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1.
Dietary supplementation for gestational diabetes prevention and management: a meta-analysis of randomized controlled trials.
Chan, KY, Wong, MMH, Pang, SSH, Lo, KKH
Archives of gynecology and obstetrics. 2021;(6):1381-1391
Abstract
PURPOSE The use of supplement to prevent and ease gestational diabetes (GDM) progression has been examined in various studies, but the results were inconclusive, and studies evaluated dietary supplements separately. The present review aimed to evaluate the efficacy of various dietary supplementation on GDM risk and the surrogate markers for cardiometabolic risk of pregnant women with GDM. METHODS A comprehensive search on multiple databases were performed to identify randomized controlled trials. Random-effects model was used to pool the results in relative risk (RR) or mean difference. RESULTS Fifty-three randomized controlled studies with 9443 pregnant women were included. Vitamin D (5 studies, RR 0.64; 95% CI 0.44, 0.94) and myo-inositol (4 studies, RR 0.34, 95% CI 0.20, 0.58) supplementation significantly reduced the risk of GDM. Myo-inositol, probiotics, and vitamin D showed significant intervention effect on surrogate markers related to glycemic control, lipid profile, inflammatory, and oxidative stress. However, the majority of included studies were clustered to Iran and Italy, which might convey a generalizability bias. CONCLUSION Dietary supplementation including vitamin D and myoinositol supplementation has the potential in primary prevention and management of GDM, whereas probiotics demonstrated its ability in GDM management by improving the levels of surrogate markers for cardiometabolic risk. The potential for dietary supplement in preventing GDM or managing cardiometabolic risk of pregnant women should receive more attentions.
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2.
Nutrition as Prevention Factor of Gestational Diabetes Mellitus: A Narrative Review.
Mierzyński, R, Poniedziałek-Czajkowska, E, Sotowski, M, Szydełko-Gorzkowicz, M
Nutrients. 2021;(11)
Abstract
Gestational diabetes mellitus (GDM) is defined as a glucose tolerance disorder with onset or first recognition during pregnancy. GDM is associated with several adverse maternal and neonatal outcomes. Management to reduce the incidence of GDM could decrease the incidence of these complications. Modification of nutrition in the prevention of GDM is postulated. The vital issue in GDM prevention is the implementation of proper dietary patterns, appropriate physical activity, and a combination of diet and lifestyle modifications. However, intervention studies examining the effects of diet and lifestyle on GDM prevention are contradictory. The aim of this study was to review the scientific evidence on nutritional prevention strategies, including diet and supplementation of some substances such as probiotics, micro/macroelements, fiber, myoinositol, and vitamins that may be effective in reducing the risk of GDM. The presented article is a narrative review. This article indicates that certain nutritional factors may have some benefit in preventing GDM. However, further studies in a variety of populations and large groups of patients are needed. At present, no definitive conclusions can be drawn as to the best intervention in the prevention of GDM.
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3.
Placental Endocrine Activity: Adaptation and Disruption of Maternal Glucose Metabolism in Pregnancy and the Influence of Fetal Sex.
Stern, C, Schwarz, S, Moser, G, Cvitic, S, Jantscher-Krenn, E, Gauster, M, Hiden, U
International journal of molecular sciences. 2021;(23)
Abstract
The placenta is an endocrine fetal organ, which secretes a plethora of steroid- and proteo-hormones, metabolic proteins, growth factors, and cytokines in order to adapt maternal physiology to pregnancy. Central to the growth of the fetus is the supply with nutrients, foremost with glucose. Therefore, during pregnancy, maternal insulin resistance arises, which elevates maternal blood glucose levels, and consequently ensures an adequate glucose supply for the developing fetus. At the same time, maternal β-cell mass and function increase to compensate for the higher insulin demand. These adaptations are also regulated by the endocrine function of the placenta. Excessive insulin resistance or the inability to increase insulin production accordingly disrupts physiological modulation of pregnancy mediated glucose metabolism and may cause maternal gestational diabetes (GDM). A growing body of evidence suggests that this adaptation of maternal glucose metabolism differs between pregnancies carrying a girl vs. pregnancies carrying a boy. Moreover, the risk of developing GDM differs depending on the sex of the fetus. Sex differences in placenta derived hormones and bioactive proteins, which adapt and modulate maternal glucose metabolism, are likely to contribute to this sexual dimorphism. This review provides an overview on the adaptation and maladaptation of maternal glucose metabolism by placenta-derived factors, and highlights sex differences in this regulatory network.
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4.
Gestational diabetes mellitus decreased umbilical cord blood polyunsaturated fatty acids: a meta-analysis of observational studies.
Hai-Tao, Y, Zhi-Heng, G, Yi-Ru, C, Yue-Ting, L, Hai-Ying, Z, Ya-Juan, L, Lin, X
Prostaglandins, leukotrienes, and essential fatty acids. 2021;:102318
Abstract
BACKGROUND Polyunsaturated fatty acid (PUFA) is important for the development of the fetal brain, and the retina. Gestational diabetes mellitus (GDM) may influence maternal and fetal fatty acid metabolism, in turn affecting fetal growth and development. In several studies, maternal and fetal PUFA metabolic differences have been reported between mothers with and without GDM, but not in other studies. Thus, the aim of this meta-analysis (registration number: CRD42020220448) was to compare levels of linoleic acid (LA), α-linolenic acid (ALA), arachidonic acid (AA), docosahexaenoic acid (DHA), and total n-3 and n-6 PUFA between mothers with and without GMD and their fetuses. METHODS We performed a meta-analysis of observational studies on maternal and fetal fatty acid metabolism, published until May 2021. In addition, we performed subgroup analysis depending on the analyzed tissues (plasma/serum, erythrocyte membrane, or placenta) and the expression modes of fatty acids (concentration or percentage). RESULTS We included 24 observational studies involving 4335 maternal datasets and 12 studies involving 1675 fetal datasets in the meta-analysis. Levels of AA, DHA, and n-6 and n-3 PUFA were lower in the cord blood of mothers with GDM than in controls (P < 0.05). Compared to that in controls, in erythrocyte membranes, the percentages of AA, DHA, and n-6 and n-3 PUFA in total fatty acid were lower in mothers with GDM (P < 0.05), but in plasma/serum, the percentages of AA, DHA, and n-6 PUFA in total fatty acid were higher in mothers with GDM (P < 0.05). CONCLUSIONS GDM appears to influence the transfer of PUFAs from mothers to fetuses. The percentage of PUFAs in maternal plasma/serum was higher, and that in erythrocyte membranes was lower in mothers with GDM compared to those with normal glucose tolerance.
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5.
Interaction between Metformin, Folate and Vitamin B12 and the Potential Impact on Fetal Growth and Long-Term Metabolic Health in Diabetic Pregnancies.
Owen, MD, Baker, BC, Scott, EM, Forbes, K
International journal of molecular sciences. 2021;(11)
Abstract
Metformin is the first-line treatment for many people with type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) to maintain glycaemic control. Recent evidence suggests metformin can cross the placenta during pregnancy, thereby exposing the fetus to high concentrations of metformin and potentially restricting placental and fetal growth. Offspring exposed to metformin during gestation are at increased risk of being born small for gestational age (SGA) and show signs of 'catch up' growth and obesity during childhood which increases their risk of future cardiometabolic diseases. The mechanisms by which metformin impacts on the fetal growth and long-term health of the offspring remain to be established. Metformin is associated with maternal vitamin B12 deficiency and antifolate like activity. Vitamin B12 and folate balance is vital for one carbon metabolism, which is essential for DNA methylation and purine/pyrimidine synthesis of nucleic acids. Folate:vitamin B12 imbalance induced by metformin may lead to genomic instability and aberrant gene expression, thus promoting fetal programming. Mitochondrial aerobic respiration may also be affected, thereby inhibiting placental and fetal growth, and suppressing mammalian target of rapamycin (mTOR) activity for cellular nutrient transport. Vitamin supplementation, before or during metformin treatment in pregnancy, could be a promising strategy to improve maternal vitamin B12 and folate levels and reduce the incidence of SGA births and childhood obesity. Heterogeneous diagnostic and screening criteria for GDM and the transient nature of nutrient biomarkers have led to inconsistencies in clinical study designs to investigate the effects of metformin on folate:vitamin B12 balance and child development. As rates of diabetes in pregnancy continue to escalate, more women are likely to be prescribed metformin; thus, it is of paramount importance to improve our understanding of metformin's transgenerational effects to develop prophylactic strategies for the prevention of adverse fetal outcomes.
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6.
Changes in serum lipid levels during pregnancy in women with gestational diabetes. A narrative review.
Cibickova, L, Schovanek, J, Karasek, D
Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2021;(1):8-12
Abstract
We review current knowledge on lipid metabolism changes during pregnancy with special focus on changes in gestational diabetes. In physiological pregnancy, total plasma cholesterol, triglyceride and HDL-cholesterol level rises, the atherogenic index (LDL-cholesterol / HDL-cholesterol remains unchanged. Compared with healthy women, women with GDM show more pronounced signs of mixed dyslipidaemia - increased levels of triglyceride, changes in cholesterol and lipoprotein concentrations with a shift towards greater small dense LDL subtractions, which is typical for insulin resistance states. Dyslipidaemia, particularly hypertriglyceridemia, is thought to be one of the key drivers of foetal macrosomia and that is why measurements of plasma lipids may be valuable in detecting the metabolic abnormality in GDM and in predicting foetal outcome. Dyslipidaemia in GDM is seen as proatherogenic and potentially harmful for the baby and therefore it should be monitored more carefully.
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7.
The Carbohydrate Threshold in Pregnancy and Gestational Diabetes: How Low Can We Go?
Sweeting, A, Mijatovic, J, Brinkworth, GD, Markovic, TP, Ross, GP, Brand-Miller, J, Hernandez, TL
Nutrients. 2021;(8)
Abstract
The original nutrition approach for the treatment of gestational diabetes mellitus (GDM) was to reduce total carbohydrate intake to 33-40% of total energy (EI) to decrease fetal overgrowth. Conversely, accumulating evidence suggests that higher carbohydrate intakes (60-70% EI, higher quality carbohydrates with low glycemic index/low added sugars) can control maternal glycemia. The Institute of Medicine (IOM) recommends ≥175 g/d of carbohydrate intake during pregnancy; however, many women are consuming lower carbohydrate (LC) diets (<175 g/d of carbohydrate or <40% of EI) within pregnancy and the periconceptual period aiming to improve glycemic control and pregnancy outcomes. This report systematically evaluates recent data (2018-2020) to identify the LC threshold in pregnancy in relation to safety considerations. Evidence from 11 reports suggests an optimal carbohydrate range of 47-70% EI supports normal fetal growth; higher than the conventionally recognized LC threshold. However, inadequate total maternal EI, which independently slows fetal growth was a frequent confounder across studies. Effects of a carbohydrate intake <175 g/d on maternal ketonemia and plasma triglyceride/free fatty acid concentrations remain unclear. A recent randomized controlled trial (RCT) suggests a higher risk for micronutrient deficiency with carbohydrate intake ≤165 g/d in GDM. Well-controlled prospective RCTs comparing LC (<165 g/d) and higher carbohydrate energy-balanced diets in pregnant women are clearly overdue.
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8.
Extracellular vesicles and their potential role inducing changes in maternal insulin sensitivity during gestational diabetes mellitus.
Nair, S, Ormazabal, V, Lappas, M, McIntyre, HD, Salomon, C
American journal of reproductive immunology (New York, N.Y. : 1989). 2021;(2):e13361
Abstract
Gestational diabetes mellitus (GDM) is one of the most common endocrine disorders during gestation and affects around 15% of all pregnancies worldwide, paralleling the global increase in obesity and type 2 diabetes. Normal pregnancies are critically dependent on the development of maternal insulin resistance balanced by an increased capacity to secrete insulin, which allows for the allocation of nutrients for adequate foetal growth and development. Several factors including placental hormones, inflammatory mediators and nutrients have been proposed to alter insulin sensitivity and insulin response and underpin the pathological outcomes of GDM. However, other factors may also be involved in the regulation of maternal metabolism and a complete understanding of GDM pathophysiology requires the identification of these factors, and the mechanisms associated with them. Recent studies highlight the potential utility of tissue-specific extracellular vesicles (EVs) in the diagnosis of disease onset and treatment monitoring for several pregnancy-related complications, including GDM. To date, there is a paucity of data defining changes in the release, content, bioactivity and diagnostic utility of circulating EVs in pregnancies complicated by GDM. Placental EVs may engage in paracellular interactions including local cell-to-cell communication between the cell constituents of the placenta and contiguous maternal tissues, and/or distal interactions involving the release of placental EVs into biological fluids and their transport to a remote site of action. Hence, the aim of this review is to discuss the biogenesis, isolation methods and role of EVs in the physiopathology of GDM, including changes in maternal insulin sensitivity during pregnancy.
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9.
Metformin administration during pregnancy - current insight.
Skibinska, M, Zurawska-Klis, M, Krekora, M, Cypryk, K
Ginekologia polska. 2021;(1):46-50
Abstract
The main mechanism of gestational diabetes mellitus (GDM) is insulin resistance, therefore using metformin as a medicine reducing insulin resistance appears to be promising. Currently, the majority of medical associations do not recommend using metformin during pregnancy as the first-line of therapy when the diet regimen is insufficient for glycaemic control. However, they do allow its administration if there is no possibility of insulin treatment. There is some evidence which suggests that using metformin during pregnancy is not related to an increased risk of obstetric complications during delivery and that its influence on the foetus can be beneficial. Since metformin crosses the placenta, the major argument for cautious use of this drug are the potential long-term effects of the treatment for the child and its development in later life. In this article, the authors attempt to discuss the use of metformin during pregnancy and the safety of the treatment in the light of current studies and recommendations.
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10.
Early Gestational Diabetes Mellitus: Diagnostic Strategies and Clinical Implications.
Bhattacharya, S, Nagendra, L, Krishnamurthy, A, Lakhani, OJ, Kapoor, N, Kalra, B, Kalra, S
Medical sciences (Basel, Switzerland). 2021;(4)
Abstract
Preexisting diabetes mellitus (DM) should be ruled out early in pregnancy in those at risk. During screening, a significant proportion of women do not reach the threshold for overt DM but fulfill the criteria used for diagnosing conventional gestational DM (cGDM). There is no consensus on the management of pregnancies with intermediate levels of hyperglycemia thus diagnosed. We have used the term early gestational DM (eGDM) for this condition and reviewed the currently available literature. Fasting plasma glucose (FPG), oral glucose tolerance test, and glycated hemoglobin (HbA1c) are the commonly employed screening tools in early pregnancy. Observational studies suggest that early pregnancy FPG and Hba1c correlate with the risk of cGDM and adverse perinatal outcomes. However, specific cut-offs, including those proposed by the International Association of the Diabetes and Pregnancy Study Group, do not reliably predict the development of cGDM. Emerging data, though indicate that FPG ≥ 92 mg/dL (5.1 mmol/L), even in the absence of cGDM, signals the risk for perinatal complication. Elevated HbA1c, especially a level ≥ 5.9%, also correlates with the risk of cGDM and worsened outcome. HbA1c as a diagnostic test is however besieged with the usual caveats that occur in pregnancy. The studies that explored the effects of intervention present conflicting results, including a possibility of fetal malnutrition and small-for-date baby in the early treatment group. Diagnostic thresholds and glycemic targets in eGDM may differ, and large multicenter randomized controlled trials are necessary to define the appropriate strategy.