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Robust separation in the metabolomic and lipidomic profiles of RBCs from patients and controls was confirmed by orthogonal projection on latent structure discriminant analysis (OPLS-DA), random forest analysis, and significance analysis of metabolites (SAM). The main changes were detected in the levels of amino acids, organic acids, creatine and phosphocreatine, lipid change length, and choline derivatives, demonstrating changes in glycolysis, BCAA metabolism, and phospholipid metabolism. Our study proves that robust differences exist in the metabolic and lipidomic profile of RBCs from T1D patients, in comparison with matched healthy individuals. Some changes were similar to alterations found already in RBCs of T2D patients, but others seemed to be specific for type 1 diabetes. Thus, many of the metabolic differences found could be biomarker candidates for an earlier diagnosis or monitoring of patients with T1D. Keywords: type 1 diabetes; NMR spectroscopy; metabolomics; lipidomics; red blood cells Author: José Raul Herance, Andreea Cuidin, Rubén Lamas-Domingo, Carolina Apararicio-Gómez, Cristina Hernández, Rafael Simó and Martina Palomino-Schätzlein Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Jan 11 09:44:10 2023 CET ModDate: Wed Jan 11 09:52:45 2023 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2182503 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- JRJJPZ+VnURWPalladioL Type 1 Custom yes yes no 10 0 TEZRCQ+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 HMVDOG+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 CBAOSM+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 CAMXTK+EURM10 Type 1 Builtin yes yes no 28 0 ZZTQUO+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 50 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 53 0 XEYJZU+CMSY10 Type 1 Builtin yes yes no 78 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 88 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 100 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 104 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 108 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 112 0 ArialMT TrueType WinAnsi no no no 121 0 BCDJEE+Calibri-Bold TrueType WinAnsi yes yes no 124 0 BCDKEE+Calibri TrueType WinAnsi yes yes no 128 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 146 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 150 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 154 0 BCDLEE+Calibri CID TrueType Identity-H yes yes yes 159 0 ArialMT TrueType WinAnsi no no no 167 0 BCDJEE+Calibri-Bold TrueType WinAnsi yes yes no 170 0 BCDKEE+Calibri TrueType WinAnsi yes yes no 174 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 188 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 192 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 196 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 200 0 ArialMT TrueType WinAnsi no no no 208 0 BCDKEE+Calibri TrueType WinAnsi yes yes no 211 0 Arial,Bold TrueType WinAnsi no no no 218 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 246 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 250 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 254 0 BCDMEE+SimSun TrueType WinAnsi yes yes no 259 0 BCDJEE+Calibri-Bold TrueType WinAnsi yes yes no 263 0 BCDKEE+Calibri TrueType WinAnsi yes yes no 267 0 BOLMEN+SFRM0900 Type 1 Custom yes yes no 278 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-03-16 02:35:26 CET RepresentationInformation: pmc_9862852.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-02-02 03:39:49 CET Size: 2182503 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 484 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Study Design and Subjects Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Peripheral Blood Samples Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Extraction of Metabolites and Lipids Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: NMR Experiments Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Data Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Info: Title: The Footprint of Type 1 Diabetes on Red Blood Cells: A Metabolomic and Lipidomic Study Author: José Raul Herance, Andreea Cuidin, Rubén Lamas-Domingo, Carolina Apararicio-Gómez, Cristina Hernández, Rafael Simó and Martina Palomino-Schätzlein Subject: The prevalence of diabetes type 1 (T1D) in the world populations is continuously growing. Although treatment methods are improving, the diagnostic is still symptom-based and sometimes far after onset of the disease. In this context, the aim of the study was the search of new biomarkers of the disease in red blood cells (RBCs), until now unexplored. The metabolomic and the lipidomic profile of RBCs from T1D patients and matched healthy controls was determined by NMR spectroscopy, and different multivariate discrimination models were built to select the metabolites and lipids that change most significantly. Relevant metabolites were further confirmed by univariate statistical analysis. Robust separation in the metabolomic and lipidomic profiles of RBCs from patients and controls was confirmed by orthogonal projection on latent structure discriminant analysis (OPLS-DA), random forest analysis, and significance analysis of metabolites (SAM). The main changes were detected in the levels of amino acids, organic acids, creatine and phosphocreatine, lipid change length, and choline derivatives, demonstrating changes in glycolysis, BCAA metabolism, and phospholipid metabolism. Our study proves that robust differences exist in the metabolic and lipidomic profile of RBCs from T1D patients, in comparison with matched healthy individuals. Some changes were similar to alterations found already in RBCs of T2D patients, but others seemed to be specific for type 1 diabetes. Thus, many of the metabolic differences found could be biomarker candidates for an earlier diagnosis or monitoring of patients with T1D. 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