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1.
Role of insulin, adenosine, and adipokine receptors in the foetoplacental vascular dysfunction in gestational diabetes mellitus.
Subiabre, M, Villalobos-Labra, R, Silva, L, Fuentes, G, Toledo, F, Sobrevia, L
Biochimica et biophysica acta. Molecular basis of disease. 2020;(2):165370
Abstract
Gestational diabetes mellitus (GDM) is a disease of pregnancy associated with maternal and foetal hyperglycaemia and altered foetoplacental vascular function. Human foetoplacental microvascular and macrovascular endothelium from GDM pregnancy show increased maximal l-arginine transport capacity via the human cationic amino acid transporter 1 (hCAT-1) isoform and nitric oxide (NO) synthesis by the endothelial NO synthase (eNOS). These alterations are paralleled by lower maximal transport activity of the endogenous nucleoside adenosine via the human equilibrative nucleoside transporter 1 (hENT1) and activation of adenosine receptors. A causal relationship has been described for adenosine-activation of A2A adenosine receptors, hCAT-1, and eNOS activity (i.e. the Adenosine/l-Arginine/Nitric Oxide, ALANO, signalling pathway). Insulin restores these alterations in GDM via activation of insulin receptor A (IR-A) form in the macrovascular but IR-A and IR-B forms in the microcirculation of the human placenta. Adipokines are secreted from adipocytes influencing the foetoplacental metabolic and vascular function. Various adipokines are dysregulated in GDM, with adiponectin and leptin playing major roles. Abnormal plasma concentration of these adipokines and the activation or their receptors are involved in the pathophysiology of GDM. However, involvement of adipokines, adenosine, and insulin receptors and membrane transporters in the aetiology of this disease of pregnancy is unknown. This review focuses on the pathophysiology of insulin and adenosine receptors and l-arginine and adenosine membranes transporters giving an overview of the key adipokines leptin and adiponectin in the foetoplacental vasculature in GDM. This article is part of a Special Issue entitled: Membrane Transporters and Receptors in Pregnancy Metabolic Complications edited by Luis Sobrevia.
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2.
Adipokines underlie the early origins of obesity and associated metabolic comorbidities in the offspring of women with pregestational obesity.
Arroyo-Jousse, V, Jaramillo, A, Castaño-Moreno, E, Lépez, M, Carrasco-Negüe, K, Casanello, P
Biochimica et biophysica acta. Molecular basis of disease. 2020;(2):165558
Abstract
Maternal pregestational obesity is a well-known risk factor for offspring obesity, metabolic syndrome, cardiovascular disease and type 2 diabetes. The mechanisms by which maternal obesity can induce alterations in fetal and later neonatal metabolism are not fully elucidated due to its complexity and multifactorial causes. Two adipokines, leptin and adiponectin, are involved in fetal and postnatal growth trajectories, and both are altered in women with pregestational obesity. The placenta synthesizes leptin, which goes mainly to the maternal circulation and in lesser amount to the developing fetus. Maternal pregestational obesity and hyperleptinemia are associated with placental dysfunction and changes in nutrient transporters which directly affect fetal growth and development. By the other side, the embryo can produce its own leptin from early in development, which is associated to fetal weight and adiposity. Adiponectin, an insulin-sensitizing adipokine, is downregulated in maternal obesity. High molecular weight (HMW) adiponectin is the most abundant form and with most biological actions. In maternal obesity lower total and HMW adiponectin levels have been described in the mother, paralleled with high levels in the umbilical cord. Several studies have found that cord blood adiponectin levels are related with postnatal growth trajectories, and it has been suggested that low adiponectin levels in women with pregestational obesity enhance placental insulin sensitivity and activation of placental amino acid transport systems, supporting fetal overgrowth. The possible mechanisms by which maternal pregestational obesity, focusing in the actions of leptin and adiponectin, affects the fetal development and postnatal growth trajectories in their offspring are discussed.
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3.
Maternal and newborn outcomes of antenatal breastmilk expression: a scoping review protocol.
Foudil-Bey, I, Murphy, MS, Keely, EJ, El-Chaâr, D
BMJ open. 2020;(5):e033101
Abstract
INTRODUCTION Mothers with diabetes face unique challenges associated with breastfeeding initiation and maintenance. Antenatal breastmilk expression (BME) may be suggested to mothers, including mothers with diabetes, to improve breastfeeding, maternal, and infant outcomes postpartum. However, there have been few evaluations of the potential harms and benefits of this practice. The objective of our scoping review will be to broadly examine the literature describing maternal and infant outcomes of antenatal BME. METHODS AND ANALYSIS This scoping review will address the research question: 'Among women who engaged in antenatal BME, what maternal and infant outcomes have been evaluated?' A search of published and unpublished studies available in English will be conducted in February 2020 using the following databases: Medline (OVID), Embase (OVID), CINAHL (EBSCOHost), and Cochrane Database of Systematic Reviews (OVID). A search of the British Library E-Theses Online Services (EThOS) database and OpenGrey will be conducted to identify relevant grey literature. This scoping review will use a five-step framework to guide the selection, extraction, and analysis of eligible studies. Clinical consultation will be included as a sixth step to our methodology. Literature reporting on the effect of antenatal BME on maternal and infant outcomes, breastfeeding initiation and duration, and the experiences of women who have engaged in the practice will be considered. The data will be summarised with attention paid to high-risk obstetrical populations such as women with diabetes. Our results will be reported as outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. ETHICS AND DISSEMINATION Research ethics board approval will not be required due to the nature of the study's methodology. The results of this review will be disseminated through peer-reviewed publication and presentation at relevant conferences. TRAIL REGISTRATION NUMBER Open Science Framework (osf.io/gfp2q).
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4.
The Human Breast Milk Metabolome in Preeclampsia, Gestational Diabetes, and Intrauterine Growth Restriction: Implications for Child Growth and Development.
Bardanzellu, F, Puddu, M, Fanos, V
The Journal of pediatrics. 2020;:S20-S28
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5.
Pregnancy As a Predictor of Maternal Cardiovascular Disease: The Era of CardioObstetrics.
Wu, P, Mamas, MA, Gulati, M
Journal of women's health (2002). 2019;(8):1037-1050
Abstract
Globally, cardiovascular disease (CVD) is the most common cause of mortality in women accounting for one in three deaths. There remains an under recognition of CVD as well as a lack of awareness of risk in women. Promotion of CVD prevention is essential, but the current risk assessment tools do not incorporate any sex-specific cardiovascular risk factors. There is increasing recognition of sex-specific risk factors that appear during pregnancy that are associated with CVD. These adverse pregnancy outcomes (APOs) include preeclampsia, gestational hypertension, preterm birth, gestational diabetes, delivery of a small-for-gestational-age infant, miscarriage, and high parity number. Although the underlying biological mechanism for these association remains to be elucidated, current international guidelines are beginning to recommend the inclusion of APOs in the assessment of CVD risk in women. This review summarizes the evidence for the association between APOs and future CVD. It also highlights the importance of considering APOs in the cardiovascular risk assessment, specifically in young women, allowing for targeted lifestyle-modifying interventions with the potential to alter their risk trajectory and improve their long-term cardiovascular health.
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6.
Maternal Omega-3 Nutrition, Placental Transfer and Fetal Brain Development in Gestational Diabetes and Preeclampsia.
Devarshi, PP, Grant, RW, Ikonte, CJ, Hazels Mitmesser, S
Nutrients. 2019;(5)
Abstract
Omega-3 fatty acids, particularly docosahexaenoic fatty acid (DHA), are widely recognized to impact fetal and infant neurodevelopment. The impact of DHA on brain development, and its inefficient synthesis from the essential alpha-linolenic acid (ALA), has led to recommended DHA intakes of 250-375 mg eicosapentaenoic acid + DHA/day for pregnant and lactating women by the Dietary Guidelines for Americans. Despite these recommendations, the intake of omega-3s in women of child-bearing age in the US remains very low. The low maternal status of DHA prior to pregnancy could impair fetal neurodevelopment. This review focuses on maternal omega-3 status in conditions of gestational diabetes mellitus (GDM) and preeclampsia, and the subsequent impact on placental transfer and cord blood concentration of omega-3s. Both GDM and preeclampsia are associated with altered maternal omega-3 status, altered placental omega-3 metabolism, reduced cord blood omega-3 levels and have an impact on neurodevelopment in the infant and on brain health later in life. These findings indicate lower DHA exposure of the developing baby may be driven by lower placental transfer in both conditions. Thus, determining approaches which facilitate increased delivery of DHA during pregnancy and early development might positively impact brain development in infants born to mothers with these diseases.
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7.
Prevention of gestational diabetes mellitus in overweight or obese pregnant women: A network meta-analysis.
Chatzakis, C, Goulis, DG, Mareti, E, Eleftheriades, M, Zavlanos, A, Dinas, K, Sotiriadis, A
Diabetes research and clinical practice. 2019;:107924
Abstract
AIMS: Several interventions have been implemented to prevent the development of gestational diabetes mellitus (GDM) in obese pregnant women, including physical exercise programs, and administration of metformin, vitamin D and probiotics. The aim of this network meta-analysis was to compare the efficiency of these interventions and identify the optimal. MATERIALS A network meta-analysis of randomized trials was performed comparing the different interventions for the development of GDM in overweight or obese women, either to each other or placebo/no intervention. A search was conducted in four electronic databases and grey literature sources. The primary outcome was the development of GDM; secondary outcomes were other complications of pregnancy. RESULTS The meta-analysis included 23 studies (4237 participants). None of the interventions was superior compared with placebo/no intervention for the prevention of GDM. Metformin and physical exercise were superior to placebo/no intervention for gestational weight gain (MD -1.21, 95% CI -2.14 to -0.28 and MD -0.96, 95% CI -1.69 to -0.22, respectively). Metformin was superior to placebo/no intervention for caesarean sections and admission to NICU. CONCLUSIONS Interventions aiming to prevent the development of GDM in overweight/obese women are not effective, when applied during pregnancy.
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8.
Guidelines for the screening and diagnosis of gestational diabetes in Italy from 2010 to 2019: critical issues and the potential for improvement.
Vitacolonna, E, Succurro, E, Lapolla, A, Scavini, M, Bonomo, M, Di Cianni, G, Di Benedetto, A, Napoli, A, Tumminia, A, Festa, C, et al
Acta diabetologica. 2019;(11):1159-1167
Abstract
AIMS: In 2010, Italian health professionals rapidly implemented the one-step screening for gestational diabetes mellitus (GDM) based on a 75 g OGTT, to comply with the diagnostic criteria proposed by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). The change was promoted by the two main Italian scientific societies of diabetology, Associazione Medici Diabetologi (AMD) and Società Italiana di Diabetologia (SID), and it took just a few months for the Istituto Superiore di Sanità, together with several scientific societies, to revise the criteria and include them in the National Guidelines System. Over the last 9 years, the implementation of these guidelines has shown some benefits and some drawbacks. METHODS In order to evaluate the critical issues arisen from the implementation of the current Italian guidelines for the diagnosis of GDM, the studies published on this topic have been reviewed. The search was performed using the following keywords: "gestational diabetes" AND "diagnostic criteria" OR screening AND Ital*. The study is an expert opinion paper, based on the relevant scientific literature published between 2010 and 2019. The databases screened for the literature review included PubMed, MEDLINE, and Scopus. RESULTS The implementation of the Guidelines for Screening and Diagnosis of GDM in Italy present some strengths and some weaknesses. One of the positive aspects is that high-risk women are required to perform an OGTT early in pregnancy. By contrast, there are several aspects in need of improvement: (1) In spite of the current indications, only a minority of high-risk women perform OGTT early in pregnancy; (2) several low-risk women are screened for GDM; (3) in some low-risk women affected by GDM, the diagnosis might be missed with the application of the current guidelines; (4) there is a lack of homogeneity in the risk assessment data from different regions. CONCLUSIONS In order to improve the current Italian GDM guidelines, some practical solutions have been suggested.
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9.
Lessons learned from lifestyle prevention trials in gestational diabetes mellitus.
Egan, AM, Simmons, D
Diabetic medicine : a journal of the British Diabetic Association. 2019;(2):142-150
Abstract
Gestational diabetes mellitus (GDM) is associated with an increased risk of adverse outcomes for mother and infant both at birth and later in life. A large body of evidence is now available relating to antenatal prevention of GDM. Overall, despite some individual trials of a variety of lifestyle interventions revealing benefit, many more have shown no effect from the second trimester onwards, even with significant gestational weight gain limitation. At-risk women often seem reluctant to engage in lifestyle changes and frequently cannot adhere to recommended interventions even within a clinical trial setting. Many trials have not considered the heterogeneity of diabetes first discovered in pregnancy, something of importance into the future. Future work should focus on designing interventions acceptable to the population at risk, whether those taking place before or during the first trimester of pregnancy are effective, and whether greater individualization can identify those women most likely to benefit.
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10.
Non-pharmacological management of gestational diabetes: The role of myo-inositol.
Guardo, FD, Currò, JM, Valenti, G, Rossetti, P, Di Gregorio, LM, Conway, F, Chiofalo, B, Garzon, S, Bruni, S, Rizzo, G
Journal of complementary & integrative medicine. 2019;(2)
Abstract
Gestational diabetes mellitus (GDM) is the most common metabolic disorder occurring in pregnancy. GDM plays an important role in the current diabetes epidemic: exposure to a high glycemic environment during the early stages of development increases the risk of the fetus to develop type two diabetes mellitus (T2DM) in adult life. Various cardiometabolic risk factors are linked to GDM. A thorough knowledge of the risk factors and genes involved in the development of GDM, along with an understanding of the underlying pathophysiological mechanisms are crucial to properly identify patients at risk of developing this condition. There is growing evidence showing that myo-inositol, combined with an appropriate therapeutic regimen for GDM, can provide additional benefits to the patient. The aim of this review is to analyze the role of inositol isomers - especially myo-inositol (MYO-INS) - in the treatment of patients with GDM.