Cardiovascular Disease-Associated MicroRNAs as Novel Biomarkers of First-Trimester Screening for Gestational Diabetes Mellitus in the Absence of Other Pregnancy-Related Complications

Abstract

We assessed the diagnostic potential of cardiovascular disease-associated microRNAs for the early prediction of gestational diabetes mellitus (GDM) in singleton pregnancies of Caucasian descent in the absence of other pregnancy-related complications. Whole peripheral venous blood samples were collected within 10 to 13 weeks of gestation. This retrospective study involved all pregnancies diagnosed with only GDM (n = 121) and 80 normal term pregnancies selected with regard to equality of sample storage time. Gene expression of 29 microRNAs was assessed using real-time RT-PCR. Upregulation of 11 microRNAs (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-23a-3p, miR-100-5p, miR-125b-5p, miR-126-3p, miR-181a-5p, miR-195-5p, miR-499a-5p, and miR-574-3p) was observed in pregnancies destinated to develop GDM. Combined screening of all 11 dysregulated microRNAs showed the highest accuracy for the early identification of pregnancies destinated to develop GDM. This screening identified 47.93% of GDM pregnancies at a 10.0% false positive rate (FPR). The predictive model for GDM based on aberrant microRNA expression profile was further improved via the implementation of clinical characteristics (maternal age and BMI at early stages of gestation and an infertility treatment by assisted reproductive technology). Following this, 69.17% of GDM pregnancies were identified at a 10.0% FPR. The effective prediction model specifically for severe GDM requiring administration of therapy involved using a combination of these three clinical characteristics and three microRNA biomarkers (miR-20a-5p, miR-20b-5p, and miR-195-5p). This model identified 78.95% of cases at a 10.0% FPR. The effective prediction model for GDM managed by diet only required the involvement of these three clinical characteristics and eight microRNA biomarkers (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-100-5p, miR-125b-5p, miR-195-5p, miR-499a-5p, and miR-574-3p). With this, the model identified 50.50% of GDM pregnancies managed by diet only at a 10.0% FPR. When other clinical variables such as history of miscarriage, the presence of trombophilic gene mutations, positive first-trimester screening for preeclampsia and/or fetal growth restriction by the Fetal Medicine Foundation algorithm, and family history of diabetes mellitus in first-degree relatives were included in the GDM prediction model, the predictive power was further increased at a 10.0% FPR (72.50% GDM in total, 89.47% GDM requiring therapy, and 56.44% GDM managed by diet only). Cardiovascular disease-associated microRNAs represent promising early biomarkers to be implemented into routine first-trimester screening programs with a very good predictive potential for GDM.

HtrA1 in Gestational Diabetes Mellitus: A Possible Biomarker?

“…These data were in agreement with previous studies, showing an increased risk of developing GDM in the presence of a high BMI before pregnancy [ 36 , 37 ]. It is possible to hypothesize that the placenta responds to altered glucose metabolism already in the first trimester, secreting high HtrA1 levels, although GDM will only be diagnosed later in pregnancy when the altered maternal blood glucose levels become visible at the OGTT test.…”

Association between Circulating MicroRNAs (miR-21-5p, miR-20a-5p, miR-29b-3p, miR-126-3p and miR-101-3p) and Chronic Allograft Dysfunction in Renal Transplant Recipients

“…Hromadnikova et al were able to predict that 47.93% of patients were destined to develop gestational diabetes mellitus (GDM) at a 10.0% false-positive rate during the first trimester of pregnancy, with 11 dysregulated microRNAs. After incorporating clinical characteristics, the team increased their detection rate to 72.5%, with a 10% false-positive rate [ 61 ]. We will consider combining the microRNAs together and then evaluating their performance when predicting CAD.…”

First-Trimester Screening for HELLP Syndrome—Prediction Model Based on MicroRNA Biomarkers and Maternal Clinical Characteristics

“…Recently, we reported an altered expression profile of microRNAs associated with the cardiovascular system in pregnant women affected with chronic hypertension [ 48 ] and in normotensive early pregnancies with subsequent onset of gestational hypertension (GH) [ 48 ], PE [ 48 ], fetal growth restriction (FGR) [ 49 ], small for gestational age (SGA) [ 49 ], preterm delivery [ 50 ], and/or gestational diabetes mellitus (GDM) [ 51 ]. Therefore, we were interested to determine whether an altered expression profile of microRNAs associated with the cardiovascular system might also be present in pregnancies developing HELLP syndrome.…”