated in both
DM and CHDDM. The comparative metabolomics strategy of multi-diseases
offers a new perspective in disease-specific markers and pathogenic
pathways.