Pôle PEDI, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium.
Specialized Pediatrics Service, Cliniques universitaires Saint-Luc, Brussels, Belgium.
Sci Rep. 2024 Sep 5;14(1):20798. 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). 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.
部分缓解（PR）仅发生在一半新诊断的 1 型糖尿病（T1D）患者中，与一个短暂的时期相对应，其特征是低日常胰岛素需求、低血糖波动和增加的内源性胰岛素分泌。虽然识别新诊断的 T1D 患者和有显著残留β细胞功能的患者可能促进个体化干预，但目前缺乏可靠的 PR 发生预测生物标志物。我们分析了新诊断的 T1D 儿童的血浆，以鉴定出在诊断时存在的预测 3 个月后 PR 的生物标志物。我们首先在 16 名新诊断的 T1D 儿童的血浆中使用液相色谱串联质谱法（LCMS/MS）进行了广泛的鸟枪法蛋白质组学分析，并对与胰岛素剂量调整糖化血红蛋白 A1c 评分（IDAA）显著相关的 98 种蛋白质进行了定量。接下来，我们应用了一系列定性和统计筛选，并选择了与与 T1D 相关的病理生理机制相关的蛋白候选物。最后，我们使用单针靶向蛋白质组学（PRM 方法）在原始血浆上对几个候选物进行了翻译验证。总之，我们鉴定了在诊断时存在的血浆生物标志物，这些标志物可能在单次质谱运行中预测 PR 的发生。我们认为，鉴定 PR 和β细胞功能的新预测生物标志物是对新诊断的 T1D 患者进行β细胞保护治疗分层的关键。
