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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\u2032-phosphate, phenethylamine, phenethylamine glucuronide) and four amino acids (isoleucine, lysine, phenylalanine, tyrosine). Diabetic subjects showed elevated phenylpyruvic acid and phenethylamine, while propionylcarnitine, pyridoxal 5\u2032-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.<\/jats:p>","DOI":"10.3390\/ijms27083375","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T09:46:23Z","timestamp":1775727983000},"page":"3375","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolomic Profiling of Tongue Coating Reveals Potential Molecular Features Linked to Type 2 Diabetes Progression"],"prefix":"10.3390","volume":"27","author":[{"given":"Po-Chi","family":"Hsu","sequence":"first","affiliation":[{"name":"School of Chinese Medicine, China Medical University, Taichung 404328, Taiwan"},{"name":"Department of Chinese Medicine, China Medical University Hospital, Taichung 404332, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5377-0138","authenticated-orcid":false,"given":"Pei-Yung","family":"Liao","sequence":"additional","affiliation":[{"name":"Graduate Institute of Chinese Medicine, China Medical University, Taichung 404328, Taiwan"},{"name":"Department of Internal Medicine, Division of Endocrinology and Metabolism, Changhua Christian Hospital, Changhua 50006, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tse-Yen","family":"Yang","sequence":"additional","affiliation":[{"name":"Molecular and Genomic Epidemiology Center, Department of Medical Research, China Medical University Hospital, Taichung 404332, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung 41354, Taiwan"},{"name":"Center for General Education, China Medical University, Taichung 404328, Taiwan"},{"name":"Master Program of Digital Health Innovation, College of Humanities and Sciences, China Medical University, Taichung 404328, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7840-1504","authenticated-orcid":false,"given":"Hen-Hong","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Chinese Medicine, China Medical University Hospital, Taichung 404332, Taiwan"},{"name":"Graduate Institute of Integrated Medicine, China Medical University, Taichung 404328, Taiwan"},{"name":"Chinese Medicine Research Center, China Medical University, Taichung 404328, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8719-4017","authenticated-orcid":false,"given":"John Y.","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan"},{"name":"Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chuen","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, China Medical University, Taichung 404328, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, Taichung 404332, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lun-Chien","family":"Lo","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, China Medical University, Taichung 404328, Taiwan"},{"name":"Department of Chinese Medicine, China Medical University Hospital, Taichung 404332, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Der-Yen","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate Institute of Integrated Medicine, China Medical University, Taichung 404328, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mansour, A., Mousa, M., Abdelmannan, D., Tay, G., Hassoun, A., and Alsafar, H. 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