Substantially Altered Expression Profile of Diabetes/Cardiovascular/Cerebrovascular Disease Associated microRNAs in Children Descending from Pregnancy Complicated by Gestational Diabetes Mellitus—One of Several Possible Reasons for an Increased Cardiovascular Risk

Abstract

Gestational diabetes mellitus (GDM), one of the major pregnancy-related complications, characterized as a transitory form of diabetes induced by insulin resistance accompanied by a low/absent pancreatic beta-cell compensatory adaptation to the increased insulin demand, causes the acute, long-term, and transgenerational health complications. The aim of the study was to assess if alterations in gene expression of microRNAs associated with diabetes/cardiovascular/cerebrovascular diseases are present in whole peripheral blood of children aged 3–11 years descending from GDM complicated pregnancies. A substantially altered microRNA expression profile was found in children descending from GDM complicated pregnancies. Almost all microRNAs with the exception of miR-92a-3p, miR-155-5p, and miR-210-3p were upregulated. The microRNA expression profile also differed between children after normal and GDM complicated pregnancies in relation to the presence of overweight/obesity, prehypertension/hypertension, and/or valve problems and heart defects. Always, screening based on the combination of microRNAs was superior over using individual microRNAs, since at 10.0% false positive rate it was able to identify a large proportion of children with an aberrant microRNA expression profile (88.14% regardless of clinical findings, 75.41% with normal clinical findings, and 96.49% with abnormal clinical findings). In addition, the higher incidence of valve problems and heart defects was found in children with a prior exposure to GDM. The extensive file of predicted targets of all microRNAs aberrantly expressed in children descending from GDM complicated pregnancies indicates that a large group of these genes is involved in ontologies of diabetes/cardiovascular/cerebrovascular diseases. In general, children with a prior exposure to GDM are at higher risk of later development of diabetes mellitus and cardiovascular/cerebrovascular diseases, and would benefit from dispensarisation as well as implementation of primary prevention strategies.

Association Analysis in Children Born from Normal and Complicated Pregnancies—Cardiovascular Disease Associated microRNAs and the Incidence of Prehypertension/Hypertension, Overweight/Obesity, Valve Problems and Heart Defects

“…Standardized blood pressure (BP) and echocardiography measurements and BMI assessment were performed as previously described [52,53,68]. More details are also available in Supplementary Materials.…”

“…Processing of samples, reverse transcription and relative quantification of microRNAs were performed as previously described [52,53,69,70]. More details are also available in Supplementary Materials.…”

“…Recently, we reported that a proportion of children affected with gestational hypertension (GH), preeclampsia (PE), fetal growth restriction (FGR) and gestational diabetes mellitus (GDM) had altered microRNA expression profiles that may contribute to the predisposition of these children to later onset of diabetes mellitus, cardiovascular and cerebrovascular diseases [ 52 , 53 ].…”

“…Prenatal exposure to maternal complications (GH, PE and GDM) or fetal complication (FGR) was associated in a proportion of children with deregulation of miR-1–3p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-26a-5p, miR-29a-3p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-133a-3p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-210-3p and miR-342-3p [ 52 , 53 ].…”

“…In addition, a prior exposure to GDM induced postnatal deregulation of miR-16-5p, miR-92a-3p, miR-100-5p, miR-143-3p, miR-155-5p, miR-221-3p, miR-499a-5p and miR-574-3p [ 53 ].…”