scholarly journals Immunobiology of Gestational Diabetes Mellitus in Post-Medawar Era

2022 ◽  
Vol 12 ◽  
Author(s):  
Surendra Sharma ◽  
Sayani Banerjee ◽  
Paula M. Krueger ◽  
Sandra M. Blois
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Immune Responses ◽  
Gestational Diabetes Mellitus ◽  
Systemic Inflammation ◽  
Pregnancy Complication ◽  
Low Grade ◽  
Autoimmune Pathology ◽  
Treg Population ◽  
Maternal Fetal Interface

Although the concepts related to fetal immune tolerance proposed by Sir Peter Medawar in the 1950s have not withstood the test of time, they revolutionized our current understanding of the immunity at the maternal-fetal interface. An important extension of the original Medawar paradigm is the investigation into the underlying mechanisms for adverse pregnancy outcomes, including recurrent spontaneous abortion, preterm birth, preeclampsia and gestational diabetes mellitus (GDM). Although a common pregnancy complication with systemic symptoms, GDM still lacks understanding of immunological perturbations associated with the pathological processes, particularly at the maternal-fetal interface. GDM has been characterized by low grade systemic inflammation that exacerbates maternal immune responses. In this regard, GDM may also entail mild autoimmune pathology by dysregulating circulating and uterine regulatory T cells (Tregs). The aim of this review article is to focus on maternal-fetal immunological tolerance phenomenon and discuss how local or systemic inflammation has been programmed in GDM. Specifically, this review addresses the following questions: Does the inflammatory or exhausted Treg population affecting the Th17:Treg ratio lead to the propensity of a pro-inflammatory environment? Do glycans and glycan-binding proteins (mainly galectins) contribute to the biology of immune responses in GDM? Our understanding of these important questions is still elementary as there are no well-defined animal models that mimic all the features of GDM or can be used to better understand the mechanistic underpinnings associated with this common pregnancy complication. In this review, we will leverage our preliminary studies and the literature to provide a conceptualized discussion on the immunobiology of GDM.

scholarly journals Is Gestational Diabetes Mellitus a Risk Factor of Maternal Breast Cancer? A Systematic Review of the Literature

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1174
Author(s):  
Julien Simon ◽  
Karine Goueslard ◽  
Sonia Bechraoui-Quantin ◽  
Patrick Arveux ◽  
Catherine Quantin
Keyword(s):  
Breast Cancer ◽  
Diabetes Mellitus ◽  
Systematic Review ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
English Language ◽  
Low Grade ◽  
Hormonal Changes ◽  
Review Of The Literature ◽  
Increased Risk

The association between gestational diabetes mellitus (GDM) and breast cancer (BC) risk is complex. We aimed to examine this association in a systematic review of the literature. This review was done using the PubMed/Medline and Web of Science databases, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Newcastle–Ottawa Scale was used for the assessment of bias and quality of studies. Only English-language articles published before 1 June 2021, were included. Fourteen studies were included in this systematic review. Among them, eight did not find statistically significant results. Three studies showed a statistically significant increased risk of BC after GDM, and they explained this potential increased risk by hyperinsulinemia, hyperglycemia, and low-grade inflammation. However, three studies showed a statistically significant decreased risk of BC after GDM, suggesting a possible protective effect of hormonal changes induced by GDM during pregnancy. These controversial results should be interpreted with caution due to both quantitative and qualitative methodological shortcomings. Further investigations are thus needed in order to gain a better understanding of the associations between GDM and BC, and their underlying mechanisms.

scholarly journals Gestational Diabetes Mellitus Affects Offspring’s Epigenome. Is There a Way to Reduce the Negative Consequences?

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2792
Author(s):  
Monika Słupecka-Ziemilska ◽  
Piotr Wychowański ◽  
Monika Puzianowska-Kuznicka
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Pregnancy Complication ◽  
Epigenetic Changes ◽  
Negative Consequences ◽  
Short Term ◽  
Related Factors ◽  
Epigenetic Programming

Gestational diabetes mellitus (GDM) is the most common pregnancy complication worldwide and may result in short-term and long-term consequences for offspring. The present review highlights evidence of epigenetic programming, mostly from human studies, which occurs in offspring exposed to maternal GDM during different stages of development, paying special attention to the differences in sensitivity of offspring to maternal hyperglycemia as a result of sex-related factors. We also aim to answer the following question: If these epigenetic changes are constant throughout the lifetime of the offspring, how do they present phenotypically?

scholarly journals Gestational Diabetes Mellitus and Maternal Immune Dysregulation: What We Know So Far

2021 ◽  
Vol 22 (8) ◽  
pp. 4261
Author(s):  
Colm J. McElwain ◽  
Fergus P. McCarthy ◽  
Cathal M. McCarthy
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Immune Dysregulation ◽  
Adverse Outcomes ◽  
Low Grade ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Visceral Adipose ◽  
Increased Susceptibility

Gestational diabetes mellitus (GDM) is an obstetric complication that affects approximately 5–10% of all pregnancies worldwide. GDM is defined as any degree of glucose intolerance with onset or first recognition during pregnancy, and is characterized by exaggerated insulin resistance, a condition which is already pronounced in healthy pregnancies. Maternal hyperglycaemia ensues, instigating a ‘glucose stress’ response and concurrent systemic inflammation. Previous findings have proposed that both placental and visceral adipose tissue play a part in instigating and mediating this low-grade inflammatory response which involves altered infiltration, differentiation and activation of maternal innate and adaptive immune cells. The resulting maternal immune dysregulation is responsible for exacerbation of the condition and a further reduction in maternal insulin sensitivity. GDM pathology results in maternal and foetal adverse outcomes such as increased susceptibility to diabetes mellitus development and foetal neurological conditions. A clearer understanding of how these pathways originate and evolve will improve therapeutic targeting. In this review, we will explore the existing findings describing maternal immunological adaption in GDM in an attempt to highlight our current understanding of GDM-mediated immune dysregulation and identify areas where further research is required.

scholarly journals Molecular pathways disrupted by gestational diabetes mellitus

2019 ◽  
Vol 63 (3) ◽  
pp. R51-R72 ◽  
Author(s):  
Caitlyn Nguyen-Ngo ◽  
Nanthini Jayabalan ◽  
Carlos Salomon ◽  
Martha Lappas
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Endothelial Cell ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Glycogen Synthase ◽  
Low Grade ◽  
Endothelial Cell Dysfunction ◽  
Cell Dysfunction

Gestational diabetes mellitus (GDM) imposes serious short- and long-term health problems for mother and baby. An effective therapeutic that can reduce the incidence of GDM and improve long-term maternal and fetal outcomes is a major research priority, crucially important for public health. A lack of knowledge about the underlying pathophysiology of GDM has hampered the development of such therapeutics. What we do know, however, is that maternal insulin resistance, low-grade inflammation and endothelial cell dysfunction are three central features of pregnancies complicated by GDM. Indeed, data generated over the past decade have implicated a number of candidate regulators of insulin resistance, inflammation and endothelial cell dysfunction in placenta, maternal adipose tissue and skeletal muscle. These include nuclear factor-κB (NF-κB), peroxisome proliferator-activated receptors (PPARs), sirtuins (SIRTs), 5′ AMP-activated protein kinase (AMPK), glycogen synthase kinase 3 (GSK3), PI3K/mTOR, inflammasome and endoplasmic reticulum (ER) stress. In this review, the identification of these as key modulators of GDM will be discussed. The biochemical pathways involved in the formation of these may represent potential sites for intervention that may translate to therapeutic interventions to prevent the development of GDM.

scholarly journals Periodontitis and Gestational Diabetes Mellitus: A Potential Inflammatory Vicious Cycle

2021 ◽  
Vol 22 (21) ◽  
pp. 11831
Author(s):  
María José Bendek ◽  
Gisela Canedo-Marroquín ◽  
Ornella Realini ◽  
Ignacio N. Retamal ◽  
Marcela Hernández ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Systemic Inflammation ◽  
Immune Cell ◽  
Bacterial Species ◽  
Susceptible Host ◽  
Periodontal Tissues ◽  
Inflammatory Status ◽  
Immune Cell Response

Periodontitis is a chronic inflammatory immune disease associated with a dysbiotic state, influenced by keystone bacterial species responsible for disrupting the periodontal tissue homeostasis. Furthermore, the severity of periodontitis is determined by the interaction between the immune cell response in front of periodontitis-associated species, which leads to the destruction of supporting periodontal tissues and tooth loss in a susceptible host. The persistent bacterial challenge induces modifications in the permeability and ulceration of the sulcular epithelium, which facilitates the systemic translocation of periodontitis-associated bacteria into distant tissues and organs. This stimulates the secretion of pro-inflammatory molecules and a chronic activation of immune cells, contributing to a systemic pro-inflammatory status that has been linked with a higher risk of several systemic diseases, such as type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM). Although periodontitis and GDM share the common feature of systemic inflammation, the molecular mechanistic link of this association has not been completely clarified. This review aims to examine the potential biological mechanisms involved in the association between periodontitis and GDM, highlighting the contribution of both diseases to systemic inflammation and the role of new molecular participants, such as extracellular vesicles and non-coding RNAs, which could act as novel molecular intercellular linkers between periodontal and placental tissues.

scholarly journals A Critical Review of Proteomic Studies in Gestational Diabetes Mellitus

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Tao Zhou ◽  
Lu Huang ◽  
Min Wang ◽  
Daozhen Chen ◽  
Zhong Chen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Disease Diagnosis ◽  
Pregnancy Complication ◽  
Sampling Time ◽  
Health It ◽  
Fetal Health ◽  
Initial Discovery

Gestational diabetes mellitus is a progressive and complex pregnancy complication, which threatens both maternal and fetal health. It is urgent to screen for specific biomarkers for early diagnosis and precise treatment, as well as to identify key moleculars to better understand the pathogenic mechanisms. In the present review, we comprehensively summarized recent studies of gestational diabetes using mass spectrometry-based proteomic technologies. Focused on the entire experimental design and proteomic results, we showed that these studies have covered a broad range of research contents in terms of sampling time, sample types, and outcome associations. Although most of the studies only stayed in the stage of initial discovery, several proteins were further verified to be efficient for disease diagnosis. Functional analysis of all the combined significant proteins also showed that a small number of proteins are known to be involved in the regulation of insulin or indirect signaling pathways. However, many factors such as diagnostic criteria, sample processing, proteomic method, and statistical method can greatly affect the identification of reproducible and reliable protein candidates. Thus, we further provided constructive suggestions and recommendations for carrying out proteomic or follow-up studies of gestational diabetes or other pregnancy complications in the future.

scholarly journals Adiponectin , ?-Cell Dysfunction in Iraqi Women with Gestational Diabetes

2016 ◽  
Vol 13 (2) ◽  
pp. 366-374
Author(s):  
Baghdad Science Journal
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Gestational Diabetes ◽  
Glucose Tolerance ◽  
Gestational Diabetes Mellitus ◽  
Control Group ◽  
Low Grade ◽  
C Reactive Protein ◽  
Cell Dysfunction ◽  
Reactive Protein

Gestational diabetes mellitus (GDM) is a complication of gestation that is characterized by impaired glucose tolerance with first recognition during gestation. It develops when ?- cell of pancreas fail to compensate the diminished insulin sensitivity during gestation. This study aims to investigate the relationship between mother adiponectin level and ?- cell dysfunction with development gestational diabetes mellitus (GDM) and other parameters in the last trimester of pregnancy. This study includes (80) subjects ( pregnant women) in the third trimester of pregnancy, (40) healthy pregnant individuals as control group aged between (17 - 42) years and (40) gestational diabetes mellitus patients with aged between (20 - 42) years. The following biochemical investigation is studied: oral glucose tolerance test (OGTT), adiponectin , insulin, C-reactive protein (CRP),body mass index (BMI), and homeostasis model assessment- insulin resistance (HOMA – IR). The adiponectin levels are significantly lesser in females who develop GDM than the control group (P?0.01), while the insulin and OGTT concentrations were significantly higher in females with GDM than control group (P?0.01).The concentrations of CRP are non significantly different between the females who develop GDM and the control group.Conclusions: Lower adiponectin concentrations are associated with an increased risk of the development of gestational diabetes mellitus and females, who develop gestational diabetes mellitus, have higher levels of insulin resistance from normal females, Obesity is a shape of persistent low grade inflammation which causes elevated concentrations of C- reactive protein.

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