Early Second-Trimester Serum MiRNA Profiling Predicts Gestational Diabetes Mellitus

Abstract

BackgroundGestational diabetes mellitus (GDM) is one type of diabetes that presents during pregnancy and significantly increases the risk of a number of adverse consequences for the fetus and mother. The microRNAs (miRNA) have recently been demonstrated to abundantly and stably exist in serum and to be potentially disease-specific. However, no reported study investigates the associations between serum miRNA and GDM.Methodology/Principal FindingsWe systematically used the TaqMan Low Density Array followed by individual quantitative reverse transcription polymerase chain reaction assays to screen miRNAs in serum collected at 16–19 gestational weeks. The expression levels of three miRNAs (miR-132, miR-29a and miR-222) were significantly decreased in GDM women with respect to the controls in similar gestational weeks in our discovery evaluation and internal validation, and two miRNAs (miR-29a and miR-222) were also consistently validated in two-centric external validation sample sets. In addition, the knockdown of miR-29a could increase Insulin-induced gene 1 (Insig1) expression level and subsequently the level of Phosphoenolpyruvate Carboxy Kinase2 (PCK2) in HepG2 cell lines.Conclusions/SignificanceSerum miRNAs are differentially expressed between GDM women and controls and could be candidate biomarkers for predicting GDM. The utility of miR-29a, miR-222 and miR-132 as serum-based non-invasive biomarkers warrants further evaluation and optimization.

Application of microRNAs in diabetes mellitus

“…In addition, Pescador et al (2013) showed that three serum miRNAs (miR-138, miR-376a, and miR-15b) are potential biomarkers for distinguishing obese patients from obese-T2D and T2D patients; meanwhile, the combination of miR-503 and miR-138 can distinguish diabetic from obese-diabetic patients. Furthermore, Zhao et al (2011) found that three serum miRNAs (miR-132, miR-29a, and miR-222) can predict gestational DM with 66.7% sensitivity and 63.3% specificity (area under the curveZ0.642).…”

Circulating microRNAs and diabetes: potential applications in medical practice

“…• Association between levels of some miRNAs and markers of microvascular impairment revealed the dysregulation of some in the serum and plasma of women who went on to develop GDM compared with the controls [43,44]. These results suggest that circulating miRNAs could be used as biomarkers for the early diagnosis or as a predictive factor for GDM.…”

“…Furthermore, the miRNA content of different types of blood cells were also deregulated in type 1 and type 2 diabetic patients compared with controls [38][39][40][41][42]. Finally, analysis of circulating miRNAs in women with gestational diabetes mellitus has revealed that in both serum and plasma some miRNAs have an altered profile compared with those in control women [43,44].…”

Peculiarities of placental microRNA expression in pregnancies complicated by gestational diabetes mellitus and preeclampsia

“…Молекулярно-генетические механизмы этих нарушений изучены недостаточно. В ряде исследований была отмечена роль микроРНК в патогенезе ГСД [4] и ПЭ [5].…”

“…Предполагается, что количественные измене-ния экспрессии некоторых микроРНК могут быть биомаркерами таких грозных осложне-ний беременности, как гестоз, гестационный сахарный диабет, хроническая плацентарная недостаточность и другие [5]. Так, значитель-ное снижение концентрации трех микроРНК (mir-29a, mir-222 и miR-132) были выявлены при сроке гестации 16-19 недель в крови бе-ременных, у которых в дальнейшим развился ГСД [4].…”