scholarly journals Downregulation of the Netrin-1 Receptor UNC5b Underlies Increased Placental Angiogenesis in Human Gestational Diabetes Mellitus

2019 ◽  
Vol 20 (6) ◽  
pp. 1408 ◽  
Author(s):  
Catalina Prieto ◽  
Bárbara Casas ◽  
Paulina Falcón ◽  
Andrea Villanueva ◽  
Pablo Lois ◽  
...  

Gestational diabetes mellitus (GDM) is a common metabolic disorder, defined by high blood glucose levels during pregnancy, which affects foetal and post-natal development. However, the cellular and molecular mechanisms of this detrimental condition are still poorly understood. A dysregulation in circulating angiogenic trophic factors, due to a dysfunction of the feto-placental unit, has been proposed to underlie GDM. But even the detailed study of canonical pro-angiogenic factors like vascular endothelial growth factor (VEGF) or basic Fibroblast Growth Factor (bFGF) has not been able to fully explain this detrimental condition during pregnancy. Netrins are non-canonical angiogenic ligands produced by the stroma have shown to be important in placental angiogenesis. In order to address the potential role of Netrin signalling in GDM, we tested the effect of Netrin-1, the most investigated member of the family, produced by Wharton’s Jelly Mesenchymal Stem Cells (WJ-MSC), on Human Umbilical Vein Endothelial Cells (HUVEC) angiogenesis. WJ-MSC and HUVEC primary cell cultures from either healthy or GDM pregnancies were exposed to physiological (5 mM) or high (25 mM) d-glucose. Our results reveal that Netrin-1 is secreted by WJ-MSC from healthy and GDM and both expression and secretion of the ligand do not change with distinct experimental glucose conditions. Noteworthy, the expression of its anti-angiogenic receptor UNC5b is reduced in GDM HUVEC compared with its expression in healthy HUVEC, accounting for an increased Netrin-1 signalling in these cells. Consistently, in healthy HUVEC, UNC5b overexpression induces cell retraction of the sprouting phenotype.

2016 ◽  
Vol 39 (4) ◽  
pp. 1317-1328 ◽  
Author(s):  
Jian Zhou ◽  
Xiaotian Ni ◽  
Xiaojie Huang ◽  
Julei Yao ◽  
Qizhi He ◽  
...  

Background: Gestational diabetes mellitus (GDM) is associated with structural and functional alterations in various tissues including endothelial dysfunction. The aim of this study was to explore the effects of hyperglycemia on fibroblast growth factor 2 (FGF2)- and vascular endothelial growth factor (VEGF)-stimulated placental angiogenesis and the underlying molecular signaling mechanisms. Methods: The density of fetal placental capillaries was examined using immunohistochemistry. Human umbilical vein endothelial cells (HUVECs) derived from GDM (dHUVECs) and normal healthy patients (nHUVECs) were used as cell models in this study. Cell proliferation, migration and tube formation were measured with an MTS assay, a transwell system and a matrigel assay, respectively. The activation of ERK1/2 was analyzed with Western blot. The specific inhibitor of extracellular signal-regulated kinases 1/2 (ERK1/2) PD98059 was used to elucidate the involved signaling pathway. Results: GDM did not alter the capillary density of the fetus-placenta. Both the GDM and hyperglycemic conditions inhibited the proliferation of the FGF2- but not the VEGF-stimulated HUVECs and the basal migratory capacity. Hyperglycemic condition significantly inhibited tube formation and ex vivo angiogenesis. Moreover, hyperglycemia inhibited the FGF2- but not the VEGF-induced activation of ERK1/2. PD98059 significantly inhibited the FGF2-activated ERK1/2 phosphorylation and the FGF2-stimulated cell proliferation in HUVECs. Conclusion: Both GDM and hyperglycemia may impair placental angiogenesis by reducing HUVEC proliferation, migration and tube formation. Hyperglycemia-inhibited cell proliferation stimulated by FGF2 probably contributed to the suppression of the MEK1/2/ERK1/2 pathways in the HUVECs.


Author(s):  
Maria da Glória Rodrigues Tavares ◽  
Érika Sales Lopes ◽  
Rosy Anne de Jesus Pereira Araújo Barros ◽  
Rossana Santiago de Sousa Azulay ◽  
Manuel dos Santos Faria

Objective Gestational diabetes mellitus (GDM) is associated with a higher risk of perinatal morbidity and mortality, and its main complication is the occurrence of large for gestational age (LGA) newborns. The present study aims to characterize pregnant women with GDM and to identify factors associated with the occurrence of LGA newborns in this population. Methods A cross-sectional study was performed based on medical records of women whose prenatal care and delivery were performed at the Maternal and Child Unit of the Hospital Universitário of the Universidade Federal do Maranhão, state of Maranhão, Brazil. A total of 116 pregnant women diagnosed with GDM were included according to the criteria of the International Association of Diabetes and Pregnancy Study Groups (IADPSG). Results The variables associated with LGA newborns after multivariate analysis were: obesity prior to pregnancy (OR = 11.6; 95% CI: 1.40–95.9), previous macrosomia (OR = 34.7; 95% CI: 4.08–295.3), high blood glucose levels in the 3rd trimester (OR = 2,67; 95% CI: 1.01–7.12) and combined change in the oral glucose tolerance test (OGTT) (fasting + postdextrose) (OR = 3.53; 95% CI: 1.25–14.2) = 1.17–10.6). Otherwise, insufficient weight gain during pregnancy reduced the risk for LGA newborns (OR = 0.04; 95% CI: 0.01–0.32). Conclusion Obesity prior to pregnancy, previous macrosomia, high blood glucose levels in the 3rd trimester, and combined change in the OGTT were independent predictive factors for LGA newborns in pregnant women with GDM.


Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 506 ◽  
Author(s):  
Susana Contreras-Duarte ◽  
Lorena Carvajal ◽  
María Jesús Garchitorena ◽  
Mario Subiabre ◽  
Bárbara Fuenzalida ◽  
...  

Gestational diabetes mellitus (GDM) associates with fetal endothelial dysfunction (ED), which occurs independently of adequate glycemic control. Scarce information exists about the impact of different GDM therapeutic schemes on maternal dyslipidemia and obesity and their contribution to the development of fetal-ED. The aim of this study was to evaluate the effect of GDM-treatments on lipid levels in nonobese (N) and obese (O) pregnant women and the effect of maternal cholesterol levels in GDM-associated ED in the umbilical vein (UV). O-GDM women treated with diet showed decreased total cholesterol (TC) and low-density lipoproteins (LDL) levels with respect to N-GDM ones. Moreover, O-GDM women treated with diet in addition to insulin showed higher TC and LDL levels than N-GDM women. The maximum relaxation to calcitonin gene-related peptide of the UV rings was lower in the N-GDM group compared to the N one, and increased maternal levels of TC were associated with even lower dilation in the N-GDM group. We conclude that GDM-treatments modulate the TC and LDL levels depending on maternal weight. Additionally, increased TC levels worsen the GDM-associated ED of UV rings. This study suggests that it could be relevant to consider a specific GDM-treatment according to weight in order to prevent fetal-ED, as well as to consider the possible effects of maternal lipids during pregnancy.


Author(s):  
Nina Meloncelli ◽  
Shelley A. Wilkinson ◽  
Susan de Jersey

AbstractGestational diabetes mellitus (GDM) is a common pregnancy disorder and the incidence is increasing worldwide. GDM is associated with adverse maternal outcomes which may be reduced with proper management. Lifestyle modification in the form of medical nutrition therapy and physical activity, as well as self-monitoring of blood glucose levels, is the cornerstone of GDM management. Inevitably, the search for the “ultimate” diet prescription has been ongoing. Identifying the amount and type of carbohydrate to maintain blood glucose levels below targets while balancing the nutritional requirements of pregnancy and achieving gestational weight gain within recommendations is challenging. Recent developments in the area of the gut microbiota and its impact on glycemic response add another layer of complexity to the success of medical nutrition therapy. This review critically explores the challenges to dietary prescription for GDM and why utopia may never be found.


2015 ◽  
Vol 7 (1) ◽  
Author(s):  
Gisele Seabra ◽  
Cláudia Saunders ◽  
Patrícia de Carvalho Padilha ◽  
Lenita Zajdenverg ◽  
Letícia Barbosa Gabriel da Silva ◽  
...  

2018 ◽  
Vol 47 (2) ◽  
pp. 754-764 ◽  
Author(s):  
Ebtisam A. Al-ofi ◽  
Hala H. Mosli ◽  
Kholoud A. Ghamri ◽  
Sarah M. Ghazali

Objectives The purpose of this study was to investigate the effect of remotely delivered telemedicine dietary advice on monitoring of blood glucose levels and weight gain of women with gestational diabetes mellitus (GDM). Methods Women with GDM were recruited and randomly allocated into two groups: a Tele-GDM group that received a telemonitoring device, and a control group that was followed-up traditionally. A telemonitoring service calculated the ratio of reaching or exceeding the pregnancy weight gain target (according to pre-pregnancy weight), following Institute of Medicine guidelines for healthy pregnancy weight gain. Results The sample comprised 27 women in the Tele-GDM group and 30 in the control group. At the end of pregnancy, the Tele-GDM group showed significantly lower 2-hour postprandial glucose levels than the control group. Most women in the Tele-GDM group reached their recommended range of weight gain at the end of pregnancy. Additionally, the Tele-GDM group showed significantly lower weight gain than the control group. Conclusions Telemonitoring can facilitate close monitoring of women with GDM and motivate patients to adopt a healthy lifestyle.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Mohamed Reda Halawa ◽  
Magdy Hassan Kolaib ◽  
Salah Hussein El-Halawany ◽  
Dina Ahmed Marwan ◽  
Ola Mohamed Mostafa Shaheen

Abstract Background Gestational diabetes mellitus (GDM) defined as glucose intolerance with onset or first diagnosis during pregnancy. While GDM usually resolves following delivery, it can have long-lasting health consequences, including increased risk for type 2 diabetes (T2DM) and cardiovascular disease (CVD) in the mother, and future obesity, CVD, T2DM, and/or GDM in the child. This contributes to a vicious intergenerational cycle of obesity and diabetes that impacts the health of the population as a whole. Fibroblast growth factor 21 (FGF21) is a hormone that is expressed predominantly in the liver, but also in other metabolically active tissues such as pancreas, skeletal muscle and adipose tissue. An elevated FGF21 level is also an independent predictor of T2DM. GDM and T2DM are proposed to have similar underlying pathophysiologies, raising the question of whether a similar relationship exists between FGF21 and GDM as it does with T2DM. Objectives assess the role of Fibroblast growth factor 21 (FGF-21) as a prognostic marker for maternal and fetal complications in patients with gestational diabetes mellitus (GDM). Patients and Methods A case control study that was conducted on 50 patients diagnosed with Gestational Diabetes Mellitus and 50 control subjects at Diabetes and Obstetrics outpatient clinic and inpatient ward at Ain Shams university hospitals in the period between December 2018 and July 2019. Patients diagnosed with gestational diabetes mellitus (GDM) at 24-28 weeks of gestation were included in this study. Results FGF 21 levels varied significantly with blood sugar values where higher levels of FGF 21 levels were found in patients with GDM with study results showing that FGF 21 can be used as a diagnostic marker for GDM at levels above 121 pg/ml with sensitivity 84% and specificity 92%. Conclusion FGF 21 can be used as a diagnostic marker for gestational diabetes. Further studies needed for better correlation between FGF 21 levels during pregnancy and maternal outcome.


Author(s):  
Otovwe Agofure ◽  
Stella Odjimogho ◽  
Oghenenioborue R. A. Okandeji-Barry ◽  
Imomotimi Glasgow

Background: Gestational diabetes mellitus is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy. Gestational diabetes which prevalence is on the increase in Nigeria may have negative consequences on the health of the foetus or mother. This study was designed to determine the prevalence of gestational diabetes mellitus and its complications among pregnant women attending antenatal services in Diette Koki memorial hospital Opolo Bayelsa State from 2014-2016.Methods: This was a retrospective study carried out at the Diette Koki Memorial Hospital Opolo in Bayelsa State. The study population comprised pregnant women that attended antenatal care services within the period of January 2014-December 2016. A designed proforma was used to collect the data from the hospital record department.Results: The results of the study showed that the prevalence of gestational diabetes in the year 2014 was 0.023% or 2.33 per 10,000 pregnancies while the prevalence for 2015 was 0.026% or 2.59% per 10000 pregnancies. Furthermore, other complications recorded were hypertension, pre-eclampsia and eclampsia. Similarly, there was a significant correlation between prevalence of gestational diabetes and other complications (r=0.898, p=0.022).Conclusions: In conclusion, prevalence of gestational diabetes was recorded among pregnant women of Diette Koki memorial hospital Opobo Bayelsa State. Therefore, prompt screening and preventive measures should be enforced by health care professionals to prevent maternal and foetal morbidity and mortality.


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