Metabolomic signatures in adults with metabolic syndrome indicate preclinical disruptions in pathways associated with high-density lipoprotein cholesterol, sugar alcohols

This study identified novel metabolite associations with known markers of T2D and CVD risk. Specific metabolites, such as alpha-tocopherol, branched-chain amino acids (BCAAs), and sugar-derived metabolites like mannose and xylose, were significantly associated with age, BMI, lipid profiles, and glucose measures. Although most sample participants had normal HDL cholesterol at baseline, 42 metabolites including branched chain amino acids were significantly associated with HDL, suggesting pre-clinical perturbations in biological pathways associated with both diabetes and cardiovascular comorbidities. Metabolomic signatures specific to prediabetes and metabolic syndrome can enhance risk stratification and enable targeted prevention strategies for T2D. Longitudinal studies are needed to understand how these associations change over time in at-risk individuals compared with controls.