Metabolomic Profiling of Tongue Coating Reveals Potential Molecular Features Linked to Type 2 Diabetes Progression

Diagnosis and monitoring of type 2 diabetes mellitus (T2DM) typically rely on invasive blood-based biomarkers. To explore non-invasive alternatives, this study examined tongue coating metabolites to identify metabolic signatures linked to diabetes progression. A case-control observational study categorized participants into control, prediabetes, and diabetes groups. Tongue coating samples were analyzed using liquid chromatography-mass spectrometry (LC-MS). Differential metabolites were correlated with clinical parameters, including HbA1c, BMI, and eGFR. Distinct metabolic profiles emerged across groups, with significant differences in five endogenous metabolites (phenylpyruvic acid, propionylcarnitine, pyridoxal 5'-phosphate, phenethylamine, phenethylamine glucuronide) and four amino acids (isoleucine, lysine, phenylalanine, tyrosine). Diabetic subjects showed elevated phenylpyruvic acid and phenethylamine, while propionylcarnitine, pyridoxal 5'-phosphate, and phenethylamine glucuronide were reduced. Phenethylamine was positively correlated with HbA1c; propionylcarnitine and phenethylamine glucuronide showed negative correlations with HbA1c and BMI. Detected total amino acids were inversely correlated with eGFR. Additionally, a diabetes index derived from these metabolic features also holds potential for discriminating disease states. These findings underscore the potential of tongue coating metabolites as a relatively non-invasive approach for evaluating T2DM states. The observed metabolic alterations provide valuable insights into diabetes-associated dysregulation, including protein glycation, obesity-related metabolic shifts, and renal impairment.