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.

Ilona Hromadnikova,Katerina Kotlabova,Jan Sirc,Lenka Dvorakova,Ladislav Krofta

doi:10.3390/cells9061557

Ilona Hromadnikova, Katerina Kotlabova + Show 3 more

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https://doi.org/10.3390/cells9061557

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Journal: Cells	Publication Date: Jun 26, 2020
Citations: 23	License type: CC BY 4.0

Affiliation: Charles University

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.

Highlights

Gestational diabetes mellitus (GDM) represents a pregnancy-related complication with the onset during the second or third trimester of gestation with worldwide increasing prevalence ranging from 7 to 14% [1,2]
The hypothesis of the assessment of potential diabetes/cardiovascular risk in children prenatally exposed to GDM was based on the knowledge that a serious of microRNAs play a role in the pathogenesis of diabetes mellitus and cardiovascular/cerebrovascular diseases (Table 1) [46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194,195,196,197,198,199,200,201,202,203,204,205,206,207,208,209,210,211,212,213,214,215,216,217,218,219,220,221]
Screening based on the combination of microRNAs with a good sensitivity only in the Receivers operating characteristic (ROC) curve analysis was superior over using individual microRNAs for the prediction of potential risk of later development of diabetes mellitus and/or cardiovascular/cerebrovascular diseases, since it was able to identify 88.14% children with an aberrant microRNA expression profile at 10.0% false positive rate (FPR)

Summary

Introduction

Gestational diabetes mellitus (GDM) represents a pregnancy-related complication with the onset during the second or third trimester of gestation with worldwide increasing prevalence ranging from 7 to 14% [1,2]. MicroRNAs are important metabolic and developmental regulators during gestation that play a role in the onset of GDM [7]. Recent studies have evaluated the expression of microRNAs playing a role in glucose homeostasis, insulin sensitivity, and beta-cell function in different sample types (placenta, umbilical vein endothelial cells, whole blood, plasma, and serum) with the aim to assess their potential as diagnostic or prognostic biomarkers of GDM [7,8,9,10,11,12,13,14,15,16,17,18,19,20,21].

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