Background and aims: Gestational diabetes (GDM) leads to increased risk of complications during pregnancy, as well as a 50% chance of developing type 2 diabetes (T2D) in later life. Metformin is used as one of the treatments for GDM and as metformin crosses the placental barrier, long-term effects on the fetus of in utero metformin exposure are possible. We therefore aimed to understand the potential effects of metformin exposure using in vitro and longitudinal clinical (MiG and MiG-TOFU) samples.

Materials and methods: Human endothelial cells and islets were cultured in defined medium and exposed to normal / high glucose concentrations with or without metformin for 4 days.  RNA was isolated from the cells and culture supernatants and it was then used for real time PCR using Whole Panel microRNA OpenArrays. Similarly, we analysed RNA isolated from serum of longitudinal samples from mothers and their offsprings enrolled in Metformin in Gestation (MiG) study.  Data was analysed using expression suite and microRNAs with >2 fold difference and p

Results: As part of this ongoing study, we assessed cellular and released microRNAs from in vitro cultures of human endothelial cells and cadaveric pancreatic islets and identified a subset of differentially expressed microRNAs from cells that were exposed to metformin as compared to those without metformin.  Longitudinal samples from MiG study were from two treatment groups; one with metformin and other with insulin. We have identified differential expression of miRNAs in these treatment groups in mothers as well as their offspring. 

Further analyses to identify associations between microRNA expression and clinical characteristics will help in understanding the potential of these circulating microRNAs as biomarkers of metabolic health.