Plasma proteomics in children with new-onset type 1 diabetes: a strong tool to identify partial remission biomarkers

ABSTRACT: Partial remission (PR) occurs in only half of patients with new-onset type 1 diabetes (T1D) and correspond to a transient period characterized by low daily insulin needs, low glycemic fluctuations and increased endogenous insulin secretion. While identification of newly-onset T1D patients with 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 nearly 1500 unique proteins with 98 significantly correlating with Insulin-Dose Adjusted glycated hemoglobin A1c score (IDAA1C). We next applied a series of both qualitative and statistical filters that yielded to the selection of 26 protein candidates that were associated to pathophysiological mechanisms related to T1D. Finally, we translationally validated several of the candidates using single-shot targeted proteomic (PRM method) on raw plasma. Taken together, we identified plasmatic 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 patients with new-onset T1D for β-cell preservation therapies

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Type 1 Diabetes Mellitus

SUBMITTER: Didier Vertommen  

LAB HEAD: Philippe A. Lysy

PROVIDER: PXD049795 | Pride | 2024-04-05

REPOSITORIES: Pride