Long-term effects of gestational diabetes mellitus on the pancreas of female mouse offspring

BACKGROUND Prolonged fetal exposure to hyperglycemia may increase the risk of developing abnormal glucose metabolism and type-2 diabetes during childhood,adolescence,and adulthood;however,the mechanisms by which gestational diabetes mellitus(GDM)predisposes offspring to metabolic disorders remain unknown.AIM To quantify the nerve axons,macrophages,and vasculature in the pancreas from adult offspring born from mouse dams with GDM.METHODS GDM was induced by i.p.administration of streptozotocin(STZ)in ICR mouse dams.At 12 wk old,fasting blood glucose levels were determined in offspring.At 15 wk old,female offspring born from dams with and without GDM were sacrificed and pancreata were processed for immunohistochemistry.We quantified the density of sensory[calcitonin gene-related peptide(CGRP)]and tyrosine hydroxylase(TH)axons,blood vessels(endomucin),and macro-phages(CD68)in the splenic pancreas using confocal microscopy.RESULTS Offspring mice born from STZ-treated dams had similar body weight and blood glucose values compared to offspring born from vehicle-treated dams.However,the density of CGRP+and TH+axons,endomucin+blood vessels,and CD68+macrophages in the exocrine pancreas was significantly greater in offspring from mothers with GDM vs control offspring.Likewise,the microvasculature in the islets was significantly greater,but not the number of macrophages within the islets of offspring born from dams with GDM compared to control mice.CONCLUSION GDM induces neuronal,vascular,and inflammatory changes in the pancreas of adult progeny,which may partially explain the higher propensity for offspring of mothers with GDM to develop metabolic diseases.

Developing and validating a predictive model of delivering large-forgestational-age infants among women with gestational diabetes mellitus

BACKGROUND The birth of large-for-gestational-age(LGA)infants is associated with many shortterm adverse pregnancy outcomes.It has been observed that the proportion of LGA infants born to pregnant women with gestational diabetes mellitus(GDM)is significantly higher than that born to healthy pregnant women.However,traditional methods for the diagnosis of LGA have limitations.Therefore,this study aims to establish a predictive model that can effectively identify women with GDM who are at risk of delivering LGA infants.AIM To develop and validate a nomogram prediction model of delivering LGA infants among pregnant women with GDM,and provide strategies for the effective prevention and timely intervention of LGA.METHODS The multivariable prediction model was developed by carrying out the following steps.First,the variables that were associated with LGA risk in pregnant women with GDM were screened by univariate analyses,for which the P value was<0.10.Subsequently,Least Absolute Shrinkage and Selection Operator regression was fit using ten cross-validations,and the optimal combination factors were se-lected by choosing lambda 1se as the criterion.The final predictors were deter-mined by multiple backward stepwise logistic regression analysis,in which only the independent variables were associated with LGA risk,with a P value<0.05.Finally,a risk prediction model was established and subsequently evaluated by using area under the receiver operating characteristic curve,calibration curve and decision curve analyses.RESULTS After using a multistep screening method,we establish a predictive model.Several risk factors for delivering an LGA infant were identified(P<0.01),including weight gain during pregnancy,parity,triglyceride-glucose index,free tetraiodothyronine level,abdominal circumference,alanine transaminase-aspartate aminotransferase ratio and weight at 24 gestational weeks.The nomogram’s prediction ability was supported by the area under the curve(0.703,0.709,and 0.699 for the training cohort,validation cohort,and test cohort,respectively).The calibration curves of the three cohorts displayed good agreement.The decision curve showed that the use of the 10%-60%threshold for identifying pregnant women with GDM who are at risk of delivering an LGA infant would result in a positive net benefit.CONCLUSION Our nomogram incorporated easily accessible risk factors,facilitating individualized prediction of pregnant women with GDM who are likely to deliver an LGA infant.

Tailored nutritional interventions: A precision approach to managing gestational diabetes mellitus

Gestational diabetes mellitus(GDM)is a risk to maternal-fetal health due to uncertain diagnostic criteria and treatment options.Luo's study demonstrated the efficacy of customized nutritional therapies in controlling GDM.Tailored strategies led to significant body weight loss,improved glucolipid metabolism,and fewer prenatal and newborn problems.This holistic approach,which emphasizes the notion of’chrononutrition’,takes into account optimal meal timing that is in sync with circadian rhythms,as well as enhanced sleep hygiene.Implementing tailored dietary therapy,managing meal timing,and ensuring appropriate sleep may improve results for women with GDM,opening up a possible avenue for multi-center trials.

Epigenetic modifications of placenta in women with gestational diabetes mellitus and their offspring

Gestational diabetes mellitus(GDM)is a pregnancy-related complication characterized by abnormal glucose metabolism in pregnant women and has an important impact on fetal development.As a bridge between the mother and the fetus,the placenta has nutrient transport functions,endocrine functions,etc.,and can regulate placental nutrient transport and fetal growth and development according to maternal metabolic status.Only by means of placental transmission can changes in maternal hyperglycemia affect the fetus.There are many reports on the placental pathophysiological changes associated with GDM,the impacts of GDM on the growth and development of offspring,and the prevalence of GDM in offspring after birth.Placental epigenetic changes in GDM are involved in the programming of fetal development and are involved in the pathogenesis of later chronic diseases.This paper summarizes the effects of changes in placental nutrient transport function and hormone secretion levels due to maternal hyperglycemia and hyperinsulinemia on the development of offspring as well as the participation of changes in placental epigenetic modifications due to maternal hyperglycemia in intrauterine fetal programming to promote a comprehensive understanding of the impacts of placental epigenetic modifications on the development of offspring from patients with GDM.

Associations of serum D-dimer and glycosylated hemoglobin levels with third-trimester fetal growth restriction in gestational diabetes mellitus

BACKGROUND Gestational diabetes mellitus(GDM)is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism;GDM is diagnosed for the first time during pregnancy and can affect fetal growth and development.AIM To investigate the associations of serum D-dimer(D-D)and glycosylated hemoglobin(HbA1c)levels with third-trimester fetal growth restriction(FGR)in GDM patients.METHODS The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology Hospital of Fudan University from January 2021 to January 2023 were analyzed retrospectively.Among these women,63 whose fetuses had FGR were included in the FGR group,and 101 women whose fetuses had normal body weights were included in the normal body weight group(normal group).Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative analysis.The diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis,and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic regression.RESULTS Serum fasting blood glucose,fasting insulin,D-D and HbA1c levels were significantly greater in the FGR group than in the normal group,while the homeostasis model assessment of insulin resistance values were lower(P<0.05).Regarding the diagnosis of FGR based on serum D-D and HbA1c levels,the areas under the curves(AUCs)were 0.826 and 0.848,the cutoff values were 3.04 mg/L and 5.80%,the sensitivities were 81.0%and 79.4%,and the specificities were 88.1%and 87.1%,respectively.The AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928,and the sensitivity and specificity were 84.1%and 91.1%,respectively.High D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients(P<0.05).CONCLUSION D-D and HbA1c levels can indicate the occurrence of FGR in GDM patients in the third trimester of pregnancy to some extent,and their combination can be used as an important index for the early prediction of FGR.

Comparative effects of insulin pump and injection on gestational diabetes mellitus pregnancy outcomes and serum biomarkers

BACKGROUND Insulin injection is the basic daily drug treatment for diabetic patients.AIM To evaluate the comparative impacts of continuous subcutaneous insulin infusion(CSII).METHODS Based on the treatment modality received,the patients were allocated into two cohorts:The CSII group and the multiple daily injections(MDI)group,with each cohort comprising 210 patients.Comparative assessments were made regarding serum levels of serum-secreted frizzled-related protein 5,homocysteine,and C1q/TNF-related protein 9.Furthermore,outcomes such as fasting plasma glucose,2-hour postprandial glucose levels,pain assessment scores,and the incidence of complications were evaluated post-treatment.RESULTS The CSII group displayed notably lower fasting plasma glucose and 2-h postprandial glucose levels in comparison to the MDI group(P<0.05).Subsequent analysis post-treatment unveiled a significantly higher percentage of patients reporting no pain in the CSII group(60.00%)in contrast to the MDI group(36.19%)(P<0.05).Additionally,the CSII group exhibited a markedly reduced occurrence of fetal distress and premature rupture of membranes compared to the MDI group(P<0.05).However,there were no significant variances observed in other pregnancy outcomes between the two groups(P>0.05).A statistical analysis revealed a significant difference in the incidence of complications between the groups(χ^(2)=11.631,P=0.001).CONCLUSION The utilization of CSII via an insulin pump,as opposed to MDI,can significantly enhance the management of insulin administration in patients with GDM by diversifying the sites of insulin delivery.This approach not only promotes optimal glycemic control but also regulates metabolic factors linked to blood sugar,reducing the likelihood of adverse pregnancy outcomes and complications.The clinical relevance and importance of CSII in GDM management highlight its wide-ranging clinical usefulness.

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

BACKGROUND 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.METHODS 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).RESULTS Forty-seven proteins were significantly differentially expressed by analyzing the serum samples between the GDMgravidas as well as the healthy ones. Among them, 31 proteins were found to be upregulated notably and the rest16 proteins were downregulated remarkably. Bioinformatic data report revealed abnormal expression of proteinsassociated with lipid metabolism, coagulation cascade activation, complement system and inflammatory responsein the GDM group. ELISA results showed that the contents of RBP4, as well as ANGPTL8, increased in the serumof GDM gravidas compared with the healthy ones, and this change was found to initiate from 12 wk to 16 wk ofgestation.CONCLUSION GDM symptoms may involve abnormalities in lipid metabolism, coagulation cascade activation, complementsystem and inflammatory response. RBP4 and ANGPTL8 are expected to be early predictors of GDM.

Future clinical prospects of C-peptide testing in the early diagnosis of gestational diabetes

Gestational diabetes is typically diagnosed in the late second or third trimester of pregnancy.It is one of the most common metabolic disorders among expectant mothers,with potential serious short-and long-term complications for both maternal and offspring health.C-peptide is secreted from pancreatic beta-cells into circulation in equimolar amounts with insulin.It is a useful biomarker to estimate the beta-cell function because it undergoes negligible hepatic clearance and consequently it has a longer half-life compared to insulin.Pregnancy induces increased insulin resistance due to physiological changes in hormonal and metabolic homeostasis.Inadequate compensation by islet beta-cells results in hyperglycemia.The standard oral glucose tolerance test at 24-28 wk of gestation sets the diagnosis.Accumulated evidence from prospective studies indicates a link between early pregnancy C-peptide levels and the risk of subsequent gestational diabetes.Elevated C-peptide levels and surrogate glycemic indices at the beginning of pregnancy could prompt appropriate strategies for secondary prevention.

The Use of Glycated Albumin in the Diagnosis of Gestational Diabetes Mellitus

Gestational diabetes mellitus is the most common endocrine disorder in pregnancy and a cause of maternal and fetal morbidities and mortalities. The oral glucose tolerance test is the gold standard for diagnosing gestational diabetes mellitus. Nevertheless, the oral glucose tolerance test is time-consuming and requires patient preparation. On the contrary, Glycated albumin does not require patient preparation or administration of any substance. Most studies on glycated albumin in pregnancy were among the non-African population, and black Americans have higher glycated albumin levels than Caucasians. This study determined the use of glycated albumin in diagnosing gestational diabetes mellitus among pregnant women. The study was a prospective study of 160 pregnant women between 24 and 28 weeks of gestation at the University of Port Harcourt Teaching Hospital. The diagnosis of gestational diabetes mellitus was based on the World Health Organization 2013 criteria. The diagnostic value of glycated albumin was determined using the area under the receiver operator characteristic curve. The prevalence of gestational diabetes mellitus was 9.4% and the mean glycated albumin was 16.91% (±2.77). The area under the receiver operator characteristic curve for glycated albumin was 0.845 (95% CI 0.733 - 0.956;p = 0.0001). The optimal cut-off value of glycated albumin in the diagnosis of gestational diabetes mellitus was 18.9%. Glycated albumin was useful in the diagnosis of gestational diabetes mellitus at 24 to 28 weeks of gestation.

Analysis of Gestational Diabetes Mellitus (GDM) and Its Impact on Maternal and Fetal Health: A Comprehensive Dataset Study Using Data Analytic Tool Power BI

Gestational Diabetes Mellitus (GDM) is a significant health concern affecting pregnant women worldwide. It is characterized by elevated blood sugar levels during pregnancy and poses risks to both maternal and fetal health. Maternal complications of GDM include an increased risk of developing type 2 diabetes later in life, as well as hypertension and preeclampsia during pregnancy. Fetal complications may include macrosomia (large birth weight), birth injuries, and an increased risk of developing metabolic disorders later in life. Understanding the demographics, risk factors, and biomarkers associated with GDM is crucial for effective management and prevention strategies. This research aims to address these aspects comprehensively through the analysis of a dataset comprising 600 pregnant women. By exploring the demographics of the dataset and employing data modeling techniques, the study seeks to identify key risk factors associated with GDM. Moreover, by analyzing various biomarkers, the research aims to gain insights into the physiological mechanisms underlying GDM and its implications for maternal and fetal health. The significance of this research lies in its potential to inform clinical practice and public health policies related to GDM. By identifying demographic patterns and risk factors, healthcare providers can better tailor screening and intervention strategies for pregnant women at risk of GDM. Additionally, insights into biomarkers associated with GDM may contribute to the development of novel diagnostic tools and therapeutic approaches. Ultimately, by enhancing our understanding of GDM, this research aims to improve maternal and fetal outcomes and reduce the burden of this condition on healthcare systems and society. However, it’s important to acknowledge the limitations of the dataset used in this study. Further research utilizing larger and more diverse datasets, perhaps employing advanced data analysis techniques such as Power BI, is warranted to corroborate and expand upon the findings of this research. This underscores the ongoing need for continued investigation into GDM to refine our understanding and improve clinical management strategies.

Gestational diabetes from A to Z

Gestational diabetes mellitus(GDM) is defined as any degree of hyperglycaemia that is recognized for the first time during pregnancy. This definition includes cases of undiagnosed type 2 diabetes mellitus(T2 DM) identified early in pregnancy and true GDM which develops later. GDM constitutes a greater impact on diabetes epidemic as it carries a major risk of developing T2 DM to the mother and foetus later in life. In addition, GDM has also been linked with cardiometabolic risk factors such as lipid abnormalities, hypertensive disorders and hyperinsulinemia. These might result in later development of cardiovascular disease and metabolic syndrome. The understanding of the different risk factors, the pathophysiological mechanisms and the genetic factors of GDM, will help us to identify the women at risk, to develop effective preventive measures and to provide adequate management of the disease. Clinical trials have shown that T2 DM can be prevented in women with prior GDM, by intensive lifestyle modification and by using pioglitazone and metformin. However, a matter of controversy surrounding both screening and management of GDM continues to emerge, despite several recent welldesigned clinical trials tackling these issues. The aim of this manuscript is to critically review GDM in a detailed and comprehensive manner, in order to provide a scientific analysis and updated write-up of different related aspects.

Cellular and molecular overview of gestational diabetes mellitus:Is it predictable and preventable?

BACKGROUND In contrast to overt diabetes mellitus(DM),gestational DM(GDM)is defined as impaired glucose tolerance induced by pregnancy,which may arise from exaggerated physiologic changes in glucose metabolism.GDM prevalence is reported to be as high as 20%among pregnancies depending on the screening method,gestational age,and the population studied.Maternal and fetal effects of uncontrolled GDM include stillbirth,macrosomia,neonatal diabetes,birth trauma,and subsequent postpartum hemorrhage.Therefore,it is essential to find the potential target population and associated predictive and preventive measures for future intensive peripartum care.AIM To review studies that explored the cellular and molecular mechanisms of GDM as well as predictive measures and prevention strategies.METHODS The search was performed in the Medline and PubMed databases using the terms“gestational diabetes mellitus,”“overt diabetes mellitus,”and“insulin resistance.”In the literature,only full-text articles were considered for inclusion(237 articles).Furthermore,articles published before 1997 and duplicate articles were excluded.After a final review by two experts,all studies(1997-2023)included in the review met the search terms and search strategy(identification from the database,screening of the studies,selection of potential articles,and final inclusion).RESULTS Finally,a total of 79 articles were collected for review.Reported risk factors for GDM included maternal obesity or overweight,pre-existing DM,and polycystic ovary syndrome.The pathophysiology of GDM involves genetic variants responsible for insulin secretion and glycemic control,pancreaticβcell depletion or dysfunction,aggravated insulin resistance due to failure in the plasma membrane translocation of glucose transporter 4,and the effects of chronic,low-grade inflammation.Currently,many antepartum measurements including adipokines(leptin),body mass ratio(waist circumference and waist-to-hip ratio),and biomarkers(microRNA in extracellular vesicles)have been studied and confirmed to be useful markers for predicting GDM.For preventing GDM,physical activity and dietary approaches are effective interventions to control body weight,improve glycemic control,and reduce insulin resistance.CONCLUSION This review explored the possible factors that influence GDM and the underlying molecular and cellular mechanisms of GDM and provided predictive measures and prevention strategies based on results of clinical studies.

Gestational diabetes mellitus combined with fulminant type 1 diabetes mellitus, four cases of double diabetes: A case report

BACKGROUND Fulminant type 1 diabetes mellitus(FT1DM)that occurs during pregnancy or the perinatal period is known as pregnancy-related FT1DM(PF),always without history of abnormal glucose metabolism.Here,we present four patients who developed FT1DM during treatment but were first diagnosed with gestational diabetes mellitus(GDM).CASE SUMMARY The clinical data of four patients with GDM combined with FT1DM admitted to our hospital between July 2018 and April 2021 were collected,and the patients and their infants were followed up.All patients were diagnosed with GDM during the second trimester and were treated.The blood glucose level elevated suddenly during the third trimester and then were diagnosed with FT1DM.Two patients had an insulin allergy,and two had symptoms of upper respiratory tract infection before onset.One patient developed ketoacidosis,and three developed ketosis.Two patients had cesarean section deliveries,and two had vaginal deliveries.The growth and development of the infants were normal.C-peptide levels were lower than those at onset,suggesting progressive impairment of islet function.The frequencies of the DRB109:01,DQB103:03,DQA103:02,DPA101:03,DPA102:02,DPB105:01,DRB401:03,G 01:01,and G 01:04 human leukocyte antigen(HLA)-G alleles were high in the present study.CONCLUSION In comparison with pregnancy-associated FT1DM(PF),patients with GDM combined with FT1DM had an older age of onset,higher body mass index,slower onset,fewer prodromal symptoms,and less acidosis.The pathogenesis may be due to various factors affecting the already fragileβ-cells of GDM patients with genetically susceptible class II HLA genotypes.We speculate that GDM combined with FT1DM during pregnancy,referred to as“double diabetes,”is a subtype of PF with its own unique characteristics that should be investigated further.

Effect of individualized nutrition interventions on clinical outcomes of pregnant women with gestational diabetes mellitus

BACKGROUND Gestational diabetes mellitus(GDM)can lead to excessive pregnancy weight gain(PWG),abnormal glucolipid metabolism,and delayed lactation.Therefore,it is necessary to provide appropriate and effective interventions for pregnant women with GDM.AIM To clarify the effects of individualized nutrition interventions on PWG,glucolipid metabolism,and lactation in pregnant women with GDM.METHODS The study population consisted of 410 pregnant women with GDM who received treatment at the Northern Jiangsu People's Hospital of Jiangsu Provinceand Yangzhou Maternal and Child Health Hospital between December 2020 and December 2022,including 200 who received routine in-terventions[control(Con)group]and 210 who received individualized nutrition interventions[research(Res)group].Data on PWG,glucolipid metabolism[total cholesterol,(TC);triglycerides(TGs);fasting blood glucose(FPG);glycosylated hemoglobin(HbA1c)],lactation time,perinatal complications(cesarean section,premature rupture of membranes,postpartum hemorrhage,and pregnancy-induced hypertension),and neonatal adverse events(premature infants,fetal macrosomia,hypo-glycemia,and respiratory distress syndrome)were collected for comparative analysis.RESULTS The data revealed markedly lower PWG in the Res group vs the Con group,as well as markedly reduced TG,TC,FPG and HbA1c levels after the intervention that were lower than those in the Con group.In addition,obviously earlier lactation and statistically lower incidences of perinatal complications and neonatal adverse events were observed in the Res group.CONCLUSION Individualized nutrition interventions can reduce PWG in pregnant women with GDM,improve their glucolipid metabolism,and promote early lactation,which deserves clinical promotion.

Effect of resveratrol in gestational diabetes mellitus and its complications

The incidence rate of diabetes in pregnancy is about 20%,and diabetes in pregnancy will have a long-term impact on the metabolic health of mothers and their offspring.Mothers may have elevated blood glucose,which may lead to blood pressure disease,kidney disease,decreased resistance and secondary infection during pregnancy.The offspring may suffer from abnormal embryonic development,intrauterine growth restriction,obesity,autism,and other adverse consequences.Resveratrol(RSV)is a natural polyphenol compound,which is found in more than 70 plant species and their products,such as Polygonum cuspidatum,seeds of grapes,peanuts,blueberries,bilberries,and cranberries.Previous studies have shown that RSV has a potential beneficial effect on complex pregnancy,including improving the indicators of diabetes and pregnancy diabetes syndrome.This article has reviewed the molecular targets and signaling pathways of RSV,including AMP-activated protein kinase,mitogen-activated protein kinases,silent information regulator sirtuin 1,miR-23a-3p,reactive oxygen species,potassium channels and CX3C chemokine ligand 1,and the effect of RSV on gestational diabetes mellitus(GDM)and its complications.RSV improves the indicators of GDM by improving glucose metabolism and insulin tolerance,regulating blood lipids and plasma adipokines,and modulating embryonic oxidative stress and apoptosis.Furthermore,RSV can ameliorate the GDM complications by reducing oxidative stress,reducing the effects on placentation,reducing the adverse effects on embryonic development,reducing offspring's healthy risk,and so on.Thus,this review is of great significance for providing more options and possibilities for further research on medication of gestational diabetes.

The Treatment of Gestational Diabetes Mellitus

Pre-pregnancy glucose metabolism is normal, only during pregnancy diabetes known as gestational diabetes mellitus. Currently, the diagnostic criteria for gestational diabetes mellitus are IADPSG criteria (International Association of Diabetes and Pregnancy Study Group), and 75 g oral glucose tolerance test is recommended at 24 - 28 weeks of gestation. Gestational diabetes is associated with many pregnancy complications, such as macrosomia, preterm delivery and increased cesarean section rates, and neonatal complications such as hypoglycemia, hypoxia, and respiratory distress syndrome. Early identification of high-risk groups can be carried out for early prevention and intervention which are conducive to improving mothers and infants perinatal outcome. For the treatment of gestational diabetes, lifestyle interventions, such as improved diet combined with exercise to control blood sugar, are recommended first. For patients with poor blood glucose control, insulin is recommended for blood glucose control, and oral drug use is still controversial.

Assessment of Barriers toward Initiating Insulin among Gestational Diabetes Pregnant Women, Diabetes Center, Hera’a General Hospital, Makkah

Background: Gestational diabetes mellitus (GDM) is one of the most common pathologies in pregnancy. Unfortunately, both clinicians and patients are often reluctant to begin insulin therapy, a phenomenon that has been known as psychological insulin resistance (PIR). Objectives: To assess the barriers of initiating insulin among GDM pregnant women. Patients and Methods: An observational cross-sectional study was conducted in the GDM clinic, Diabetes Center in Hera’a General Hospital, Makkah, Saudi Arabia in a period of 4 months. A self-administered validated questionnaire was adopted. It included socio-demographic data of women, perceived (personal, social, pharmacological, occupational and misconception) barriers towards insulin therapy and possible solutions to overcome these barriers. Results: A total of 164 pregnant women with gestational diabetes were included in the study. The age of 36.4% of them exceeded 35 years. Among personal barriers, preferring other treatment methods over insulin (56.4%) and unaware of insulin dose control method (45.4%) were commonly reported. Regarding family barriers, 23.6% reported past family experience of insulin-related complications. Concerning side effects, fear of hypoglycemia (59.4%) and fear of weight gain (50.9%) were most frequently reported barriers against use of insulin. Regarding misconceptions about insulin injections, 26% believed that insulin is addictive;the injection will continue for life. Among work-related barriers, irregular eating times during working hours and long working hours (55.2%) were barriers for insulin use. Facilitating access to healthcare services (94%), engage the patient in decision-making and development of the treatment plan (91.6%), activate virtual clinics and social media for remote follow-up (86.6%) and organize social support groups for pregnant women who use insulin to share their experiences were the most frequently reported possible solutions to initiate and commit to insulin therapy. Conclusion: Various barriers were identified against initiation of insulin therapy in the management of gestational diabetes;mostly due to personal factors, misconception and work-related factors. Prompt actions are needed to overcome these barriers.

Advanced glycation end-products change placental barrier function and tight junction in rats with gestational diabetes mellitus via the receptor for advanced glycation end products/nuclear factor-κB pathway

The placenta plays an important role in nutrient transport to maintain the growth and development of the embryo.Gestational diabetes mellitus(GDM),the most common complication during pregnancy,highly affects placental function in late gestation.Advanced glycation end-products(AGEs),a complex and heterogeneous group of compounds engaged by the receptor for AGEs(RAGE),are closely associated with diabetes-related complications.In this study,AGEs induced a decrease in the expression of tight junction(TJ)proteins in BeWo cells and increased the paracellular permeability of trophoblast cells by regulating RAGE/NF-κB.Sprague-Dawley(SD)rats injected with 100 mg/kg AGEs-rat serum albumin(RSA)via the tail vein from embryo day 2 were set as the placental barrier dysfunction model group(n=10).The effect of AGEs on placental permeability was determined using the Evans-Blue dye extravasation method.The ultrastructure of the placenta samples was observed by transmission electron microscopy.The effects of AGEs on the placenta were confirmed by treating rats with RAGE antagonist FPS-ZM1 and soluble forms of RAGE(sRAGE).AGEs treatment increased placental permeability and disrupted the tight junctions in pregnant rat placenta,but has no effect on blood glucose.The expression of TJ-related proteins,including ZO-1,Occludin,and Claudin 5,were downregulated after AGEs treatment.Further,AGEs treatment increased the expression of RAGE and nuclear factor-κB in the placenta of rats and upregulated the levels of vascular endothelial growth factor.The effects of AGEs on the placenta were blocked by RAGE antagonist FPS-ZM1 and sRAGE.This study demonstrates the mechanism underlying AGEs-induced disturbance in placental function in pregnant rats and highlights the potential of AGEs in the treatment of GDM.

Causal relationship association of cheese intake with gestational hypertension and diabetes result from a Mendelian randomization study

BACKGROUND The evidence from observational studies has been inconclusive on the causal relationship between cheese intake and gestational hypertension or diabetes.AIM To determine whether cheese consumption was causally related to hypertension and diabetes during pregnancy.METHODS This was a two-sample Mendelian randomized(MR)study.Summary-level genetic data for cheese intake was exposure and corresponding outcome data for gestational hypertension and gestational diabetes were extracted from the IEU OpenGWAS database.MR analysis was conducted using inverse variance weighting.For sensitivity analyses,MR-Egger regression,weighted median,weighted mode,and leave-one-out methods were conducted.A fixed-effect model was used to meta-analyze two sample MR estimates.The traits of gestational hypertension were pregnancy hypertension(123579 individuals)and oedema,proteinuria and hypertensive disorders in pregnancy,childbirth and the puerperium(123579 individuals),and traits of gestational diabetes were gestational diabetes(123579 individuals)and diabetes mellitus in pregnancy(116363 individuals),respectively.RESULTS Cheese intake per standard deviation increase has causally reduced the risks of gestational hypertension[odds ratio(OR)=0.60,95%confidence interval(CI):0.47-0.76,P<0.001]and gestational diabetes(OR=0.41,95%CI:0.30-0.55,P<0.001)in inverse variance weighted analysis.Sensitivity analysis showed no heterogeneity(all P>0.05)nor horizontal pleiotropy(all P>0.05)in the relationship between cheese intake and gestational hypertension,but heterogeneity presented(all P<0.05)in relation to gestational diabetes in the two-sample MR analysis.CONCLUSION Cheese intake was inversely associated with gestational hypertension and gestational diabetes in MR analysis,suggesting that cheese consumption may be beneficial in preventing hypertension and diabetes during pregnancy.

Maternal Vitamin D Deficiency and Risk of Development of Gestational Diabetes Mellitus: A Scoping Review

Background: Maternal vitamin D status is a critical determinant during pregnancy, because it plays an important role in the body not only in calcium homeostasis and bone remodeling, but also in the glucose metabolism. Vitamin D deficiency is associated with adverse pregnancy outcomes including gestational diabetes mellitus. Objective: To review evidence on the association between maternal vitamin D deficiency and incidence of gestational diabetes mellitus (GDM). Methods: PRISMA for scoping review guideline and scoping review guidelines of Arksey & O’Malley (2005) was followed in methodological process. A comprehensive search strategy was carried out across the Google Scholar and PubMed from January 2012 to December 2022, using the search terms of “gestational diabetes mellitus/pregnancy outcomes” combined with “vitamin D”, “cholecalciferol” or “25-hydroxyvitamin D” and/or “deficiency”. Articles were screened at the title and the abstract level and at full text by three co-investigators of the study independently with a fourth reviewer resolving discrepancies. Research studies published only in English language were selected. Research using pregnant mothers with multiple pregnancy and chronic diseases was excluded. Results: After screening 134 titles and abstracts, finally 55 original research articles were selected. It involved 48 observational studies and 7 Randomized Control Trials (RCT). Only 30 research articles had found an association between maternal vitamin D deficiency and GDM. Conclusion: As results of previous studies are mixed and inconclusive, further research including more RCTs is needed to clarify the exact mechanism of vitamin D on glucose metabolism during pregnancy.