Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, Charles University, 10000 Prague, Czech Republic.
Institute for the Care of the Mother and Child, Third Faculty of Medicine, Charles University, 14700 Prague, Czech Republic.
Cells. 2020 Jun 26;9(6):1557. doi: 10.3390/cells9061557.
Gestational diabetes mellitus (GDM), one of the major pregnancy-related complications, characterized as a transitory form of diabetes induced by insulin resistance accompanied by a low/absent pancreatic beta-cell compensatory adaptation to the increased insulin demand, causes the acute, long-term, and transgenerational health complications. The aim of the study was to assess if alterations in gene expression of microRNAs associated with diabetes/cardiovascular/cerebrovascular diseases are present in whole peripheral blood of children aged 3-11 years descending from GDM complicated pregnancies. A substantially altered microRNA expression profile was found in children descending from GDM complicated pregnancies. Almost all microRNAs with the exception of miR-92a-3p, miR-155-5p, and miR-210-3p were upregulated. The microRNA expression profile also differed between children after normal and GDM complicated pregnancies in relation to the presence of overweight/obesity, prehypertension/hypertension, and/or valve problems and heart defects. Always, screening based on the combination of microRNAs was superior over using individual microRNAs, since at 10.0% false positive rate it was able to identify a large proportion of children with an aberrant microRNA expression profile (88.14% regardless of clinical findings, 75.41% with normal clinical findings, and 96.49% with abnormal clinical findings). In addition, the higher incidence of valve problems and heart defects was found in children with a prior exposure to GDM. The extensive file of predicted targets of all microRNAs aberrantly expressed in children descending from GDM complicated pregnancies indicates that a large group of these genes is involved in ontologies of diabetes/cardiovascular/cerebrovascular diseases. In general, children with a prior exposure to GDM are at higher risk of later development of diabetes mellitus and cardiovascular/cerebrovascular diseases, and would benefit from dispensarisation as well as implementation of primary prevention strategies.
妊娠期糖尿病（GDM）是一种主要的妊娠相关并发症，其特征为一种胰岛素抵抗引起的短暂性糖尿病形式，伴有胰岛β细胞对增加的胰岛素需求的低/无代偿适应，导致急性、长期和代际健康并发症。本研究旨在评估与糖尿病/心血管/脑血管疾病相关的 microRNA 基因表达改变是否存在于年龄为 3-11 岁来自 GDM 合并妊娠的儿童的全外周血中。在来自 GDM 合并妊娠的儿童中发现了明显改变的 microRNA 表达谱。除了 miR-92a-3p、miR-155-5p 和 miR-210-3p 之外，几乎所有的 microRNA 都上调了。microRNA 表达谱也因儿童超重/肥胖、高血压前期/高血压以及/或瓣膜问题和心脏缺陷的存在而在正常妊娠和 GDM 合并妊娠的儿童之间有所不同。基于 microRNA 的联合筛查始终优于使用单个 microRNA，因为在假阳性率为 10.0%的情况下，它能够识别出很大一部分存在异常 microRNA 表达谱的儿童（无论临床发现如何，88.14%；正常临床发现，75.41%；异常临床发现，96.49%）。此外，在曾暴露于 GDM 的儿童中发现了更高的瓣膜问题和心脏缺陷发生率。在来自 GDM 合并妊娠的儿童中异常表达的所有 microRNA 的广泛预测靶标文件表明，这些基因中有很大一部分涉及糖尿病/心血管/脑血管疾病的本体论。总的来说，曾暴露于 GDM 的儿童以后发生糖尿病和心血管/脑血管疾病的风险更高，因此需要进行常规检查，并实施初级预防策略。
