Pathogenesis Of Gestational Diabetes Mellitus Research Articles

Exploring the influence of microbiota on gestational diabetes and its potential as a biomarker

Gestational diabetes mellitus (GDM) represents a significant health concern during pregnancy, impacting both maternal and fetal well-being. While conventional diagnostic protocols typically rely on blood glucose levels in the latter stages of pregnancy, there is a pressing need for early detection methods to mitigate potential risks. A plethora of glucose-based or non-glucose-based biomarkers have been investigated for their potential to predict GDM in early pregnancy. Though specific biomarkers showed promise in predicting GDM, their clinical usage has been constrained by the lack of validation and limitation in translating them into routine clinical use. This review aims to highlight and discuss the potential and practical utility of existing biomarkers and emergent biomarkers, such as microbiomes, in diagnosing GDM. A comprehensive analysis of recent studies reveals significant alterations in the composition and diversity of microbiota among women with GDM, suggesting their potential utility as predictive markers for this condition. For instance, distinct microbial profiles characterized by an increased abundance of Eisenbergiella, Tyzzerella 4, and Lachnospiraceae NK4A136, alongside decreased levels of Parabacteroides, Parasutterella, and Ruminococcaceae UCG 002, correlated with fasting blood glucose levels, hinting at their relevance in early GDM detection. Furthermore, proposed microbiota-targeted panels demonstrated promising predictive accuracy. Beyond gut microbiota, recent investigations have also explored the potential of oral microbiota as predictive biomarkers for GDM. Studies have highlighted the discriminatory capacity of specific oral microbes, such as Streptococcus in saliva and Leptotrichia in dental plaque, in distinguishing GDM from healthy pregnancies. Moreover, the examination of gut microbiota-derived metabolites has shown promising results in serum-based GDM prediction. These findings collectively underscore the potential of microbiota and its metabolites as valuable biomarkers for the early detection of GDM. However, further research is warranted to elucidate the mechanistic links between microbial dysbiosis and GDM pathogenesis, ultimately facilitating the development of targeted therapeutic interventions and personalized management strategies.

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.

Investigation of Phosphorylated and O-Glycosylated Proteins in Gestational Diabetes Mellitus

Gestational Diabetes Mellitus (GDM) is a common but temporary type of diabetes that develops among 10-20% of all pregnant women. It is a major cause of several pre- and post-pregnancy diseases in both mother and offspring. The main causative is altered pregnancy hormones that lead to deficient glucose metabolism. Complications can be preeclampsia, caesarean sections and cardiovascular diseases. This study was designed to determine the phosphorylated and glycosylated proteins present in GDM and to investigate the role of their post-translational modifications (PTMs) in the pathogenesis of GDM. The study was performed on 30 blood samples from pregnant diabetic women (diseased), 30 pregnant non-diabetic women (control) and 30 women without pregnancy and gestational diabetes (normal). Protein extraction was done from blood plasma, and phosphorylated and glycosylated proteins were determined by Enzyme-Linked Immuno-Sorbent Assay (ELISA) by use of specific antibodies. This study showed that proteins found in GDM are highly phosphorylated and O-glycosylated (p<0.01). Furthermore, a bioinformatic investigation was done, which showed that blood coagulation proteins such as the Fibrinogen alpha chain and lipid metabolism-regulating proteins apolipoprotein E, L1 and C-III showed a high potential for phosphorylation, which suggests that phosphorylation can be used as a therapeutic marker in GDM.

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.

Exposure to Short- and Medium-Chain Chlorinated Paraffins and the Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study in Eastern China.

Toxicological studies have indicated that exposure to chlorinated paraffins (CPs) may disrupt intracellular glucose and energy metabolism. However, limited information exists regarding the impact of human CP exposure on glucose homeostasis and its potential association with an increased risk of developing gestational diabetes mellitus (GDM). Here, we conducted a prospective study with a nested case-control design to evaluate the link between short- and medium-chain CP (SCCPs and MCCPs) exposures during pregnancy and the risk of GDM. Serum samples from 102 GDM-diagnosed pregnant women and 204 healthy controls were collected in Hangzhou, Eastern China. The median (interquartile range, IQR) concentration of SCCPs was 161 (127, 236) ng/mL in the GDM group compared to 127 (96.9, 176) ng/mL in the non-GDM group (p < 0.01). For MCCPs, the GDM group had a median concentration of 144 (117, 174) ng/mL, while the control group was 114 (78.1, 162) ng/mL (p < 0.01). Compared to the lowest quartile as the reference, the adjusted odds ratios (ORs) of GDM were 7.07 (95% CI: 2.87, 17.40) and 3.34 (95% CI: 1.48, 7.53) in the highest quartile of ∑SCCP and ∑MCCP levels, respectively, with MCCPs demonstrating an inverted U-shaped association with GDM. Weighted quantile sum regression evaluated the joint effects of all CPs on GDM and glucose homeostasis. Among all CP congeners, C13H23Cl5 and C10H16Cl6 were the crucial variables driving the positive association with the GDM risk. Our results demonstrated a significant positive association between CP concentration in maternal serum and GDM risk, and exposure to SCCPs and MCCPs may disturb maternal glucose homeostasis. These findings contribute to a better understanding of the health risks of CP exposure and the role of environmental contaminants in the pathogenesis of GDM.

Protein Profiling of Placental Extracellular Vesicles in Gestational Diabetes Mellitus.

Throughout pregnancy, some degree of insulin resistance is necessary to divert glucose towards the developing foetus. In gestational diabetes mellitus (GDM), insulin resistance is exacerbated in combination with insulin deficiency, causing new-onset maternal hyperglycaemia. The rapid reversal of insulin resistance following delivery strongly implicates the placenta in GDM pathogenesis. In this case-control study, we investigated the proteomic cargo of human syncytiotrophoblast-derived extracellular vesicles (STBEVs), which facilitate maternal-fetal signalling during pregnancy, in a UK-based cohort comprising patients with a gestational age of 38-40 weeks. Medium/large (m/l) and small (s) STBEVs were isolated from GDM (n = 4) and normal (n = 5) placentae using ex vivo dual-lobe perfusion and subjected to mass spectrometry. Bioinformatics were used to identify differentially carried proteins and mechanistic pathways. In m/lSTBEVs, 56 proteins were differently expressed while in sSTBEVs, no proteins reached statistical difference. Differences were also observed in the proteomic cargo between m/lSTBEVs and sSTBEVs, indicating that the two subtypes of STBEVs may have divergent modes of action and downstream effects. In silico functional enrichment analysis of differentially expressed proteins in m/lSTBEVs from GDM and normal pregnancy found positive regulation of cytoskeleton organisation as the most significantly enriched biological process. This work presents the first comparison of two populations of STBEVs' protein cargos (m/l and sSTBEVs) from GDM and normal pregnancy isolated using placenta perfusion. Further investigation of differentially expressed proteins may contribute to an understanding of GDM pathogenesis and the development of novel diagnostic and therapeutic tools.

Aberrant NK cell profile in gestational diabetes mellitus with fetal growth restriction.

Gestational diabetes mellitus (GDM) is a gestational disorder characterized by hyperglycemia, that can lead to dysfunction of diverse cells in the body, especially the immune cells. It has been reported that immune cells, specifically natural killer (NK) cells, play a crucial role in normal pregnancy. However, it remains unknown how hyperglycemia affects NK cell dysfunction thus participates in the development of GDM. In this experiment, GDM mice were induced by an intraperitoneal injection of streptozotocin (STZ) after pregnancy and it has been found that the intrauterine growth restriction occurred in mice with STZ-induced GDM, accompanied by the changed proportion and function of NK cells. The percentage of cytotoxic CD27-CD11b+ NK cells was significantly increased, while the proportion of nourished CD27-CD11b- NK cells was significantly reduced in the decidua of GDM mice. Likewise, the same trend appeared in the peripheral blood NK cell subsets of GDM patients. What's more, after intrauterine reinfusion of NK cells to GDM mice, the fetal growth restriction was alleviated and the proportion of NK cells was restored. Our findings provide a theoretical and experimental basis for further exploring the pathogenesis of GDM.

Evaluation of miRNA Expression in Patients with Gestational Diabetes Mellitus: Investigating Diagnostic Potential and Clinical Implications.

Gestational diabetes mellitus (GDM) is common pregnancy complication (8%), characterized by hyperglycemia resulting from pathological homeostatic mechanisms. There's a concerning trend of increasing GDM prevalence. New markers, particularly epigenetic ones, are sought for early detection and enhanced care. miRNA are small non-coding RNA molecules. The main goal was to investigate the potential role of miRNA (miR-16-5p, miR-222-3p, miR-21-5p) in GDM and their association with clinical features. The study included 72 pregnant patients, with 42 having GDM and 30 in the control group. miRNA expression was measured using ELISA. There were no significant differences in miR-222-3p expression between GDM patients and the control group. The GDM group exhibited a positive correlation between miR-16-5p expression and miR-21-5p expression as well as between miR-16-5p expression and insulin resistance. In the GDM group, a positive correlation was observed between miR-21-5p expression and fasting glucose levels. Results do not confirm the role of miR-222-3p in GDM pathogenesis or as a diagnostic marker. Additionally, a role for miR-16-5p in GDM pathogenesis was observed. Furthermore, a potential role for miR-21-5p in monitoring GDM treatment is indicated.

Association of MTHFD1 G1958A Polymorphism with Gestational Diabetes Mellitus.

Background The MTHFD1 G1958A polymorphism is a common variation in the gene encoding methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), an enzyme crucial for folate metabolism. This study investigated the association between the MTHFD1 G1958A polymorphism, which is involved in folate metabolism, and gestational diabetes mellitus (GDM) risk. Methods A case-control study was conducted and 304 pregnant women (152 with gestational diabetes as cases and 152 healthy pregnantas controls) participated in the study. The polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) techniques were used to determine the MTHFD1 1958G>A polymorphism genotypes. Results Analysis of genotype frequencies revealed a statistically significant difference (p-value < 0.05) between the GDM group and the control group, suggesting a potential association between this gene variant and the development of GDM. Interestingly, while allele frequencies alone did not show a significant association with GDM risk, analysis in a recessive model (both severe and mild forms) demonstrated a strong link between the homozygous AA genotype and increased susceptibility to GDM. Conclusion This study provides the first evidence linking the MTHFD1 G1958A polymorphism and GDM risk in an Indian setting. These findings warrant further investigation into the functional impact of the MTHFD1 G1958A polymorphism and its potential role in the pathogenesis of GDM.

Genetics and epigenetics of gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy. Its prevalence is increasing every year with increasing obesity, sedentary lifestyle, poor or unhealthy diet and increasing age of pregnant women. GDM is known to be accompanied by multiple short- and long-term complications for both mother and child. Research in genetics and epigenetics has provided new insights into the pathophysiology of GDM, which provides an opportunity to develop new strategies to improve the diagnosis, prevention and treatment of GDM and its complications.This review describes the role of genetic and epigenetic factors on the risks of developing GDM and its complications. The review also discusses the similarities in the genetic changes underlying type 2 diabetes mellitus and GDM, indicating a multifactorial pathogenesis of GDM.

Interaction and Metabolic Pathways: Elucidating the Role of Gut Microbiota in Gestational Diabetes Mellitus Pathogenesis.

Gestational diabetes mellitus (GDM) is a complex metabolic condition during pregnancy with an intricate link to gut microbiota alterations. Throughout gestation, notable shifts in the gut microbial component occur. GDM is marked by significant dysbiosis, with a decline in beneficial taxa like Bifidobacterium and Lactobacillus and a surge in opportunistic taxa such as Enterococcus. These changes, detectable in the first trimester, hint as the potential early markers for GDM risk. Alongside these taxa shifts, microbial metabolic outputs, especially short-chain fatty acids and bile acids, are perturbed in GDM. These metabolites play pivotal roles in host glucose regulation, insulin responsiveness, and inflammation modulation, which are the key pathways disrupted in GDM. Moreover, maternal GDM status influences neonatal gut microbiota, indicating potential intergenerational health implications. With the advance of multi-omics approaches, a deeper understanding of the nuanced microbiota-host interactions via metabolites in GDM is emerging. The reviewed knowledge offers avenues for targeted microbiota-based interventions, holding promise for innovative strategies in GDM diagnosis, management, and prevention.

Placenta-derived exosomes exacerbate beta cell dysfunction in gestational diabetes mellitus through delivery of miR-320b.

Recent studies have shown placenta-derived exosome (pdE) acts as an important mediator of organ-to-organ interplay regulating maternal metabolic alterations, however, the function and mechanisms of placental exosomes on pancreatic β-cell maladaptation in gestational diabetes mellitus (GDM) remain unclear. The purpose of this investigation was to ascertain how placental exosomes affected the β-cell dysfunction associated with the onset of GDM. Exosomes were isolated from chorionic villi explants of pregnant mice and humans with normal glucose tolerance (NGT) and GDM. The effects of pdE from GDM on glucose tolerance in vivo and islets function in vitro were determined. Isolated islets from mice fed on the chow diet displayed an increase in apoptosis and observed their glucose-stimulated insulin secretion (GSIS) greatly diminished by PdE from GDM mice. Mice that accepted PdE from mice with GDM possessed glucose intolerance.Based on miRNA microarray assay and bioinformatics analysis from human placental exosomes, we identified miR-320b selectively enriched in PdE secreted in GDM compared with NGT. Importantly, the level of placental miR-320b was positively correlated with the 1h-glucose and 2-h glucose of a 75g oral glucose tolerance test (OGTT) during human pregnancies. Furthermore, miR-320 overexpression attributed to impaired insulin secretion and increased apoptosis in MIN6 cells and islets obtained from mice with normal insulin sensitivity. This study firstly proposed that altered miRNAs in pdE contribute to defective adaptation of β cells during pregnancy, which expands the knowledge of GDM pathogenesis. Exosomes from the placenta may be an emerging therapeutic target for GDM.

Expression and correlation analysis of silent information regulator 1 (SIRT1), sterol regulatory element-binding protein-1 (SREBP1), and pyroptosis factor in gestational diabetes mellitus

Background and aim Globally, the prevalence of gestational diabetes mellitus (GDM) is rising each year, yet its pathophysiology is still unclear. To shed new light on the pathogenesis of gestational diabetes mellitus and perhaps uncover new therapeutic targets, this study looked at the expression levels and correlations of SIRT1, SREBP1, and pyroptosis factors like NLRP3, Caspase-1, IL-1, and IL-18 in patients with GDM. Methods This study involved a comparative analysis between two groups. The GDM group consisted of 50 GDM patients and the control group included 50 pregnant women with normal pregnancies. Detailed case data were collected for all participants. We utilized real-time quantitative PCR and Western Blot techniques to assess the expression levels of SIRT1 and SREBP1 in placental tissues from both groups. Additionally, we employed an enzyme-linked immunosorbent assay to measure the serum levels of SIRT1, SREBP1, and pyroptosis factors, namely NLRP3, Caspase-1, IL-1β, and IL-18, in the patients of both groups. Subsequently, we analyzed the correlations between these factors and clinical. Results The results showed that there were significantly lower expression levels of SIRT1 in both GDM group placental tissue and serum compared to the control group (p < 0.01). In contrast, the expression of SREBP1 was significantly higher in the GDM group than in the control group (p < 0.05). Additionally, the serum levels of NLRP3, Caspase-1, IL-1β, and IL-18 were significantly elevated in the GDM group compared to the control group (p < 0.01). The expression of SIRT1 exhibited negative correlations with the expression of FPG, OGTT-1h, FINS, HOMA-IR, SREBP1, IL-1β, and IL-18. However, there was no significant correlation between SIRT1 expression and OGTT-2h, NLRP3, or Caspase-1. On the other hand, the expression of SREBP1 was positively correlated with the expression of IL-1β, Caspase-1, and IL-18, but has no apparent correlation with NLRP3. Conclusions Low SIRT1 levels and high SREBP1 levels in placental tissue and serum, coupled with elevated levels of pyroptosis factors NLRP3, Caspase-1, IL-1β, and IL-18 in serum, may be linked to the development of gestational diabetes mellitus. Furthermore, these three factors appear to correlate with each other in the pathogenesis of GDM, offering potential directions for future research and therapeutic strategies.

Влияние общих патогенетических механизмов преэклампсии и гестационного сахарного диабета на их клинические проявления и строение плаценты

Preeclampsia (PE) and gestational diabetes mellitus (GDM) are frequently combined, both diseases causing common pregnancy complications and adverse perinatal outcomes for a mother and newborn. Placental ischemia is the initial factor of PE development followed by endothelial dysfunction, oxidative stress, and inflammation, which determine PE symptoms. Hyperglycemia and insulin resistance accompanying GDM contribute to placental ischemia and increase PE symptoms, thereby exacerbating maternal health. Abnormal development causes placental malperfusion and leads to preeclampsia. Hyperglycemia accompanying GDM prevents the appropriate evolution of villi, which can trigger placental ischemia. This review describes the pathogenesis of PE and GDM and focuses on their clinical features and placental pathology. Keywords: pregnancy, gestational diabetes mellitus, endothelial dysfunction, placenta, preeclampsia

Correlation of Serum Th1/Th2 Cytokines with Insulin Resistance in Gestational Diabetes Mellitus

Objective: To investigate the correlation between serum Th1/Th2 cytokines and insulin resistance in gestational diabetes mellitus (GDM). Methods: A total of 50 cases of pregnant women diagnosed with GDM and 50 healthy pregnant women who visited the Affiliated Hospital of Hebei University from January 2019 to December 2022 were recruited and divided into the GDM group and control group. Serum Th1/Th2 cytokines were observed and analyzed. Results: In the GDM group, serum IFN-γ levels were significantly higher than in the control group (P &lt; 0.01), while there was no statistically significant difference in IL-4 levels (P &gt; 0.05). Within the GDM group, HOMA-IR showed a positive correlation with IFN-γ (r = 0.67, P &lt; 0.01) and no correlation with IL-4 (r = 0.19, P &gt; 0.05). Within the control group, HOMA-IR did not correlate with either IFN-γ or IL-4 (r = 0.23, P &gt; 0.05; r = 0.15, P &gt; 0.05). Conclusion: The study concludes that the serum Th1 cytokine IFN-γ is correlated with insulin resistance in GDM, providing a novel perspective on the pathogenesis of GDM. Future studies should further explore the mechanisms and interventions to offer improved treatment options for patients with GDM.

Comparative Evaluation of Adipokine Metrics for the Diagnosis of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is one of the most common medical disorders in pregnancy. Adipokines, predominantly secreted by adipose tissue, are involved in numerous metabolic processes. The exact role of adipokines in the pathogenesis of GDM is still not well known, and numerous adipokines have been analysed throughout pregnancy and proposed as biomarkers of GDM. This study aimed to evaluate serum adiponectin, chemerin, lipocalin and apelin levels in GDM and non-GDM women, to assess them as clinically useful biomarkers of the occurrence of GDM and to demonstrate the correlation between the levels of the above adipokines in the blood serum and the increased risk of the development of GDM. The role of these adipokines in the pathogenesis of GDM was also analysed. The statistically significant differences between the levels of adiponectin (7234.6 vs. 9837.5 ng/mL, p < 0.0001), chemerin (264.0 vs. 206.7 ng/mL, p < 0.0001) and lipocalin (39.5 vs. 19.4 ng/mL, p < 0.0001) were observed between pregnant women with GDM and healthy ones. The diagnostic usefulness of the tested adipokines in detecting GDM was also assessed. The research results confirm the hypothesis on the significance of adiponectin, chemerin, lipocalin and apelin in the pathophysiological mechanisms of GDM. We speculate that these adipokines could potentially be established as novel biomarkers for the prediction and early diagnosis of GDM.

The Role of the FGF19 Family in the Pathogenesis of Gestational Diabetes: A Narrative Review.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. Understanding the pathogenesis and appropriate diagnosis of GDM enables the implementation of early interventions during pregnancy that reduce the risk of maternal and fetal complications. At the same time, it provides opportunities to prevent diabetes, metabolic syndrome, and cardiovascular diseases in women with GDM and their offspring in the future. Fibroblast growth factors (FGFs) represent a heterogeneous family of signaling proteins which play a vital role in cell proliferation and differentiation, repair of damaged tissues, wound healing, angiogenesis, and mitogenesis and also affect the regulation of carbohydrate, lipid, and hormone metabolism. Abnormalities in the signaling function of FGFs may lead to numerous pathological conditions, including metabolic diseases. The FGF19 subfamily, also known as atypical FGFs, which includes FGF19, FGF21, and FGF23, is essential in regulating metabolic homeostasis and acts as a hormone while entering the systemic circulation. Many studies have pointed to the involvement of the FGF19 subfamily in the pathogenesis of metabolic diseases, including GDM, although the results are inconclusive. FGF19 and FGF21 are thought to be associated with insulin resistance, an essential element in the pathogenesis of GDM. FGF21 may influence placental metabolism and thus contribute to fetal growth and metabolism regulation. The observed relationship between FGF21 and increased birth weight could suggest a potential role for FGF21 in predicting future metabolic abnormalities in children born to women with GDM. In this group of patients, different mechanisms may contribute to an increased risk of cardiovascular diseases in women in later life, and FGF23 appears to be their promising early predictor. This study aims to present a comprehensive review of the FGF19 subfamily, emphasizing its role in GDM and predicting its long-term metabolic consequences for mothers and their offspring.

Protective effect of tretinoin derivative and TXNRD1 protein on streptozotocin induced gestational diabetes via an age-rage signaling-pathway.

In the present study effect of tretinoin derivative was investigated on the pathogenesis of gestational diabetes mellitus (GDM) in mice model in vivo. Diabetes was induced in mice by injecting Streptozotocin (STZ) for 5consecutive days at a dose of 65 mg/kg body weight through the intraperitoneal route. Tretinoin derivative was given to the mice at 0.12 and 0.25 mg/kg doses through gavage in normal saline alternately for one week after STZ injection. The results demonstrated that tretinoin derivative administration to the diabetic mice significantly (P<0.05) alleviated the blood FBG and FINS levels. Administration of tretinoin derivative to the diabetic mice significantly (P<0.05) promoted the blood HDL level and alleviated TC and TG levels. The administration of tretinoin derivative to the diabetic mice significantly (P<0.05) alleviated the CRP, IL-6and TNF-α production in pancreatic tissues. Tretinoin derivative administration to the diabetic mice significantly (P<0.05) elevated the SOD activity, and CAT level and lowered the MDA level in pancreatic tissues. The TXNRD1 expression in diabetic mice was comparable to that in the normal group after administration of tretinoin derivativeat the dose of 0.25 mg/kg dose. In silico data demonstrated that tretinoin derivativeinteracts with TXNRD1 protein with the binding affinity ranging from -10 to 9.4 kcal/ mol. In conclusion, tretinoin derivative administration effectively regulated streptozotocin-induced changes in fasting blood glucose, insulin level, high-density lipid level and triglyceride level in diabetic mice in vivo. The streptozotocin-induced excessive production of C-reactive protein and inflammatory cytokines was also down-regulated in diabetic mice on administration of tretinoin derivative. Therefore, tretinoin derivative can be investigated further as a therapeutic agent for the treatment of gestational diabetes mellitus.

Role of CircCHD2 in the pathogenesis of gestational diabetes mellitus by regulating autophagy via miR-33b-3p/ULK1 axis

Gestational diabetes mellitus (GDM) is a common pregnancy complication with a high incidence in women; however, its pathophysiology remains unknown. Our previous study suggested that the circCHD2/miR-33b-3p/ULK1 axis may be involved in GDM pathogenesis. However, the mechanism through which circCHD2 regulates GDM development requires further investigation. We found that high-glucose (HG, 25 mmol/L) significantly induced the expression of circCHD2, increased autophagy and apoptosis, and decreased cell viability in human placental trophoblast HTR-8/SVneo cells. In contrast, the downregulation of circCHD2 significantly attenuated the effects of HG on HTR-8/SVneo cells. MiR-33b-3p downregulated in the placenta of GDM patients was reduced by HG and detected as a target of circCHD2 using bioinformatics analysis, a dual-luciferase reporter assay, and qRT-PCR assay. Further studies showed that the inhibition of miR-33b-3p significantly blocked the effects of circCHD2 downregulation on cell viability, apoptosis, and autophagy in HG-treated HTR-8/SVneo cells. ULK1 is a target of miR-33b-3p, based on bioinformatics analysis, a dual-luciferase reporter assay, qRT-PCR assay, and Western blot analysis. Compared to miR-33b-3p, ULK1 is upregulated in the placenta of GDM patients. ULK1 overexpression notably blocked the effects of miR-33b-3p mimics on cell viability, apoptosis, and autophagy in HG-treated HTR-8/SVneo cells. These findings suggested that circCHD2 acts as an autophagy promoter via the miR-33b-3p/ULK1 axis to induce apoptosis in HTR-8/SVneo cells, suggesting that circCHD2 is a potential diagnostic and therapeutic target for GDM.

Genetic and Epigenetic Factors in Gestational Diabetes Mellitus Pathology

Gestational diabetes (GDM) is the carbohydrate intolerance occurring during pregnancy. The risk factors of GDM include obesity, advanced maternal age, polycystic ovary syndrome, multigravidity, a sedentary lifestyle, and pre-existing hypertension. Additionally, complex genetic and epigenetic processes are also believed to play a crucial role in the development of GDM. In this narrative review, we discuss the role of genetic and epigenetic factors in gestational diabetes mellitus pathogenesis.