Pregestational Diabetes and Congenital Heart Defects / Diabetes pré-gestacional e defeitos cardíacos congênitos

Abstract Studies have consistently shown a significant increase in the risk of congenital heart defects in the offspring of diabetic mothers compared with those of nondiabetic pregnancies. Evidence points that all types of pregestational diabetes have the capacity of generating cardiac malformations in a more accentuated manner than in gestational diabetes, and there seems to be an increased risk for all congenital heart defects phenotypes in the presence of maternal diabetes. Currently, the application of some therapies is under study in an attempt to reduce the risks inherent to diabetic pregnancies; however, it has not yet been possible to fully prove their effectiveness. The present review aims to better understand the mechanisms that govern the association between pregestational diabetes and congenital heart defects and how maternal diabetes interferes with fetal cardiac development, as there is still a long way to go in the investigation of this complex process.

Resumo Estudos têm demonstrado consistentemente um aumento significativo no risco de defeitos cardíacos congênitos em filhos de mães diabéticas em comparação com os de gestações não diabéticas. Evidências apontam que todos os tipos de diabetes pré-gestacional têm capacidade de gerar malformações cardíacas mais acentuadas do que no diabetes gestacional e parece haver um risco aumentado para todos os fenótipos de cardiopatias congênitas na presença de diabetes materno. Atualmente, está em estudo a aplicação de algumas terapias na tentativa de diminuir os riscos inerentes à gravidez diabética; no entanto, ainda não foi possível comprovar totalmente a sua eficácia. A presente revisão visa compreender melhor os mecanismos que regem a associação entre diabetes pré-gestacional e cardiopatias congênitas e como o diabetes materno interfere no desenvolvimento cardíaco fetal, pois ainda há um longo caminho a percorrer na investigação deste processo complexo.

Protective effect of NeuroEPO on the reproduction of diabetic rats / Efecto protector de la NeuroEPO en la reproducción de ratas diabéticas

Introduction: Pregestational diabetes constitutes a reproductive risk which requires new treatment strategies. NeuroEPO, a variant of the recombinant human erythropoietin produced in Cuba, has neuroprotective and hypoglycemic effects which can be considered for the treatment of this entity. Objective: To evaluate the protective effect of NeuroEPO on the reproduction of diabetic rats. Material and Methods: Four groups of adult female Wistar rats with streptozotocin-induced diabetes were used. During pregnancy, one group received the vehicle and the rest of the groups received different doses of NeuroEPO (0,5 mg/kg, 0,75 mg/kg, and 1 mg/kg) subcutaneously, on alternate days, for a total of six applications. A group of non-diabetic rats was used as a control group. Glycemia and reproductive variables were evaluated. For comparisons, Analysis of Variance and Fisher's Exact Test were used. There were significant differences with p-values less than 0,05. Results: The group with vehicle presented maintained hyperglycemia, fewer implantations, and embryos, and increased gestational losses. In the group receiving 0,5 mg/kg of NeuroEPO, glycemia decreased significantly and the results of the reproductive variables were similar to the group of non-diabetic rats. With higher doses of NeuroEPO, gestational losses were increased. No congenital malformations were identified in either group. Conclusions: The repeated administration of 0,5 mg/kg of NeuroEPO has a beneficial effect on the reproduction of diabetic rats, which may be associated with the reduction of hyperglycemia. Other cytoprotective mechanisms of NeuroEPO should be evaluated in future studies(AU)

Introducción: la diabetes pre-gestacional constituye un riesgo reproductivo, lo que requiere nuevas estrategias de tratamiento. Teniendo en cuenta que la NeuroEPO, una variante de la eritropoyetina recombinante humana producida en Cuba, tiene efectos neuroprotectores e hipoglicemiantes. Objetivo: evaluar el efecto protector de la NeuroEPO en la reproducción de ratas diabéticas. Material y Métodos: se utilizaron cuatro grupos de ratas Wistar hembras adultas, con diabetes inducida por estreptozotocina. Durante la gestación, un grupo recibió el vehículo y el resto diferentes dosis de NeuroEPO (0,5 mg/kg, 0,75 mg/kg y 1 mg/kg), por vía subcutánea, en días alternos, para un total de seis aplicaciones. Se empleó un grupo de ratas no-diabéticas como control. Se evaluó la glicemia y variables reproductivas. Para las comparaciones se empleó el Análisis de Varianza y la Prueba Exacta de Fisher. Las diferencias se consideraron significativas con valores de p menores que 0,05. Resultados: el grupo con vehículo presentó hiperglicemia mantenida, menor número de implantaciones y embriones, e incremento de las pérdidas gestacionales. En el grupo que recibió 0,5 mg/kg de NeuroEPO, la glicemia disminuyó de forma significativa y los resultados de las variables reproductivas fueron similares al grupo de ratas no-diabéticas. Con las dosis superiores de NeuroEPO se incrementaron las pérdidas gestacionales. No se identificaron malformaciones congénitas en ninguno de los grupos. Conclusiones: la administración reiterada de 0,5 mg/kg de NeuroEPO tiene efecto beneficioso en la reproducción de ratas diabéticas, que puede estar asociado a la reducción de la hiperglicemia. Otros mecanismos citoprotectores de la NeuroEPO deben ser evaluados en futuros estudios(AU)

Repercussões do diabetes mellitus no feto: alterações obstétricas e malformações estruturais / Repercussions of diabetes mellitus in the fetus: obstetric changes and structural malformations

Atualmente o número de pessoas afetadas pelo diabetes mellitus (DM) está aumentando, principalmente devido ao aumento do envelhecimento populacional e de comorbidades como obesidade e hipertensão. Para o ano de 2030, é estimado que o DM seja a sétima doença mais prevalente e a sétima causa de morte no mundo. O DM pré-gestacional (DMPG) e o DM gestacional (DMG) podem causar danos ao desenvolvimento fetal e à saúde materna. O objetivo do presente estudo foi analisar a influência do DMPG e do DMG sobre o surgimento de complicações durante a gestação e no desenvolvimento de malformações congênitas (MCs). Foi realizada uma pesquisa de literatura no banco de dados do PubMed. Foram analisados estudos em humanos e animais, publicados entre janeiro de 2012 e junho de 2017. Foram encontradas 131 publicações, das quais 73 foram utilizadas. Os estudos analisados demonstraram que o DMPG e o DMG estão associados a um aumento das complicações gestacionais e ao risco de desenvolver MCs. O DMPG e o DMG estão associados a um aumento no risco de desenvolver MCs nos sistemas cardiovascular, nervoso, genital, esquelético e urinário. As malformações cardíacas são as mais relatadas; dentre as quais, destacam-se os defeitos septais. Esta revisão conclui que o DM na gravidez deve ser prevenido principalmente na fase de organogênese, por meio do controle de peso e do sedentarismo materno, com o diagnóstico precoce das alterações hiperglicêmicas, tendo o intuito de evitar uma epidemia de morbimortalidade em gerações afetadas pelo diabetes no período gestacional. (AU)

Currently the number of people affected by diabetes mellitus (DM) is increasing, mainly due to the increase of the aging population and of comorbidities such as obesity and hypertension. By the year 2030 it is estimated that DM is the seventh most prevalent disease and the seventh cause of death in the world. Pre-gestational DM (PGDM) and gestational DM (GDM) can cause damage to fetal development and maternal health. Objective of the present study was to analyze the influence of PGDM and GDM on the development of complications during pregnancy and the development of congenital malformations (MCs). A literature search was made on the PUBMED database. We analyzed human and animal studies, published between January 2012 and June 2017. We found 131 publications, of which 73 were used. Studies have shown that DMPG and DMG are associated with an increase in gestational complications and the risk of developing MCs. DMPG and DMG in pregnancy is associated with an increased risk of developing MCs in the cardiovascular, nervous, genital, skeletal, and urinary systems. Cardiac malformations are the most frequently reported, among which septal defects are prominent. This review concludes that DM in pregnancy should be prevented mainly in the organogenesis phase, with weight control and maternal sedentarism and with the early diagnosis of hyperglycemic alterations, in order to avoid an epidemic of morbidity and mortality in generations affected by diabetes in the gestational period.(AU)

Factores predisponentes y repercusión del accidente hipoglucémico en embarazadas diabéticas pre-gestacionales bajo tratamiento insulínico intensivo / Predisposing factors and impact of the hypoglycaemic accident on pregnant women with pregestational diabetes under intensive insulin treatment

Objetivo: analizar los factores que predisponen al accidente hipoglucémico durante el embarazo en diabéticas pre-gestacionales y su repercusión materna y perinatal. Métodos: se estudiaron retrospectivamente 175 embarazadas diabéticas pre-gestacionales (73 B, 22 C, 66 D, 4 F, 1 H, 5 R, y 4 F-R) en el período 2001-2006, todas estuvieron sometidas a tratamiento dietético e insulínico y este último aplicado según el método descrito por los profesores Valdés Amador y Márquez Guillén. Los resultados maternos y perinatales se analizan comparativamente entre las que sufrieron del accidente y las que no, para lo cual utilizamos el test X2 de Fisher con un significado de p< 0,05. RESULTADOS: se detectó un accidente hipoglucémico en 78 pacientes (44,6 por ciento), de ellas, calificado de leve en 54 (30,9 por ciento) y en 24 (13,7 por ciento) de grave. La frecuencia de hipoglucemia resultó significativamente más frecuente en las diabéticas tipo 1, de 25 años o menos, nulíparas, con bajo o normo peso corporal y algún grado de lesión vascular presente. No detectamos repercusión en morbi-mortalidad perinatal, ni anomalías congénitas por motivo de la complicación. Conclusiones: las embarazadas diabéticas tipo 1, con algún grado de lesión vascular y de bajo o normo peso corporal son más propensas al accidente muy probablemente por la reportada pérdida de la reacción hormonal contrarregulatoria.

Objective: to analyze the factors predisposing the hypoglycaemic accident during pregnancy in pregestational diabetic women and its maternal and perinatal repercussion. Methods: 175 pregnant women affected by pregestational diabetes (73 B, 22 C, 66 D, 4 F, 1 H, 5 R, y 4 F-R) were retrospectively studied from 2001 to 2006. All of them were under dietetic and insulin treatment. The latter was applied by the method described by professors Valdés Amador and Márquez Guillén. The maternal and perinatal results were comparatively analyzed among those who suffered the accident and those who did not, for which we used Fisher's chi square test with a significance of p< 0.05. RESULTS: a hypoglycaemic accident was detected in 78 patients (44.6 percent). It was mild in 54 (30.9 percent) and severe in 24 (13.7 percent). Hypoglycaemia was more significantly frequent in type-1 diabetic women aged 25 or under, nuliparous, with low or normal body weight and with some grade of vascular lesion. No impact was detected on perinatal morbimortality, and no congenital anomalies were observed as a result of the complication. Conclusions: type-1 diabetic women with some grade of vascular lesion and with low or normal body weight are proner to the accident due very probably to the reported loss of counterregulatory hormonal reaction.