Plasma proteomics in children with new-onset type 1 diabetes identifies new potential biomarkers of partial remission

• Published in: Scientific reports Vol. 14; no. 1; pp. 20798 - 13
• Main Authors: Pollé, Olivier G., Pyr dit Ruys, Sébastien, Lemmer, Julie, Hubinon, Camille, Martin, Manon, Herinckx, Gaetan, Gatto, Laurent, Vertommen, Didier, Lysy, Philippe A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.09.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 692/163/2743/137/1418; 692/308/3187; 692/53/2423; Adolescent; Beta cells; Biomarkers; Biomarkers - blood; Blood Proteins - analysis; Blood Proteins - metabolism; Child; Child, Preschool; Children; Chromatography, Liquid; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - blood; Diagnosis; Female; Glycated Hemoglobin - analysis; Glycated Hemoglobin - metabolism; Hemoglobin; Humanities and Social Sciences; Humans; Insulin; Insulin - blood; Insulin secretion; Liquid chromatography; Male; multidisciplinary; Plasma; Proteomics; Proteomics - methods; Remission; Remission Induction; Science; Science (multidisciplinary); Scientific imaging; Spectrometry; Tandem Mass Spectrometry
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-71717-4

Partial remission (PR) occurs in only half of people with new-onset type 1 diabetes (T1D) and corresponds to a transient period characterized by low daily insulin needs, low glycemic fluctuations and increased endogenous insulin secretion. While identification of people with newly-onset T1D and significant residual beta-cell function may foster patient-specific interventions, reliable predictive biomarkers of PR occurrence currently lack. We analyzed the plasma of children with new-onset T1D to identify biomarkers present at diagnosis that predicted PR at 3 months post-diagnosis. We first performed an extensive shotgun proteomic analysis using Liquid Chromatography-Tandem-Mass-Spectrometry (LCMS/MS) on the plasma of 16 children with new-onset T1D and quantified 98 proteins significantly correlating with Insulin-Dose Adjusted glycated hemoglobin A1c score (IDAA 1C ). We next applied a series of both qualitative and statistical filters and selected protein candidates that were associated to pathophysiological mechanisms related to T1D. Finally, we translationally verified several of the candidates using single-shot targeted proteomic (PRM method) on raw plasma. Taken together, we identified plasma biomarkers present at diagnosis that may predict the occurrence of PR in a single mass-spectrometry run. We believe that the identification of new predictive biomarkers of PR and β-cell function is key to stratify people with new-onset T1D for β-cell preservation therapies.