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.

Highlights

  • Gestational diabetes mellitus (GDM), defined as any degree of glucose intolerance at first recognition during pregnancy, is one of the most common pregnancy complications and affects approximately 3–8% of all pregnancies [1,2]

  • Most protocols for screening and diagnosis are initiated at 24–28 gestational weeks, and previously studies have demonstrated a number of serum markers measured in the first and early second trimesters are associated with the later diagnosis of GDM [20,21,22,23]

  • The present study firstly revealed a serum miRNA signature for predicting GDM in the early second trimester and found that signatures of the miRNAs aberrant expressed prior to serum glucose abnormality

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Summary

Introduction

Gestational diabetes mellitus (GDM), defined as any degree of glucose intolerance at first recognition during pregnancy, is one of the most common pregnancy complications and affects approximately 3–8% of all pregnancies [1,2]. As recommended by the American College of Obstetricians and Gynecologists (ACOG) and the American Diabetes Association (ADA), the serum-based screening for GDM typically begins at 24–28 weeks of gestation; as many use a 2-step process, testing may not be completed until 32 weeks [8]. This leaves little time for intervention and management of GDM. Detection of women at higher risk of GDM early in pregnancy is a desirable goal, because interventions, such as diet, medication and exercise, may be applied earlier to have a positive effect on maternal and fetal outcomes. No reported study investigates the associations between serum miRNA and GDM

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