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The prevalence of both obesity and gestational diabetes mellitus (GDM) is rising worldwide. The complications of diabetes affecting the mother and fetus are well known. Maternal complications include preterm labor, pre-eclampsia, nephropathy, birth trauma, cesarean section, and postoperative wound complications, among others. Fetal complications include fetal wastage from early pregnancy loss or congenital anomalies, macrosomia, shoulder dystocia, stillbirth, growth restriction, and hypoglycemia, among others. The presence of obesity among diabetic patients compounds these complications. The above-mentioned short-term complications can be mediated by achieving the desired level of glycemic control during pregnancy. However, GDM during pregnancy is associated with increased risk of early obesity, type 2 diabetes during adolescence and the development of metabolic syndrome in early childhood. Additionally, GDM is a marker for the development of overt type 2 diabetes and metabolic syndrome for the mother in the early future.
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PMID:Obesity, gestational diabetes and pregnancy outcome. 1892 84

Gestational diabetes occurs in 5 to 9 percent of pregnancies in the United States and is growing in prevalence. It is a controversial entity, with conflicting guidelines and treatment protocols. Recent studies show that diagnosis and management of this disorder have beneficial effects on maternal and neonatal outcomes, including reduced rates of shoulder dystocia, fractures, nerve palsies, and neonatal hypoglycemia. Diagnosis is made using a sequential model of universal screening with a 50-g one-hour glucose challenge test, followed by a diagnostic 100-g three-hour oral glucose tolerance test for women with a positive screening test. Treatment consists of glucose monitoring, dietary modification, exercise, and, when necessary, pharmacotherapy to maintain euglycemia. Insulin therapy is the mainstay of treatment, although glyburide and metformin may become more widely used. In women receiving pharmacotherapy, antenatal testing with nonstress tests and amniotic fluid indices beginning in the third trimester is generally used to monitor fetal well-being. The method and timing of delivery are controversial. Women with gestational diabetes are at high risk of subsequent development of type 2 diabetes. Lifestyle modification should therefore be encouraged, along with regular screening for diabetes.
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PMID:Diagnosis and management of gestational diabetes mellitus. 1962 46

Women with gestational diabetes mellitus (GDM) have higher rates of foetal macrosomia, shoulder dystocia and pregnancy-induced hypertension, and are at higher risk of developing type 2 diabetes. Herein, we introduce a new conceptual term, "gestational prediabetes", which requires the absence of diabetes before pregnancy, and the presence of blood glucose levels (or a related marker) in early pregnancy that are higher than normal, but not yet high enough to meet the diagnostic criteria for GDM. Identifying women with gestational prediabetes might be done in early pregnancy (e.g., 12 weeks' gestation) using conventional glycaemic testing, assessment of visceral abdominal adiposity or hepatic fat by ultrasonography, or measuring serum sex hormone-binding globulin or adiponectin. However, none of these approaches has been systematically compared to conventional predictors, such as maternal body mass index or waist circumference. Any early-pregnancy predictor of gestational prediabetes risk needs to have low cost, ease of administration, and a short turnaround time. The theoretical advantage of identifying women with gestational prediabetes would be to "prevent" the onset of GDM (and its inherent risks to the pregnancy) in a timelier manner. One sensible starting point would be an intervention to prevent early excessive weight gain in pregnancy, which is currently being evaluated by two randomized clinical trials. In addition, early intervention could offset the need for resource-intense GDM management or insulin therapy.
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PMID:Gestational prediabetes: a new term for early prevention? 2084 69

Maternal diabetes constitutes an unfavorable environment for embryonic and fetoplacental development. Despite current treatments, pregnant women with pregestational diabetes are at increased risk for congenital malformations, materno-fetal complications, placental abnormalities and intrauterine malprogramming. The complications during pregnancy concern the mother (gravidic hypertension and/or preeclampsia, cesarean section) and the fetus (macrosomia or intrauterine growth restriction, shoulder dystocia, hypoglycemia and respiratory distress). The fetoplacental impairment and intrauterine programming of diseases in the offspring's later life induced by gestational diabetes are similar to those induced by type 1 and type 2 diabetes mellitus. Despite the existence of several developmental and morphological differences in the placenta from rodents and women, there are similarities in the alterations induced by maternal diabetes in the placenta from diabetic patients and diabetic experimental models. From both human and rodent diabetic experimental models, it has been suggested that the placenta is a compromised target that largely suffers the impact of maternal diabetes. Depending on the maternal metabolic and proinflammatory derangements, macrosomia is explained by an excessive availability of nutrients and an increase in fetal insulin release, a phenotype related to the programming of glucose intolerance. The degree of fetal damage and placental dysfunction and the availability and utilisation of fetal substrates can lead to the induction of macrosomia or intrauterine growth restriction. In maternal diabetes, both the maternal environment and the genetic background are important in the complex and multifactorial processes that induce damage to the embryo, the placenta, the fetus and the offspring. Nevertheless, further research is needed to better understand the mechanisms that govern the early embryo development, the induction of congenital anomalies and fetal overgrowth in maternal diabetes.
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PMID:Consequences of gestational and pregestational diabetes on placental function and birth weight. 2208 56

New proposals for the diagnosis of gestational diabetes (GDM), promulgated by the International Association of Diabetes and Pregnancy Study Groups (IADPSG), will substantially increase the number of women diagnosed with GDM. This will have an enormous impact on healthcare resources, diverting attention away from genuinely high risk diabetic pregnancies. Randomized trials in 'mild' GDM indicate that the main effects of treatment are a 2 %-3 % reduction in birth weight, fewer 'big babies', and less shoulder dystocia. However, these studies used different diagnostic criteria, and women diagnosed by the broader IADPSG criteria may not derive the same modest benefit. Modeling indicates a very high cost per QALY, unless later development of type 2 diabetes can be prevented. Far from producing consensus, the IADPSG suggestion has thrown sharply into focus the need to assess critically the risks, costs and benefits of adopting criteria that may pathologize a large number of otherwise normal pregnancies.
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PMID:Establishing consensus in the diagnosis of gestational diabetes following HAPO: where do we stand? 2305 48

Obesity in women of reproductive age is increasing in prevelance worldwide. Obesity reduces fertility and increases time taken to conceive, and obesity-related comorbidities (such as type 2 diabetes and chronic hypertension) heighten the risk of adverse outcomes for mother and child if the woman becomes pregnant. Pregnant women who are obese are more likely to have early pregnancy loss, and have increased risk of congenital fetal malformations, delivery of large for gestational age infants, shoulder dystocia, spontaneous and medically indicated premature birth, and stillbirth. Late pregnancy complications include gestational diabetes and pre-eclampsia, both of which are associated with long-term morbidities post partum. Women with obesity can also experience difficulties during labour and delivery, and are more at risk of post-partum haemorrhage. Long-term health risks are associated with weight retention after delivery, and inherent complications for the next pregnancy. The wellbeing of the next generation is also compromised. All these health issues could be avoided by prevention of obesity among women of reproductive age, which should be viewed as a global public health priority. For women who are already obese, renewed efforts should be made towards improved management during pregnancy, especially of blood glucose, and increased attention to post-partum weight management. Effective interventions, tailored to ethnicity and culture, are needed at each of these stages to improve the health of women and their children in the context of the global obesity epidemic.
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PMID:Preconceptional and maternal obesity: epidemiology and health consequences. 2774 79

Gestational diabetes mellitus (GDM) affects approximately 6% of pregnant women, and prevalence is increasing in parallel with the obesity epidemic. Protocols for screening/diagnosing GDM are controversial with several guidelines available. Treatment of GDM results in a reduction in the incidence of preeclampsia, shoulder dystocia, and macrosomia. If diet and lifestyle changes do not result in target glucose levels, then treatment with metformin, glyburide, or insulin should begin. It is generally recommended that pregnancies complicated by GDM do not go beyond term. For women identified to have prediabetes, intensive lifestyle intervention and metformin have been shown to prevent or delay progression to type 2 diabetes.
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PMID:Gestational Diabetes: Diagnosis, Classification, and Clinical Care. 2849 31

Artificial selection towards a desired phenotype/trait has modified the genomes of livestock dramatically that generated breeds that greatly differ in morphology, production and environmental adaptation traits. Angus cattle are among the famous cattle breeds developed for superior beef quality. This paper aimed at exploring genomic regions under selection in Angus cattle that are associated with meat quality traits and other associated phenotypes. The whole genome of 10 Angus cattle was compared with 11 Hanwoo (A-H) and 9 Jersey (A-J) cattle breeds using a cross-population composite likelihood ratio (XP-CLR) statistical method. The top 1% of the empirical distribution was taken as significant and annotated using UMD3.1. As a result, 255 and 210 genes were revealed under selection from A-H and A-J comparisons, respectively. The WebGestalt gene ontology analysis resulted in sixteen (A-H) and five (A-J) significantly enriched KEGG pathways. Several pathways associated with meat quality traits (insulin signaling, type II diabetes mellitus pathway, focal adhesion pathway, and ECM-receptor interaction), and feeding efficiency (olfactory transduction, tight junction, and metabolic pathways) were enriched. Genes affecting beef quality traits (e.g., FABP3, FTO, DGAT2, ACS, ACAA2, CPE, TNNI1), stature and body size (e.g., PLAG1, LYN, CHCHD7, RPS20), fertility and dystocia (e.g., ESR1, RPS20, PPP2R1A, GHRL, PLAG1), feeding efficiency (e.g., PIK3CD, DNAJC28, DNAJC3, GHRL, PLAG1), coat color (e.g., MC1-R) and genetic disorders (e.g., ITGB6, PLAG1) were found to be under positive selection in Angus cattle. The study identified genes and pathways that are related to meat quality traits and other phenotypes of Angus cattle. The findings in this study, after validation using additional or independent dataset, will provide useful information for the study of Angus cattle in particular and beef cattle in general.
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PMID:Deciphering signature of selection affecting beef quality traits in Angus cattle. 2989 1

Gestational diabetes mellitus, the most frequent medical complication of pregnancy, affects 5-6% of women in the United States with the use of the currently predominant Carpenter-Coustan criteria, which still represent the preferred approach of the American College of Obstetricians and Gynecologists. Alternative criteria proposed by the International Association of Diabetes in Pregnancy Study Groups would likely increase gestational diabetes mellitus prevalence to 15-20%, because of both a 1-step testing policy and the requirement for only 1 elevated glucose value for diagnosis. Increasing gestational diabetes mellitus prevalence relates to older maternal age and the increasing prevalence of overweight and obesity. This increased gestational diabetes mellitus prevalence is consistent with 29.3% prevalence of prediabetes and 4.5% prevalence of known diabetes outside pregnancy in US adults from 20-44 years of age. Gestational diabetes mellitus according to the International Association of Diabetes in Pregnancy Study Groups criteria is associated with almost twice the risk of large-for-gestational-age babies, increased fetal adiposity, neonatal hyperinsulinemia and preeclampsia, and a 50% higher risk of preterm delivery and shoulder dystocia. The recent publication of the Hyperglycemia and Adverse Pregnancy Outcome Follow Up Study provides further evidence regarding the influence of gestational diabetes mellitus on long-term maternal and infant health. This study clearly demonstrates that hyperglycemia in pregnancy, untreated and identified post hoc by the International Association of Diabetes in Pregnancy Study Groups criteria, carries a 41.5% risk of maternal prediabetes (odds ratio, 3.72; 95% confidence interval, 3.09-4.47) and 10.7% risk of type 2 diabetes (odds ratio, 7.63; 95% confidence interval, 5.33-10.95) after 11.4 years of follow up. Gestational diabetes mellitus was also associated with higher rates of childhood overweight and obesity (prevalence 39.3% with maternal gestational diabetes mellitus; odds ratio, 1.5; 95% confidence interval, 1.56-2.44). This article places these findings in the context of other recent studies that have demonstrated that interventions that include lifestyle measures and/or metformin offer a >50% reduction in the risk of women with gestational diabetes mellitus experiencing the development of overt diabetes mellitus after their index gestational diabetes mellitus pregnancy. Although prevention of obesity and prediabetes in offspring by pregnancy treatment of gestational diabetes mellitus has not been demonstrated to date, we argue that the immediate pregnancy benefits and opportunities for long-term improvements in maternal health justify a reevaluation of the current ambivalent approach taken by the American College of Obstetricians and Gynecologists to gestational diabetes mellitus diagnosis, which currently allow for a choice of alternative criteria. The Carpenter-Coustan or National Diabetes Data Group criteria, listed as preferred criteria by American College of Obstetricians and Gynecologists, markedly limit the frequency of gestational diabetes mellitus in comparison with the International Association of Diabetes in Pregnancy Study Groups criteria and limit the opportunity for immediate and long-term follow up and treatment. We consider that new information from the Hyperglycemia and Pregnancy Outcome Follow Up Study and other recent publications on long-term maternal and offspring risk provides compelling arguments for a more comprehensive approach to the promotion of maternal and infant health through all the life cycle.
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PMID:Evidence in support of the International Association of Diabetes in Pregnancy study groups' criteria for diagnosing gestational diabetes mellitus worldwide in 2019. 3080 66

Objective: Both gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) are associated with increased risks of preeclampsia, macrosomia, shoulder dystocia, and irreversible brachial plexus injury (BPI). Compared to the conventional second trimester oral glucose tolerance test (OGTT), screening with the HbA1c assay in the first trimester with a diagnostic second trimester OGTT has been shown to diagnose more cases of T2DM and GDM earlier. Our study examined the effect of treatment based on varied positivity thresholds in high-risk pregnancies.Study design: A decision analysis model was created using TreeAge 2016 software to compare the outcomes of screening with an HbA1C in the first trimester verses no first trimester screening, with positivity thresholds ranging from 5.9 to 6.4%. Outcomes examined included neonatal mortality, preeclampsia, preterm delivery, cerebral palsy, macrosomia, permanent BPI, cost, and quality adjusted life years (QALYs) of the mother and neonate. Probabilities, utilities, and costs were derived from the literature, and a cost-effectiveness threshold was set at $100,000/QALY. Univariate analyses were used to investigate the impact of screening positivity.Results: First trimester screening was not cost-effective with an incremental cost effectiveness ratio of 5.87 when compared to screening with a positivity threshold of 6.4%. In a theoretical cohort of one million pregnancies, a screening threshold of 5.9% was the most cost-effective strategy. This strategy resulted in 2.999 million more QALYs, one less neonatal death, 346 fewer cases of preeclampsia, 66 less preterm deliveries, one less instance of cerebral palsy, and 615 fewer cases of macrosomia with nine less PBI cases. The 5.9% threshold provided an overall cost savings of $29.72 million.Conclusions: Screening for diabetes in high risk pregnancies with the HbA1c assay in the first trimester is not cost effective compared to no screening; however, if screening is preformed, 5.9% should be used as the positivity threshold for diagnosis and treatment.Brief rationale: With the increasing prevalence of diabetes mellitus among high-risk women in the USA, screening during pregnancy has become more important than ever. As a laboratory test, the HbA1c is relatively simple to obtain clinically, inexpensive, and its use has been well documented in the diagnosis and management of diabetes. However, there is limited data on its use in pregnancy and in particular during the first trimester. We sought to characterize the cost-effectiveness of screening with an HbA1c assay at various positivity thresholds for gestational diabetes mellitus and pre-existing type 2 diabetes in high-risk pregnancies in the first trimester. We found that this screening strategy is not cost-effective compared to no HbA1c in the first trimester and traditional oral glucose tolerance testing in the late second trimester. However, if screening is preformed, a positivity threshold of 5.9% should be used as the positivity threshold for diagnosis and treatment as it is associated with the best outcomes.
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PMID:Positivity thresholds of HbA1c assay as a screening test for diabetes mellitus in the first trimester in high-risk populations. 3214 61


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