Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM), Barcelona, Spain.
Pathogenesis and Prevention of Diabetes Laboratory, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Rosselló 149-153, 08036, Barcelona, Spain.
J Endocrinol Invest. 2020 Apr;43(4):451-459. doi: 10.1007/s40618-019-01129-z. Epub 2019 Nov 12.
Type 2 diabetes frequently remains undiagnosed for years, whereas early detection of affected individuals would facilitate the implementation of timely and cost-effective therapies, hence decreasing morbidity. With the intention of identifying novel diagnostic biomarkers, we characterized the miRNA profile of microvesicles isolated from retroactive serum samples of normoglycemic individuals and two groups of subjects with prediabetes that in the following 4 years either progressed to overt diabetes or remained stable.
We profiled miRNAs in serum microvesicles of a selected group of control and prediabetic individuals participating in the PREDAPS cohort study. Half of the subjects with prediabetes were diagnosed with diabetes during the 4 years of follow-up, while the glycemic status of the other half remained unchanged.
We identified two miRNAs, miR-10b and miR-223-3p, which target components of the insulin signaling pathway and whose ratio discriminates between these two subgroups of prediabetic individuals at a stage at which other features, including glycemia, are less proficient at separating them. In global, the profile of miRNAs in microvesicles of prediabetic subjects primed to progress to overt diabetes was more similar to that of diabetic patients than the profile of prediabetic subjects who did not progress.
We have identified a miRNA signature in serum microvesicles that can be used as a new screening biomarker to identify subjects with prediabetes at high risk of developing diabetes, hence allowing the implementation of earlier, and probably more effective, therapeutic interventions.
2 型糖尿病常常多年未被诊断,而早期发现受影响的个体将有助于及时实施具有成本效益的治疗,从而降低发病率。为了确定新的诊断生物标志物,我们对来自血糖正常个体的回溯性血清样本中分离的微泡的 miRNA 谱进行了特征描述,并对两组处于糖尿病前期的个体进行了研究,这两组个体在接下来的 4 年内要么进展为显性糖尿病,要么保持稳定。
我们对参与 PREDAPS 队列研究的选定对照组和糖尿病前期个体的血清微泡中的 miRNA 进行了分析。糖尿病前期个体的一半在 4 年的随访期间被诊断为糖尿病,而另一半的血糖状况保持不变。
我们发现了两个 miRNA,miR-10b 和 miR-223-3p,它们靶向胰岛素信号通路的组成部分,其比值可以区分这两组糖尿病前期个体,而在其他特征(包括血糖)更难以区分它们的阶段。总的来说,进展为显性糖尿病的糖尿病前期个体的微泡中 miRNA 的特征与糖尿病患者的特征更为相似,而未进展的糖尿病前期个体的特征则不相似。
我们已经确定了血清微泡中存在的 miRNA 特征,可以用作新的筛选生物标志物,以识别有发展为糖尿病风险的糖尿病前期个体,从而可以更早地实施可能更有效的治疗干预措施。