Diabetes in Pregnancy and MicroRNAs: Promises and Limitations in Their Clinical Application

Abstract

Maternal diabetes is associated with an increased risk of complications for the mother and her offspring. The latter have an increased risk of foetal macrosomia, hypoglycaemia, respiratory distress syndrome, preterm delivery, malformations and mortality but also of life-long development of obesity and diabetes. Epigenetics have been proposed as an explanation for this long-term risk, and microRNAs (miRNAs) may play a role, both in short- and long-term outcomes. Gestation is associated with increasing maternal insulin resistance, as well as β-cell expansion, to account for the increased insulin needs and studies performed in pregnant rats support a role of miRNAs in this expansion. Furthermore, several miRNAs are involved in pancreatic embryonic development. On the other hand, maternal diabetes is associated with changes in miRNA both in maternal and in foetal tissues. This review aims to summarise the existing knowledge on miRNAs in gestational and pre-gestational diabetes, both as diagnostic biomarkers and as mechanistic players, in the development of gestational diabetes itself and also of short- and long-term complications for the mother and her offspring.

Diabetes Mellitus and Cardiovascular Risk Assessment in Mothers with a History of Gestational Diabetes Mellitus Based on Postpartal Expression Profile of MicroRNAs Associated with Diabetes Mellitus and Cardiovascular and Cerebrovascular Diseases

“…In compliance with our study, which showed a low sensitivity of miR-20a-5p (10.81%) to select women with a higher cardiovascular risk after GDM gestation based on its upregulated profile, miR-20a-5p also added little value as the predictor of GDM due to its low predictive value based on its upregulated profile (ROC, AUC just 0.740) [21,173].…”

“…However, most of microRNAs, which were the subjects of our interest, have not yet been observed by other investigators to be dysregulated in maternal circulation (peripheral blood, plasma, or serum samples) of women with clinically established GDM or before the onset of GDM [20,21,37,80,92,143,149,[172][173][174][175][176]. So, it is feasible that epigenetic profiles of a series of microRNAs have also been changing with time by force of various circumstances as a result of the interaction between genetic and environmental factors [177].…”

“…In addition, from the portfolio of microRNAs we tested, just miR-16-5p, miR-17-5p, miR-20a-5p, and miR-29a were identified by other investigators as the most promising biomarkers of GDM or the best predictors of GDM, respectively [21,173], which is consistent with our current finding, since during the course of postpartum screening, miR-16-5p (20.72%), miR-17-5p (21.62%), and miR-29a-3p (21.62%) upregulation persisted in a larger proportion of women with a prior exposure to GDM.…”

“…Moreover, a set of circulating microRNAs associated with cardiovascular/cerebrovascular diseases (miR-16-5p, miR-17-5p, miR-20a-5p, miR-29a-3p, miR-125b-5p, and miR-195-5p) was reported by several independent studies [20,21,80,92,143,172,173] to be upregulated during various gestational ages in serum or plasma of mothers with already-diagnosed GDM or mothers who were destined to develop GDM later during pregnancy. The data resulting from these prenatally ongoing studies and interaction network analysis [20,21,80,92,98,125,143,172,173] may support our current finding referring to upregulated expression profile of these particular microRNAs in whole peripheral blood of women with a prior exposure to GDM.…”

Insulin Therapy in Gestational Diabetes

“…Micro-RNAs are now extensively studied in different domains and might apply to diagnosing and selecting GDM patients that require insulin treatment [92].…”