Metformin versus glyburide in treatment and control of gestational diabetes mellitus: a systematic review with meta-analysis

ABSTRACT Objective To compare the major outcomes of use of metformin and glyburide in treatment of gestational diabetes mellitus. Methods Studies published in English, in the last 10 years, in the databases MEDLINE®, SciELO, LILACS and Cochrane Library were analyzed, and randomized controlled trials were selected. Health Sciences Descriptors were used to compose the search phrase, and the keywords "Gestational diabetes", "Glyburide", "Metformin" and their variations were searched in the Medical Subject Headings. PRISMA systematization was used to prepare this review, and a meta-analysis was conducted aiming to mathematically show the results of fasting blood glucose, postprandial blood glucose, birth weight and weight gain during pregnancy after using metformin and glyburide. Results The studies evaluated birth weight, neonatal hypoglycemia, mode of delivery, need for intensive care, Apgar score, macrosomia, fasting glucose, postprandial glucose and weight gain during pregnancy. In 60% of studies, there were no statistically significant differences regarding safety and efficacy of administration of metformin and glyburide. Meta-analysis demonstrated the absence of statistical differences between these drugs in fasting blood glucose (p=0.821), postprandial blood glucose (p=0.217) and birth weight (p=0.194). However, significant differences were shown in weight gain during pregnancy (p=0.036). Conclusion The methods are effective, but the adverse effects of glyburide are more common; therefore, the use of metformin should be recommended, if in monotherapy.

Antidiabéticos orais no diabetes gestacional: revisão de literatura / Oral antidiabetics in gestational diabetes: literature review

O diabetes mellitus gestacional (DMG) é um distúrbio metabólico por déficit na produção e/ou ação insulínica. Tem relação direta com um constante estado catabólico associado com maior resistência à ação da insulina. Doença de difícil controle, implica risco materno-fetal elevado. O objetivo é estudar a eficácia das drogas antidiabéticas orais sobre o controle glicêmico no DMG e sua segurança quanto aos desfechos gestacionais e perinatais. Trata-se de revisão de literatura descritiva baseada em dados de artigos, livros-texto e guidelines emitidos nos últimos cinco anos. O antidiabético oral pode ser uma boa alternativa no controle do DMG em fase inicial da doença, na presença de distúrbio metabólico e como complemento da terapia com insulina. Entretanto, por causa de sua passagem placentária, há preocupações com seus efeitos fetais e perinatais. Estudos comparativos destacam a metformina no manejo do DMG, considerando principalmente a segurança materno-fetal.(AU)

Gestational diabetes mellitus (GDM) is a metabolic disorder caused by deficit in production and/or insulin action. It is directly related to a constant catabolic state associated with greater resistance to insulin action. Disease difficult to control, implies high maternal-fetal risk. To study the efficacy of oral antidiabetic drugs on glycemic control in GDM and its safety regarding gestational and perinatal outcomes. Descriptive literature review based on data from articles, textbooks and guidelines issued in the last five years. Oral antidiabetic can be a good alternative in the control of GDM in the initial phase of the disease, in the presence of metabolic disorder and as a complement to insulin therapy. However, there are concerns about its placental passage and perinatal effects. Comparative studies highlight metformin in the management of DMG considering mainly maternal-fetal safety.(AU)

Tratamento para o diabetes mellitus gestacional: uma revisão de literatura / Treatment for gestational diabetes mellitus: a literature review

O diabetes mellitus gestacional (DMG) é uma complicação que atinge o metabolismo da gestante, resultando em intolerância à glicose e consequente hiperglicemia, originada pela insuficiência de insulina materna. Este estudo tem como objetivo identificar os tratamentos disponíveis e mais utilizados para o DMG. Trata-se de um uma revisão de literatura, feita a partir de 22 referências, acerca dos tratamentos para o DMG. As bases de dados escolhidas foram Google Acadêmico, UpToDate, SciELO e o acervo da Universidade do Planalto Catarinense. Estudos apontam a insulina humana ­ NPH e regular ­ como a principal escolha, quando comparada aos seus análogos, apesar de ainda existirem muitas controvérsias quanto ao início do tratamento, o esquema terapêutico e os ajustes das doses. Pesquisas têm demonstrado bons resultados sobre a eficácia e a segurança dos hipoglicemiantes orais ­ gliburida e metformina ­ no tratamento de gestantes diabéticas, mas é evidente a necessidade de mais estudos para confirmar a efetividade deles e garantir um bom desenvolvimento do concepto. Concluiu-se que o controle dietético e o exercício físico são a primeira opção de tratamento para o DMG. Todavia, caso a euglicemia não seja atingida, opta-se pelo tratamento medicamentoso por meio da insulinoterapia ou hipoglicemiantes orais, o que possibilita a redução da incidência dos efeitos adversos ao binômio materno-fetal.(AU)

Gestational diabetes mellitus (DMG) is a complication that affects the pregnant woman's metabolism, resulting in glucose intolerance and consequent hyperglycemia, caused by insufficient maternal insulin. This study aims to identify the available and most used treatments for DMG. This is a literature review, based on 22 references, about treatments for Gestational Diabetes; the databases chosen were Google Scholar, UpToDate, SciELO and the collection of the Universidade do Planalto Catarinense. Studies point to human insulin ­ NPH and regular ­ as the main choice when compared to its analogues, although there are still many controversies about the beginning of treatment, therapeutic scheme and dose adjustments. Researches have shown good results on the efficacy and safety of oral hypoglycemic agents ­ glyburide and metformin ­ in the treatment of diabetic pregnant women, but it is evident the need for further studies to confirm their effectiveness and to guarantee a good development of the fetus. It was concluded that dietary control and physical exercise are the first treatment option for DGM. However, if euglycemia is not achieved, drug treatment is chosen through insulin therapy or oral hypoglycemic agents, which makes it possible to reduce the incidence of adverse effects to the maternal-fetal binomial.(AU)

Caracterización clínica epidemiológica de la diabetes mellitus en dos áreas de salud. Municipio Cárdenas. 2017 / Clinico-epidemiological characterization of diabetes mellitus in two health areas. Municipality of Cardenas. 2017

RESUMEN Introducción: la diabetes mellitus es un trastorno metabólico caracterizado por hiperglucemia crónica con alteraciones en los carbohidratos, grasas y proteínas. Las tasas de morbimortalidad han aumentado al igual que la obesidad, constituye un problema de salud en el mundo, Cuba y la provincia de Matanzas. Objetivo: realizar una caracterización clínica epidemiológica de la diabetes mellitus tipo 2 en dos áreas de salud, conocer las variables e identificar las barreras para una posterior intervención. Materiales y métodos: se realizó un estudio epidemiológico descriptivo- transversal a 750 diabéticos tipo 2 mayores de 18 años en dos áreas de salud. Se realizaron encuestas, procesándose en el programa Epi-Info, obteniéndose la frecuencia de las variables, y las diferencias estadísticas significativas entre variables de las dos aéreas de salud, utilizándose el valor de p < 0,05 % y el Chi2. Resultados: el promedio de edad fue de 62,2 años, predominio del sexo femenino y color de la piel blanca. La hipertensión arterial y la obesidad fueron las enfermedades más asociadas, y el tabaquismo, la ingestión de bebidas alcohólicas y azucaradas, y la no realización de ejercicios físicos fueron los factores asociados más relevantes. Los medicamentos más utilizados fueron la glibenclamida y la metformina. Conclusiones: la diabetes mellitus es la primera causa de fracaso renal en el mundo occidental, siendo la insuficiencia renal una de las complicaciones crónicas más graves de esta enfermedad. Entre las principales causas de muerte de esta enfermedad son las complicaciones macrovasculares, manifestadas clínicamente como cardiopatía isquémica, insuficiencia cardíaca, la enfermedad vascular cerebral y la insuficiencia arterial periférica.

ABSTRACT Introduction: diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia with alterations in carbohydrates, fats and proteins. Morbi-mortality rates have increased as have done obesity, being a health problem in the world, Cuba and the province of Matanzas. Objective: to carry out clinical-epidemiological characterization of type 2 diabetes mellitus in two health areas, knowing the variables and identifying the barriers for a subsequent intervention. Materials and methods: a cross-sectional descriptive study was carried out in 750 type-2 diabetic patients over 18 years in two health areas. Surveys were made and processed in Epi-Info program, showing significant statistic differences among variables of both health areas; p < 0,05 % value and Chi2 were used. Results: the average age was 62.2 years, predominating female sex and white skin color. The most commonly associated diseases were arterial hypertension and obesity; smoking and drinking alcoholic and sugar-sweetened beverages and sedentary life were the most relevant associated factors. The most commonly used medications were glibenclamide and metformin. Conclusions: diabetes is the first cause of renal failure in the Western world, being renal insufficiency one of the most serious chronic complications of this disease. The main causes of death of this disease are macro vascular complications clinically manifested as ischemic heart disease, heart failure, cerebra-vascular disease and peripheral arterial insufficiency.

Granuloma anular, pronóstico de diabetes mellitus. A propósito de un caso / Annular granuloma, prognosis of diabetes mellitus. On the purpose of a case

RESUMEN El granuloma anular es una dermatosis de relativa frecuencia en niños, jóvenes y adultos. Está caracterizado por lesiones cutáneas eritemato-pápulo-nodulares, que adoptan una disposición anular. Su etiopatogenia es desconocida, pero con numerosos factores predisponentes, desencadenantes o asociados a ella; como es la diabetes mellitus y/o procesos neoplásicos o paraneoplásicos. Resulta importante el estudio de pacientes con este diagnóstico por su asociación con entidades como las antes mencionadas. Se realizó el reporte de un caso en adulto mayor de 65 años, con diagnóstico de granuloma anular, diabetes mellitus y neoplasia de páncreas.

ABSTRACT Annular granuloma is a dermatosis relatively frequent in children, young and adult people. It is characterized by erythematous-papular-nodular skin lesions adopting annular disposition. Its etio-pathogenesis is unknown, but there are many predisposal, unleashing factors, or associated to this disease, like diabetes mellitus and/or neoplastic or paraneoplastic processes. It is important to study the patients diagnosed with the disease due to its association with entities like those before mentioned. The reported case is the case of a patient elder than 65 years, diagnosed with annular granuloma, diabetes mellitus and pancreas neoplasia.

TeleCondutas: diabetes e gestação / TeleGuides: diabetes and gestation

Os quadros hiperglicêmicos que são diagnosticados na gravidez são classificados pela Organização Mundial da Saúde (OMS) em duas categorias: 1) "Diabetes Mellitus (DM) na gestação": hiperglicemia compatível com DM fora na gestação, mas que o diagnóstico é feito na gestação (overt Diabetes em inglês) e; 2) "Diabetes Mellitus Gestacional" (DMG): estado de hiperglicemia, em valores que não preenchem critérios para DM, usualmente diagnosticado após a metade da gestação e que tende a se resolver com o término da gestação. No Brasil, a prevalência de DMG no Sistema Único de Saúde (SUS) passou de 7,5% para 18%, conforme os critérios diagnósticos atuais. Tanto o DM na gestação quanto o DMG aumentam o risco de desfechos maternos e fetais graves, devendo, portanto, ser identificados, adequadamente tratados na Atenção Primária à Saúde (APS) e, quando indicado, nos serviços especializados em Pré-natal de alto risco. Esta guia apresenta informação que orienta a conduta para casos de diabetes e gestação no contexto da Atenção Primária à Saúde, incluindo: fatores de risco para dmg, classificação, rastreamento, tratamento dm gestacional, tratamento dm na gestação, controle glicêmico, avaliação pré-concepcional em diabéticas, avaliação complementar, momento e via de parto, acompanhamento pós-parto, encaminhamento para serviço especializado, referências anexo 1 - orientações nutricionais.

Seguridad cardiovascular de los antidiabéticos orales / Cardiovascular safety of oral antidiabetics

Resumen La Diabetes Mellitus tipo 2 (DM-2) es un equivalente de riesgo cardiovascular. Existe una gran variedad de fármacos para el control de la glicemia en los pacientes con DM-2, los cuales tienen diferencias en su perfil cardiovascular, unos han demostrado un beneficio en la reducción de riesgo de eventos cardiovasculares, otros tienen un efecto neutro, y en el caso de otros fármacos como las sulfonilureas y las tiazolinedionas existe dudas sobre su seguridad cardiovascular. Sien do DM-2 un equivalente de riesgo coronario, es fundamental tomar en cuenta el perfil de riesgo cardiovascular de estos medicamentos a la hora de iniciar alguna de estas drogas y no solo su eficacia para controlar los niveles de glicemia. El objetivo de esta revisión es comentar sobre los estudios más recientes que evalúan el riesgo cardiovascular con el uso de los distintos antidiabéticos orales.

Abstract Cardiovascular Safety of Oral Antidiabetics Diabetes Mellitus type 2 (DM-2) is an equivalent of cardiovascular risk. There is a wide variety of drugs for the glycemic control in patients with DM-2, which have differences in their cardiovascular profile, some have shown a benefit in reducing the risk of cardiovascular events, others have a neutral effect, and in the case of other drugs such as sulfonylurea and thiazolidinedione, there are doubts about their cardiovascular safety. Being DM-2 an equivalent of coronary risk, it is essential to consider the cardiovascular risk profile of these medicines when starting any of these drugs and not only their effectiveness in controlling glycaemia levels. The objective of this review is to comment on the most recent studies evaluating cardiovascular risk with the use of different oral antidiabetics.

Seguridad y eficacia de vildagliptina en el tratamiento de pacientes adultos mayores con diagnóstico de diabetes mellitus tipo 2, con riesgo de hipoglicemia y limitantes para uso de insulina (con alto grado de dependencia), sin control metabólico adecuado (según HBA1C) a pesar de tratamiento con metformina a dosis máxima y glibenclamida / Safety and efficacy of vildagliptin in the treatment of elderly patients with a diagnosis of type 2 diabetes mellitus, with risk of hypoglycemia and limitations of insulin use (with a high degree of dependence), without adequate metabolic control

INTRODUCCIÓN: Antecedentes: El Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) ha recibido la solicitud de evaluar el uso de vildagliptina para su uso en pacientes adultos mayores con diagnóstico de diabetes mellitus tipo 2, con riesgo de hipoglicemia y limitantes para uso de insulina (con alto grado de dependencia), sin control metabólico adecuado (según HBA1c) a pesar de tratamiento con metformina a dosis máxima y Glibenclamida dentro del sistema de EsSalud, indicación actualmente no contemplada en el petitorio de medicamentos. Generalidades: La diabetes mellitus tipo 2 (DM-2), forma que representa el 90-95% de los casos de diabetes. Es una enfermedad metabólica crónica que se caracteriza por la pérdida paulatina de la capacidad de secretar insulina a nivel de las células beta del páncreas así como por el aumento progresivo de la resistencia a la insulina, lo cual hace que los pacientes mantengan y eventualmente sufran las consecuencias de mantener niveles elevados de glucosa en su sangre. Como tal la DM-2 constituye una seria amenaza para la salud pública tanto a nivel mundial como en el Perú donde se prevé que pronto se convertirá uno de los principales contribuyentes a la carga de enfermedad en el país. Su incidencia en el Perú se encuentra en aumento. Tecnología Sanitaria de Interés: Los Inhibidores de DPP-4: Los inhibidores de DPP-4 son hipoglicemiantes orales que actúan como inhibidores reversibles de las enzima DPP-4 (dipeptidil peptidasa 4, EC 3.4.14.5), una enzima que está implicada en la inactivación de las hormonas incretinas GLP-1 (péptido similar al glucagón 1) y GIP (polipéptido insulinotrópico dependiente de la glucosa), ambas a su vez implicadas en la regulación fisiológica de la homeostasis de la glucosa. Descubiertos hace ya más de una década, a la fecha en el mercado internacional se disponen de más de ocho diferentes inhibidores de DPP-4. METODOLOGÍA: Estrategia de Búsqueda: El protocolo de esta revisión sistemática fue preparado y revisado con el equipo técnico de IETSI. Las siguientes fuentes han sido revisadas y consultadas: Medline/Pubmed, Embase, Scopus, Web of Science, Trip Database, The Cochrane Library, The National Institute for Health and Care Excellence (NICE) del Reino Unido, The National Guideline Clearinghouse (NCG) de los Estados Unidos, The International Diabetes Federation (IFD). RESULTADOS: uego de revisar un total de 837 documentos resultados de nuestra búsqueda bibliográfica, logramos filtrar 61 estudios relevantes para nuestra pregunta PICO de interés (Tabla 1), de los cuales sólo 8 fueron finalmente seleccionados para nuestro análisis toda vez que constituían estudios relevantes que resumían la mejor evidencia disponible (5 ensayos clínicos, 1 meta-análisis y una guía clínica) sobre la eficacia y seguridad atribuible al uso de un inhibidor de DPP-4 en regímenes de terapia doble (combinado con metformina) o triple (combinado con metformina y una sulfonilurea) comparados con metformina más una sulfonilurea en el manejo de pacientes con diagnóstico de diabetes mellitus de tipo 2. CONCLUSIONES: A la fecha no se puede recomendar el uso de inhibidores de DPP-4 como una alternativa tan o más eficaz y segura a la terapia combinada con metformina y una sulfonilurea, ya sea en regímenes de terapia doble (como reemplazo de la sulfonilurea) o triple (como un tercer hipoglicemiante oral adicional a este esquema de tratamiento) en el manejo de pacientes con diabetes mellitus tipo 2 con mal control metabólico no tributarios de manejo con insulina. La evidencia disponible sugiere que el uso de inhibidores de DDP-4 en un régimen doble (metformina más un inhibidor de DPP-4) si bien es una alternativa de tratamiento que se asocia con un riesgo igual o menor de eventos adversos que la terapia combinada con metformina y una sulfonilurea, no ofrece mayor beneficio en términos de eficacia; mientras que por el contrario, en el caso de la terapia triple (metformina más una sulfonilurea y un inhibidor de DPP-4) si bien sí constituye una alternativa de tratamiento más eficaz que la terapia combinada con metformina y una sulfonilurea se asocia con un mayor riesgo de eventos adversos asociados al tratamiento, y en particular con un mayor riesgo de eventos hipoglicémicos. Asimismo a la fecha, poco se sabe con respecto la seguridad del uso de inhibidores de DPP-4 al largo plazo, en cualquier régimen de tratamiento, desconociéndose en particular cuál puede ser impacto en el riesgo cardiovascular de los pacientes al largo plazo. En consecuencia, no podemos recomendar el uso de ningún inhibidor de DPP-4 en regímenes de terapia dual o triple, en el tratamiento de pacientes adulto mayores de 60 años con diagnóstico de DM-2, con riesgo de hipoglicemia y limitantes para uso de insulina (con alto grado de dependencia*), sin control metabólico adecuado (según HbAl c) con metformina a dosis máxima y Glibenclamida por cuanto no se disponen de evidencias suficientes para sobrepesar los beneficios con respecto a los riesgos al largo plazo que su uso pueda tener.

Permanent neonatal diabetes by a new mutation in KCNJ11: unsuccessful switch to sulfonylurea

Permanent neonatal diabetes (PNDM) can result from activating heterozygous mutations in KCNJ11 gene, encoding the Kir6.2 subunit of the pancreatic ATP-sensitive potassium channels (KATP). Sulfonylureas promote KATP closure and stimulate insulin secretion, being an alternative therapy in PNDM, instead of insulin. Male, 20 years old, diagnosed with diabetes at 3 months of age. The genetic study identified a novel heterozygous mutation in exon 1 of the KCNJ11 gene – KCNJ11:c1001G>7 (p.Gly334Val) – and confirmed the diagnosis of PNDM. Therefore it was attempted to switch from insulin therapy to sulfonylurea. During glibenclamide institution C-peptide levels increased, however the suboptimal glycemic control lead us to restart an intensive insulin scheme. This new variant of KCNJ11 mutation had a phenotypic lack of response to sulfonylurea therapy. Age, prior poor metabolic control and functional change of KATP channel induced by this specific mutation may explain the observed unsuccessful switch to sulfonylurea. Interestingly, C-peptide levels raise during glibenclamide administration support some degree of improvement in insulin secretory capacity induced by the treatment. Understanding the response to sulfonylurea is crucial as successful treatment may be life-changing in these patients.

Metformina y gliburida en el tratamiento de la diabetes gestacional / Metformin and glyburide in the treatment of gestational diabetes

INTRODUCCIÓN: La diabetes gestacional es una alteración de la tolerancia a la glucosa de severidad variable reconocida por primera vez en el embarazo en curso. La insulina ha sido el tratamiento farmacológico estándar para la diabetes gestacional, sin embargo la metformina y la gliburida son alternativas terapéuticas para el control de la glicemia. OBJETIVO: Determinar las ventajas de la metformina y la gliburida sobre la insulina en el tratamiento de la diabetes gestacional. MATERIALES Y MÉTODOS: Se realizó una búsqueda sistemática en las bases de datos Medline (PubMed) y Scielo. Los términos DeCS utilizados fueron: "Diabetes Gestacional", "Gliburida", y "Metformina" en diferentes combinaciones; sus homólogos MeSH fueron: "Diabetes, Gestational", "Glyburide" y "Metformin". La búsqueda obtenida incluyó 130 artículos, de los cuáles fueron seleccionados 53. RESULTADOS: La gliburida es un medicamento categoría C en el embarazo. Sus concentraciones en cordón umbilical son insignificantes y es considerado seguro. Su tasa de éxito para lograr el control de la glicemia c varía del 79% al 86%. La metformina es un medicamento categoría B en el embarazo. No ha mostrado efectos teratógenos en el primer trimestre del embarazo y logra un control de la glicemia en 24 horas. CONCLUSIONES: La metformina y la gliburida logran valores de control de glicemia en diabetes gestacional similares a la insulina y no aumentan la teratogénesis en el primer trimestre del embarazo. Las complicaciones perinatales por su uso deben ser más estudiadas

INTRODUCTION: Gestational diabetes is an impaired glucose tolerance of variable severity first recognized in the current pregnancy. Insulin has been the standard drug treatment for gestational diabetes, however metformin and glyburide are therapeutic alternatives to control glycemia. OBJECTIVE: Determine the advantages of metformin and glyburide over insulin in the treatment of gestational diabetes. MATERIALS AND METHODS: A systematic research was performed in the databases Medline (PubMed) and Scielo. The DeCS terms used were: "Diabetes Gestacional", "Gliburida", and "Metformina" in different combinations; MeSH counterparts were: "Diabetes, Gestational", "Glyburide" and "Metformin". The search obtained covered 130 articles, of which 53 were selected. RESULTS: Glyburide is a category C drug in pregnancy. Their concentrations in umbilical cord are insignificant and is considered safe. Its success rate to achieve glycemic control ranges from 79% to 86%. Metformin is a category B drug in pregnancy. It has shown no teratogenic effects in the first trimester of pregnancy. It achieves glycemic control in 24 hours. CONCLUSIONS: Metformin and glyburide achieved glycemic control values in gestational diabetes similar to insulin. They do not increase the teratogenesis in the first trimester of pregnancy. Perinatal complications from its use should be more studied

Uso de hipoglicemiantes orais em pacientes com Diabetes Mellitus gestacional / Oral hypoglycemic in patients with gestational Diabetes Mellitus

O Diabetes Mellitus Gestacional (DMG) é definido como intolerância a carboidratos com início ou diagnóstico durante a gestação. Em gestantes com DMG, é importante o controle da glicemia a fim de reduzir ou evitar efeitos adversos como abortamento, malformações congênitas e crescimento fetal anormal. Tradicionalmente, a insulina é usada como medicamento de escolha, segura para mãe e feto e eficaz no sentido de controlar os valores glicêmicos maternos. A Metformina é um hipoglicemiante oral que age aumentando a sensibilidade dos tecidos à insulinaNos estudos disponíveis, quando comparada à insulina, a Metformina mostra uma menor taxa de hipoglicemia neonatal grave, porém, não foi observada diferença significativa em relação a outros resultados perinatais, tal como prematuridade. A gliburida é um hipoglicemiante que aumenta a secreção de insulina pelas células beta pancreáticas. É uma droga bem tolerada e apresenta baixa taxa de hipoglicemia materna, em torno de 1,5% das pacientes. A gliburida mostrou eficácia semelhante à insulina em diversos estudos no controle glicemico. Mais estudos clínicos randomizados se fazem necessários no momento atual de discussão sobre os reais benefícios e riscos dessas drogas, a fim de definir seu papel efetivo no tratamento do DMG, consolidando ou não, sua recomendação e seu uso amplo.(AU)

Gestational Diabetes (GMD) is defined as carbohydrate intolerance with onset or first recognition during pregnancy. In pregnants, with GMD the glucose control is important to minimize the risk of miscarriage, fetal congenital malformations and macrossomia. Traditionally, insulin is used, since it does not cross the placenta, being considered safe for the woman and the fetus. Metformin is a hypoglycemic agent that acts as an insulin sensitizer, inhibits gluconeogenesis, suppresses hepatic glucose output and increase intestinal glucose absorption. It crosses the placenta, but it is not considered teratogenic. When compared with insulin, Metformin shows a lower incidence of severe neonatal hypoglycemia, with no difference in rates of other perinatal complications, as prematurity. Glyburide is a hypoglycemic that increases insulin secretion by pancreatic beta cells and sensitivity in peripheral tissues and reducing hepatic clearance of insulin. It shows similar efficacy of insulin on glucose control with a lower rate of maternal hypoglycemia, around 1.5% of patients. The glyburide showed similar efficacy to insulin in several studies in glycemic control. It is still suggested that the use of agent hypoglycemic on DMG can induce a lower maternal weight gain and more treatment adherence. More randomized clinical studies are required to ensure the real benefits and risks of these drugs, in order to define its use on GMD treatment.(AU)

Hipoglicemiantes orales para el tratamiento de la diabetes mellitus gestacional: revisión sistemática de la literatura / Oral hypoglycaemic agents for the treatment of gestational diabetes mellitus: systematic review of the literature

Antecedentes: la diabetes mellitus gestacional (DMG) se asocia a mayor riesgo materno y perinatal. El manejo habitual de ésta patología es la dieta, el ejercicio y la insulina. Los hipoglicemiantes orales (HGO) son una terapia emergente para el tratamiento de la DMG. Objetivos: realizar una revisión sistemática de toda la evidencia tipo I disponible acerca del uso de HGO para tratamiento de DMG y realizar un metaanálisis de los resultados maternos y perinatales significativos. Resultados: diez estudios cumplieron criterios de selección. Tres estudios comparaban metformina vs insulina, cuatro gliburide vs insulina y tres metformina vs gliburide. Los estudios no encontraron diferencias significativas en control glicémico ni en complicaciones perinatales entre metformina vs insulina, gliburide vs insulina y metformina vs gliburide. Nuestro metaanálisis mostró que la glicemia de ayuno es significativamente menor (DM 1,74; IC95 por ciento 0,383,10) y la glicemia postprandial a las 2 horas es significativamente mayor en el grupo insulina vs HGO (DM -2,97; IC95 por ciento -27,24 a -5,36). Nuestro metaanálisis muestra que la incidencia de fetos grandes para edad gestacional fue significativamente menor en el grupo metformina vs gliburide (OR 0,38; IC95 por ciento 0,18-0,78). El fracaso del tratamiento con gliburide fue significativamente menor que con metformina (27,6 por ciento vs 38,5 por ciento, p<0,0001; IC95 por ciento 1,21-1,60). Conclusión: los HGO son un tratamiento seguro y efectivo para DMG. Recomendamos gliburide (glibenclamida) para el tratamiento de las pacientes con DMG que fracasan su control glicémico con dieta y ejercicio, por no cruzar la placenta, tener menor tasa de fallo y ser igualmente efectiva que metformina.

Background: gestational diabetes mellitus (GDM) is associated to a higher maternal and perinatal risk. Usually GDM is controlled with diet, exercise and insulin. Oral hypoglycaemic agents (OHA) are an emergent therapy for the treatment of GDM. Objectives: conduct a systematic review of all class I evidence available regarding the use of OHA for GDM treatment, and perform a metaanalysis of significant maternal and perinatal outcomes. Results: ten studies accomplished inclusion criteria. Three studies compared metformin to insulin, four compared glyburide to insulin and three compared metformin to glyburide. Studies showed no significant differences in glycaemic control or perinatal complications, between metformin and insulin, between glyburide and insulin, or between metformin and glyburide. Our metaanalysis comparing OHA to insulin shows significantly lower fasting blood glucose (MD 1.74; 95 percent IC 0.38-3.10) and larger 2-hr postprandial glucose in the insulin group compared to OHA groups (MD -2.97; 95 percent IC -27.24-5.36). Our metaanalysis comparing shows a significantly lower incidence of large for gestational age in the metformin vs. gliburide group (OR 0.38; 95 percent IC 0.18-0.78). Failure of treatment was significantly lower using gliburide than metformin (27.6 percent vs. 38.5 percent, p<0.0001; 95 percent IC 1.21-1.60). Conclusion: OHA are a safe and effective treatment for GDM. We recommend the use of glyburide (glibenclamide) in GDM patients that fail to obtain glycemic control with diet and exercise, since glyburide does not crosses the placental barrier, has a lower rate of treatment failure and is equally affective as metformin.

Economic evaluation of outpatients with type 2 diabetes mellitus assisted by a pharmaceutical care service / Avaliação econômica de pacientes ambulatoriais portadores de diabetes melito tipo 2 assistidos por um serviço de atenção farmacêutica

OBJECTIVE: To analyze the costs related to visits and drug prescription in outpatients with type 2 diabetes mellitus assisted by a pharmaceutical care service. SUBJECTS AND METHODS: A prospective and experimental study was carried out. Seventy one patients were divided into two groups: control and pharmaceutical care. Patients in the pharmaceutical care group were followed up monthly by a single clinical pharmacist. RESULTS: The pharmaceutical care group had a statistically significant reduction in costs of metformin and emergency department visits, and increased costs with their family physicians. On the other hand, the control group had a statistically significant increase of 21.3 percent in the general costs of treatment and visits. CONCLUSION: The pharmaceutical care group maintained the same costs related to drugs and visits, while the control group showed a significant increase in general costs.

OBJETIVO: Analisar os custos relacionados a medicamentos e consultas em pacientes portadores de diabetes melito tipo 2 acompanhados por um programa de atenção farmacêutica. SUJEITOS E MÉTODOS: Estudo prospectivo e experimental foi realizado em 71 pacientes, os quais foram divididos em dois grupos: atenção farmacêutica e controle. Os pacientes do grupo atenção farmacêutica foram acompanhados mensalmente por um farmacêutico clínico. RESULTADOS: O grupo atenção farmacêutica apresentou redução estatisticamente significativa no custo da metformina e nas visitas de pronto atendimento e aumento no custo das consultas de atenção primária. Por outro lado, o grupo controle apresentou elevação estatisticamente significativa nos custos gerais de tratamento farmacológico e nas consultas em geral na ordem de 21,3 por cento. CONCLUSÃO: O grupo atenção farmacêutica apresentou manutenção dos custos relacionados a consultas e medicamentos, enquanto o grupo controle apresentou aumento destes.

Diabetes mellitus tipo 2 en adolescentes: reporte de tres casos / Type 2 diabetes mellitus in adolescents: Three cases report

Se reporta tres casos de pacientes adolescentes con diagnóstico de diabetes mellitus tipo 2 (DM2), un varón y dos mujeres, con características clínicas en común como obesidad, acantosis nigricans y malos hábitos alimentarios. El primero de ellos debutó con cetoacidosis diabética por lo que fue tratado con insulina; luego de un mes se suspendió la insulina y se indicó dieta y metformina, disminuyendo de peso y con glicemias normales. El segundo caso es una mujer que debutó con polidipsia, poliuria y polifagia, tratada con dieta y metformina la cual no fue tolerada por lo se cambió a glibenclamida y ya no presentó eventos adversos, cursa con Hb1Ac 6,3 por ciento y disminución de peso. El tercer caso es una mujer con síntomas de hiperglicemia, recibió insulina y educación, luego de tres meses se suspendió la insulina y se continuó sólo con dieta y ejercicios manteniendo niveles estables de glucosa. Este tipo de presentaciones que se observan con cierta frecuencia en adultos con debut de DM2 hay que tenerlo en cuenta en nuestros adolescentes con sobrepeso y obesidad ya que lo más probable es que se presenten otros casos similares a estos, porque la incidencia y prevalencia de obesidad se seguirá incrementando, y es donde hay que hacer prevención.

We report three cases of adolescent patients diagnosed with DM2, one male and two female, with clinical features in common as obesity, acanthosis nigricans and bad eating habits. The first one starts with diabetic ketoacidosis and was treated with insulin; one month later insulin was stopped and diet plus metformin were indicated, reaching decreased glycemia and a normal body weight. The second case was a female patient that debuts with polydipsia, polyphagia and polyuria, being treated with diet and metformin, and because of intolerance the latter was switched to glybenclamide, then reaching Hb1Ac 6,3 percent and a decreased body weight. The third case was a woman with symptoms of hyperglycemia, received insulin and education, and three months later insulin was stopped following up with only diet and exercise and normal glycemia. Such clinical presentations are seen with some frequency in debut of with adults diabetes mellitus type 2 and must be taken into account in the overweight and obese adolescents because it is likely that similar new cases will be presenting due to the increasing incidence and prevalence of obesity so prevention measures are needed.

Efecto del extracto atomizado de las hojas de Calophyllum brasiliense ôlagarto caspiõ sobre la glicemia / Effect of the atomized of calophylum brasiliense ôlagarto caspiõ leaves on the glycemia

OBJETIVO: Evaluar el efecto hipoglicemiante del Calophylum brasiliense. MATERIAL Y MÉTODO: Preparamos los extractos atomizado, acuoso, hexánico, diclorometánico, metanólico y etanólico de las hojas de Calophyllum brasiliense. La diabetes experimental fue inducida por administración intraperitoneal de 100 mg/kg de estreptozotocina. El efecto hipoglicemiante de Calophyllum brasiliense fue evaluado en ratas hiperglicémicas, con niveles de glucosa superiores a 300 mg/dLy la dosis usada fue 250, 500, 1000 y 1500 mg/kg, comparándolo con el grupo control negativo que recibió 10 ml de agua destilada vía oral y un grupo control positivo al que se le administró Glibenclamida a la dosis de 10 mg/Kg. Los valores de glucosa fueron determinados a las 1, 2, 3 y 4 horas, después de administrar los extractos y los controles. Finalmente el extracto atomizado fue fraccionado con el fin de caracterizar los principios activos de la planta. RESULTADOS: Observamos efecto hipoglicemiante una hora después de administrados los extractos. El mayor efecto observado con la dosis de 1000 mg/Kg, fue 69.28% superior a la Glibenclamida, duró todo el tiempo del experimento (4 horas), y demostramos la presencia de Calanólidas por Resonancia Magnética Nuclear (RMNH/RMNC). CONCLUSIONES: El extracto atomizado de Calophyllum brasiliense posee un buen efecto hipoglicemiante a la dosis de 1000 mg/Kg (100%), en comparación con Glibenclamida.

OBJETIVE: To evaluate the hypoglycemic effect of Calophylum brasiliense. MATERIALS AND METHOD: We prepared the atomized, aqueous, methanolic, hexanic, dicloromethanic and ethanolic, extracts from the leaves of Calophyllum brasiliense. The experimental diabetes was induced by intraperitoneal administration of 100 mg/kg of streptozotocin. The hypoglycemic effect of Calophyllum brasiliense was evaluated on hyperglycemic rats with levels of glucose higher than 300 mg/dL and the doses used were 250, 500, 1000 and 1500 mg/kg, compared with negative control group that received 10 ml of distilled water by mouth and the positive control group that received 10 mg of Glibenclamide. The blood glucose was determined at 1, 2, 3 and 4 hours after the administration of the extracts and the controls. Finally the atomized extract was fractioned in order to elucidate the active principles of the plant. RESULTS: We observed hypoglycemic effect since one hour after the administration of the extracts, the greatest effect was observed with the dose of 1000 mg/kg, even superior to Glibenclamide. The effect persisted all the time that we did the experiments (4 hours). We demonstrated the presence of calanolides with nuclear magnetic resonance (RMNH / RMNC). CONCLUSIONS: Our results indicate that Calophyllum brasiliense has a good hypoglycemic effect even superior to the Glibenclamide.

Diabetes gestacional: como tratar?: [revisão] / Gestational diabetes: how to treat?: [review]

O diabetes gestacional está associado a aumento do risco de complicações para o binômio materno-fetal e sua incidência é crescente. O tratamento específico é recomendado para reduzir complicações durante a gravidez, o parto e a vida adulta. O objetivo principal desta revisão foi pesquisar evidências acerca das opções de tratamento do diabetes gestacional, incluindo monitoramento glicêmico, dieta, exercícios físicos e, para algumas pacientes, farmacoterapia e conduta obstétrica específica, como antecipação do parto. A insulinoterapia é efetiva e segura, sendo considerada como o padrão-ouro de tratamento. Atualmente, são limitados os dados que embasam o uso dos análogos da insulina de ação prolongada durante a gravidez, porém, experiências recentes mostraram segurança da utilização do análogo de ação rápida lispro. Alguns estudos randomizados controlados têm demonstrado resultados promissores sobre a segurança e a eficácia dos antidiabéticos orais gliburida e metformina no tratamento das gestantes diabéticas. No entanto, devido a preocupações de longo prazo, maiores estudos randomizados controlados com metodologias comparáveis e, consequentemente, novas meta-análises serão necessárias para confirmar a segurança e a eficácia dessas drogas durante a gravidez e aumentar a sua aceitação na comunidade médica. O efeito do parto eletivo (indução ou cesárea) no prognóstico gestacional permanece indefinido.

Gestational diabetes is associated with an increased risk of complications both for the mothers and for her children, and its incidence has increased. Specific treatment is recommended in order to reduce risks during pregnancy, birth and adult life. This review's main objective was to analyze the evidences of the options for treatment of gestational diabetes, including glycemic monitoring, diet, physical exercises and, for some patients, pharmacotherapy and specific obstetric management such as anticipation of delivery. Insulin therapy is both effective and safe, qualities that make it the gold standard of treatment. Nowadays, there are limited data to support the use of long-acting insulin analogs, but recent studies reported that the rapid-acting analog lispro is safe. Some randomized controlled trials have demonstrated promising findings regarding safety and efficacy of the oral antidiabetics glyburide and metformin used for the treatment of diabetic pregnancies. However, because of long-term concerns, larger randomized controlled trials with comparable methodologies and, consequently, new meta-analysis are needed to confirm the safety and efficacy of these drugs during pregnancy and to gather widespread acceptability in the medical community. The effect of labor induction or elective cesarean on pregnancy prognosis remains unclear.

Chronic treatment with ethanolic extract of the leavesof Azadirachta indica ameliorates lesions of pancreatic islets in streptozotocin diabetes / Tratamiento crónico con extracto etanólico de hojas de Azadirachta indica disminuye las lesiones de los islotes pancreáticos en diabetes por estreptozotocina

Botanical drugs are complementary therapies in the management of diabetes mellitus. In this work, we studied the effects of chronic treatment of diabetic rats with A. indica (neem) on blood glucose, pancreatic islet histopathology, and oxidative status of the pancreas. Fifty-four Wistar rats (5-8 weeks old) were randomly assigned to 5 treatment groups. Hyperglycemia was induced in 34 fasted rats with a single i.p. injection of STZ (70 mg/kg bw/d). Ethanolic extract of A. indica leaves (500 mg/kg bw/d) was given orally to diabetic rats (n=12) for 50d. Glibenclamide was given (p.o) at 600 µg/ kg bw/d. In each group, blood glucose, islet histopathology, and pancreatic oxidative status, were assessed. All hyperglycemic rats in the neem-treated group had become normoglycemic at the end of week 2. By 50d, the number of viable b cells was highest in the neem-treated diabetic rats (compared with the diabetic and glibenclamide groups). Similarly, islet histology showed marked improvement in this group, in addition to improved oxidative stress. Our findings confirmed the hypoglycemic effect of neem. Besides, the improved islet morphology and oxidative status in neem-treated diabetic rats suggest the potential of this herb at improving lesions of the pancreatic islet in diabetes mellitus.

Los medicamentos a base de plantas son terapias complementarias en el manejo de la diabetes mellitus. En este trabajo se estudiaron los efectos del tratamiento crónico de ratas diabéticas con A. indica (Neem) sobre la glucosa de la sangre, la histopatología de los islotes pancreáticos, y el estado oxidativo del páncreas. Cincuenta y cuatro ratas Wistar (5-8 semanas de edad) fueron asignadas aleatoriamente a 5 grupos de tratamiento. La hiperglucemia fue inducida en 34 ratas en ayunas con una única inyección IP de STZ (70 mg/kg peso corporal/d). El extracto etanólico de hojas de A. indica (500 mg/kg de peso corporal/día) fue administrado por vía oral a ratas diabéticas (n=12) por 50d. Glibenclamida fue dada (PO) a 600 mg/kg peso corporal/d. En cada grupo, la glucosa en la sangre, la histopatología de los islotes, y el estado oxidativo de páncreas, se evaluaron. Todas las ratas de hiperglucemia en el grupo tratado con el Neem se habían convertido en normoglucémicas al final de la semana 2. Por 50d, el número de células b viables fue mayor en el Neem ratas tratadas con diabetes (en comparación con los grupos de diabéticos y glibenclamida). Del mismo modo, la histología de los islotes mostró una notable mejoría en este grupo, además de mejorar el estrés oxidativo. Nuestros resultados confirman el efecto hipoglucemiante de Neem. Además, la mejora de la morfología de los islotes y el estado de oxidación en el neem tratados con ratas diabéticas sugieren el potencial de esta hierba en la mejora de las lesiones de los islotes pancreáticos en la diabetes mellitus.

Hipoglicemiantes orais na gestação: metformina versus glibenclamida / Oral hypoglycemic agents in pregnancy: metformin versus glyburide

O diabetes gestacional é uma patologia frequente durante a gestação e com graves repercussões perinatais. Seu tratamento visa bom controle glicêmico, por dieta e atividade física, quando ocorre falha nesta terapêutica inicial está indicada insulinoterapia. Atualmente, na literatura mundial, vários estudos apresentam uma alternativa, os hipoglicemiantes orais, que sempre foram contraindicados durante a gestação, devido ao aumento da incidência de malformações, hipoglicemia neonatal e óbito, resultados estes baseados em estudos com pequena casuística, em série de casos ou caso-controle. Revisando a literatura foram encontrados vários estudos randomizados, controlados, com um grande número de casos, comparando a glibenclamida e a metformina com a insulinoterapia, mostrando que estas drogas são eficazes no controle glicêmico e não diferem da insulinoterapia quanto às complicações perinatais.(AU)

Gestational diabetes is a common condition during pregnancy with serious perinatal outcomes. The management of this disease aims to achieve adequate blood glucose control, through diet and regular exercises, in its failure insulin therapy can be indicated. In current literature, several studies offer an alternative to insulin therapy: oral hypoglycemic agents. These have always been counter-indicated during pregnancy because of increased incidence of malformations, hypoglycemia and neonatal death. These results were based on small scale studies, series of cases or case-control studies. A review of literature has shown several randomized, controlled, large-scale studies comparing the use of glyburide and metformin with insulin therapy. These studies have shown that these drugs are effective in controlling blood glucose and do not differ from insulin therapy regarding perinatal complications.(AU)

Glibenclamide unresponsiveness in a Brazilian child with permanent neonatal diabetes mellitus and DEND syndrome due to a C166Y mutation in KCNJ11 (Kir6.2) gene / Falha de resposta à glibenclamida em criança brasileira com diabetes melito neonatal permanente e síndrome DEND devido a mutação C166Y no gene KCNJ11 (Kir6.2)

Heterozygous activating mutations of KCNJ11 (Kir6.2) are the most common cause of permanent neonatal diabetes mellitus (PNDM) and several cases have been successfully treated with oral sulfonylureas. We report on the attempted transfer of insulin therapy to glibenclamide in a 4-year old child with PNDM and DEND syndrome, bearing a C166Y mutation in KCNJ11. An inpatient transition from subcutaneous NPH insulin (0.2 units/kg/d) to oral glibenclamide (1 mg/kg/d and 1.5 mg/kg/d) was performed. Glucose and C-peptide responses stimulated by oral glucose tolerance test (OGTT), hemoglobin A1c levels, the 8-point self-measured blood glucose (SMBG) profile and the frequency of hypoglycemia episodes were analyzed, before and during treatment with glibenclamide. Neither diabetes control nor neurological improvements were observed. We concluded that C166Y mutation was associated with a form of PNDM insensitive to glibenclamide.

As mutações ativadoras, heterozigóticas do gene KCNJ11 (Kir6.2) são a causa mais freqüente de diabetes melito neonatal permanente (DMNP) e a terapêutica oral com sulfoniluréias tem sido bem sucedida em muitos destes casos. Relatamos o processo de substituição da insulinoterapia convencional para o tratamento oral com glibenclamida em uma paciente de 4 anos, portadora de DMNP e síndrome DEND devido a uma mutação C166Y no gene KCNJ11. A insulina NPH (0,2 U/kg/dia) foi substituída pela glibenclamida (1 mg/kg/dia e 1,5 mg/kg/dia) durante internação hospitalar. As respostas de glicose e peptídeo-C no teste de tolerância oral à glicose (OGTT), os níveis de hemoglobina glicada, o perfil de glicemias capilares de 8 pontos e a freqüência de hipoglicemias foram comparados antes e durante o tratamento com glibenclamida. Não houve melhora no controle glicêmico, nem no quadro neurológico. Concluímos que a mutação C166Y associa-se a uma forma de DMNP insensível à glibenclamida.

Relationship between plasma leptin and plasma insulin levels in type-2 diabetic patients before and after treatment with glibenclamide and glimepiride.

Type 2 diabetes affects 100 million people throughout the world. Among the various factors implicated in the causation of this disease, the role of leptin, an obesity gene product, is increasingly being investigated. This especially assumes importance in the light of knowledge that obesity confers a minimum of 3-10 fold higher risk of diabetes. This study was planned to investigate the relationship between leptin and insulin levels in type 2 diabetic patients before and after treatment with glibenclamide or glimepiride. 60 type 2 diabetic patients were recruited for the study and were divided into 2 groups-one receiving glimepiride and the other group receiving glibenclamide for duration of 10 weeks. This study demonstrated a highly positive correlation of plasma leptin levels with BMI, plasma insulin and insulin resistance. No gender specific differences were observed in leptin concentrations. The study, however, failed to demonstrate any possible relationship between glycemic control as assessed by blood sugars/ glycosylated hemoglobin (HbAlc) and plasma leptin. The administration of glibenclamide or glimepiride significantly lowered blood glucose levels coupled with a decrease in (HbAlc). Both the drugs increased insulin concentrations. Glibenclamide increased leptin levels but they remained unaltered with glimepiride. Glibenclamide and glimepiride were found to be equally effective in their glucose lowering action. However, the patients receiving glibenclamide experienced higher episode of hypoglycaemic spells than those receiving glimepiride.