Urinary Metabolomics Unravels Diagnostic Biomarkers for Type 2 Diabetes Mellitus via High-Performance Anion Exchange...

Type 2 diabetes mellitus (T2DM) imposes a significant global mortality and economic burden, with increasing prevalence among younger populations driven by unhealthy lifestyles. Definitive asymptomatic diagnosis is therefore crucial for effective intervention. In this study, urine metabolomic profiles were elucidated using high-performance anion exchange chromatography (HPAEC), and differences in organic acids, anions, amino acids, and glucose between T2DM patients and healthy controls (HC) were quantified. Statistically significant alterations were identified in seven urinary metabolite such as glycolic acid, lactate, taurine, glycine, glutamate, chloride, and glucose. A multivariate biomarker panel comprising glycolate, lactate, and glycine demonstrated exceptional diagnostic performance for T2DM (AUC = 0.990; sensitivity = 95.8%, specificity = 95.8%) at a threshold > -0.863. Four metabolic pathways were significantly upregulated in T2DM patients including taurine and hypotaurine metabolism (impact score: 0.4286), starch and sucrose metabolism (impact score: 0.4207), glycine-serine-threonine metabolism, and glyoxylate-dicarboxylate metabolism. The first two pathways exhibited the highest perturbation, indicating profound metabolic dysregulation in T2DM. These findings expand urine metabolomic knowledge and highlight quantifiable combined metabolite biomarkers for differentiating T2DM.