Gestational Diabetes Mellitus Patients Research Articles

Maternal and Umbilical Cord Heat-Shock Protein 70 Levels in Patients with Gestational Diabetes Mellitus

AIMS: The purpose of this study is to determine if heat shock protein 70 (Hsp-70), a marker of cellular stress, is elevated in maternal serum and umbilical cord in pregnancies complicated by gestational diabetes mellitus (GDM) and to determine whether altered serum Hsp-70 concentrations in umbilical cord are related to serve as an indicator of early term delivery (37 0/7–38 6/7 weeks of gestation) in women with GDM and control group. METHODS: The study included 62 patients with GDM (GDM group) and 22 non-diabetic, healthy women before caesarean section in this case-control study. We analyzed serum levels of Hsp-70 in pregnancies and umbilical cord sera and other biochemical and anthropometric markers, early term delivery in all subjects. RESULTS: Maternal Serum levels of Hsp-70 were significantly higher in patients with GDM than in healthy pregnant women. The umbilical cord levels of Hsp-70 in GDM patients were also increased as compared to healthy pregnant women but missed the commonly acceptable significance level. Cord Hsp-70 levels showed a negatively significant correlation with time of delivery, in women with GDM patients. Cord Hsp-70 levels showed a negatively significant correlation with time of delivery, also in the whole group. CONCLUSIONS: Maternal Hsp-70 was significantly higher in patients with GDM. The obtained results seem to indicate that elevated umbilical cord Hsp-70 values may potentially be used as indicators of risk factor for early term delivery in pregnancies.

PREVALENCE OF GESTATIONAL DIABETES AND RELATED COMPLICATIONS IN DISTRICT SIALKOT

Gestational diabetes mellitus (GDM) is a prevalent medical complication during pregnancy, associated with adverse maternal and neonatal outcomes. Understanding the impact of GDM on pregnancy complications is essential for effective management and care. Objective: This study aimed to compare the incidence of various complications between pregnant women with and without GDM.  Method: A total of 200 pregnant women were recruited from Govt. Sardar Begum Teaching Hospital Sialkot and Civil Hospital Sialkot. These patients were given 75 g oral glucose irrespective of the meals, and their plasma glucose was estimated at two h. Patients with plasma glucose values of 140 mg/dl were labelled GDM; the rest were the control or non-GDM groups. All GDM patients were followed up and treated with diet and insulin therapy till delivery to know maternal and fetal outcomes. Results: Among the enrolled pregnant women, 70 (35%) were diagnosed with GDM. Significant differences were observed between the Non-GDM and GDM groups in terms of Cesarean section delivery (23.8% vs 55.7%, P=0.001), hypertension (13.8% vs 74.3%, P=0.031), and preterm birth (17.7% vs 24.3%, P=0.001). However, no significant difference was found in the incidence of fetal abnormalities between the two groups (9.2% vs. 8.6%, P=0.012). Additionally, the risk of intrauterine fetal demise was comparable between the Non-GDM and GDM groups (10.0% vs. 11.4%, P=0.031). Conclusion: Pregnant women with GDM are at increased risk of Cesarean section delivery, hypertension, and preterm birth compared to those without GDM. However, the incidence of fetal abnormalities and intrauterine fetal demise does not significantly differ between the two groups. Early detection and management of GDM are crucial to minimise adverse pregnancy outcomes.

The application of plasma circRAD18 in the prediction of gestational diabetes mellitus (GDM) and its adverse effects

BackgroundIn cancer biology, circRAD18 promotes glucose metabolism, potentially indicating its involvement in glucose metabolism-related disorders, such as gestational diabetes mellitus (GDM). The present study investigated the predictive role of circRAD18 in GDM and its potential adverse effects.MethodsA total of 482 women who intended to get pregnant in short-term were enrolled. For those who successfully conceived, plasma samples were collected and followed up until delivery to monitor the occurrence of GDM and its associated adverse events. The accumulation of circRAD18 in plasma was analyzed using RT-qPCR. GDM-free curves and ROC curves were plotted to assess the predictive value of plasma circRAD18 for GDM.ResultsAfter admitting 482 female patients, 388 of them achieved pregnancy within half a year. During the follow-up period, 52 cases were diagnosed with GDM. Compared to non-GDM group (n = 336), the GDM group (n = 52) had a lower accumulation level of circRAD18 on the day of pregnancy confirmation. In addition, low levels of circRAD18 accumulation on that day distinguished potential GDM patients from non-GDM cases. The 388 cases were divided into high and low circRAD18 level groups (n = 194). GDM-free curve analysis showed that patients in the low circRAD18 level group had a higher incidence of GDM compared to the high level group (43/194 vs. 9/194). A close association was found between low levels of plasma circRAD18 and hypertension, but not premature delivery, intrauterine death, malformation, intrauterine infection, miscarriage, macrosomia or intrauterine distress.ConclusionThe reduction in the accumulation of plasma circRAD18 is predictive of GDM and hypertension in pregnant women.

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.

Hsa_circ_0006260 Mediates Trophoblast Function by Fibronectin Type III Domains Containing Protein 5 via Interacting with miR-770-5p.

A series of studies have confirmed the relationship between circular RNAs (circRNAs) and metabolic diseases. Hsa_circ_0006260 has been reported to be lowly expressed in the placenta of gestational diabetes mellitus (GDM) patients, but the underlying mechanism and its biological functions remain obscure. Placental tissues were collected from 37 pregnant women with normal glucose tolerance (NGT) and 37 pregnant women with GDM. Expression changes of hsa_circ_0006260 in placentas and high glucose (HG)-stimulated HTR-8/SVneo cells were detected using real-time quantitative polymerase chain reaction. Cell viability and migration were determined by cell counting and transwell assays, respectively. Measurement of cytokines was done by enzyme-linked immunosorbent assay. Cell apoptosis was estimated by flow cytometry assay. The molecular mechanisms were identified using dual-luciferase reporter and RNA-binding protein immunoprecipitation assays. Hsa_circ_0006260 expression was remarkably lowered in GDM patient-derived placentas and HG-stimulated HTR-8/SVneo cells. Functionally, hsa_circ_0006260 overexpression weakened HG-mediated repression of HTR-8/SVneo cell viability and migration, as well as promotion of HTR-8/SVneo cell inflammatory response and apoptosis. Mechanistically, hsa_circ_0006260 functioned as a miR-770-5p decoy to mediate fibronectin type III domains containing protein 5 (FNDC5) expression. Ectopic expression of miR-770-5p weakened hsa_circ_0006260 overexpression-mediated repression of HG-induced HTR-8/SVneo cell dysfunction. Also, FNDC5 knockdown lessened miR-770-5p overexpression-mediated promotion of HG-induced HTR-8/SVneo cell dysfunction. Our findings manifested a novel mechanism by which hsa_circ_0006260 could lower HG-induced HTR-8/SVneo cell dysfunction by upregulating FNDC5 via binding to miR-770-5p, which shed new light on circRNA mediated GDM pathogenesis.

Role of HbA1c in Prediction of Gestational Diabetes Mellitus Patients

Role of HbA1c in Prediction of Gestational Diabetes Mellitus Patients

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.

SCUBE1 Promotes Gestational Diabetes Mellitus: A Bioinformatics and Experimental Investigation.

Gestational diabetes mellitus (GDM) is one of the most common metabolic diseases in pregnant women, posing significant risks to the life and health of both mothers and fetuses. With improving living standards, the incidence of GDM is increasing rapidly. Therefore, understanding the underlying mechanism of GDM is of paramount importance. We downloaded two datasets from the Gene Expression Omnibus (GEO) database, containing sequencing data specifically related to "gestational diabetes" and "placenta". By merging these two datasets, a mRNA expression dataset was obtained and subjected to bioinformatics analyses. To screen out corresponding genes, differential analysis and weighted correlation network analysis (WGCNA) were carried out. Lasso, support vector machine and random forest analyses were subsequently performed for identifying key genes from the differentially expressed genes (DEGs) jointly screened out through differential analysis and WGCNA. Afterwards, immunoinfiltration and correlation analysis were performed to screen immune cells that play a role in disease progression and explore the correlation between the screened key genes and immune cells, after which Western Blot, quantitative real-time polymerase chain reaction, Immunohistochemistry, methyl thiazolyl tetrazolium, flow cytometry, scratch and Transwell assays were, respectively, performed for verification. For further verification, we found that the expression levels of MAP6D1 and SCUBE1 in embryonic tissues of GDM patients was higher compared to those of healthy pregnant women, which was consistent with the results of bioinformatics analysis. Consequently, SCUBE1 was selected for follow-up experiment. In order to explore the role of SCUBE1 in the development of GDM, we treated the trophoblastic cells HTR-8/SVneo with high glucose, and on this basis downregulated the expression of SCUBE1. Through further analysis, we observed that SCUBE1 had a role in reducing cell activity, migration and invasion, and promoting cell apoptosis. In summary, SCUBE1 promotes the development of GDM by increasing cell apoptosis and reducing cell activity, migration, and invasion.

Development and validation of interprofessional health education module for the management of gestational diabetes mellitus

BACKGROUND: Gestational diabetes mellitus (GDM) is a glucose intolerance that shows its first onset during pregnancy. In India, GDM affects as many as 5 million women annually. The interprofessional collaborative educational intervention is crucial for GDM management. This study illustrates the collaborative effort in developing and validating an interprofessional health education module designed for healthcare professionals during consultation sessions with GDM patients. MATERIALS AND METHODS: The investigation involved three stages: 1) needs assessment for module contents and objectives, 2) health education module development by an interprofessional team, and 3) module validation. We received ethics approval from the institution’s ethics committee. RESULTS: The interprofessional team developed and validated the evidence-based English-printed module. The module had 27 units and covered six topics: an introduction to GDM and its management, dietary recommendations for GDM, exercise, yoga recommendations for GDM, weight control, and postpartum care. CONCLUSION: The interprofessional team developed the educational module, wherein there is an integration of the domains of exercise and yoga along with medicines and nutrition therapy. The module was developed based on local requirements and evidence-based practices. Healthcare professionals can use the interprofessional health education module when advising diabetic pregnant patients.

Substance P Concentration in Gestational Diabetes and Excessive Gestational Weight Gain and Its Impact on Neonatal Anthropometry.

Fetal programming is a process initiated by intrauterine conditions, leaving a lasting impact on the offspring's health, whether they manifest immediately or later in life. It is believed that children born to mothers with gestational diabetes mellitus (GDM) and excessive gestational weight gain (EGWG) may be at an increased risk of developing type 2 diabetes mellitus (T2DM) and obesity later in their adult lives. Substance P is a neurotransmitter associated with obesity development and impairment of insulin signaling. Dysregulation of substance P could lead to several pregnancy pathologies, such as preeclampsia and preterm birth. Our study aimed to compare substance P concentrations in serum and umbilical cord blood in patients with GDM, EGWG, and healthy women with a family history of gestational weight gain. Substance P levels in umbilical cord blood were significantly higher in the GDM group compared to the EGWG and control groups. Substance P levels in serum and umbilical cord blood were positively correlated in all groups and the GDM group. A very interesting direction for future research is the relationship between the concentration of substance P in newborns of diabetic mothers and the occurrence of respiratory distress syndrome as a complication of impaired surfactant synthesis. To our knowledge, it is the first study assessing substance P concentration in GDM and EGWG patients.

Characteristics and functions of memory regulatory T cells in normal pregnancy cycle and pregnancy complications

Regulatory T cells (Tregs) are activated and expanded after exposure to fetal-specific (paternal) antigens. A proportion of Tregs differentiate into memory Tregs (mTregs), exhibiting immune memory function and exerting more potent immunosuppression than naive Tregs (nTregs). However, it is unclear how mTregs are regulated during normal and pathological pregnancies (e.g., gestational diabetes mellitus (GDM) and preeclampsia (PE)). In this study, PD-1, HLA-G, and HLA-DR expressions on memory CD4+ T cells, naive CD4+ T cells, Tregs, mTregs, and nTregs in healthy non-pregnant women (n=20), healthy first (n=20), second (n=20), and third-trimester women (n=20), postpartum women (n=20), GDM (n=20), and PE patients (n=20) were analyzed. The proportion of mTregs out of Tregs was increased (P<0.05) in the first trimester compared with that in non-pregnancy and reduced in the second and third trimesters. The proportions of PD-1+ Tregs and mTregs were significantly increased during the first trimester compared to those of non-pregnancy (P<0.01), reached their maximum in the second trimester. Moreover, the proportions of HLA-G+ memory CD4+ T cells, Tregs, and mTregs were increased in the first and second trimesters (P<0.01), reached their maximum in the third trimester. GDM patients were characterized by significantly lower percentages of PD-1+ and HLA-G+ mTregs (P<0.01), while PE patients were characterized by significantly lower percentages of HLA-G+ mTregs (P<0.01), compared with the healthy third-trimester women. In general, as demonstrated by this study, mTregs increase in number and enhance maternal-fetal immunoregulation during pregnancy, and their dysfunction can result in pregnancy complications such as GMD or PE.

Serum proteins differentially expressed in gestational diabetes mellitus assessed using isobaric tag for relative and absolute quantitation proteomics.

As a well-known fact to the public, gestational diabetes mellitus (GDM) could bring serious risks for both pregnant women and infants. During this important investigation into the linkage between GDM patients and their altered expression in the serum, proteomics techniques were deployed to detect the differentially expressed proteins (DEPs) of in the serum of GDM patients to further explore its pathogenesis, and find out possible biomarkers to forecast GDM occurrence. To investigation serum proteins differentially expressed in GDM were assessed using isobaric tag for relative and absolute quantitation (iTRAQ) proteomics and bioinformatics analyses. Subjects were divided into GDM and normal control groups according to the IADPSG diagnostic criteria. Serum samples were randomly selected from four cases in each group at 24-28 wk of gestation, and the blood samples were identified by applying iTRAQ technology combined with liquid chromatography-tandem mass spectrometry. Key proteins and signaling pathways associated with GDM were identified by bioinformatics analysis, and the expression of key proteins in serum from 12 wk to 16 wk of gestation was further verified using enzyme-linked immunosorbent assay (ELISA). Forty-seven proteins were significantly differentially expressed by analyzing the serum samples between the GDM gravidas as well as the healthy ones. Among them, 31 proteins were found to be upregulated notably and the rest 16 proteins were downregulated remarkably. Bioinformatic data report revealed abnormal expression of proteins associated with lipid metabolism, coagulation cascade activation, complement system and inflammatory response in the GDM group. ELISA results showed that the contents of RBP4, as well as ANGPTL8, increased in the serum of GDM gravidas compared with the healthy ones, and this change was found to initiate from 12 wk to 16 wk of gestation. GDM symptoms may involve abnormalities in lipid metabolism, coagulation cascade activation, complement system and inflammatory response. RBP4 and ANGPTL8 are expected to be early predictors of GDM.

Alternative polyadenylation regulates the translation of metabolic and inflammation-related proteins in adipose tissue of gestational diabetes mellitus

In gestational diabetes mellitus (GDM), adipose tissue undergoes metabolic disturbances and chronic low-grade inflammation. Alternative polyadenylation (APA) is a post-transcriptional modification mechanism that generates mRNA with variable lengths of 3' untranslated regions (3'UTR), and it is associated with inflammation and metabolism. However, the role of APA in GDM adipose tissue has not been well characterized. In this study, we conducted transcriptomic and proteomic sequencing on subcutaneous and omental adipose tissues from both control and GDM patients. Using Dapars, a novel APA quantitative algorithm, we delineated the APA landscape of adipose tissue, revealing significant 3'UTR elongation of mRNAs in the GDM group. Omental adipose tissue exhibited a significant correlation between elongated 3'UTRs and reduced translation levels of genes related to metabolism and inflammation. Validation experiments in THP-1 derived macrophages (TDMs) demonstrated the impact of APA on translation levels by overexpressing long and short 3'UTR isoforms of a representative gene LRRC25. Additionally, LRRC25 was validated to suppress proinflammatory polarization in TDMs. Further exploration revealed two underexpressed APA trans-acting factors, CSTF3 and PPP1CB, in GDM omental adipose tissue. In conclusion, this study provides preliminary insights into the APA landscape of GDM adipose tissue. Reduced APA regulation in GDM omental adipose tissue may contribute to metabolic disorders and inflammation by downregulating gene translation levels. These findings advance our understanding of the molecular mechanisms underlying GDM-associated adipose tissue changes.

Effect of complex micronutrient supplement and vitamin D as adjunct to insulin therapy in patients with gestational diabetes mellitus

Purpose: To determine the effect of complex micronutrient supplements and vitamin D as adjunct therapy on pancreatic function, oxidative stress, glucose metabolism and pregnancy outcomes in patients diagnosed with gestational diabetes mellitus (GDM). &#x0D; Methods: 100 GDM patients admitted to Hangzhou Linping District Maternal and Child Health Care Hospital, China between March 2022 and February 2023, were randomly allocated to control and study groups (50 patients each). Control group received insulin injections, whereas study group received complex micronutrients with vitamin D as supplements to insulin. Differences in terms of pancreatic function (homeostatic model assessment-insulin resistance index (HOMA-IR), homeostatic model assessment-beta-cell function index (HOMA-β)), oxidative stress (total antioxidant capacity (TAC), malondialdehyde (MDA)), glucose metabolism indicators (fasting blood glucose (FBG), 2-hour postprandial glucose (2hPG), glycated hemoglobin (HbA1c)) and pregnancy outcomes was assessed. &#x0D; Results: After treatment, both groups showed reductions in serum levels of FBG, 2hPG and HbA1c, but study group exhibited a considerably greater decrease (p &lt; 0.05). In addition, study group had lower HOMA-IR and MDA levels as well as higher HOMA-β and TAC levels (p &lt; 0.05). Negative delivery outcomes occurred less frequently in study group than in control group (p &lt; 0.05). &#x0D; Conclusion: Complex micronutrient supplements (rich in magnesium, calcium, and zinc) in combination with vitamin D as adjunct to insulin treatment effectively reduce pancreatic function and oxidative stress, significantly control blood glucose levels and lower the occurrence of adverse pregnancy outcomes in GDM patients. Further studies will be required in a larger more diverse population to determine the mechanism of enhancing pancreatic function.

Incidence of and factors associated with emergency caesarean section in pregnant women with gestational diabetes mellitus: A retrospective cohort study.

The incidence of factors associated with emergency cesarean section (ECS) in patients with gestational diabetes mellitus (GDM) have not been well investigated. We conducted a retrospective cohort study of patients diagnosed with GDM between 2011 and 2020 at a tertiary care hospital in Japan. Clinical data, vital signs, and laboratory results of the patients were collected from electronic medical records. We constructed a multivariate logistic regression model to identify the clinical characteristics associated with ECS. We included 1189 patients diagnosed with GDM, the mean maternal age was 33 years, and 507 (42.6%) patients were aged ≥35 years. In total, 114 patients underwent ECS (9.6%). The previous assisted reproductive technology (ART) use (odds ratio [OR], 1.81; 95% confidence interval [CI], 1.12-2.93), previous artificial abortion (OR, 1.94; 95% CI, 1.13-3.33), high pre-pregnancy body mass index (BMI) (OR, 1.07; 95% CI, 1.02-1.11), and late diagnosis of GDM (OR, 1.02; 95% CI, 1.003-1.05) were independently associated with ECS. One of every 10 GDM patients required ECS. Previous ART use, previous artificial abortion, high pre-pregnancy BMI, and late diagnosis of GDM were risk factors for ECS in GDM patients.

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.

Phenotypic characterisation of regulatory T cells in patients with gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is a common complication that occurs during pregnancy. Emerging evidence suggests that immune abnormalities play a pivotal role in the development of GDM. Specifically, regulatory T cells (Tregs) are considered a critical factor in controlling maternal–fetal immune tolerance. However, the specific characteristics and alterations of Tregs during the pathogenesis of GDM remain poorly elucidated. Therefore, this study aimed to investigate the changes in Tregs among pregnant women diagnosed with GDM compared to healthy pregnant women. A prospective study was conducted, enrolling 23 healthy pregnant women in the third trimester and 21 third-trimester women diagnosed with GDM. Participants were followed up until the postpartum period. The proportions of various Treg, including Tregs, mTregs, and nTregs, were detected in the peripheral blood of pregnant women from both groups. Additionally, the expression levels of PD-1, HLA-G, and HLA-DR on these Tregs were examined. The results revealed no significant differences in the proportions of Tregs, mTregs, and nTregs between the two groups during the third trimester and postpartum period. However, GDM patients exhibited significantly reduced levels of PD-1+ Tregs (P < 0.01) and HLA-G+ Tregs (P < 0.05) in the third trimester compared to healthy pregnant women in the third trimester. Furthermore, GDM patients demonstrated significantly lower levels of PD-1+ mTregs (P < 0.01) and HLA-G+ (P < 0.05) mTregs compared to healthy pregnant women in the third trimester. Overall, the proportion of Tregs did not exhibit significant changes during the third trimester in GDM patients compared to healthy pregnant women. Nevertheless, the observed dysregulation of immune regulation function in Tregs and mTregs may be associated with the development of GDM in pregnant women.

Sh- Ambra1 inhibits IRS-1/PI3K/Akt signalling pathway to reduce autophagy in gestational diabetes.

Gestational diabetes mellitus (GDM) is the most common metabolic disease in pregnancy. However, studies of activating molecule of Beclin1-regulated autophagy (Ambra1) affecting the insulin substrate receptor 1/phosphatidylinositol 3 kinase/protein kinase B (IRS-1/PI3K/Akt) signalling pathway in GDM have not been reported. The aim of the study was to detect the difference of Ambra1 expression in the placenta of normal pregnant women and GDM patients. An in vitro model of gestational diabetes mellitus was established by inducing HTR8/Svneo cells from human chorionic trophoblast layer with high glucose. The changes of cell morphology were observed by inverted microscope, and the expression levels of Ambra1 gene and protein in model cells were detected. After this, Ambra1 gene was silenced by shRNA transfection, and PI3K inhibitor was added to detect changes in Ambra1, autophagy, and insulin (INS) signalling pathways. The protein expression levels of Ambra1, Bcl-2 interacting protein (Beclin-1), and microtubule-associated proteins 1A/1B light chain 3B (LC3-II) in the placentas of GDM pregnant women were higher than those of normal pregnant women. High glucose induces morphological changes in HTR8/Svneo cells and increases Ambra1 transcription and translation levels. sh-Ambra1 increased survival of HTR8/SvNEO-HG cells and inhibited Ambra1, Beclin1, and LC3-II transcription and translation levels. Also, sh-Ambra1 increased IRS-1/PI3K/Akt protein phosphorylation levels and inhibited the IRS-1/PI3K/Akt signalling pathway and its resulting autophagy. sh-Ambra1 increased IRS-1/PI3K/Akt protein phosphorylation levels to reduce autophagy in gestational diabetes.

Bioinformatics-based Identification of Ferroptosis-Related Genes and their Diagnostic Value in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is considered a risk factor for heart metabolic disorder in future mothers and offspring. Ferroptosis is a new type of programmed cell death, which may participate in the occurrence and development of GDM. This study aims to identify ferroptosis-related genes in GDM by bioinformatics methods and to explore their clinical diagnostic value. The dataset GSE103552 was analyzed using the Gene Expression Omnibus (GEO) database to screen for differentially expressed genes (DEGs) in GDM. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and proteinprotein interaction (PPI) network were performed. Gene sets for ferroptosis were retrieved in MSigDB and GSVA gene set analysis was performed on the database. Finally, logistic regression was performed to differentiate between GDM patients and controls to screen for diagnostic markers. A total of 179 DEGs were identified in the expression profile of GDM. GO and KEGG enrichment analysis revealed significant enrichment in the TGF-β, p53 signaling pathway, platelet activation, glutathione metabolism, sensory perception of taste, and leukocyte and vascular endothelial cell migration regulation. DEGs (n = 107) associated with the ferroptosis gene set were screened by GSVA analysis. The screened DEGs for disease and DEGs for ferroptosis scores were intersected and 35 intersected genes were identified. PPI identified two key genes associated with GDM as CCNB2 and CDK1. Wilcox-test showed low expression of CCNB2 and CDK1 in GDM. The area under the ROC curve (AUC) of the CCNB2 and CDK1 prognostic model was 0.822. The genes associated with ferroptosis in GDM were CCNB2 and CDK1, which can be used as valid indicators for the diagnosis of GDM.