scholarly journals Could gestational diabetes mellitus be managed through dietary bioactive compounds? Current knowledge and future perspectives

2016 ◽  
Vol 115 (7) ◽  
pp. 1129-1144 ◽  
Author(s):  
Carmela Santangelo ◽  
Alessandra Zicari ◽  
Elisabetta Mandosi ◽  
Beatrice Scazzocchio ◽  
Emanuela Mari ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Bioactive Compounds ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Virgin Olive Oil ◽  
Dietary Polyphenols ◽  
Insulin Signalling Pathway ◽  
Dietary Bioactive Compounds

AbstractGestational diabetes mellitus (GDM) is a serious problem growing worldwide that needs to be addressed with urgency in consideration of the resulting severe complications for both mother and fetus. Growing evidence indicates that a healthy diet rich in fruit, vegetables, nuts, extra-virgin olive oil and fish has beneficial effects in both the prevention and management of several human diseases and metabolic disorders. In this review, we discuss the latest data concerning the effects of dietary bioactive compounds such as polyphenols and PUFA on the molecular mechanisms regulating glucose homoeostasis. Several studies, mostly based onin vitroand animal models, indicate that dietary polyphenols, mainly flavonoids, positively modulate the insulin signalling pathway by attenuating hyperglycaemia and insulin resistance, reducing inflammatory adipokines, and modifying microRNA (miRNA) profiles. Very few data about the influence of dietary exposure on GDM outcomes are available, although this approach deserves careful consideration. Further investigation, which includes exploring the ‘omics’ world, is needed to better understand the complex interaction between dietary compounds and GDM.

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 A High Adherence to Six Food Targets of the Mediterranean Diet in the Late First Trimester is Associated with a Reduction in the Risk of Materno-Foetal Outcomes: The St. Carlos Gestational Diabetes Mellitus Prevention Study

Nutrients ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 66 ◽  
Author(s):  
Carla Assaf-Balut ◽  
Nuria García de la Torre ◽  
Manuel Fuentes ◽  
Alejandra Durán ◽  
Elena Bordiú ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Virgin Olive Oil ◽  
First Trimester ◽  
Prevention Study ◽  
High Adherence ◽  
Tract Infections

A prenatal diet affects materno-foetal outcomes. This is a post hoc analysis of the St. Carlos gestational diabetes mellitus (GDM) Prevention Study. It aims to evaluate the effect of a late first-trimester (>12 gestational weeks) degree of adherence to a MedDiet pattern—based on six food targets—on a composite of materno-foetal outcomes (CMFCs). The CMFCs were defined as having emergency C-section, perineal trauma, pregnancy-induced hypertension and preeclampsia, prematurity, large-for-gestational-age, and/or small-for-gestational-age. A total of 874 women were stratified into three groups according to late first-trimester compliance with six food targets: >12 servings/week of vegetables, >12 servings/week of fruits, <2 servings/week of juice, >3 servings/week of nuts, >6 days/week consumption of extra virgin olive oil (EVOO), and ≥40 mL/day of EVOO. High adherence was defined as complying with 5–6 targets; moderate adherence 2–4 targets; low adherence 0–1 targets. There was a linear association between high, moderate, and low adherence, and a lower risk of GDM, CMFCs, urinary tract infections (UTI), prematurity, and small-for-gestational-age (SGA) newborns (all p < 0.05). The odds ratios (95% CI) for GDM and CMFCs in women with a high adherence were 0.35((0.18–0.67), p = 0.002) and 0.23((0.11–0.48), p < 0.001), respectively. Late first-trimester high adherence to the predefined six food targets is associated with a reduction in the risk of GDM, CMFCs, UTI, prematurity, and SGA new-borns.

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 &lt; .01), and its expression was closely related with serum estradiol level (P &lt; .05). Furthermore, miR-222 expression was significantly increased in 3T3-L1 adipocytes with a high concentration of 17β-estradiol stimulation (P &lt; .01), whereas the expressions of estrogen receptor (ER)-α protein and insulin-sensitive membrane transporter glucose transporter 4 (GLUT4) protein (P &lt; .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 &lt; .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.

scholarly journals Previous Gestational Diabetes Mellitus and Markers of Cardiovascular Risk

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Nikolaos Vrachnis ◽  
Areti Augoulea ◽  
Zoe Iliodromiti ◽  
Irene Lambrinoudaki ◽  
Stavros Sifakis ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Current Knowledge ◽  
Normal Pregnancy ◽  
Metabolic Abnormalities ◽  
Cvd Risk ◽  
Maternal Complications

The prevalence of gestational diabetes mellitus (GDM) in the developed world has increased at an alarming rate over the last few decades. GDM has been shown to be associated with postpartum diabetes, insulin resistance, hypertension, and dyslipidemia. A history of previous GDM (pGDM), associated or not with any of these metabolic abnormalities, can increase the risk of developing not only type 2 diabetes mellitus but also cardiovascular disease (CVD) independent of a diagnosis of type 2 diabetes later in life. In this paper we discuss the relationship among inflammatory markers, metabolic abnormalities, and vascular dysfunction in women with pGDM. We also review the current knowledge on metabolic modifications occurring in normal pregnancy and the link between alterations of a normal metabolic state with the long-term maternal complications that may result in increased CVD risk. Our review of studies on pGDM prompts us to recommend that these women be considered a population at risk for later CVD events, which however could be avoided via the use of specially designed follow-up programs in the future.

scholarly journals A Mediterranean Diet with an Enhanced Consumption of Extra Virgin Olive Oil and Pistachios Improves Pregnancy Outcomes in Women Without Gestational Diabetes Mellitus: A Sub-Analysis of the St. Carlos Gestational Diabetes Mellitus Prevention Study

2018 ◽  
Vol 74 (1) ◽  
pp. 69-79 ◽  
Author(s):  
Carla Assaf-Balut ◽  
Nuria García de la Torre ◽  
Alejandra Duran ◽  
Manuel Fuentes ◽  
Elena Bordiú ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Virgin Olive Oil ◽  
Caloric Intake ◽  
Extra Virgin Olive Oil ◽  
Large For Gestational Age ◽  
Prevention Study

Aims: The aim of the study was to evaluate the effect of a Mediterranean diet (MedDiet), enhanced with extra virgin olive oil (EVOO) and nuts, on a composite of adverse maternofoetal outcomes of women with normoglycemia during pregnancy. Methods: This was a sub-analysis of the St Carlos gestational diabetes mellitus Prevention Study. Only normoglycemic women were analysed (697). They were randomized (at 8–12th gestational weeks) to: standard-care control group (337), where fat consumption was limited to 30% of total caloric intake; or intervention group (360), where a MedDiet, enhanced with EVOO and pistachios (40–42% fats of total caloric intake) was recommended. The primary outcome was a composite of maternofoetal outcomes (CMFOs): at least having 1 event of emergency C-section, perineal trauma, pregnancy-induced hypertension and preeclampsia, prematurity, large-for-gestational-age and small-for gestational-age. Results: Crude relative risk showed that the intervention was associated with a significant reduction in the risk of CMFOs (0.48 [0.37–0.63]; p = 0.0001), with a number-needed-to-treat = 5. Risk of urinary tract infections, emergency C-sections, perineal trauma, large-for-gestational-age and small-for gestational age new-borns were also significantly reduced. Conclusion: A MedDiet, enhanced with EVOO and nuts, was associated with a risk reduction of CMFOs in over 50% in normoglycemic pregnant women. Therefore, it might be a potentially adequate diet for pregnant women. Trial registration: Identifier ISRCTN84389045. The study was registered on September 27, 2013. Last edited on September 26, 2018

scholarly journals Histone H3 lysine 9 acetylation is downregulated in GDM Placentas and Calcitriol supplementation enhanced this effect

2018 ◽  
Vol 19 (12) ◽  
pp. 4061 ◽  
Author(s):  
Paula Hepp ◽  
Stefan Hutter ◽  
Julia Knabl ◽  
Simone Hofmann ◽  
Christina Kuhn ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Histone H3 ◽  
Western Blots ◽  
Specific Analysis ◽  
Villous Trophoblast ◽  
Rising Incidence

Despite the ever-rising incidence of Gestational Diabetes Mellitus (GDM) and its implications for long-term health of mothers and offspring, the underlying molecular mechanisms remain to be elucidated. To contribute to this, the present study’s objectives are to conduct a sex-specific analysis of active histone modifications in placentas affected by GDM and to investigate the effect of calcitriol on trophoblast cell’s transcriptional status. The expression of Histone H3 lysine 9 acetylation (H3K9ac) and Histone H3 lysine 4 trimethylation (H3K4me3) was evaluated in 40 control and 40 GDM (20 male and 20 female each) placentas using immunohistochemistry and immunofluorescence. The choriocarcinoma cell line BeWo and primary human villous trophoblast cells were treated with calcitriol (48 h). Thereafter, western blots were used to quantify concentrations of H3K9ac and the transcription factor FOXO1. H3K9ac expression was downregulated in GDM placentas, while H3K4me3 expression was not significantly different. Cell culture experiments showed a slight downregulation of H3K9ac after calcitriol stimulation at the highest concentration. FOXO1 expression showed a dose-dependent increase. Our data supports previous research suggesting that epigenetic dysregulations play a key role in gestational diabetes mellitus. Insufficient transcriptional activity may be part of its pathophysiology and this cannot be rescued by calcitriol.

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