Progression Of Gestational Diabetes Mellitus Research Articles

ChIP-seq and RNA-seq Reveal the Involvement of Histone Lactylation Modification in Gestational Diabetes Mellitus.

Lactylation is a novel post-translational modification of proteins. Although the histone lactylation modification has been reported to be involved in glucose metabolism, its role and molecular pathways in gestational diabetes mellitus (GDM) are still unclear. This study aims to elucidate the histone lactylation modification landscapes of GDM patients and explore lactylation-modification-related genes involved in GDM. We employed a combination of RNA-seq analysis and chromatin immunoprecipitation sequencing (ChIP-seq) analysis to identify upregulated differentially expressed genes (DEGs) with hyperhistone lactylation modification in GDM. We demonstrated that the levels of lactate and histone lactylation were significantly elevated in GDM patients. DEGs were involved in diabetes-related pathways, such as the PI3K-Akt signaling pathway, Jak-STAT signaling pathway, and mTOR signaling pathway. ChIP-seq analysis indicated that histone lactylation modification in the promoter regions of the GDM group was significantly changed. By integrating the results of RNA-seq and ChIP-seq analysis, we found that CACNA2D1 is a key gene for histone lactylation modification and is involved in the progression of GDM by promoting cell vitality and proliferation. In conclusion, we identified the key gene CACNA2D1, which upregulated and exhibited hypermodification of histone lactylation in GDM. These findings establish a theoretical groundwork for the targeted therapy of GDM.

Mean Platelet Volume as a Predictive Marker for GDM

Background: Gestational Diabetes Mellitus (GDM) is defined as first onset of any glucose intolerance diagnosed in pregnancy and certain proportion has risk of developing type 2 diabetes later in life, but risk of type 1 is also increased. Screening at the earliest and enhanced diagnostic tools can help reduce burden of GDM and further progression as it is majorly a lifestyle disease. One of the easiest and cost-effective inflammatory markers are thrombocyte indices. Objective: To determine the potential value of MPV, an inexpensive and easy tool obtained from routine complete blood picture used to study morphology of platelet and whether it can be an indicator in prediction of GDM. Methods: Hospital based comparative study was done on 100 antenatal women attending OPD during first trimester. Case group includes women with recently diagnosed GDM as per guidelines of American diabetes Association by one-step 2-hour 75g OGTT and the cut off values were considered as per IADPSG. MPV is assessed amongst cases and controls and its association was studied in both groups. Results: The present study observed that MPV values of the GDM patients were significantly higher than those compared to normal pregnancies. The current investigation reveals that MPV values in GDM patients significantly exceed those observed in normal pregnancies. Specifically, the median MPV in the GDM group is 8.6 (IQR: 6.9-11.2), while in the non-GDM group, it is 7.4 (IQR: 4.8-10.4). The Mann-Whitney U test yielded a statistic of 905, with a corresponding p-value of 0.0175, which falls below the significance threshold of 0.05. Hence, there exists a statistically significant disparity in MPV between the groups. Conclusion: GDM is found to have underlying chronic inflammatory background and varied insulin resistance which states that these parameters may exist even before clinically diagnosable glucose intolerance occurs. This may direct that GTT might not detect GDM if done early in pregnancy, but inflammatory markers might diagnose as they have already been existing. One such economical marker is the MPV as a part of routine CBC. Keywords: Mean Platelet Volume; Gestational Diabetes Mellitus; IADPSG; Exclusive Real World Evidence

Vitronectin promotes insulin resistance in trophoblast cells by activating JNK in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a common disorder in the clinic, which may lead to severe detrimental outcomes both for mothers and infants. However, the underlying mechanisms for GDM are still not clear. In the present study, we performed label-free proteomics using placentas from GDM patients and normal controls. Vitronectin caused our attention among differentially expressed proteins due to its potential role in the pathological progression of GDM. Vitronectin was increased in the placentas of GDM patients, which was confirmed by Western blot analysis. Vitronectin represses insulin signal transduction in trophoblast cells, whereas the knockdown of vitronectin further potentiates insulin-evoked events. Neutralization of CD51/61 abolishes the repressed insulin signal transduction in vitronectin-treated trophoblast cells. Moreover, vitronectin activates JNK in a CD51/61-depedent manner. Inhibition of JNK rescues impaired insulin signal transduction induced by vitronectin. Overall, our data indicate that vitronectin binds CD51/61 in trophoblast cells to activate JNK, and thus induces insulin resistance. In this regard, increased expression of vitronectin is likely a risk factor for the pathological progression of GDM. Moreover, blockade of vitronectin production or its receptors (CD51/61) may have therapeutic potential for dealing with GDM.

Histopathological changes in the placentas of pregnant women with Gestational Diabetes Mellitus

Objectives: Placental damage might be the primary underlying cause of the high rates of fetal adverse outcomes in cases with gestational diabetes mellitus (GDM). Histopathological changes were considered to be associated with GDM in the literature. However, there are also studies showing no changes in the placenta in some gestational diabetic women. The pathophysiology of these placental alterations remains elusive. Therefore, this study aimed to examine the histopathological changes in the placentas of patients with GDM and compare them with the placentas of the healthy control group.
 Material and methods: This experimental non-randomized case-control study was conducted with 40 GDM patients and 40 healthy pregnant women at Dicle University Faculty of Medicine between March 2023 and December 2023. Placental tissues obtained following cesarean delivery were subjected to routine tissue processing. Placental samples were stained with hematoxylin-eosin and examined histopathologically using a light microscope.
 Results: When histopathological findings were compared between the GDM and control groups, villous degeneration, congestion in blood vessels, fibrinoid accumulation, inflammation and intervillous hemorrhage were higher in the GDM group than in the control group (p<0.001).
 Conclusion: The intricate relationship between GDM and placental pathology underscores the profound impact of metabolic changes on placental structure and function throughout pregnancy. Understanding these pathological changes is crucial for elucidating the progression of GDM and its implications for maternal and fetal health, highlighting the importance of comprehensive placental analysis in managing pregnancies complicated by GDM.
 Keywords: Gestational diabetes, hematoxylin-eosin staining, histopathological examination

The role of hsa_circ_0042260/miR-4782-3p/LAPTM4A axis in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a common metabolic condition during pregnancy, posing risks to both mother and fetus. CircRNAs have emerged as important players in various diseases, including GDM. We aimed to investigate the role of newly discovered circRNA, hsa_circ_0042260, in GDM pathogenesis. Using GSE194119 dataset, hsa_circ_0042260 was identified and its expression in plasma, placenta, and HG-stimulated HK-2 cells was examined. Silencing hsa_circ_0042260 in HK-2 cells assessed its impact on cell viability, apoptosis, and inflammation. Bioinformatics analysis revealed downstream targets of hsa_circ_0042260, namely miR-4782-3p and LAPTM4A. The interaction between hsa_circ_0042260, miR-4782-3p, and LAPTM4A was validated through various assays. hsa_circ_0042260 was upregulated in plasma from GDM patients and HG-stimulated HK-2 cells. Silencing hsa_circ_0042260 improved cell viability, suppressed apoptosis and inflammation. Hsa_circ_0042260 interacted with miR-4782-3p, which exhibited low expression in GDM patient plasma and HG-stimulated cells. MiR-4782-3p targeted LAPTM4A, confirmed by additional assays. LAPTM4A expression increased in GDM patient plasma and HG-induced HK-2 cells following hsa_circ_0042260 knockdown or miR-4782-3p overexpression. In rescue assays, inhibition of miR-4782-3p or overexpression of LAPTM4A counteracted the effects of hsa_circ_0042260 downregulation on cell viability, apoptosis, and inflammation. In conclusion, the hsa_circ_0042260/miR-4782-3p/LAPTM4A axis plays a role in regulating GDM progression in HG-stimulated HK-2 cells.

Metabolomic profiling reveals decreased serum cysteine levels during gestational diabetes mellitus progression.

Gestational diabetes mellitus (GDM) is a pregnancy-related metabolic disorder associated with short-term and long-term adverse health outcomes, but its pathogenesis has not been clearly elucidated. Investigations of the dynamic changes in metabolomic markers in different trimesters may reveal the underlying pathophysiology of GDM progression. Therefore, in the present study, we analyzed the metabolic profiles of 75 women with GDM and 75 women with normal glucose tolerance (NGT) throughout the three trimesters. We found that the variation trends of 38 metabolites were significantly different during GDM development. Specifically, longitudinal analyses revealed that cysteine (Cys) levels significantly decreased over the course of GDM progression. Further study showed that Cys alleviated GDM in female mice at gestational day 14.5 possibly by inhibiting phosphoenolpyruvate carboxykinase to suppress hepatic gluconeogenesis. Taken together, these findings suggest that the Cys metabolic pathway might play a crucial role in GDM and that Cys supplementation represents a potential new treatment strategy for GDM patients.

MicroRNA-125b regulates vitamin D resistance by targeting CYP24A1 in the progression of gestational diabetes mellitus

Vitamin D deficiency is prevalent in pregnancy and has been associated with increased occurrences of preeclampsia, cesarean delivery, neonatal bacterial vaginosis, and gestational diabetes. CYP24A1, recognized as a key factor in vitamin D metabolism homeostasis, encodes 24-hydroxylase responsible for converting 25(OH)D3 and 1,25(OH)2D3 into inactive metabolites. Recently, we have reported CYP24A1 overexpression in patients with gestational diabetes mellitus (GDM) and trophoblast cells exposed to hyperglycemia. In this study, we explored miRNA-mediated regulation of CYP24A1 in GDM progression, validating our findings through silencing experiments in a trophoblast cell line. In silico tools identified miR-125b-5p as a putative target of CYP24A1. Expression analysis revealed downregulation of miR-125b-5p in blood samples from early GDM and GDM compared to healthy pregnant women, positively correlating with vitamin D levels. Hyperglycemic exposure in human trophoblastic cell lines (BeWo) decreased miR-125b-5p expression, concomitant with an increase in CYP24A1. To confirm the regulatory role of miR-125b on CYP24A1, we transfected BeWo cells with antimiR-125b or miR-125b mimic. AntimiR-125b transfection heightened CYP24A1 levels, while miR-125b mimic overexpression resulted in decreased CYP24A1 expression. These findings establish miR-125b as a regulator of CYP24A1. To explore the influence of miR-125b on vitamin D metabolism, trophoblast cells overexpressing miR-125b were treated with 0.1 and 1 µM calcitriol. Hyperglycemic conditions exhibited a reduction in CYP24A1 levels. Collectively, our results indicate that miR-125b may regulate vitamin D metabolism by targeting CYP24A1, contributing to GDM progression. These findings may pave the way for understanding vitamin D resistance in concurrent GDM development and identifying novel miRNAs targeting CYP24A1.

Recent progress in metabolic reprogramming in gestational diabetes mellitus: a review.

Gestational diabetes mellitus is a prevalent metabolic disease that can impact the normal course of pregnancy and delivery, leading to adverse outcomes for both mother and child. Its pathogenesis is complex and involves various factors, such as insulin resistance and β-cell dysfunction. Metabolic reprogramming, which involves mitochondrial oxidative phosphorylation and glycolysis, is crucial for maintaining human metabolic balance and is involved in the pathogenesis and progression of gestational diabetes mellitus. However, research on the link and metabolic pathways between metabolic reprogramming and gestational diabetes mellitus is limited. Therefore, we reviewed the relationship between metabolic reprogramming and gestational diabetes mellitus to provide new therapeutic strategies for maternal health during pregnancy and reduce the risk of developing gestational diabetes mellitus.

Is there a causal association between gestational diabetes mellitus and immune mediators? A bidirectional Mendelian randomization analysis.

Diabetes that only appears or is diagnosed during pregnancy is referred to as gestational diabetes mellitus (GDM). The maternal physiological immune profile is essential for a positive pregnancy outcome. However, the causal relationship between GDM and immunophenotypes is not fully defined. Based on the high-density genetic variation data at the genome-wide level, we evaluated the logical associations between 731 specific immune mediators and GDM using bidirectional Mendelian randomization (MR). The inverse variance weighted (IVW) was the main method employed for MR analysis. We performed multiple methods to verify the robustness and dependability of the MR results, and sensitivity measures were applied to rule out potential heterogeneity and horizontal pleiotropy. A substantial causal association between several immune mediators and GDM was detected. After FDR testing, HLA DR++ monocyte %leukocyte and HLA DR on plasmacytoid DC were shown to increase the risk of GDM; in contrast, CD127 on CD28+ CD45RA+ CD8br and CD19 on PB/PC were shown to attenuate the effect of GDM. Moreover, the progression of GDM has been shown to decrease the maternal levels of CD39+ activated Treg AC, CD39+ activated Treg %CD4 Treg, CD39+ resting Treg AC, CD39+ resting Treg %CD4 Treg, and CD39+ CD8BR %T cell. Our findings support a possible causal association between GDM and various immunophenotypes, thus facilitating the provision of multiple options for preventive recognition as well as for the diagnostic and therapeutic management of GDM in clinical practice.

METTL14-mediated lncRNA XIST silencing alleviates GDM progression by facilitating trophoblast cell proliferation and migration via the miR-497-5p/FOXO1 axis.

Gestational diabetes mellitus (GDM),a prevalent complication during the gestation period, has been linked to impaired proliferation and migration of trophoblasts causing placental maldevelopment. We previously found that lncRNA X-inactive specific transcript (XIST)played an essential role in GDM progression. Here, we investigated the precise biological functions as well as the upstream and downstream regulatory mechanisms of XIST in GDM. We found that XISTand forkheadbox O1 (FOXO1) were conspicuously upregulated and miR-497-5p and methyltransferase-like 14 (METTL14) were downregulated in the placentas of GDM patients. XIST silencing facilitated proliferation and migration and inhibited cell apoptosis and cell cycle arrest in HG-cultured HTR8/SVneo cells. METTL14 inhibited XIST expression through m6A methylation modification. XIST overexpression abrogated the positive effect of METTL14 overexpression on HG-cultured HTR8/SVneo cell progression. MiR-497-5p and FOXO1 are downstream regulatory genes of XIST in HTR8/SVneo cells. Reverse experiments illustrated that XIST mediated HTR8/SVneo cell functions by regulating the miR-497-5p/FOXO1 axis. Additionally, XIST silencing augmented glucose tolerance and alleviated fetal detrimental changes in GDM rats. To conclude, METTL14-mediated XIST silencing facilitated proliferation and migration and inhibited cell apoptosis and cell cycle arrest in HG-cultured HTR8/SVneo cells via the miR-497-5p/FOXO1 axis, thereby alleviating GDM progression in rats.

Fentanyl Promoted the Growth of Placenta Trophoblast Cells through Regulating the METTL14 Mediated CCL5 Levels.

Gestational diabetes mellitus (GDM) is an important cause of the increase in incidence rate and mortality of pregnant women and perinatal infants. This study aimed to analyze the role of fentanyl, a μ-opioid agonist, in the GDM progression. The high glucose (HG) treatment HTR8/SVneo cells was used as a GDM model in vitro. The cell viability was assessed with cell counting kit-8 assay. The apoptosis rate was analyzed with flow cytometry and the transwell assay was conducted to test the cell migration and invasion. RT-quantitative PCR (qPCR) assay was performed to determine the relative expressions of related genes. The N6-Methyladenosine (m6A) levels were analyzed with MeRIP analysis. The tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and IL-10 levels of the cells were analyzed with commercial kits. The results showed that fentanyl increased the cell viability, migration and invasion, and IL-10 levels, and declined the apoptosis rate, TNF-α and IL-1β levels of the HG stimulated HTR8/SVneo cells. The chemokine ligand 5 (CCL5) was over expressed in GDM tissues and HG stimulated HTR8/SVneo cells, which was depleted after fentanyl treatment. Over expressed CCL5 neutralized the fentanyl roles in the HG stimulated HTR8/SVneo cells. The methyltransferase-like protein 14 (METTL14) levels was decreased in HG stimulated HTR8/SVneo cells, which was up-regulated after fentanyl treatment. Additionally, METTL14 silenced prominently decreased the m6A and mRNA levels, along with the mRNA stability of CCL5. In conclusion, fentanyl promoted the growth and inhibited the apoptosis of the HG stimulated HTR8/SVneo cells through regulating the METTL14 mediated CCL5 levels.

Lachnospiraceae-derived butyrate mediates protection of high fermentable fiber against placental inflammation in gestational diabetes mellitus.

Inflammation-associated insulin resistance is a key trigger of gestational diabetes mellitus (GDM), but the underlying mechanisms and effective interventions remain unclear. Here, we report the association of placental inflammation (tumor necrosis factor-α) and abnormal maternal glucose metabolism in patients with GDM, and a high fermentable dietary fiber (HFDF; konjac) could reduce GDM development through gut flora-short-chain fatty acid-placental inflammation axis in GDM mouse model. Mechanistically, HFDF increases abundances of Lachnospiraceae and butyrate, reduces placental-derived inflammation by enhancing gut barrier and inhibiting the transfer of bacterial-derived lipopolysaccharide, and ultimately resists high-fat diet-induced insulin resistance. Lachnospiraceae and butyrate have similar anti-GDM and anti-placental inflammation effects, and they can ameliorate placental function and pregnancy outcome effects probably by dampening placental immune dysfunction. These findings demonstrate the involvement of important placental inflammation-related mechanisms in the progression of GDM and the great potential of HFDFs to reduce susceptibility to GDM through gut-flora-placenta axis.

Longitudinal metabolomics integrated with machine learning identifies novel biomarkers of gestational diabetes mellitus

BackgroundEvidence from longitudinal studies is crucial to enhance our understanding of the role of metabolites in the progression of gestational diabetes mellitus (GDM). Herein, a longitudinal untargeted metabolomic study was conducted to reveal the metabolomic profiles and biomarkers associated with the progression of GDM, and characterize the changing patterns of metabolites. MethodsWe collected serum samples at three trimesters from 30 patients with GDM and 30 healthy Chinese pregnant women with pre-pregnancy BMI, age, and parity matched, and untargeted metabolomic analysis was performed, followed by machine learning approaches that integrated bootstrap and LASSO. Cluster analysis was conducted to elucidate the patterns of metabolite changes. Pathway analyses were conducted to gain insights into the underlying pathways involved. ResultsA total of 32 metabolites, mainly belonging to amino acid and its derivatives, were significantly associated with GDM across three trimesters, and were clustered into three distinct patterns. Metabolites belonging to phosphatidylcholines, lysophosphatidylcholines, lysophosphatidic acids, and lysophosphatidylethanolamines were consistently upregulated, and 2,3-Dihydroxypropyl dihydrogen phosphate was downregulated in GDM group. Amino acid-related, glycerophospholipid, and vitamin B6 metabolism were enriched in multiple trimesters. The levels of allantoic acid, which was positively correlated with blood glucose, was consistently higher in GDM patients and exhibited good discriminatory ability for GDM in the early and mid-pregnancy. ConclusionWe identified and characterized distinct patterns of metabolites associated with GDM throughout pregnancy, and found that allantoic acid was a potential biomarker for early diagnosis of GDM.

Comparison of Anthropometric Measurements of Infants Born to Bahraini Mothers with and Without Gestational Diabetes Mellitus (GDM)

Gestational Diabetes Mellitus is a major cause of morbidity and mortality to both mother and fetus. It is defined as the development of hyperglycemia during pregnancy in women who were not previously diagnosed with Diabetes Mellitus (DM) (1). Diagnosis usually occurs during the 24th to 28th weeks of gestation (1). The prevalence of GDM varies worldwide and was reported to be in Bahrain in 2012 at 10.1% of pregnancies, which was increased from 7.2% in 2002 (6). For this study, a total sample of 10,865 patients was used, dating from May 2016 to January 2020. The sample size is set in King Hamad University Hospital (KHUH), Kingdom of Bahrain. They were chosen based on inclusion and exclusion criteria. The data collected included the GDM status of the mother (GDM or Non-GDM), gestational age of the fetus (weeks), birth weight (grams) of the fetus, length (centimeters) of the fetus, head circumference (centimeters) of the fetus and placental weight (grams) upon delivery. In our study, the results showed an increase in anthropometric measurements in infants born to GDM mothers. 10 out of 200 (5%) neonates had a macrocosmic birth weight in GDM infants. However, when comparing to the birth weight, p= 0.940 was found, showing a non-significant difference between both groups. There was a faster acceleration in head circumference in neonates born to mothers with GDM, and there was no significant difference in average head circumference between both groups. Moreover, 153 out of 200 (76%) of the GDM group had a placental weight of more than 500 grams, whereas 179 out of 200 (89.5%) of the non-GDM group had a placental weight of more than 500 grams. GDM is a common yet serious complication encountered throughout pregnancy, most commonly via routine screening. One of the commonly observed outcomes of GDM in pregnancy is increased fetal growth through various mechanisms, which can result in an increased risk of neonatal morbidity and mortality. This study helps to reaffirm that routine screening of GDM is required, and perhaps placental weight is another factor to be taken into consideration after further study as an indicator of fetal growth and GDM progression.

The Incidence and Management of Type 2 Diabetes Mellitus After Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) refers to a transient state of impaired glucose tolerance that develops during pregnancy, affecting a significant proportion of expectant mothers globally. This review aimed to comprehensively examine the subsequent incidence and management of type 2 diabetes mellitus (T2DM) in women who have previously experienced GDM. The transition from GDM to T2DM is a well-recognized continuum, with affected women facing an increased risk of developing T2DM postpartum. Several studies have demonstrated that women with a history of GDM face a substantially higher risk of developing T2DM compared to normoglycemic pregnant women. The long-term consequences of developing T2DM following GDM are significant, as it not only affects the health of the mother but also poses risks to the offspring. The most common risk factors associated with the progression of GDM to T2DM include pregnancy at an advanced age, insulin treatment during pregnancy, and delivering an overweight baby. As GDM women are at higher risk of developing T2DM, effective management strategies such as lifestyle changes, postpartum care, breastfeeding, screening tests, and gaining awareness of risk are crucial to mitigate the risk of T2DM in this population. The current review was conducted to guide healthcare providers and women with a history of GDM about the potential risks of T2DM and management strategies to prevent the condition. This review provides a summary of evidence on the incidence rate of T2DM in GDM patients, its associated risk factors, and approaches to mitigate this challenge.

Gut Microbiota and Critical Metabolites: Potential Target in Preventing Gestational Diabetes Mellitus?

Gestational diabetes mellitus (GDM) is an intractable issue that negatively impacts the quality of pregnancy. The incidence of GDM is on the rise, becoming a major health burden for both mothers and children. However, the specific etiology and pathophysiology of GDM remain unknown. Recently, the importance of gut microbiota and related metabolic molecules has gained prominence. Studies have indicated that women with GDM have significantly distinct gut microbiota and gut metabolites than healthy pregnant women. Given that the metabolic pathways of gut flora and related metabolites have a substantial impact on inflammation, insulin signaling, glucose, and lipid metabolism, and so on, gut microbiota or its metabolites, such as short-chain fatty acids, may play a significant role in both pathogenesis and progression of GDM. Whereas the role of intestinal flora during pregnancy is still in its infancy, this review aims to summarize the effects and mechanisms of gut microbiota and related metabolic molecules involved in GDM, thus providing potential intervention targets.

Risk Estimation of Gestational Diabetes Mellitus in the First Trimester.

There is no early, first-trimester risk estimation available to predict later (gestational week 24-28) gestational diabetes mellitus (GDM); however, it would be beneficial to start an early treatment to prevent the development of complications. We aimed to identify early, first-trimester prediction markers for GDM. The present case-control study is based on the study cohort of a Hungarian biobank containing biological samples and follow-up data from 2545 pregnant women. Oxidative-nitrative stress-related parameters, steroid hormone, and metabolite levels were measured in the serum/plasma samples collected at the end of the first trimester from 55 randomly selected control and 55 women who developed GDM later. Pregnant women who developed GDM later during the pregnancy were older and had higher body mass index. The following parameters showed higher concentration in their serum/plasma samples: fructosamine, total antioxidant capacity, testosterone, cortisone, 21-deoxycortisol; soluble urokinase plasminogen activator receptor, dehydroepiandrosterone sulfate, dihydrotestosterone, cortisol, and 11-deoxycorticosterone levels were lower. Analyzing these variables using a forward stepwise multivariate logistic regression model, we established a GDM prediction model with a specificity of 96.6% and sensitivity of 97.5% (included variables: fructosamine, cortisol, cortisone, 11-deoxycorticosterone, SuPAR). Based on these measurements, we accurately predict the development of later-onset GDM (24th-28th weeks of pregnancy). Early risk estimation provides the opportunity for targeted prevention and the timely treatment of GDM. Prevention and slowing the progression of GDM result in a lower lifelong metabolic risk for both mother and offspring.

Long Non-Coding RNA Nuclear Paraspeckle Assembly Transcript 1: A Regulator of Trophoblast Cells in the Progression of Gestational Diabetes Mellitus

The potential function of NEAT1 in the progression of Gestational diabetes mellitus (GDM) and the molecular mechanisms are explored. NEAT1 levels in multiple types of cell lines and placental tissues collected from healthy, GDM and preeclampsia pregnancies were detected by quantitative real-time polymerase chain reaction (qRT-PCR). After intervening NEAT1 level in HTR-8/SVneo cells, proliferative, migratory and apoptotic potentials were examined by cell counting kit-8 (CCK-8), 5-Ethynyl-2′-deoxyuridine (EdU), transwell assay and flow cytometry. The regulatory effect of NEAT1 on the transcriptional activity of NSD1 was predicted by bioinformatic analysis and further confirmed by dual-luciferase reporter assay. In addition, histone modifications of NEAT1 on NSD1 transcription were examined by chromatin immunoprecipitation (ChIP). NEAT1 was upregulated in placental tissues collected from GDM patients. Overexpression of NEAT1 stimulated proliferative and migratory potentials, but inhibited apoptosis in HTR-8/SVneo cells. Knockdown of NEAT1 had the opposite outcomes. NEAT1 was able to regulate the transcriptional activity of NSD1 through histone modifications on H3K27Me3 and H3K27Cro. NEAT1 is upregulated in GDM cases, which triggers proliferative and migratory potentials in trophoblast cells mainly through regulating transcriptional activity of NSD1 via histone modification.

The role of chemerin in the regulation of cGAS-STING pathway in gestational diabetes mellitus placenta.

Recent studies already confirmed that placenta mitochondrial dysfunction is associated with the progression of gestational diabetes mellitus (GDM). Besides, a possible relationship between adipokine chemerin and disulfide-bond A oxidoreductase-like protein (DsbA-L) had been revealed, whereas the potential interaction remains unclear. In addition, very little is still known about the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway and its mechanisms of action in the context of GDM. The present study aims to investigate the underlying mechanism of cGAS-STING pathway and its regulatory relationship with chemerin in GDM. A total of 50 participants, including 25 cases of GDM patients and 25 pregnant women with normal glucose tolerance, were enrolled, and their placenta tissues at term labor were collected. Besides, an insulin resistance cell model was established on the human trophoblastic cell line to explore the molecular mechanism of chemerin on cGAS-STING pathway. Results showed that there were mitochondrial pathological changes in GDM placenta, accompanied by the decreased expression of DsbA-L, increased level of chemerin, and the activation of cGAS-STING pathway. In the insulin resistant cell model, overexpression of chemerin upregulated protein expression of DsbA-L, and recombinant chemerin presented time-dependent inhibition on the cGAS-STING pathway, but this effect was not dependent on DsbA-L. In conclusion, elevated chemerin is probably a protective mechanism, which may be a potential therapeutic strategy for GDM.

Diagnostic Biomarkers for Gestational Diabetes Mellitus Using Spectroscopy Techniques: A Systematic Review.

Gestational diabetes mellitus (GDM) is associated with adverse maternal and foetal consequences, along with the subsequent risk of type 2 diabetes mellitus (T2DM) and several other diseases. Due to early risk stratification in the prevention of progression of GDM, improvements in biomarker determination for GDM diagnosis will enhance the optimization of both maternal and foetal health. Spectroscopy techniques are being used in an increasing number of applications in medicine for investigating biochemical pathways and the identification of key biomarkers associated with the pathogenesis of GDM. The significance of spectroscopy promises the molecular information without the need for special stains and dyes; therefore, it speeds up and simplifies the necessary ex vivo and in vivo analysis for interventions in healthcare. All the selected studies showed that spectroscopy techniques were effective in the identification of biomarkers through specific biofluids. Existing GDM prediction and diagnosis through spectroscopy techniques presented invariable findings. Further studies are required in larger, ethnically diverse populations. This systematic review provides the up-to-date state of research on biomarkers in GDM, which were identified via various spectroscopy techniques, and a discussion of the clinical significance of these biomarkers in the prediction, diagnosis, and management of GDM.