Influence of maternal overnutrition and gestational diabetes on the programming of metabolic health outcomes in the offspring: experimental evidence

2015 ◽  
Vol 93 (5) ◽  
pp. 438-451 ◽  
Author(s):  
Troy J. Pereira ◽  
Brittany L. Moyce ◽  
Stephanie M. Kereliuk ◽  
Vernon W. Dolinsky
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Maternal Obesity ◽  
Obesity And Diabetes ◽  
Intergenerational Effect ◽  
Major Factors ◽  
Maternal Overnutrition

The incidence of obesity and type 2 diabetes mellitus have risen across the world during the past few decades and has also reached an alarming level among children. In addition, women are currently more likely than ever to enter pregnancy obese. As a result, the incidence of gestational diabetes mellitus is also on the rise. While diet and lifestyle contribute to these trends, population health data show that maternal obesity and diabetes during pregnancy during critical stages of development are major factors that contribute to the development of chronic disease in adolescent and adult offspring. Fetal programming of metabolic function, through physiological and (or) epigenetic mechanisms, may also have an intergenerational effect, and as a result may perpetuate metabolic disorders in the next generation. In this review, we summarize the existing literature that characterizes how maternal obesity and gestational diabetes mellitus contribute to metabolic and cardiovascular disorders in the offspring. In particular, we focus on animal studies that investigate the molecular mechanisms that are programmed by the gestational environment and lead to disease phenotypes in the offspring. We also review interventional studies that prevent disease with a developmental origin in the offspring.

scholarly journals Compositional analysis of the bacterial community in colostrum samples from women with gestational diabetes mellitus and obesity

2020 ◽  
Author(s):  
July Stephany Gámez-Valdez ◽  
José Francisco García-Mazcorro ◽  
Alan Heriberto Montoya Rincón ◽  
Dalia Liliana Rodríguez Reyes ◽  
Gelacio Jiménez Blanco ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Maternal Obesity ◽  
Population Diversity ◽  
Vicious Cycle ◽  
Microbial Composition ◽  
The Impact

Abstract Background. Gestational Diabetes Mellitus (GDM) and obesity are threatening health conditions during pregnancy, as they affect the normal function of multiple systems, including neuro-hormonal networks, and adipose, liver, muscle and placenta. GDM and maternal obesity are main triggers to a vicious cycle of metabolic and cardiovascular diseases perpetuated trans-generationally. One of the first stages of this vicious cycle occurs during early lactation as the infant feeds of “disbalanced” breastmilk microbiota and macromolecule level. Despite the importance of breastmilk microbiota on newborn development, few studies have characterized breastmilk microbiota in association with obesity and GDM. Maternal obesity decreases the diversity of breastmilk microbiota, with increased proportions Staphylococcus compared to Bifidobacterium and Bacteroides. However, the extent to which GDM together with maternal obesity affect breastmilk microbiota is unknown. Here, we applied 16S-rRNA high-throughput sequencing to characterize colostrum microbiota of 43 mothers with exclusive GDM and obesity in order to address the impact of GDM/obesity on breastmilk microbiota.Results. We identified a total of 1,496 amplicon sequence variants (ASVs), being Proteobacteria and Firmicutes the dominant phyla. We found Staphylococcus, Corynebacterium-1, Anaerococcus and Prevotella overrepresented in samples of women with obesity and women with GDM. Population diversity indicators, such as Shannon/Faith phylogenetic index and UniFrac/robust Aitchison distances show distinct microbial composition for GDM (female-newborn subgroup) and obesity (male-newborn subgroup) compared to controls. Finally, Differential abundance analysis showed that Rhodobacteraceae was distinct for GDM and five families (Bdellovibrionaceae, Halomonadaceae, Shewanallaceae, Saccharimonadales and Vibrionaceae) were distinct for obesity groups.Conclusions. Our study indicates that GDM and obesity are related to a higher microbial diversity. Preliminary functional analysis suggests that this could be attributed to overrepresentation of amino acid and carbohydrate metabolism bacterial pathways. However, there is a strong influence of the infant´s gender and the utilization of antibiotics intrapartum. To our knowledge, this study represents the first characterization of the taxonomical changes of colostrum breastmilk in mothers with GDM. We think this study contributes to future design of functional metagenomic studies aiming to understand molecular mechanisms by which breastmilk from mothers with GDM/obesity affect the development and future adult physiology of their suckling infants.

scholarly journals An Audit of Pre-Pregnancy Maternal Obesity and Diabetes Screening in Rural Regional Tasmania and Its Impact on Pregnancy and Neonatal Outcomes

2021 ◽  
Vol 18 (22) ◽  
pp. 12006
Author(s):  
Sharon P. Luccisano ◽  
Heinrich C. Weber ◽  
Giuliana O. Murfet ◽  
Iain K. Robertson ◽  
Sarah J. Prior ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Pregnant Women ◽  
Maternal Obesity ◽  
Overweight And Obesity ◽  
Oral Glucose ◽  
Obesity And Diabetes ◽  
High Prevalence ◽  
Pregnant Mothers

Maternal obesity in pregnancy, a growing health problem in Australia, adversely affects both mothers and their offspring. Gestational diabetes mellitus (GDM) is similarly associated with adverse pregnancy and neonatal complications. A low-risk digital medical record audit of antenatal and postnatal data of 2132 pregnant mothers who gave birth between 2016–2018 residing in rural-regional Tasmania was undertaken. An expert advisory group guided the research and informed data collection. Fifty five percent of pregnant mothers were overweight or obese, 43.6% gained above the recommended standards for gestational weight gain and 35.8% did not have an oral glucose tolerance test. The audit identified a high prevalence of obesity among pregnant women and low screening rates for gestational diabetes mellitus associated with adverse maternal and neonatal pregnancy outcomes. We conclude that there is a high prevalence of overweight and obesity among pregnant women in rural regional Tasmania. Further GDM screening rates are low, which require addressing.

Effects of Maternal Obesity and Gestational Diabetes Mellitus on the Placenta: Current Knowledge and Targets for Therapeutic Interventions

2020 ◽  
Vol 19 (2) ◽  
pp. 176-192
Author(s):  
Samantha Bedell ◽  
Janine Hutson ◽  
Barbra de Vrijer ◽  
Genevieve Eastabrook
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Maternal Obesity ◽  
Environmental Changes ◽  
Current Knowledge ◽  
Therapeutic Interventions ◽  
Placental Development ◽  
Exchange Site ◽  
And Function

: Obesity and gestational diabetes mellitus (GDM) are becoming more common among pregnant women worldwide and are individually associated with a number of placenta-mediated obstetric complications, including preeclampsia, macrosomia, intrauterine growth restriction and stillbirth. The placenta serves several functions throughout pregnancy and is the main exchange site for the transfer of nutrients and gas from mother to fetus. In pregnancies complicated by maternal obesity or GDM, the placenta is exposed to environmental changes, such as increased inflammation and oxidative stress, dyslipidemia, and altered hormone levels. These changes can affect placental development and function and lead to abnormal fetal growth and development as well as metabolic and cardiovascular abnormalities in the offspring. This review aims to summarize current knowledge on the effects of obesity and GDM on placental development and function. Understanding these processes is key in developing therapeutic interventions with the goal of mitigating these effects and preventing future cardiovascular and metabolic pathology in subsequent generations.

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 ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Growth Factor ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Trophic Factors ◽  
High Blood Glucose ◽  
Glucose Levels ◽  
Placental Angiogenesis

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.

scholarly journals The Pathophysiology of Gestational Diabetes Mellitus

2018 ◽  
Vol 19 (11) ◽  
pp. 3342 ◽  
Author(s):  
Jasmine Plows ◽  
Joanna Stanley ◽  
Philip Baker ◽  
Clare Reynolds ◽  
Mark Vickers
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Overweight And Obesity ◽  
Chronic Hyperglycemia ◽  
Increased Risk

Gestational diabetes mellitus (GDM) is a serious pregnancy complication, in which women without previously diagnosed diabetes develop chronic hyperglycemia during gestation. In most cases, this hyperglycemia is the result of impaired glucose tolerance due to pancreatic β-cell dysfunction on a background of chronic insulin resistance. Risk factors for GDM include overweight and obesity, advanced maternal age, and a family history or any form of diabetes. Consequences of GDM include increased risk of maternal cardiovascular disease and type 2 diabetes and macrosomia and birth complications in the infant. There is also a longer-term risk of obesity, type 2 diabetes, and cardiovascular disease in the child. GDM affects approximately 16.5% of pregnancies worldwide, and this number is set to increase with the escalating obesity epidemic. While several management strategies exist—including insulin and lifestyle interventions—there is not yet a cure or an efficacious prevention strategy. One reason for this is that the molecular mechanisms underlying GDM are poorly defined. This review discusses what is known about the pathophysiology of GDM, and where there are gaps in the literature that warrant further exploration.

scholarly journals Differential Expression of MicroRNAs in Omental Adipose Tissue From Gestational Diabetes Mellitus Subjects Reveals miR-222 as a Regulator of ERα Expression in Estrogen-Induced Insulin Resistance

Endocrinology ◽  
2014 ◽  
Vol 155 (5) ◽  
pp. 1982-1990 ◽  
Author(s):  
Zhonghua Shi ◽  
Chun Zhao ◽  
Xirong Guo ◽  
Hongjuan Ding ◽  
Yugui Cui ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Differential Expression ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Luciferase Assay ◽  
Omental Adipose Tissue

Omental adipose tissue plays a central role in insulin resistance in gestational diabetes mellitus (GDM), and the molecular mechanisms leading to GDM remains vague. Evidence demonstrates that maternal hormones, such as estradiol, contribute to insulin resistance in GDM. In this study we determined the differential expression patterns of microRNAs (miRNAs) in omental adipose tissues from GDM patients and pregnant women with normal glucose tolerance using AFFX miRNA expression chips. MiR-222, 1 of 17 identified differentially expressed miRNAs, was found to be significantly up-regulated in GDM by quantitative real-time PCR (P < .01), and its expression was closely related with serum estradiol level (P < .05). Furthermore, miR-222 expression was significantly increased in 3T3-L1 adipocytes with a high concentration of 17β-estradiol stimulation (P < .01), whereas the expressions of estrogen receptor (ER)-α protein and insulin-sensitive membrane transporter glucose transporter 4 (GLUT4) protein (P < .01) were markedly reduced. In addition, ERα was shown to be a direct target of miR-222 in 3T3-L1 adipocytes by using the luciferase assay. Finally, antisense oligonucleotides of miR-222 transfection was used to silence miR-222 in 3T3-L1 adipocytes. The results showed that the expressions of ERα and GLUT4, the insulin-stimulated translocation of GLUT4 from the cytoplasm to the cell membrane and glucose uptake in mature adipocytes were dramatically increased (P < .01). In conclusion, miR-222 is a potential regulator of ERα expression in estrogen-induced insulin resistance in GDM and might be a candidate biomarker and therapeutic target for GDM.

Impact of Gestational Diabetes Mellitus and Maternal Obesity on Cord Blood Dynamic Thiol/Disulfide Homeostasis

2016 ◽  
Vol 36 (1) ◽  
pp. 8-15 ◽  
Author(s):  
Sibel Ozler ◽  
Efser Oztas ◽  
Ozcan Erel ◽  
Basak Gumus Guler ◽  
Merve Ergin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Cord Blood ◽  
Maternal Obesity

scholarly journals Effect of Maternal Gestational Diabetes on Infant Feeding and Growth

Proceedings ◽  
2019 ◽  
Vol 37 (1) ◽  
pp. 26
Author(s):  
Manerkar ◽  
Harding ◽  
Conlon ◽  
McKinlay
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Infant Feeding ◽  
Health Problem ◽  
Major Health Problem ◽  
Major Health ◽  
Obesity And Diabetes ◽  
In Pregnancy

Gestational diabetes mellitus (GDM) is a major health problem not only in pregnancy but alsofor lifelong health, with increased risks of obesity and diabetes in offspring [...]

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