Early identification of gestational diabetes mellitus (GDM) aims to reduce the risk of adverse maternal and perinatal outcomes. Currently, no circulating biomarker has proven clinically useful for accurate prediction of GDM. In this study, we tested if a panel of small non-coding circulating RNAs could improve early prediction of GDM. We performed a nested case-control study of participants from the European multicenter 'Vitamin D and lifestyle intervention for GDM prevention (DALI)' trial using serum samples from obese pregnant women (BMI ≥ 29 kg/m2) entailing 82 GDM cases (early- and late- GDM), and 41 age- and BMI-matched women with normal glucose tolerance (NGT) throughout pregnancy (controls). Anthropometric, clinical and biochemical characteristics were obtained at baseline (<20 weeks of gestation) and throughout gestation. Baseline serum microRNAs (miRNAs) were measured using quantitative real time PCR (qPCR). Elevated miR-16-5p, -29a-3p, and -134-5p levels were observed in women, who were NGT at baseline and later developed GDM, compared with controls who remained NGT. A combination of the three miRNAs could distinguish later GDM from NGT cases (AUC 0.717, p = 0.001, compared with fasting plasma glucose (AUC 0.687, p = 0.004)) as evaluated by area under the curves (AUCs) using Receiver Operator Characteristics (ROC) analysis. Elevated levels of individual miRNAs or a combination hereof were associated with higher odds ratios of GDM. Conclusively, circulating miRNAs early in pregnancy could serve as valuable predictive biomarkers of GDM.

The Predictive Value of miR-16, -29a and -134 for Early Identification of Gestational Diabetes: A Nested Analysis of the DALI Cohort.

Substantial evidence indicates that microRNA-155 (miR-155) plays a crucial role in the pathogenesis of diabetes mellitus (DM) and its complications. A number of clinical studies reported low serum levels of miR-155 in patients with type 2 diabetes (T2D). Preclinical studies revealed that miR-155 partakes in the phenotypic switch of cells within the islets of Langerhans under metabolic stress. Moreover, miR-155 was shown to regulate insulin sensitivity in liver, adipose tissue, and skeletal muscle. Dysregulation of miR-155 expression was also shown to predict the development of nephropathy, neuropathy, and retinopathy in DM. Here, we systematically describe the reports investigating the role of miR-155 in DM and its complications. We also discuss the recent results from in vivo and in vitro models of type 1 diabetes (T1D) and T2D, discussing the differences between clinical and preclinical studies and shedding light on the molecular pathways mediated by miR-155 in different tissues affected by DM.

https://www.mdpi.com/2311-553X/7/3/39/pdf

Functional Role of miR-155 in the Pathogenesis of Diabetes Mellitus and Its Complications.

MicroRNAs (miRNAs) are potentially involved in the regulation of glucose and lipid metabolism. The aim of this study was to investigate potential miRNA regulators for serum lipids and blood glucose...

Circulating miRNAs miR-574-5p and miR-3135b are potential metabolic regulators for serum lipids and blood glucose in gestational diabetes mellitus.

Introduction Circulating 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 Methods The 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. Results Among 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). Conclusion We 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.

/pdf/mirnas-as-predictive-factors-in-early-diagnosis-of-5morgcfn.pdf

miRNAs as Predictive Factors in Early Diagnosis of Gestational Diabetes Mellitus

Polycystic ovary syndrome (PCOS) is known as the most common metabolic/endocrine disorder among women of reproductive age. Its complicated causality assessment and diagnostic emphasized the role of non‐coding regulatory RNAs as molecular biomarkers in studying, diagnosing and even as therapeutics of PCOS. This review discusses a comparative summary of research into microRNAs (miRNAs) and long non‐coding RNAs (lncRNAs) that are molecularly or statistically related to PCOS. We categorize the literature in terms of centering on either miRNAs or lncRNAs and discuss the combinatory studies and promising ideas as well. Additionally, we compare the pros and cons of the prominent research methodologies used for each of the abovementioned research themes and discuss how errors can be stopped from propagation by selecting correct methodologies for future research. Finally, it can be concluded that research into miRNAs and lncRNAs has the potential for identifying functional networks of regulation with multiple mRNAs (and hence, functional proteins). This new understanding may eventually afford clinicians to control the molecular course of the pathogenesis better. With further research, RNA (with statistical significance and present in the blood) may be used as biomarkers for the disease, and more possibilities for RNA therapy agents can be identified.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jcmm.17139

microRNAs and long non‐coding RNAs as biomarkers for polycystic ovary syndrome

Pregnant women with polycystic ovary syndrome (PCOS) are at increased risk of gestational diabetes (GDM). We aimed to assess the expressions of candidate microRNAs (miRs) in leukocytes of pregnant ...

Identification of miR-16-5p and miR-155-5p microRNAs differentially expressed in circulating leukocytes of pregnant women with polycystic ovary syndrome and gestational diabetes

Numerous settlements have been identified during the surveys in Şırnak province (Turkey) since the beginning of the 19th century. The potsherds found in the central of such settlements have been thought to be affected by Mesopotamian culture, and the ones from the hillside of the Şah Valley were considered as the most eastern examples of the Hassuna Samara culture. This study presents the results regarding one of the first detailed archaeometric investigations carried out for the Late Neolithic ceramic findings unearthed from Şah Valley (Şırnak province, Turkey). The ceramics were initially characterized by means of portable X-ray florescence (p-XRF) and X-ray diffraction (XRD) in order to enlighten the chemical and mineralogical features of the samples, respectively. The results indicated use of calcareous raw material sources and a low firing temperature range (ca. 700-800oC). The potsherds were also investigated through petrography which showed the presence of quartz, opaque minerals, plagioclase and biotite as the minerals, and clay, claystone and marl rock contents as the rock types for the samples, in general. Fourier transformed infrared (FTIR) spectroscopy was additionally applied for the potsherds. This complementary technique provided information about the vibrations of the chemical bands in the ceramics which displayed the characteristic bond vibrations of decisive minerals in the ceramic fabrics, such as calcite, clay minerals and quartz. Considering the whole archaeometric data, it can be deduced that the Neolithic ceramics of the Şah Valley have been subjected to low firing temperatures which could be assigned to a basic production procedure presumably claiming daily-use wares.

/pdf/chemical-and-mineralogical-analyses-of-the-late-neolithic-vl3xor2o.pdf

Esra Kaynak

Papers

Identification of miR-16-5p and miR-155-5p microRNAs differentially expressed in circulating leukocytes of pregnant women with polycystic ovary syndrome and gestational diabetes

Chemical and mineralogical analyses of the late neolithic ceramics from şah valley (singuber), turkey