MicroRNA profiling of second trimester maternal plasma in patients with gestational diabetes

Background: Gestational diabetes (GDM) is defined as glucose intolerance that presents during pregnancy. It increases the risk of developing diabetes later in life. Recent studies have revealed an important role of microRNAs (miRNAs) in the pathogenesis of diabetes, including GDM. However, there is still little information on the plasma miRNA profile in GDM patients at the late second trimester, at which time the glucose metabolism disorder manifests. The aim of the present study was to comparatively determine the plasma miRNA expression profiles of pregnant women with GDM and of pregnant controls using the real-time PCR array method.

Methods: The study involved 22 single-pregnancy women (mean age ± standard deviation of 29.9 ± 4.5 years old), of whom 13 were diagnosed with GDM based on a glucose tolerance test which was undertaken between 23 and 31 weeks of gestation. MiRNAs were purified from plasma samples and reverse transcribed to cDNA using miRNeasy and MiScript II RT kits (Qiagen), respectively. MiScript® miRNA PCR Array was used to profile the expression of 84 miRNAs together with the DIANA Tools mirPath v.3 software and KEGG database to identify associated target genes and pathways.

Results: We identified 15 upregulated miRNAs in the GDM patients that were involved in 41 pathways. Among the top 10 associated pathways, fatty acid biosynthesis and fatty acid metabolism were targeted by the most, of the miRNAs investigated, with very low p values (p < 0.001). MiR-195-5p, which targeted the highest number of genes important in fatty acid metabolism, showed the highest upregulation in GDM. 

Conclusions: The increased miRNA expression, especially miR-195-5p, in plasma is characteristic of and may be causally related to the development of GDM. 

This study was supported by the European Regional Development Fund and Estonian Ministry of Education and Resrearch grants nr SF0180035s08 and IUT20-43.