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

Abstract

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 (IDAA1C). 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.