Progression Of Gestational Diabetes Mellitus Research Articles

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.

Gut Microbiome Changes in Gestational Diabetes.

Gestational diabetes mellitus (GDM), one of the most common endocrine pathologies during pregnancy, is defined as any degree of glucose intolerance with onset or first discovery in the perinatal period. Physiological changes that occur in pregnant women can lead to inflammation, which promotes insulin resistance. In the general context of worldwide increasing obesity in young females of reproductive age, GDM follows the same ascending trend. Changes in the intestinal microbiome play a decisive role in obesity and the development of insulin resistance and chronic inflammation, especially in patients with type 2 diabetes mellitus (T2D). To date, various studies have also associated intestinal dysbiosis with metabolic changes in women with GDM. Although host metabolism in women with GDM has not been fully elucidated, it is of particular importance to analyze the available data and to discuss the actual knowledge regarding microbiome changes with potential impact on the health of pregnant women and newborns. We analyzed peer-reviewed journal articles available in online databases in order to summarize the most recent findings regarding how variations in diet and metabolic status of GDM patients can contribute to alteration of the gut microbiome, in the same way that changes of the gut microbiota can lead to GDM. The most frequently observed alteration in the microbiome of patients with GDM was either an increase of the Firmicutes phylum, respectively, or a decrease of the Bacteroidetes and Actinobacteria phyla. Gut dysbiosis was still present postpartum and can impact the development of the newborn, as shown in several studies. In the evolution of GDM, probiotic supplementation and regular physical activity have the strongest evidence of proper blood glucose control, favoring fetal development and a healthy outcome for the postpartum period. The current review aims to summarize and discuss the most recent findings regarding the correlation between GDM and dysbiosis, and current and future methods for prevention and treatment (lifestyle changes, pre- and probiotics administration). To conclude, by highlighting the role of the gut microbiota, one can change perspectives about the development and progression of GDM and open up new avenues for the development of innovative therapeutic targets in this disease.

Impact of iron supplementation on gestational diabetes mellitus: A literature review.

Gestational diabetes mellitus (GDM) is a common complication of pregnancy, affecting 14% of pregnancies worldwide, and the prevention of pathological hyperglycaemia during pregnancy is meaningful for global public health. The role of iron supplementation in the progression of GDM has been of significant interest in recent years. Iron is a micronutrient that is vital during pregnancy; however, given the toxic properties of excess iron, it is probable that prophylactic iron supplementation will increase the risk of adverse pregnancy outcomes, including GDM. It is critical to clarify the effect of iron supplementation on the risk of GDM. Therefore, in this review, we comprehensively assess the role of iron in pregnancy. This review aimed to analyse the necessity of iron supplementation and maintenance of iron homeostasis during pregnancy, particularly reviewing the role and function of iron in beta cells and examining the mechanisms of excess iron contributing to the pathogenesis of GDM. Moreover, we aimed to discuss the association of haemoglobin and ferritin with GDM and identify priority areas for research.

Predictive Gestational Diabetes Biomarkers With Sustained Alterations Throughout Pregnancy.

Gestational diabetes mellitus (GDM) results in an increased risk of pre- and postpartum health complications for both mother and child. Metabolomics analysis can potentially identify predictive biomarkers and provide insight into metabolic alterations associated with GDM pathogenesis and progression, but few metabolomics studies investigate alterations observed across the first and third trimester. We hypothesize that metabolites altered in first-trimester GDM that remain altered in late pregnancy may best inform interventions. Metabolomic studies comparing plasma and serum metabolite alterations in GDM vs non-GDM pregnancies were retrieved by searching PubMed, Medline, and CINAHL Plus databases. The present scoping review summarizes the metabolites found to be consistently altered throughout the course of GDM and proposes mechanisms that explain how these metabolic perturbations relate to GDM development and progression. Metabolites involved in fatty acid metabolism, reductive carboxylation, branched-chain amino acid metabolism, cell membrane lipid metabolism, purine degradation, and the gut microbiome were found to be altered throughout GDM pregnancies, with many of these pathways showing mechanistic links to insulin resistance, inflammation, and impaired cell signaling. Future studies are required to investigate if normalization of these perturbed pathways can be the targets of interventions.

Machine Learning-Derived Prenatal Predictive Risk Model to Guide Intervention and Prevent the Progression of Gestational Diabetes Mellitus to Type 2 Diabetes: Prediction Model Development Study.

BackgroundThe increasing prevalence of gestational diabetes mellitus (GDM) is concerning as women with GDM are at high risk of type 2 diabetes (T2D) later in life. The magnitude of this risk highlights the importance of early intervention to prevent the progression of GDM to T2D. Rates of postpartum screening are suboptimal, often as low as 13% in Asian countries. The lack of preventive care through structured postpartum screening in several health care systems and low public awareness are key barriers to postpartum diabetes screening.ObjectiveIn this study, we developed a machine learning model for early prediction of postpartum T2D following routine antenatal GDM screening. The early prediction of postpartum T2D during prenatal care would enable the implementation of effective strategies for diabetes prevention interventions. To our best knowledge, this is the first study that uses machine learning for postpartum T2D risk assessment in antenatal populations of Asian origin.MethodsProspective multiethnic data (Chinese, Malay, and Indian ethnicities) from 561 pregnancies in Singapore’s most deeply phenotyped mother-offspring cohort study—Growing Up in Singapore Towards healthy Outcomes—were used for predictive modeling. The feature variables included were demographics, medical or obstetric history, physical measures, lifestyle information, and GDM diagnosis. Shapley values were combined with CatBoost tree ensembles to perform feature selection. Our game theoretical approach for predictive analytics enables population subtyping and pattern discovery for data-driven precision care. The predictive models were trained using 4 machine learning algorithms: logistic regression, support vector machine, CatBoost gradient boosting, and artificial neural network. We used 5-fold stratified cross-validation to preserve the same proportion of T2D cases in each fold. Grid search pipelines were built to evaluate the best performing hyperparameters.ResultsA high performance prediction model for postpartum T2D comprising of 2 midgestation features—midpregnancy BMI after gestational weight gain and diagnosis of GDM—was developed (BMI_GDM CatBoost model: AUC=0.86, 95% CI 0.72-0.99). Prepregnancy BMI alone was inadequate in predicting postpartum T2D risk (ppBMI CatBoost model: AUC=0.62, 95% CI 0.39-0.86). A 2-hour postprandial glucose test (BMI_2hour CatBoost model: AUC=0.86, 95% CI 0.76-0.96) showed a stronger postpartum T2D risk prediction effect compared to fasting glucose test (BMI_Fasting CatBoost model: AUC=0.76, 95% CI 0.61-0.91). The BMI_GDM model was also robust when using a modified 2-point International Association of the Diabetes and Pregnancy Study Groups (IADPSG) 2018 criteria for GDM diagnosis (BMI_GDM2 CatBoost model: AUC=0.84, 95% CI 0.72-0.97). Total gestational weight gain was inversely associated with postpartum T2D outcome, independent of prepregnancy BMI and diagnosis of GDM (P=.02; OR 0.88, 95% CI 0.79-0.98).ConclusionsMidgestation weight gain effects, combined with the metabolic derangements underlying GDM during pregnancy, signal future T2D risk in Singaporean women. Further studies will be required to examine the influence of metabolic adaptations in pregnancy on postpartum maternal metabolic health outcomes. The state-of-the-art machine learning model can be leveraged as a rapid risk stratification tool during prenatal care.Trial RegistrationClinicalTrials.gov NCT01174875; https://clinicaltrials.gov/ct2/show/NCT01174875

Estradiol (E2) Improves Glucose-Stimulated Insulin Secretion and Stabilizes GDM Progression in a Prediabetic Mouse Model.

Female New Zealand obese (NZO) mice are an established model of preconceptional (pc.) prediabetes that progresses as gestational diabetes mellitus (GDM) during gestation. It is known that NZO mice show improvement in insulin sensitivity and glucose-stimulated insulin secretion (GSIS) during gestation in vivo. The latter is no longer detectable in ex vivo perifusion experiments in isolated islets of Langerhans, suggesting a modulation by extrapancreatic factors. Here, we demonstrated that plasma 17β-estradiol (E2) levels increased markedly in NZO mice during gestation. The aim of this work was to determine whether these increased E2 levels are responsible for the improvement in metabolism during gestation. To achieve this goal, we examined its effects in isolated islets and primary hepatocytes of both NZO and metabolically healthy NMRI mice. E2 increased GSIS in the islets of both strains significantly. Hepatic glucose production (HGP) failed to be decreased by insulin in NZO hepatocytes but was reduced by E2 in both strains. Hepatocytes of pregnant NZO mice showed significantly lower glucose uptake (HGU) compared with NMRI controls, whereby E2 stimulation diminished this difference. Hepatocytes of pregnant NZO showed reduced glycogen content, increased cyclic adenosine monophosphate (cAMP) levels, and reduced AKT activation. These differences were abolished after E2 stimulation. In conclusion, our data indicate that E2 stabilizes and prevents deterioration of the metabolic state of the prediabetic NZO mice. E2 particularly increases GSIS and improves hepatic glucose utilization to a lower extent.

Oxidative stress in maternal milk and cord blood in gestational diabetes mellitus: a prospective study.

Reduced antioxidant defenses may reflect a poor protective response against oxidative stress and this may be implicated in progression of gestational diabetes mellitus (GDM). Oxidative stress induced by hyperglycemia plays a major role in micro and macrovascular complications, which imply endothelial dysfunction. Our aim in this study was to investigate the association between GDM and oxidative stress markers measured in plasma, with regard to revealing changes to total antioxidant capacity (TAC) and total oxidant status (TOS) among mothers showing impairments in oral glucose tolerance tests (OGTTs). Prospective study at a university hospital in Turkey. The study group consisted of 50 mothers with GDM, and 59 healthy mothers served as controls. Umbilical cord blood samples were taken from all mothers during delivery and breast milk samples on the fifth day after delivery. TAC, TOS, thiol and disulfide levels were measured. No statistically significant relationship between the blood and milk samples could be found. An analysis on correlations between TAC, TOS and certain parameters revealed that there were negative correlations between TOS and total thiol (r = -0.386; P < 0.001) and between TOS and disulfide (r = -0.388; P < 0.001) in milk in the control group. However, these findings were not observed in the study group. Our findings suggested that a compensatory mechanism of oxidative stress was expected to be present in gestational diabetes mellitus and that this might be ameliorated through good glycemic regulation and antioxidant supplementation.

Long-noncoding RNA HOXA transcript at the distal tip ameliorates the insulin resistance and hepatic gluconeogenesis in mice with gestational diabetes mellitus via the microRNA-423-5p/wingless-type MMTV integration site family member 7A axis

ABSTRACT Long-noncoding RNA HOXA transcript at the distal tip (HOTTIP) has been probed to exert essential effects on diabetes progression, while its function in gestational diabetes mellitus (GDM) remains unclear. This study was committed to unravel the effects of HOTTIP on GDM progression via the microRNA (miR)-423-5p/wingless-type MMTV integration site family member 7A (WNT7A) axis. The GDM mouse model was established. HOTTIP, miR-423-5p and WNT7A levels in GDM mice were examined. The saline with dissolved various constructs altering HOTTIP, miR-423-5p and WNT7A expression was injected into GDM mice to detect the levels of GDM‐related biochemical indices, HOMA indices, liver gluconease: expression levels of phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G-6-Pase), glucose transporter 2 (GLUT2) and pathological changes of pancreatic tissues, and the apoptosis rate of pancreatic cells in GDM mice. The relations among HOTTIP, miR-423-5p and WNT7A were validated. HOTTIP and WNT7A levels were decreased while miR-423-5p was elevated in GDM mice. The enriched HOTTIP or silenced miR-423-5p alleviated the levels of GDM‐relatedbiochemical indices, enhanced the insulin homeostasis, elevated GLUT2 expression and decreased G-6-pase and PEPCK expression, mitigated the pathological changes of pancreatic tissues, and hindered the apoptosis of pancreatic cells. MiR-143-5p upregulation abrogated the effects of elevated HOTTIP on repressing GDM; whereas WNT7A deletion reversed the therapeutic effects of reduced miR-423-5p. HOTTIP sponged miR-423-5p that targeted WNT7A. HOTTIP ameliorates insulin resistance and hepatic gluconeogenesis in GDM mice via the modulation of the miR-423-5p/WNT7A axis. This study affords novel therapeutic modalities for GDM treatment.

Inflammatory markers are associated with the progression of gestational diabetes to metabolic syndrome

The progression of gestational diabetes mellitus (GDM) to metabolic syndrome (MetS) is associated with systemic inflammation. The aim of this study was to compare the levels of inflammatory markers in former GDM patients with and without MetS. Medical records were screened retrospectively for patients who were diagnosed with GDM 10 (±2) years ago. Former GDM patients were invited to the hospital for an assessment of their current health status. Of 52 women with former GDM, 27 (52%) had MetS. C-reactive protein (CRP), interleukin-6 and plasminogen activator inhibitor-1 (PAI-1) levels were significantly higher in the MetS group while adiponectin was significantly lower (p < .001, p = .037, p = .002 and p = .013, respectively). There was no significant difference in plasma levels of visfatin and tumour necrosis factor-α. Interleukin-6, CRP, PAI-1 and adiponectin may be used as biomarkers to detect MetS in the pre-clinical phase. With timely diagnosis, early interventions can be implemented. IMPACT STATEMENT What is already known on this subject? The progression of ‘gestational diabetes mellitus’ to ‘metabolic syndrome’ is associated with systemic inflammation. Up to half of cases with former gestational diabetes mellitus (GDM) eventually progress to metabolic syndrome (MetS). What do the results of this study add? Interleukin-6, C-reactive protein, plasminogen activator inhibitor-1 and adiponectin may be used as biomarkers to detect MetS in the pre-clinical phase. What are the implications of these findings from clinical practice and/or further research? The progression of GDM to MetS is associated with systemic inflammation. Potential therapies should therefore target this inflammatory state. Interleukin-6, C-reactive protein, plasminogen activator inhibitor-1 and adiponectin may be used as biomarkers to detect MetS in the pre-clinical phase. With timely diagnosis, early interventions and lifestyle changes can be implemented to prevent morbidity and mortality associated with full-blown MetS.

MicroRNA-7 Regulates Insulin Signaling Pathway by Targeting IRS1, IRS2, and RAF1 Genes in Gestational Diabetes Mellitus.

Small non-coding micro RNAs (miRNAs) are indicated in various metabolic processes and play a critical role in disease pathology, including gestational diabetes mellitus (GDM). The purpose of this study was to examine the altered expression of miRNAs and their target genes in placental tissue (PL), cord blood (CB), and maternal blood (MB) of matched non-glucose tolerant (NGT) and GDM mother. In a case-control study, micro-RNA was quantified from forty-five serum (MB n = 15, CB n = 15, and PL n = 15) and matched placental tissue using stem-loop RT-qPCR followed by target prediction, network construction and functional and pathways enrichment analysis. Further, target genes were verified in-vitro through transfection and RT-qPCR. Five miRNAs, namely hsa-let 7a-5P, hsa-miR7-5P, hsa-miR9-5P, hsa-miR18a-5P, and hsamiR23a- 3P were significantly over-expressed (p < 0.05) in all three samples namely PL, CB, and MB of GDM patients. However, the sample-wise comparison reveals higher expression of miRNA 7 in MB while lowest in CB than control. Furthermore, a comparison of fold change expression of target genes discloses a lower expression of IRS1, IRS2, and RAF1 in MB while comparatively higher expression of NRAS in MB and CB. In-vitro validation reveals lower expression of IRS1/2 and RAF1 in response to overexpression of miR-7 and vice-versa. Thus it is evident that increased miRNA7 expression causes down-regulation of its target genes IRS1, IRS2, and RAF1 in GDM mother compared to control. Further, target prediction, pathway enrichment, and hormone analysis (significantly higher FSH & LH in MB of GDM compared to NGT) revealed insulin signaling, inflammatory and GnRH signaling as major pathways regulated by miRNA7. Thus, an elevated level of miRNA7 may be associated with the progression of GDM by altering the multiple pathways like insulin, GnRH, and inflammatory signaling pathways via targeting IRS1, IRS2, and RAF1, implicating a new therapeutic target for GDM.

Evaluation of a Postpartum Cardiovascular Risk Screening Clinic: An Analysis of Interpregnancy and Subsequent Pregnancy Outcomes.

At the Maternal Health Clinic (MHC), women with certain pregnancy complications are seen for appointments focusing on lifestyle modification and future pregnancy counselling. This study's objective is to determine whether women who attended the MHC following a pregnancy complicated by gestational diabetes mellitus (GDM) or a hypertensive disorder of pregnancy (HDP) have improved interpregnancy and subsequent pregnancy outcomes, compared with non-attendees. A retrospective cohort study was conducted including all pregnancies ≥20 weeks gestation at Kingston Health Sciences Centre (KHSC) from April 2010 to Dec 2019. Women with ≥2 deliveries were eligible for inclusion, with 2 pregnancies per woman included. These criteria identified 178 patients who attended the MHC and 133 who did not. Continuous variables with normal distribution were assessed with independent sample t tests. Continuous variables without normal distribution and ordinal variables were assessed with Mann-WhitneyUtests. Categorical variables were assessed with Pearson's χ2 tests. Preterm delivery, HDP and GDM recurrence, HDP and GDM progression, and change in first-trimester blood pressure and pre-pregnancy weight were examined using multivariate regression modelling. Probability values <0.05 determined significance. MHC attendance was associated with improvements in interpregnancy weight reduction (P=0.002), fewer interpregnancy type II diabetes diagnoses (P < 0.001), and a later gestational age at delivery (P < 0.001). There were no differences in subsequent pregnancy complication recurrence rates of GDM (P=0.731) or an HDP (P=0.139) between cohorts. In our examination of MHC outcomes, we found improvements in certain interpregnancy and subsequent pregnancy outcomes. These results support the continued development and funding of these clinics.

MicroRNA-195-5p facilitates endothelial dysfunction by inhibiting vascular endothelial growth factor A in gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is a common disorder during pregnancy associated with endothelial dysfunction in the placental vasculature. MicroRNAs (miRNAs), which are short noncoding RNAs that modulate post-transcriptional gene expression, affect GDM progression. MiR-195-5p was reported to be a putative biomarker for GDM diagnosis, whose expression was markedly elevated in serum of GDM patients. Therefore, our study intended to explore whether miR-195-5p regulates endothelial cell dysfunction in GDM. Human placental microvascular endothelial cells (hPMECs) were treated with high concentration of glucose to establish an in vitro GDM model. The apoptosis, proliferation and angiogenesis of hPMECs were detected by flow cytometry analysis, CCK-8 assay and tube formation assay. The binding between vascular endothelial growth factor A (VEGFA) and miR-195-5p was verified by luciferase reporter assay. GDM mouse model was established by intraperitoneal injection of streptozocin. Cell apoptosis and the pathological changes in GDM mouse placenta tissues were evaluated by TUNEL staining and HE staining. Gene expression was detected by RT-qPCR. Protein levels were evaluated by western blotting. In this study, miR-195-5p knockdown promoted the proliferation and angiogenesis as well as inhibited the apoptosis of HG-treated hPMECs. MiR-195-5p targeted VEGFA, whose expression was downregulated in HG-treated hPMECs. VEGFA silencing antagonized the influence of miR-195-5p knockdown on the phenotypes of HG-treated hPMECs. Additionally, miR-195-5p inhibition decelerated cell apoptosis and improved pathological changes in GDM mouse placenta tissues. MiR-195-5p level was negatively correlated to VEGFA level in GDM mouse placenta tissues. Overall, miR-195-5p facilitates the endothelial cell dysfunction by inhibiting VEGFA in GDM.

Circ_FOXP1 promotes the growth and survival of high glucose-treated human trophoblast cells through the regulation of miR-508-3p/SMAD family member 2 pathway.

Gestational diabetes mellitus (GDM) is a health risk for pregnant women and infants. Emerging evidence suggests that the deregulation of circular RNAs (circRNAs) is associated with the progression of this disorder. The objective of this study was to investigate the role of circ_FOXP1 in GDM. Cell models of GDM were established by treating human trophoblast cells with high glucose (HG). The expression of circ_FOXP1, miR-508-3p and SMAD family member 2 (SMAD2) mRNA was detected by quantitative real-time PCR (qPCR). Cell proliferation was assessed by EdU assay and MTT assay, and cell cycle and cell apoptosis were determined by flow cytometry assay. The protein levels of proliferation- and apoptosis-related markers and SMAD2 were measured by western blot. The relationship between miR-508-3p and circ_FOXP1 or SMAD2 was validated by dual-luciferase reporter assay or pull-down assay. The expression of circ_FOXP1 was downregulated in HG-treated HTR-8/SVneo cells. Circ_FOXP1 overexpression promoted HG-inhibited HTR-8/SVneo cell proliferation and suppressed HG-induced HTR-8/SVneo cell cycle arrest and apoptosis. Circ_FOXP1 positively regulated the expression of SMAD2 by targeting miR-508-3p. MiR-508-3p was overexpressed in HG-treated HTR-8/SVneo cells, and its overexpression reversed the effects of circ_FOXP1 overexpression. MiR-508-3p inhibition also alleviated HG-induced HTR-8/SVneo cell injuries, while the knockdown of SMAD2 abolished these effects. Collectively, circ_FOXP1 promotes the growth and survival of HG-treated human trophoblast cells through the miR-508-3p/SMAD2 pathway, hinting that circ_FOXP1 was involved in GDM progression.

Downregulation of microRNA-342-3p Eases Insulin Resistance and Liver Gluconeogenesis via Regulating Rfx3 in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a worldwide public health problem. MicroRNAs (miRNAs) have been reported to be associated with GDM progression. We intended to figure out the function of miR-342-3p in the insulin resistance (IR) and liver gluconeogenesis in GDM. GDM mouse models were established by intraperitoneal injection of streptozocin. The expression of miR-342-3p and regulatory factor X3 (Rfx3) in placenta and pancreatic tissues of GDM mice were evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). GDM mice were treated with lentivirus-mediated antagomir-miR-342-3p for miR-342-3p downregulation. Enzyme-linked immunosorbent assay, hematoxylin-eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and periodic acid-Schiff staining were conducted to detect the influence of miR-342-3p knockdown on the levels of blood glucose, insulin, biochemical indices as well as the apoptosis and pathological changes in placenta or pancreatic tissues of GDM mice. The binding between Rfx3 and miR-342-3p was validated by dual luciferase reporter assays. miR-342-3p was upregulated and Rfx3 was downregulated in placenta and pancreatic tissues of GDM mice. Moreover, miR-342-3p bound with Rfx3 3'-UTR and therefore downregulated the expression of Rfx3. miR-342-3p expression was negatively correlated to Rfx3 expression in placenta tissues of GDM mice. In addition, miR-342-3p depletion decreased the levels of blood glucose, insulin, biochemical indices as well as restrained the apoptosis and pathological changes in GDM mouse placenta and pancreatic tissues. Furthermore, Rfx3 silencing countervailed the alleviative influence of miR-342-3p downregulation on IR and liver gluconeogenesis in GDM mice. Collectively, downregulation of miRNA-342-3p inhibits IR and liver gluconeogenesis in GDM by upregulating Rfx3, which may provide novel insight for GDM treatment.

MiR-210-3p Impairs Pancreatic β-Cell Function by Targeting Dtx1 in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM), a common complication in pregnancy, could threaten the health of both pregnancies and their offspring. miR-210-3p has been reported that play a crucial role in many diseases. Nevertheless, the molecular mechanism and clinical significance of miR-210-3p in the GDM is still unclear. miR-210-3p was overexpressed in the pancreas of the GDM mouse model. Meanwhile, miR-210-3p weakens cell viability and promotes the apoptosis of pancreatic β cells, impairing the function of pancreatic β cells. Bioinformatics analysis showed that miR-210-3p directly targets the expression of Dtx1, and miR-210-3p negatively regulated dtx1. Down-expression of Dtx1 could increase the expression of insulin and boost the function of pancreatic β cells through inhibiting expressions of p-Akt, p-mTOR, p-4E-BP1, and p-SGK1. Rescue experiments verified that miR-210-3p could regulate the function of pancreatic β cells and adjust the content of TG, TC, and HDL in the blood of mice with GDM via regulating the expression of Dtx1. The study demonstrated that miR-210-3p is significantly overexpressed in the pancreas of the GDM mouse model, which could impair the function and cell viability of pancreatic β cells via suppressing the expression of Dtx1 promotes the progression of GDM. These findings provide a novel strategy to treat GDM.

Evaluation of bone mineral density in patients with gestational diabetes mellitus by ultrasonic bone mineral density measurement combined with Vitamin-D deficiency and analysis of influencing factors.

Objectives:To investigate the evaluation of bone mineral density (BMD) in patients with gestational diabetes mellitus (GDM) by ultrasonic bone mineral density measurement combined with Vitamin-D deficiency and its influencing factors.Methods:A total of 100 patients with gestational diabetes mellitus (GDM) admitted to our hospital from January 2017 to December 2020 were selected as the GDM group, and another 100 pregnant volunteers who underwent physical examination in our hospital were selected as the healthy control group. The levels of triacylglycerol (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), glycated hemoglobin (HbA1c), fasting insulin (FINS), C-peptide, procollagen, parathyroid hormone (PTH), serum calcium, 25-hydroxyvitamin-D3 (25-OH-D) and ultrasonic BMD Z-score were determined and compared between the two groups. Moreover, the effects of different levels of 25-OH-D on the above indexes were compared, and multivariate logistic regression analysis was performed.Results:Compared with the healthy reference group, the levels of TG, TC, LDL-C, PTH, HbA1c, FINS and C-peptide of GDM group were significantly increased (P < 0.05), while BMD Z-score and 25-OH-D levels were significantly decreased. In the GDM group, the lower the 25-OH-D levels, the higher the FPG, HbA1c and FINS levels and the lower the serum calcium level and BMD Z-score, with statistically significant differences (P < 0.05). Multivariate logistic regression analysis showed that 25-OH-D was an independent risk factor affecting BMD in patients with GDM (P<0.05).Conclusions:Patients with GDM have lower BMD and 25-hydroxyVitamin-D3 levels. Measurement of BMD and 25-hydroxyVitamin-D3 levels can help assess the progression of GDM. BMD has a close bearing on Vitamin-D deficiency in patients with GDM.

Risk factors for women with gestational diabetes mellitus developing type 2 diabetes and the impact on children's health.

The study aimed to explore the risk factors for progression to type 2 diabetes in women with gestational diabetes mellitus and the long-term impact of gestational diabetes mellitus on the health of their children. The occurrence of gestational diabetes mellitus in women is the strongest predictor of the development of type 2 diabetes in the future. A non-concurrent cohort and case-control study design and the guidelines forSTROBE checklist were used for the study. We reviewed medical records for the time period from the archives of the hospitals. The short-listed women and their children were invited to participate in a 'Women with gestational diabetes mellitus' research activity from November 2012-February 2016. Blood tests, physiological indicators and demographic questionnaires were applied for data collection. A total of 57 women and 57 children participated in the research activity. The risk factors for progression of gestational diabetes mellitus to type 2 diabetes included education level and the 1-h blood glucose level for the antepartum 100-g oral glucose tolerance test and the 2-h blood glucose level for the postpartum 75-g oral glucose tolerance test. However, these risk factors did not have a significant impact on the body mass index and body fat of the women's children. Healthcare providers should adopt a breadth of health education strategies to remind women with gestational diabetes mellitus to be aware of certain risk factors, and to urge them and their children to return for regular follow-up visits. Identification of the risk factors developing type 2 diabetes can make healthcare units incorporate the postpartum follow-up of gestational diabetes mellitus into their standard protocol and case managers continue to follow-up and manage the health of the women and that of their children to reduce adverse health of them.

High pre-pregnancy BMI with a history of gestational diabetes mellitus is associated with an increased risk of type 2 diabetes in Korean women.

Despite the importance of pre-pregnancy body mass index (BMI) and a history of gestational diabetes mellitus (GDM) in the progression of GDM to type 2 diabetes, few studies have evaluated the combined effect of high pre-pregnancy BMI and GDM status on the future development of type 2 diabetes in Korean women. This study aimed to examine the relationship of pre-pregnancy BMI and GDM history with the risk of type 2 diabetes among Korean women. In addition, the effects of pre-pregnancy BMI and current BMI on the risk of type 2 diabetes were evaluated. Women who gave birth in the Health Examinees Study of the Korean Genome and Epidemiology Study from 2004 to 2013 (n = 59,258) were included in this study. Multivariable logistic regression was used to examine the association of pre-pregnancy BMI categories (underweight: <18.5 kg/m2; normal: 18.5–22.9 kg/m2; overweight: 23.0–24.9 kg/m2; obese: ≥25.0 kg/m2) and GDM history with the risk of type 2 diabetes after controlling for the following covariates: age, education, income, smoking status before the first pregnancy, alcohol consumption, regular exercise, menarche age, first pregnancy age, and first pregnancy outcome. Compared to women with normal pre-pregnancy BMIs, women with overweight and obese pre-pregnancy BMIs had higher odds of developing type 2 diabetes (adjusted odds ratio [AOR]: 1.13, 95% confidence interval [CI]: 1.02–1.25 and AOR: 1.29, 95% CI: 1.10–1.50, respectively) after controlling for covariates. Women with pre-pregnancy BMIs <23 kg/m2 and current BMIs ≥23 kg/m2 had increased odds of developing type 2 diabetes (AOR: 1.64, 95% CI: 1.51–1.78) compared to those with pre-pregnancy BMIs <23 kg/m2 and current BMIs <23 kg/m2. Among women without a history of GDM, those with overweight and obese pre-pregnancy BMIs had increased odds of developing type 2 diabetes compared to those with normal pre-pregnancy BMIs (AOR: 1.12, 95% CI: 1.01–1.24 and AOR: 1.23, 95% CI: 1.05–1.44, respectively). Among women with GDM, those with obese pre-pregnancy BMIs had increased odds of developing type 2 diabetes (AOR: 3.84, 95% CI: 1.52–9.87). This study showed that there was a higher likelihood of developing type 2 diabetes in women who were overweight or obese before pregnancy with a history of GDM compared to their counterparts without a history of GDM. Furthermore, high pre-pregnancy BMI or high current BMI increased the risk of type 2 diabetes in Korean women, regardless of GDM history. This emphasizes the importance of maintaining a healthy weight status before and after pregnancy to prevent the future risk of type 2 diabetes.

Risk of Developing Type 2 Diabetes Mellitus in South Asian Women with History of Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Background:Gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) represent two different components of the spectrum of diabetes mellitus (DM). Women with GDM have a high chance of developing T2DM in later life and this relative risk depends on a number of factors including ethnicity.Aim:To compare and estimate the risk of developing T2DM in South Asian women with a history of GDM compared to those without a history of GDM.Methods:This is a systematic review of PubMed and MEDLINE articles reporting the progression of GDM to T2DM that were published in English from 2000 to 2020. We performed meta-analysis to calculate risk ratios (RR).Results:We selected 6 studies considering the inclusion and exclusion criteria after sorting 25 full-text articles. Of the 44165 South Asian women assessed, 3095 had GDM and 41070 were without GDM. 995 women in GDM group and 1525 women in non-GDM group had developed T2DM. The RR of women with GDM over non-GDM in developing T2DM was 10.81 (95% confidence interval (CI): 7.61–15.35) suggesting that women with GDM are at 10.81 times more risk of developing T2DM than non-GDM. The cumulative incidence of T2DM in GDM group was 17.34% at 5 years of follow-up and 33% at more than 10 years of follow-up.Conclusion:The risk of developing T2DM in later life is higher in South Asian women with GDM than without GDM. Therefore, lifestyle and pharmacological interventions, patient communication, timely screening, and long-term follow-up of GDM patients are important to reduce the risk.