Metabolomics Analysis Reveals Links between Stress Hyperglycemia and Underlying Differences in Branched-Chain Amino-Acid Metabolism and Microbiome-Host Interactions

The mechanisms that lead to stress-hyperglycemia are poorly understood. We examined metabolic signatures associated with stress-hyperglycemia in patients without diabetes undergoing cardiac surgery. We enrolled patients without diabetes [BG ≤125mg/dl and HbA1c<6.5%] undergoing CABG surgery and compared those with stress hyperglycemia (“High”, mean glucose >140 or glucose >180mg/dl) vs those with preserved glucose metabolism (“Low”). Utilizing untargeted LCMS-derived high-resolution metabolomics (HRM) analysis we examined metabolites and metabolic pathways associated with incident stress hyperglycemia. Metabolic pathways were identified from HILIC positive and Reverse Phase C18 analysis, with metabolites mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG) human pathways. A total of 36 patients (age: 62.7 years, 83% male, HbA1c 5.5%) underwent CABG surgery. Nine patients developed stress hyperglycemia immediately after starting surgery and showed differences in branched-chain amino acids (BCAA, e.g., methyl-oxopentanoate), lipid metabolism (e.g., diacylglycerols), and microbiome metabolism (e.g., linoleate), figure. This analysis reveals links between stress-hyperglycemia and BCAA, and lipid metabolism, and microbiome-host interactions among nondiabetic patients undergoing cardiac stress. Disclosure A. Abraham: None. M.R. Smith: None. M. Perez-Guzman: None. F. Zahedi Tajrishi: None. L.I. Guerrero Arroyo: None. A. Chakragiri: None. J. Varghese: None. F.J. Pasquel: Consultant; Dexcom, Inc., Medscape. Research Support; Dexcom, Inc., Ideal Medical Technologies. Funding National Institutes of Health (K23GM128221)