{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T02:47:43Z","timestamp":1786243663132,"version":"build-2736575974"},"reference-count":69,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,5,21]],"date-time":"2019-05-21T00:00:00Z","timestamp":1558396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia associated with alterations in carbohydrate, lipid, and protein metabolism. The prognosis of T2DM patients is highly dependent on the development of complications, and therefore the identification of biomarkers of T2DM progression, with minimally invasive techniques, is a huge need. In the present study, we applied a 1H-Nuclear Magnetic Resonance (1H-NMR)-based metabolomic approach coupled with multivariate data analysis to identify serum metabolite profiles associated with T2DM development and progression. To perform this, we compared the serum metabolome of non-diabetic subjects, treatment-na\u00efve non-complicated T2DM patients, and T2DM patients with complications in insulin monotherapy. Our analysis revealed a significant reduction of alanine, glutamine, glutamate, leucine, lysine, methionine, tyrosine, and phenylalanine in T2DM patients with respect to non-diabetic subjects. Moreover, isoleucine, leucine, lysine, tyrosine, and valine levels distinguished complicated patients from patients without complications. Overall, the metabolic pathway analysis suggested that branched-chain amino acid (BCAA) metabolism is significantly compromised in T2DM patients with complications, while perturbation in the metabolism of gluconeogenic amino acids other than BCAAs characterizes both early and advanced T2DM stages. In conclusion, we identified a metabolic serum signature associated with T2DM stages. These data could be integrated with clinical characteristics to build a composite T2DM\/complications risk score to be validated in a prospective cohort.<\/jats:p>","DOI":"10.3390\/jcm8050720","type":"journal-article","created":{"date-parts":[[2019,5,21]],"date-time":"2019-05-21T10:52:51Z","timestamp":1558435971000},"page":"720","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["NMR-Based Metabolomic Approach Tracks Potential Serum Biomarkers of Disease Progression in Patients with Type 2 Diabetes Mellitus"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4805-7538","authenticated-orcid":false,"given":"Laura","family":"Del Coco","sequence":"first","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies, University of Salento, via Monteroni, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2396-7674","authenticated-orcid":false,"given":"Daniele","family":"Vergara","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies, University of Salento, via Monteroni, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9219-4081","authenticated-orcid":false,"given":"Serena","family":"De Matteis","sequence":"additional","affiliation":[{"name":"Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Mens\u00e0","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences, DISCLIMO, Universit\u00e0 Politecnica delle Marche, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9947-6778","authenticated-orcid":false,"given":"Jacopo","family":"Sabbatinelli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences, DISCLIMO, Universit\u00e0 Politecnica delle Marche, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2959-2658","authenticated-orcid":false,"given":"Francesco","family":"Prattichizzo","sequence":"additional","affiliation":[{"name":"IRCCS MultiMedica, 20099 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9619-0181","authenticated-orcid":false,"given":"Anna Rita","family":"Bonfigli","sequence":"additional","affiliation":[{"name":"Scientific Direction, IRCCS INRCA, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Storci","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0075-8538","authenticated-orcid":false,"given":"Sara","family":"Bravaccini","sequence":"additional","affiliation":[{"name":"Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7629-2439","authenticated-orcid":false,"given":"Francesca","family":"Pirini","sequence":"additional","affiliation":[{"name":"Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2198-6185","authenticated-orcid":false,"given":"Andrea","family":"Ragusa","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies, University of Salento, via Monteroni, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6289-7202","authenticated-orcid":false,"given":"Andrea","family":"Casadei-Gardini","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Bonaf\u00e8","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Maffia","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies, University of Salento, via Monteroni, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3073-5772","authenticated-orcid":false,"given":"Francesco Paolo","family":"Fanizzi","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies, University of Salento, via Monteroni, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9606-1144","authenticated-orcid":false,"given":"Fabiola","family":"Olivieri","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences, DISCLIMO, Universit\u00e0 Politecnica delle Marche, 60121 Ancona, Italy"},{"name":"Center of Clinical Pathology and Innovative Therapy, IRCCS INRCA, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9204-040X","authenticated-orcid":false,"given":"Anna Maria","family":"Giudetti","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies, University of Salento, via Monteroni, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1002\/iub.1396","article-title":"Type-2 diabetes: Current understanding and future perspectives","volume":"67","author":"Pandey","year":"2015","journal-title":"IUBMB Life"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2S","DOI":"10.1016\/j.amjmed.2003.10.014","article-title":"The diabetes epidemic: A national and global 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