Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland.
Post-Graduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland.
Pediatr Diabetes. 2018 Dec;19(8):1407-1415. doi: 10.1111/pedi.12783. Epub 2018 Oct 12.
BACKGROUND/OBJECTIVE: In type 1 diabetes mellitus (T1DM), the introduction of insulin is typically followed by a brief remission period, with subsequent gradual decline in beta-cell function. Several studies described altered profile of circulating miRNAs (microRNAs) in T1DM patients and proposed them as biomarkers of associated pathologic processes.
Serum miRNA expression profile reflects residual beta-cell function and autoimmunity in T1DM.
The profiling group included patients with: GCK-MODY (N = 13), T1DM (N = 9), and 10 healthy controls. The longitudinal group included 34 patients with samples collected at diagnosis of T1DM and first, third, and fourth to eighth year since diagnosis.
We reanalyzed data from the profiling group for miRNAs differentially expressed between patients with T1DM, other types of diabetes and controls. Afterward, we shortlisted miRNAs on the basis of this reanalysis and literature review and quantified their expression with quantitative polymerase chain reaction. Additionally, we measured the levels of anti-islet antibodies (islet cell antibodies, glutamic acid decarboxylase antibodies, IA2 antibodies, and ZnT8A) and C-peptide concentrations across the four timepoints in the longitudinal group.
miR-24 and let-7g serum expression differed significantly between GCK-MODY, controls, and HbA1c-matched T1DM patients; P < 0.05, false discovery rate < 0.05. Autoantibodies levels showed decreasing linear trend in repeated timepoints (all P < 0.0001). C-peptide concentration peaked during the first year after diagnosis, corresponding to remission phase, and declined in consecutive measurements. This dynamic was evidenced for let-7g expression levels (P = 0.0058).
The pattern of let-7g expression change during the course of diabetes mirrors that of C-peptide levels, hinting at this microRNA's association with the residual mass of the beta cells in patients with T1DM.
背景/目的：在 1 型糖尿病（T1DM）中，引入胰岛素后通常会出现短暂的缓解期，随后β细胞功能逐渐下降。几项研究描述了 T1DM 患者循环 miRNA（microRNA）谱的改变，并提出它们作为相关病理过程的生物标志物。
血清 miRNA 表达谱反映了 T1DM 患者残余β细胞功能和自身免疫。
该分析组包括以下患者：GCK-MODY（N=13）、T1DM（N=9）和 10 名健康对照者。纵向组包括 34 名 T1DM 患者，在诊断时以及诊断后第一、第三和第四至第八年采集样本。
我们重新分析了分析组中 T1DM 患者、其他类型糖尿病患者和对照组之间差异表达的 miRNA 数据。在此重新分析和文献综述的基础上，我们筛选出 miRNA，并通过定量聚合酶链反应对其表达进行定量。此外，我们还在纵向组的四个时间点测量了抗胰岛自身抗体（胰岛细胞抗体、谷氨酸脱羧酶抗体、IA2 抗体和 ZnT8A）和 C 肽水平。
GCK-MODY、对照组和糖化血红蛋白匹配的 T1DM 患者之间，miR-24 和 let-7g 的血清表达差异有统计学意义；P<0.05，假发现率<0.05。在重复时间点，自身抗体水平呈下降线性趋势（均 P<0.0001）。C 肽浓度在诊断后第一年达到峰值，对应于缓解期，随后连续测量时下降。这种动态与 let-7g 表达水平相关（P=0.0058）。
在糖尿病病程中，let-7g 表达模式的变化与 C 肽水平的变化相吻合，提示该 miRNA 与 T1DM 患者β细胞残余量有关。
