miRNAs as Predictive Factors in Early Diagnosis of Gestational Diabetes Mellitus

Abstract

IntroductionCirculating miRNAs are important mediators in epigenetic changes. These non-coding molecules regulate post-transcriptional gene expression by binding to mRNA. As a result, they influence the development of many diseases, such as gestational diabetes mellitus (GDM). Therefore, this study investigates the changes in the miRNA profile in GDM patients before hyperglycemia appears.Materials and MethodsThe study group consisted of 24 patients with GDM, and the control group was 24 normoglycemic pregnant women who were matched for body mass index (BMI), age, and gestational age. GDM was diagnosed with an oral glucose tolerance test between the 24th and 26th weeks of pregnancy. The study had a prospective design, and serum for analysis was obtained in the first trimester of pregnancy. Circulating miRNAs were measured using the NanoString quantitative assay platform. Validation with real time-polymerase chain reaction (RT-PCR) was performed on the same group of patients. Mann-Whitney U-test and Spearman correlation were done to assess the significance of the results.ResultsAmong the 800 miRNAs, 221 miRNAs were not detected, and 439 were close to background noise. The remaining miRNAs were carefully investigated for their average counts, fold changes, p-values, and false discovery rate (FDR) scores. We selected four miRNAs for further validation: miR-16-5p, miR-142-3p, miR-144-3p, and miR-320e, which showed the most prominent changes between the studied groups. The validation showed up-regulation of miR-16-5p (p<0.0001), miR-142-3p (p=0.001), and miR-144-3p (p=0.003).ConclusionWe present changes in miRNA profile in the serum of GDM women, which may indicate significance in the pathophysiology of GDM. These findings emphasize the role of miRNAs as a predictive factor that could potentially be useful in early diagnosis.

Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life

“…Notably, miR-16-5p inhibits the apoptosis of high glucose-induced pancreatic β cells via targeting of chemokine with CXC motif ligand 10 [ 387 ]. Circulating serum levels of miR-16-5p were upregulated in women with gestational diabetes [ 388 ]. Remarkably, miR-16-5p directly targets sestrin 1 ( SESN1 ) [ 389 ], whereas miR-148a-3p converges with miR-16-5p in targeting sestrin 2 ( SESN2 ) [ 390 ].…”

Systematic review of transcriptome and microRNAome associations with gestational diabetes mellitus

“…MiR-16-5p is a powerful regulator of the insulin signaling pathway, pancreatic β-cell proliferation and apoptosis, and branched chain amino acids involved in insulin dysregulation ( 45 – 48 ). Target genes of miR-16-5p in mouse model and in vitro mechanistic studies include those that encode for insulin receptor substrate (IRS) proteins 1 and 2, the insulin receptor (INSR), and at least 24 other targets in the insulin signaling pathway like ak strain transforming (AKT) protein 1 and 3 ( 45 – 48 ). Other targets include genes encoding for the mammalian target of rapamycin (mTOR) protein and b-cell leukemia/lymphoma 2 protein (BCL-2) expression ( 45 , 48 ), among others.…”

“…Target genes of miR-16-5p in mouse model and in vitro mechanistic studies include those that encode for insulin receptor substrate (IRS) proteins 1 and 2, the insulin receptor (INSR), and at least 24 other targets in the insulin signaling pathway like ak strain transforming (AKT) protein 1 and 3 ( 45 – 48 ). Other targets include genes encoding for the mammalian target of rapamycin (mTOR) protein and b-cell leukemia/lymphoma 2 protein (BCL-2) expression ( 45 , 48 ), among others.…”

“…Our review found that miR-16-5p was upregulated compared to the control group in 80% (4 out of 5) of the included studies that reported it in their findings ( Table 4 ). It was upregulated prior to onset of GDM in the first trimester (weeks 9-12) ( 48 ), during weeks 16-19 ( 27 , 37 ), and in weeks 24-28 ( 25 , 37 , 48 ). Elevated gestational miR-16-5p may persist beyond pregnancy and may be permanently altered in women with GDM ( 35 ).…”

The Role of microRNAs in Inflammation

“…The levels of miR-122, miR-758, and miR-133a were also shown to be up-regulated in the maternal sera of patients suffering from HELLP syndrome [ 198 ]. miR-16-5p, miR-142-3p, and miR-144-3p are also shown to be up-regulated in the sera of women with gestational diabetes mellitus (GDM) and could serve as biomarkers for GDM [ 199 ].…”