Plasma exosomal microRNAs associated with metabolism as early predictor of gestational diabetes mellitus

To date, the microRNA (miRNA) expression profile of plasma exosomes in women whose pregnancy is complicated by gestational diabetes mellitus (GDM) has not been fully clarified. In this study, differentially expressed miRNAs in plasma exosomes were identified by high-throughput small RNA sequencing in 12 GDM and 12 normal glucose tolerance (NGT) pregnant women and validated in 102 GDM and 101 NGT pregnant women. A total of 22 exosomal miRNAs were found and five of them were verified by qRT-PCR. Exosmal miR-423-5p was upregulated, while miR-122-5p, miR-148a-3p, miR-192-5p, and miR-99a-5p were downregulated in women whose pregnancy is complicated by GDM. IGF1R and GYS1 as target genes of miR-423-5p, and G6PC3 and FDFT1 as target genes of miR-122-5p, were associated with insulin and AMPK signaling pathways and may participate in the regulation of metabolism in GDM. The five exosomal miRNAs showed an AUC of 0.82 (95%CI, 0.73~0.91) in early prediction of GDM. Our study demonstrated that dysregulated exosomal miRNAs in plasma from GDM pregnant women might influence the insulin and AMPK signaling pathways and could contribute to the early prediction of GDM.