Systematic review of transcriptome and microRNAome associations with gestational diabetes mellitus

Abstract

PurposeGestational diabetes (GDM) is associated with increased risk for preterm birth and related complications for both the pregnant person and newborn. Changes in gene expression have the potential to characterize complex interactions between genetic and behavioral/environmental risk factors for GDM. Our goal was to summarize the state of the science about changes in gene expression and GDM.DesignThe systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.MethodsPubMed articles about humans, in English, from any date were included if they described mRNA transcriptome or microRNA findings from blood samples in adults with GDM compared with adults without GDM.ResultsSixteen articles were found representing 1355 adults (n=674 with GDM, n=681 controls) from 12 countries. Three studies reported transcriptome results and thirteen reported microRNA findings. Identified pathways described various aspects of diabetes pathogenesis, including glucose and insulin signaling, regulation, and transport; natural killer cell mediated cytotoxicity; and fatty acid biosynthesis and metabolism. Studies described 135 unique miRNAs that were associated with GDM, of which eight (miR-16-5p, miR-17-5p, miR-20a-5p, miR-29a-3p, miR-195-5p, miR-222-3p, miR-210-3p, and miR-342-3p) were described in 2 or more studies. Findings suggest that miRNA levels vary based on the time in pregnancy when GDM develops, the time point at which they were measured, sex assigned at birth of the offspring, and both the pre-pregnancy and gestational body mass index of the pregnant person.ConclusionsThe mRNA, miRNA, gene targets, and pathways identified in this review contribute to our understanding of GDM pathogenesis; however, further research is warranted to validate previous findings. In particular, longitudinal repeated-measures designs are needed that control for participant characteristics (e.g., weight), use standardized data collection methods and analysis tools, and are sufficiently powered to detect differences between subgroups. Findings may be used to improve early diagnosis, prevention, medication choice and/or clinical treatment of patients with GDM.

Multigenerational diabetes mellitus

“…Lewis et al. performed a systematic review on maternal miRNAs in GDM however reported difficulty forming conclusions due to significant heterogeneity between studies (timepoints collected, diagnostic criteria used, inconsistent recording of ethnicity) and lack of adjustment for confounders ( 114 ). The most validated circulating miRNAs in maternal blood for GDM identified are summarized in the table below ( Table 2 ).…”

MicroRNAs Associated with Metformin Treatment in the Diabetes Prevention Program

“…Research in both human and mouse models suggests that expression of miRs in males and females may be either consistently, differentially, or oppositely expressed in speci c diseases (i.e., one sex is upregulated and the other sex is downregulated). [32,45] More work is needed to understand sex-biased expression of the miRs in patients with T2D, and to differentiate the effects of biological sex from self-reported gender related to miR expression and risk for T2D.…”

Value of Non-Coding RNA Expression in Biofluids to Identify Patients at Low Risk of Pathologies Associated with Pregnancy

“…However, the authors underlined limitations linked to the heterogeneity of the studies. A literature review of 16 studies involving 1355 patients (n = 674 with GDM, n = 681 controls), Lewis et al showed that 135 miRNAs were associated with GDM, including 8 described in at least two studies (miRNA-16-5p, miRNA -17-5p, miRNA-20a-5p, miRNA-29a-3p, miRNA-195-5p, miRNA-222-3p, miRNA-210-3p, and miRNA-342-3p) [88]. These results suggest that miRNA levels vary depending on the term of pregnancy when GDM develops, fetal sex, and BMI both before and during pregnancy.…”