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Open AccessArticle

NMR-Based Metabolomic Approach Tracks Potential Serum Biomarkers of Disease Progression in Patients with Type 2 Diabetes Mellitus

1
Department of Biological and Environmental Sciences and Technologies, University of Salento, via Monteroni, 73100 Lecce, Italy
2
Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy
3
Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, 60121 Ancona, Italy
4
IRCCS MultiMedica, 20099 Milan, Italy
5
Scientific Direction, IRCCS INRCA, 60121 Ancona, Italy
6
Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy
7
Division of Medical Oncology, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena, 41125 Modena, Italy
8
Center of Clinical Pathology and Innovative Therapy, IRCCS INRCA, 60121 Ancona, Italy
*
Authors to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(5), 720; https://doi.org/10.3390/jcm8050720
Received: 26 April 2019 / Revised: 10 May 2019 / Accepted: 15 May 2019 / Published: 21 May 2019
(This article belongs to the Special Issue Clinical Research on Diabetic Complications)
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-naïve 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. View Full-Text
Keywords: branched-chain amino acids; metabolomics; NMR spectroscopy; type 2 diabetes mellitus branched-chain amino acids; metabolomics; NMR spectroscopy; type 2 diabetes mellitus
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MDPI and ACS Style

Del Coco, L.; Vergara, D.; De Matteis, S.; Mensà, E.; Sabbatinelli, J.; Prattichizzo, F.; Bonfigli, A.R.; Storci, G.; Bravaccini, S.; Pirini, F.; Ragusa, A.; Casadei-Gardini, A.; Bonafè, M.; Maffia, M.; Fanizzi, F.P.; Olivieri, F.; Giudetti, A.M. NMR-Based Metabolomic Approach Tracks Potential Serum Biomarkers of Disease Progression in Patients with Type 2 Diabetes Mellitus. J. Clin. Med. 2019, 8, 720. https://doi.org/10.3390/jcm8050720

AMA Style

Del Coco L, Vergara D, De Matteis S, Mensà E, Sabbatinelli J, Prattichizzo F, Bonfigli AR, Storci G, Bravaccini S, Pirini F, Ragusa A, Casadei-Gardini A, Bonafè M, Maffia M, Fanizzi FP, Olivieri F, Giudetti AM. NMR-Based Metabolomic Approach Tracks Potential Serum Biomarkers of Disease Progression in Patients with Type 2 Diabetes Mellitus. Journal of Clinical Medicine. 2019; 8(5):720. https://doi.org/10.3390/jcm8050720

Chicago/Turabian Style

Del Coco, Laura; Vergara, Daniele; De Matteis, Serena; Mensà, Emanuela; Sabbatinelli, Jacopo; Prattichizzo, Francesco; Bonfigli, Anna R.; Storci, Gianluca; Bravaccini, Sara; Pirini, Francesca; Ragusa, Andrea; Casadei-Gardini, Andrea; Bonafè, Massimiliano; Maffia, Michele; Fanizzi, Francesco P.; Olivieri, Fabiola; Giudetti, Anna M. 2019. "NMR-Based Metabolomic Approach Tracks Potential Serum Biomarkers of Disease Progression in Patients with Type 2 Diabetes Mellitus" J. Clin. Med. 8, no. 5: 720. https://doi.org/10.3390/jcm8050720

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