Changes of serum selenium in pregnant women with gestational diabetes mellitus

Gestational diabetes is one of the most common diseases in pregnancy. In the present work, the possible relationship between serum selenium concentration and gestational diabetes was investigated. Blood samples of 234 pregnant women were collected, including 98 subjects with impaired glucose tolerance (IGT), 46 subjects with gestational diabetes mellitus (GDM), and 90 normal pregnant women (NPW). An additional 17 samples of normal women of fertile age (NW) were collected for comparison. The hydride generation atomic fluorescence spectrometry was used for selenium determination. The mean serum selenium levels obtained for each group were 0.0741±0.0167 mg/L for NPW, 0.0631±0.0132 mg/L for IGT, 0.0635±0.0120 mg/L for GDM, and 0.108±0.0170 mg/L for NW. Serum selenium levels were significantly lower in pregnant woman with IGT (p<0.001) and GDM (p<0.001) than in NPW. Furthermore, an inverse correlation between the serum selenium concentration and the gestational period was also observed. Selenium supplementation during gestation for pregnant women, especially with IGT and GDM, should be considered.     

Features of insulin receptor interaction in placenta from normal,overt and poorly controlled gestational diabetic patients

Features of insulin binding to trophoblast plasma membranes were studied in six normal pregnant women (NP), six overt diabetes (ODP) and six poorly controlled glycemic gestational patients (PCDP) i.e. women who did not strictly follow the management of diabetes mellitus during pregnancy. A decreased maximum specific insulin receptor binding per 0.1 mg membrane protein in placenta from PCDP (12%) was found comparing with that from ODP or NP (17.5% and 36.2%, respectively, P<0.01), The insulin binding in PCDP declined at a faster rate until it reached minimum when studied at a higher temperature (25–37°C). The binding equilibrium was likewise attained faster at this temperature than that at lower temperature of 4°C for all studied groups.The insulin receptor binding in all studied groups was pH dependent. The maximum binding in ODP and PCDP groups was attained at pH 7.8 while for NP maximum binding was at pH 7.4. The competitive dinding assay was carried out with 14 concentrations of unlabelled insulin and the half maximal displacement of¹²⁵I-insulin was at 8×10^–9 M, 6×10^–9 M and 4×10^–9 M for NP, ODP and PCDP, respectively (P<0.05) suggesting the differences in the effect of glycemic control on the insulin binding. Furthermore the binding yielded curvilinear Scatchard plots with the apparent affinity of the receptors being affected in the ODP and PCDP groups.The molecular characteristics of the receptors in the diabetic patients as revealed by the cross-linking technique used in this study did not reveal any changes in the subunit structures when compared with normals except that the¹²⁵I-insulin bound as shown by the band intensity was much less in PCDP. These findings indicate that control of hyperglycemia could optimize the outcome of insulin receptor function during diabetic pregnancy.     

First‐trimester blood urea nitrogen and risk of gestational diabetes mellitus

Prior studies indicated that urea increased insulin resistance and higher blood urea nitrogen (BUN) was associated with incident diabetes mellitus. However, it remains unclear whether BUN during the first trimester of pregnancy increases risk of gestational diabetes mellitus (GDM). We aimed to investigate the association between first‐trimester BUN and risk of incident GDM. We conducted a prospective, multicenter cohort study of pregnant women. A total of 13 448 eligible pregnant women with measured first‐trimester BUN levels were included in this analysis. Logistic regression analysis was used to estimate the relationship between BUN and GDM. Discrimination and reclassification for GDM by BUN were analysed. A total of 2973 (22.1%) women developed GDM. Compared with the lowest quartile of BUN, the third and fourth quartiles were associated with increased risk of GDM (adjusted odds ratios 1.21 [95% CI 1.07‐1.37] and 1.50 [95% CI 1.33‐1.69], respectively, P for trend <.001). The addition of BUN to conventional factor model improved discrimination (C statistic 0.2%, P = .003) and reclassification (net reclassification index 14.67%, P < .001; integrated discrimination improvement 0.12%, P < .001) for GDM. In conclusion, higher BUN concentrations during the first trimester of pregnancy were associated with increased risk of GDM, suggesting that BUN could be a potential predictor for GDM.     

Serum metabonomics study of pregnant women with gestational diabetes mellitus based on LC-MS

ObjectiveThrough metabolomics method, the objective of the paper is to differentially screen serum metabolites of GDM patients and healthy pregnant women, to explore potential biomarkers of GDM and analyze related pathways, and to explain the potential mechanism and biological significance of GDM.MethodsThe serum samples from 30 GDM patients and 30 healthy pregnant women were selected to conduct non-targeted metabolomics study by liquid chromatography-mass spectrometry. The differential metabolites between the two groups were searched and the metabolic pathway was analyzed by KEGG database.ResultsMultivariate statistical analysis found that serum metabolism in GDM patients was different significantly from healthy pregnant women, 36 differential metabolites and corresponding metabolic pathways were identified in serum, which involved several metabolic ways like, fatty acid metabolism, butyric acid metabolism, bile secretion, and amino acid metabolism.ConclusionThe discovery of these biomarkers provided a new theoretical basis and experimental basis for further study of the early diagnosis and pathogenesis of GDM. At the same time, LC-MS-based serum metabolomics methods also showed great application values in disease diagnosis and mechanism research.     

Epigenetic alternations of microRNAs and DNA methylation contribute to gestational diabetes mellitus

This study aimed to identify epigenetic alternations of microRNAs and DNA methylation for gestational diabetes mellitus (GDM) diagnosis and treatment using in silico approach. Data of mRNA and miRNA expression microarray ({"type":"entrez-geo","attrs":{"text":"GSE103552","term_id":"103552"}}GSE103552 and {"type":"entrez-geo","attrs":{"text":"GSE104297","term_id":"104297"}}GSE104297) and DNA methylation data set ({"type":"entrez-geo","attrs":{"text":"GSE106099","term_id":"106099"}}GSE106099) were obtained from the GEO database. Differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs) and differentially methylated genes (DMGs) were obtained by limma package. Functional and enrichment analyses were performed with the DAVID database. The protein‐protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape. Simultaneously, a connectivity map (CMap) analysis was performed to screen potential therapeutic agents for GDM. In GDM, 184 low miRNA‐targeting up‐regulated genes and 234 high miRNA‐targeting down‐regulated genes as well as 364 hypomethylation–high‐expressed genes and 541 hypermethylation–low‐expressed genes were obtained. They were mainly enriched in terms of axon guidance, purine metabolism, focal adhesion and proteasome, respectively. In addition, 115 genes (67 up‐regulated and 48 down‐regulated) were regulated by both aberrant alternations of miRNAs and DNA methylation. Ten chemicals were identified as putative therapeutic agents for GDM and four hub genes (IGF1R, ATG7, DICER1 and RANBP2) were found in PPI and may be associated with GDM. Overall, this study identified a series of differentially expressed genes that are associated with epigenetic alternations of miRNA and DNA methylation in GDM. Ten chemicals and four hub genes may be further explored as potential drugs and targets for GDM diagnosis and treatment, respectively.     

基于PacBio SMRT测序技术评估妊娠期糖尿病人的肠道菌群

[目的]肠道菌群是位于人体肠道内的微生物菌群,其组成与人类多种疾病相关。例如,已有研究表明肠道菌群的变化与妊娠期糖尿病（gestational diabetes mellitus,GDM）的发病密切相关。因此本研究基于PacBio SMRT测序技术评估及比较了不同民族（汉族和蒙古族）及是否患GDM的孕妇的肠道菌群。[方法]本研究利用PacBio SMRT测序技术对97例患有GDM及健康的汉族和蒙古族孕妇粪便样本进行了全长16S rRNA测序及分析。[结果]总体来说,处于相同孕期的4组孕妇肠道菌群的组成相似,不同核心菌群展现出不同强弱的相关性。本研究在种的水平上共鉴定到了44个种。在汉族人中,患有妊娠期糖尿病的孕妇肠道菌群中Akkermansia muciniphila菌的相对丰度要显著低于健康孕妇;而在蒙古族人中,健康孕妇与GDM孕妇间差异并不明显。在健康对照中发现汉族孕妇肠道菌群中Bacteroides uniformis菌的相对丰度显著高于蒙古族孕妇;但在患有GDM组中未找到不同民族分组间的差异。另外,功能预测结果发现四组样本菌群功能组成高度相似,大多数功能基因都与能量代谢有关。汉族GDM患者与健康对照组间没有发现显著差异,但在蒙古族GDM患者中发现无机离子运输等功能相对丰度显著高于与蒙古族正常孕妇。[结论]在相同的孕期,妊娠期孕妇的核心肠道菌群结构与功能是相对稳定的,而民族差异也不会对妊娠期菌群产生显著性影响。但在四组间可以检测到一些低丰度的差异菌群,如Akkermansia muciniphila,其丰度的变化可能导致了肠道中一些与肠道营养吸收等有关的代谢发生变化,而这些变化可能与妊娠期糖尿病的发生密切相关。本研究将有助于探究肠道菌群在GDM发病机制中的作用。     

The oral microbiome of pregnant women facilitates gestational diabetes discrimination

The oral microbiota plays an important role in the development of various diseases,whereas its association with gestational diabetes mellitus (GDM) remains largely unclear.The aim of this study is to identify biomarkers from the oral microbiota of GDM patients by analyzing the microbiome of the saliva and dental plaque samples of 111 pregnant women.We find that the microbiota of both types of oral samples in GDM patients exhibits differences and significantly varies from that of patients with periodontitis or dental caries.Using bacterial biomarkers from the oral microbiota,GDM classification models based on support vector machine and random forest algorithms are constructed.The area under curve (AUC) value of the classification model constructed by combination of Lautropia and Neisseria in dental plaque and Streptococcus in saliva reaches 0.83,and the value achieves a maximum value of 0.89 by adding clinical features.These findings suggest that certain bacteria in either saliva or dental plaque can effectively distinguish women with GDM from healthy pregnant women,which provides evidence of oral microbiome as an informative source for developing noninvasive biomarkers of GDM.     

Association between gestational diabetes and biomarkers: a role in diagnosis

Background: We investigated the association between markers of insulin resistance, chronic inflammation, and adipokines and GDM.

Methods: In our case-cohort study in Johannesburg we included women with GDM and controls. We tested the ability of biomarkers to identify women at high risk of GDM.

Results: Of the 262 pregnant women, 83 (31.7%) had GDM. Women with GDM were heavier (p?=?0.04) and had more clinical risk factors (p?=?0.008). We found a significant difference in fasting insulin (p?p?=?0.046), HOMA (p?p?Conclusions: Insulin sensitivity markers are promising tools to identify women at high risk of GDM.     

A genetic variant in LINGO2 contributes to the risk of gestational diabetes mellitus in a Chinese population

Genome-wide association studies (GWASs) showed that three single nucleotide polymorphisms (SNPs; rs10968576, rs1412239, and rs824248) in the leucine-rich repeat and Ig domain containing 2 (LINGO2) were associated with obesity or type 2 diabetes (T2D). We aimed to determine the influence of the LINGO2 variants on the gestational diabetes mellitus (GDM) risk. Thus, we performed a case–control study including 964 GDM cases and 1,021 controls to test the associations between the three LINGO2 variants (rs10968576, rs1412239, and rs824248) and susceptibility to GDM. Logistic regression analyses showed no significant association between LINGO2 variations (rs10968576 and rs1412239) and GDM susceptibility, but we observed that LINGO2 rs824248 A > T was significantly associated with an increased risk of GDM using the dominant model (TT/AT vs. AA: adjusted odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.05–1.51; p = 0.012) and the additive model (TT vs. AT vs. AA: adjusted OR = 1.16, 95% CI = 1.03–1.31; p = 0.016). In the additive model, a stronger risk effect of rs824248 was observed among obese women (prepregnancy body mass index [BMI] > 22 kg/m², adjusted OR = 1.34, 95% CI = 1.12–1.59) compared with that in lean women (prepregnancy BMI ≤ 22 kg/m², adjusted OR = 1.0², 95% CI = 0.86–1.21; p = 0.029 for heterogeneity test). Further interactive analyses also detected a significant multiplicative interaction between rs824248 and prepregnancy BMI for the risk of GDM (p = 0.041). These findings indicate that LINGO2 rs824248 may serve as a susceptibility marker for GDM in Chinese females.     

Elevated serum squalene and cholesterol synthesis markers in pregnant obese women with gestational diabetes mellitus

We examined serum cholesterol synthesis and absorption markers and their association with neonatal birth weight in obese pregnancies affected by gestational diabetes mellitus (GDM). Pregnant women at risk for GDM (BMI >30 kg/m²) were enrolled from maternity clinics in Finland. GDM was determined from the results of an oral glucose tolerance test. Serum samples were collected at six time-points, one in each trimester of pregnancy, and at 6 weeks, 6 months, and 12 months postpartum. Analysis of serum squalene and noncholesterol sterols by gas-liquid chromatography revealed that in subjects with GDM (n = 22), the serum Δ8-cholestenol concentration and lathosterol/sitosterol ratio were higher (P < 0.05) than in the controls (n = 30) in the first trimester, reflecting increased cholesterol synthesis. Also, subjects with GDM had an increased ratio of squalene to cholesterol (100 × μmol/mmol of cholesterol) in the second (11.5 ± 0.5 vs. 9.1 ± 0.5, P < 0.01) and third (12.1 ± 0.8 vs. 10.0 ± 0.7, P < 0.05) trimester. In GDM, the second trimester maternal serum squalene concentration correlated with neonatal birth weight (r = 0.70, P < 0.001). In conclusion, in obesity, GDM associated with elevated serum markers of cholesterol synthesis. Correlation of maternal serum squalene with neonatal birth weight suggests a potential contribution of maternal cholesterol synthesis to newborn weight in GDM.     

Implication of SH2B1 gene polymorphism studies in gestational diabetes mellitus in Saudi pregnant women

Genome-wide association studies have identified loci that are firmly associated with obesity. The Src-homology-2 B adaptor protein 1 (SH2B1) loci is abundantly expressed in the brain, liver, heart, muscle, and fat tissues. Gestational diabetes mellitus (GDM) is a growing health concern that usually appears during the latter half of pregnancy, and it is characterized by carbohydrate intolerance of variable severity. The SH2B1 gene polymorphism has been linked with an increased risk of weight gain in several but not all population studies. This study aimed to investigate the genetic association of rs4788102 variants in the SH2B1 gene with GDM in Saudi pregnant women. Genomic DNA samples from 200 women with GDM and 300 women without GDM were genotyped using the TaqMan method. The distribution of the GG, GA, and AA genotypes was significantly different between GDM and non-GDM women (p < 0.05). Thus, we identified rs4788102 variants as additional risk factors for GDM in Saudi women, and we suggest that these variants may have a prognostic value.     

Dysregulation of microRNA-657 influences inflammatory response via targeting interleukin-37 in gestational diabetes mellitus

A number of studies have implicated that microRNAs (miRNAs) play a critical role in the development of gestational diabetes mellitus (GDM). However, the role of miR-657 in GDM remains vague up to date. We aim to investigate the modifying effect of miR-657 on GDM, which will provide new insight into the pathogenesis of GDM and may help to identify new diagnostic or therapeutic targets for GDM. Increased expression of miR-657 but decreased expression of interleukin-37 (IL-37) was observed in patients with GDM. Besides, negative association between miR-657 and IL-37 was demonstrated in this study. miR-657 could targetedly regulate IL-37 and enhance the proliferation of mononuclear macrophages. Moreover, miR-657 promoted the generation of inflammatory cytokines (IL-6 and tumor necrosis factor-α [TNF-α]) and activation of nuclear factor κB (NF-κB) in lipopolysaccharide-induced mononuclear macrophages, while its effect was significantly inhibited when exogenous recombinant IL-37 was administrated into cells. Accordingly, dysregulation of miR-657 contributes to the pathogenesis of GDM via IL-37/NF-κB signaling axis.     

Elemental contents in serum of pregnant women with gestational diabetes mellitus

Diabetes mellitus is characterized by hyperglycemia and is closely related to trace elements. Quite a few pregnant women suffer from impaired glucose tolerance (IGT) or gestational diabetes mellitus (GDM). Investigation of the changes of elemental contents in serum of the pregnant women with IGT and GDM is significant in the etiological research and cure of the diseases. In the present work, the elements Cu, Zn, Ca, Sr, Mg, P, Fe, and Al in the serum of pregnant women were determined. The elemental contents in different experimental groups were compared. Also, the correlation between elemental contents and gestational period was observed. The results showed that compared with normal pregnant women, the Cu contents in serum of pregnant women with GDM increased, but Zn contents had a decreasing trend. In addition, for all pregnant women, the Ca contents in serum had an obvious inverse correlation with gestational period.     

Concentrations of preptin,salusins and hepcidins in plasma and milk of lactating women with or without gestational diabetes mellitus

This study was undertaken to ascertain whether human milk contains preptin, salusin-alpha (salusin-α) and -beta (salusin-β) and pro-hepcidin and hepcidin-25, and whether there are relationships between plasma and milk preptin, salusin-α and -β and pro-hepcidin and hepcidin-25 concentrations in lactating mothers with and without gestational diabetes mellitus (GDM). Blood was obtained from non-lactating women (n = 12), non-diabetic lactating women (n = 12), and GDM lactating women (n = 12). Colostrum, transitional milk, and mature milk samples were collected just before suckling from healthy and GDM lactating women. Peptides concentrations were determined by ELISA and EIA. Mammary gland tissues were screened immunohistochemically for these peptides. Women with GDM had significantly higher plasma and colostum preptin concentrations than healthy lactating women during the colostral and transitional milk period. Salusin-alpha and -beta levels in milk and plasma were lower in women with GDM. Salusin-α and -β were significantly lower in both plasma and colostrums of GDM than of healthy lactating women. Women with GDM had significantly higher colostum prohepcidin and hepcidin-25 concentrations than healthy lactating women during the colostral period. Plasma prohepcidin was also higher in women with GDM than in healthy lactating women during the colostral period, but plasma prohepcidin and hepcidin-25 levels decreased during mature milk period. Transitional milk pro-hepcidin and hepcidin-25 levels in women with GDM were higher than in healthy lactating women. All these results revealed that the mammary gland produces those peptides, which were present in milk at levels correlating with plasma concentrations.     

Placenta-derived exosomal miR-135a-5p promotes gestational diabetes mellitus pathogenesis by activating PI3K/AKT signalling pathway via SIRT1

Most people are aware of gestational diabetes mellitus (GDM), a dangerous pregnancy complication in which pregnant women who have never been diagnosed with diabetes develop chronic hyperglycaemia. Exosomal microRNA (miRNA) dysregulation has been shown to be a key player in the pathophysiology of GDM. In this study, we looked into how placental exosomes and their miRNAs may contribute to GDM. When compared to exosomes from healthy pregnant women, it was discovered that miR-135a-5p was elevated in placenta-derived exosomes that were isolated from the maternal peripheral plasma of GDM women. Additionally, we discovered that miR-135a-5p encouraged HTR-8/SVneo cell growth, invasion and migration. Further research revealed that miR-135a-5p activates HTR-8/SVneo cells' proliferation, invasion and migration by promoting PI3K/AKT pathway activity via Sirtuin 1 (SIRT1). The transfer of exosomal miR-135a-5p generated from the placenta could be viewed as a promising agent for targeting genes and pertinent pathways involved in GDM, according to our findings.