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
TL;DR: The present study shows for the first time that increased miR-16-5p expression is associated with PCOS in pregnancy and downregulated mi R-155-5P expression was found in relation with GDM.
Abstract: 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 ...
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TL;DR: In this article, 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) entailed 82 GDM cases (early and late- GDM), and 41 age and BMI-matched women with normal glucose tolerance (NGT) throughout pregnancy (controls).
Abstract: 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.
25 citations
TL;DR: This work systematically describes the reports investigating the role of miR-155 in DM and discusses 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.
Abstract: 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.
23 citations
Cites background from "Identification of miR-16-5p and miR..."
...Low plasma levels of miR-155 were also found in gestational DM [54]....
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...Pregnant women with gestational diabetes and healthy pregnant women 69 peripheral white blood cells ↓miR-155 in pregnant women with gestational diabetes compared to healthy controls [54]...
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TL;DR: In this article, the authors investigated potential miRNA regulators for serum lipids and blood glucose, and found that miRNAs are potentially involved in the regulation of glucose and lipid metabolism.
Abstract: 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...
18 citations
TL;DR: The role of miRNAs as a predictive factor that could potentially be useful in early diagnosis of gestational diabetes mellitus is emphasized, and changes in miRNA profile in the serum of GDM women may indicate significance in the pathophysiology of G DM.
Abstract: 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.
11 citations
TL;DR: 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) and may eventually afford clinicians to control the molecular course of the pathogenesis better.
Abstract: 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.
11 citations
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TL;DR: G*Power 3 provides improved effect size calculators and graphic options, supports both distribution-based and design-based input modes, and offers all types of power analyses in which users might be interested.
Abstract: G*Power (Erdfelder, Faul, & Buchner, 1996) was designed as a general stand-alone power analysis program for statistical tests commonly used in social and behavioral research. G*Power 3 is a major extension of, and improvement over, the previous versions. It runs on widely used computer platforms (i.e., Windows XP, Windows Vista, and Mac OS X 10.4) and covers many different statistical tests of thet, F, and χ2 test families. In addition, it includes power analyses forz tests and some exact tests. G*Power 3 provides improved effect size calculators and graphic options, supports both distribution-based and design-based input modes, and offers all types of power analyses in which users might be interested. Like its predecessors, G*Power 3 is free.
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TL;DR: Since the 1990 NIH-sponsored conference on polycystic ovary syndrome, it has become appreciated that the syndrome encompasses a broader spectrum of signs and symptoms of ovarian dysfunction than those defined by the original diagnostic criteria.
8,217 citations
TL;DR: The Brazilian study provided evidence that adverse perinatal outcomes are associated with levels of maternal glycemia below those diagnostic of GDM by American Diabetes Association or World Health Organization criteria, however, the results were potentially confounded by the treatment of G DM.
Abstract: In the accompanying comment letter (1), Weinert summarizes published data from the Brazilian Gestational Diabetes Study (2) and comments on applying International Association of Diabetes and Pregnancy Study Groups (IADPSG) Consensus Panel recommendations (3) for the diagnosis of gestational diabetes mellitus (GDM) to that cohort.
The Brazilian study provided evidence that adverse perinatal outcomes are associated with levels of maternal glycemia below those diagnostic of GDM by American Diabetes Association or World Health Organization criteria. However, the results were potentially confounded by the treatment of GDM. It did find that women with GDM were at increased risk for some …
1,265 citations
TL;DR: The present results suggest that miRNAs that play an important role in metabolic and immune system processes are influenced by obesity and circulating androgen concentrations.
Abstract: Context: MicroRNAs (miRNAs) are small, noncoding RNA sequences that negatively regulate gene expression at the post-transcriptional level. miRNA-21, miRNA-27b, miRNA-103, and miRNA-155 have been associated with metabolic disorders such as obesity and diabetes, which are also associated with polycystic ovary syndrome (PCOS). Objective: We aimed to evaluate the effects of sex, sex hormones, and PCOS and their interactions with obesity on the expression in the circulation of these miRNAs. Design: This was a case-control study. Settings: The setting was an academic hospital. Participants: We included 12 control women, 12 patients with PCOS, and 12 men selected as to have similar body mass index (BMI) and age. Six subjects per group had normal weight (BMI < 25 kg/m2), and six subjects per group were obese (BMI ≥ 30 kg/m2). Interventions: Blood samples were collected early in the morning after a 12-hour fast. Main Outcome Measures: We measured whole blood expression of miRNA-21, miRNA-27b, miRNA-103, and miRNA-...
141 citations
TL;DR: It is emphasized that circulating miRNAs are strongly impacted by age, BMI, and sex, and these parameters should be considered as covariates in association studies based on plasma miRNA levels.
Abstract: Non-cellular blood circulating microRNAs (plasma miRNAs) represent a promising source for the development of prognostic and diagnostic tools owing to their minimally invasive sampling, high stability, and simple quantification by standard techniques such as RT-qPCR. So far, the majority of association studies involving plasma miRNAs were disease-specific case-control analyses. In contrast, in the present study, plasma miRNAs were analysed in a sample of 372 individuals from a population-based cohort study, the Study of Health in Pomerania (SHIP). Quantification of miRNA levels was performed by RT-qPCR using the Exiqon Serum/Plasma Focus microRNA PCR Panel V3.M covering 179 different miRNAs. Of these, 155 were included in our analyses after quality-control. Associations between plasma miRNAs and the phenotypes age, body mass index (BMI), and sex were assessed via a two-step linear regression approach per miRNA. The first step regressed out the technical parameters and the second step determined the remaining associations between the respective plasma miRNA and the phenotypes of interest. After regressing out technical parameters and adjusting for the respective other two phenotypes, 7, 15, and 35 plasma miRNAs were significantly (q < 0.05) associated with age, BMI, and sex, respectively. Additional adjustment for the blood cell parameters identified 12 and 19 miRNAs to be significantly associated with age and BMI, respectively. Most of the BMI-associated miRNAs likely originate from liver. Sex-associated differences in miRNA levels were largely determined by differences in blood cell parameters. Thus, only 7 as compared to originally 35 sex-associated miRNAs displayed sex-specific differences after adjustment for blood cell parameters. These findings emphasize that circulating miRNAs are strongly impacted by age, BMI, and sex. Hence, these parameters should be considered as covariates in association studies based on plasma miRNA levels. The established experimental and computational workflow can now be used in future screening studies to determine associations of plasma miRNAs with defined disease phenotypes.
136 citations