RESUMO
This study was designed to evaluate the effectiveness of recombinant polypeptide-p derived from Momordica charantia on diabetic rats. In this research, the optimized sequence of polypeptide-p gene fused to a secretion signal tag was cloned into the expression vector and transformed into probiotic Saccharomyces boulardii. The production of recombinant secretion protein was verified by western blotting, HPLC, and mass spectrometry. To assay recombinant yeast bioactivity in the gut, diabetic rats were orally fed wild-type and recombinant S. boulardii, in short SB and rSB, respectively, at two low and high doses as well as glibenclamide as a reference drug. In untreated diabetic and treated diabetic + SB rats (low and high doses), the blood glucose increased from 461, 481, and 455 (mg/dl), respectively, to higher than 600 mg/dl on the 21st day. Whereas glibenclamide and rSB treatments showed a significant reduction in the blood glucose level. The result of this study promised a safe plant-source supplement for diabetes through probiotic orchestration.
Assuntos
Diabetes Mellitus Experimental , Probióticos , Saccharomyces boulardii , Ratos , Animais , Saccharomyces boulardii/genética , Saccharomyces cerevisiae/genética , Glicemia/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Glibureto/metabolismo , Glibureto/uso terapêutico , Peptídeos/metabolismo , Proteínas Recombinantes/metabolismo , Clonagem MolecularRESUMO
Cytoprotection has emerged as an effective therapeutic strategy for mitigating brain injury following acute ischemic stroke (AIS). The sulfonylurea receptor 1-transient receptor potential M4 (SUR1-TRPM4) channel plays a pivotal role in brain edema and neuroinflammation. However, the practical use of the inhibitor glyburide (GLB) is hindered by its low bioavailability. Additionally, the elevated reactive oxygen species (ROS) after AIS exacerbate SUR1-TRPM4 activation, contributing to irreversible brain damage. To overcome these challenges, GLB and superoxide dismutase (SOD) were embedded in a covalent organic framework (COF) with a porous structure and great stability. The resulting S/G@COF demonstrated significant improvements in survival and neurological functions. This was achieved by eliminating ROS, preventing neuronal loss and apoptosis, suppressing neuroinflammation, modulating microglia activation, and ameliorating blood-brain barrier (BBB) disruption. Mechanistic investigations revealed that S/G@COF concurrently activated the Wnt/ß-catenin signaling pathway while suppressing the upregulation of SUR1-TRPM4. This study underscores the potential of employing multi-target therapy and drug modification in cytoprotective strategies for ischemic stroke.
Assuntos
AVC Isquêmico , Estruturas Metalorgânicas , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/tratamento farmacológico , Estruturas Metalorgânicas/metabolismo , Estruturas Metalorgânicas/farmacologia , Doenças Neuroinflamatórias , Espécies Reativas de Oxigênio/metabolismo , Barreira Hematoencefálica , Glibureto/metabolismo , Glibureto/farmacologia , Glibureto/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismoRESUMO
OBJECTIVE: The purpose of this study was to describe the impact of enteral glyburide on cerebral edema formation and hypoglycemia when used to treat patients diagnosed with acute ischemic stroke (AIS). METHODS: This study was a single-center, retrospective medical record review that included all patients aged ≥18 years diagnosed with AIS who received ≥1 dose of enteral glyburide for the prevention of cerebral edema from January 1, 2018 to March 31, 2022. The primary outcome was the percentage of patients requiring intervention for cerebral edema management after glyburide initiation, and the safety outcome was the occurrence of hypoglycemia in this patient population. RESULTS: The final evaluation included 44 patients, with 6 patients (14%) requiring intervention for cerebral edema after glyburide initiation. The average baseline National Institutes of Health stroke scale score was 19. Overall, in-hospital mortality was 36% (n = 17), and hypoglycemia occurred in 7 patients (15%). Of the 44 patients, 20 (45%) received a partial duration of enteral glyburide (1-4 doses) and 24 (55%) received a full duration of enteral glyburide (5-7 doses). The rate of intervention for cerebral edema (10% vs. 17%) and the incidence of hypoglycemia (5% vs. 23%) were lower in the partial duration than in the full duration group. The in-hospital all-cause mortality rate was higher in the partial duration group than in the full duration group (43% vs. 31%). CONCLUSIONS: Despite the relatively low rates of intervention for cerebral edema, hypoglycemia was common, especially for patients receiving 5-7 doses of enteral glyburide for the prevention of cerebral edema after moderate-to-severe AIS.
Assuntos
Edema Encefálico , Glibureto , Hipoglicemiantes , AVC Isquêmico , Humanos , Edema Encefálico/prevenção & controle , Edema Encefálico/etiologia , Feminino , Masculino , Glibureto/uso terapêutico , Glibureto/administração & dosagem , AVC Isquêmico/prevenção & controle , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/administração & dosagem , Administração Oral , Idoso de 80 Anos ou mais , Hipoglicemia/prevenção & controle , Mortalidade Hospitalar , AdultoRESUMO
Diabetic renal injury is a microvascular complication associated with inflammation and oxidative stress, culminating in renal dysfunction. Conventionally, it is treated with hypoglycemic agents to address metabolic perturbations. However, the way to mitigate immunological, inflammation, and oxidative stress have seldom been studied. Hence, in the present study, the nephroprotective role of immunosuppressive and anti-inflammatory drugs, mycophenolate mofetil (MMF) in combination with the oral hypoglycemic agent glibenclamide, on streptozotocin (STZ)- induced diabetic renal damage was studied. Bodyweight, fasting blood glucose, and glycosylated hemoglobin levels were altered in the diabetic rats. Furthermore, renal injury was indicated by abnormal levels of urinary protein and creatinine and serum markers of renal function in diabetic rats. Hyperglycemia-induced oxidative stress and inflammation were also observed in the diabetic rats. The combination of MMF and glibenclamide treatment significantly attenuated the abnormal effects of hyperglycemia, oxidative stress, and inflammation-induced renal injury in diabetic rats. Histopathological studies confirmed the nephroprotective role of MMF and glibenclamide by reversing renal injury in diabetic rats. The present study suggests that MMF and glibenclamide have a protective role in STZ-induced diabetic renal damage.
Assuntos
Glicemia , Diabetes Mellitus Experimental , Nefropatias Diabéticas , Glibureto , Hipoglicemiantes , Rim , Ácido Micofenólico , Estresse Oxidativo , Ratos Wistar , Animais , Glibureto/farmacologia , Glibureto/uso terapêutico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Ácido Micofenólico/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Masculino , Nefropatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/tratamento farmacológico , Rim/efeitos dos fármacos , Rim/patologia , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Imunossupressores/farmacologia , Estreptozocina , Quimioterapia Combinada , Ratos , Biomarcadores/sangue , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêuticoRESUMO
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.
Assuntos
Humanos , Feminino , Gravidez , Diabetes Gestacional/tratamento farmacológico , Metformina/efeitos adversos , Metformina/uso terapêutico , Glicemia , Glibureto/efeitos adversos , Glibureto/uso terapêutico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêuticoRESUMO
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)
Assuntos
Humanos , Feminino , Gravidez , Complicações na Gravidez/tratamento farmacológico , Diabetes Gestacional/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Administração Oral , Fatores de Risco , Glibureto/uso terapêutico , Acarbose/uso terapêutico , Metformina/uso terapêuticoRESUMO
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)
Assuntos
Humanos , Feminino , Gravidez , Diabetes Gestacional/dietoterapia , Diabetes Gestacional/tratamento farmacológico , Diabetes Gestacional/terapia , Diabetes Mellitus/tratamento farmacológico , Exercício Físico , Bases de Dados Bibliográficas , Glibureto/efeitos adversos , Glibureto/uso terapêutico , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Insulina/uso terapêutico , Metformina/efeitos adversos , Metformina/uso terapêuticoRESUMO
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.
Assuntos
Humanos , Adulto , Fatores de Risco , Glibureto/uso terapêutico , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/etiologia , Diabetes Mellitus/mortalidade , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Metformina/uso terapêutico , Tabagismo/diagnóstico , Epidemiologia Descritiva , Estudos Transversais , Isquemia Miocárdica/mortalidade , Acidente Vascular Cerebral/mortalidade , Alcoolismo/diagnóstico , Insuficiência Renal/complicações , Comportamento Sedentário , Doença Arterial Periférica/mortalidade , Insuficiência Cardíaca/mortalidade , Hipertensão/diagnóstico , Obesidade/diagnósticoRESUMO
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.
Assuntos
Humanos , Masculino , Idoso , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Granuloma Anular/classificação , Granuloma Anular/complicações , Granuloma Anular/diagnóstico , Granuloma Anular/etiologia , Granuloma Anular/patologia , Granuloma Anular/tratamento farmacológico , Glibureto/uso terapêutico , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/etiologia , Diabetes Mellitus/tratamento farmacológico , Insulina/uso terapêutico , Pele/lesões , Seguimentos , Anamnese , Nevo/diagnósticoRESUMO
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.
Assuntos
Humanos , Glicemia , Glibureto/uso terapêutico , Tiazolidinedionas/uso terapêutico , Complicações do Diabetes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Rosiglitazona/uso terapêutico , Pioglitazona/uso terapêutico , Glipizida/uso terapêutico , Hipoglicemiantes , Metformina/uso terapêuticoRESUMO
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
Assuntos
Humanos , Feminino , Gravidez , Diabetes Gestacional/tratamento farmacológico , Glibureto/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Glicemia/análise , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/sangueRESUMO
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.
Assuntos
Humanos , Masculino , Adulto Jovem , Substituição de Medicamentos , Diabetes Mellitus/genética , Glibureto/uso terapêutico , Hipoglicemiantes/uso terapêutico , Mutação , Canais de Potássio Corretores do Fluxo de Internalização/genética , Compostos de Sulfonilureia/uso terapêutico , Glicemia/análise , Peptídeo C/sangue , Diabetes Mellitus/tratamento farmacológico , Falha de TratamentoRESUMO
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)
Assuntos
Feminino , Gravidez , Diabetes Gestacional/tratamento farmacológico , Glibureto/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Cuidado Pré-Natal , Bases de Dados Bibliográficas , Hipoglicemiantes/metabolismo , Insulina/efeitos adversosRESUMO
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.
Assuntos
Humanos , Feminino , Gravidez , Diabetes Gestacional/tratamento farmacológico , Glibureto/administração & dosagem , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Metformina/administração & dosagem , Administração Oral , Glibureto/uso terapêutico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Metformina/uso terapêuticoRESUMO
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.
Assuntos
Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , /tratamento farmacológico , Custos de Cuidados de Saúde/estatística & dados numéricos , Hipoglicemiantes/economia , Conduta do Tratamento Medicamentoso/economia , Estudos de Casos e Controles , /economia , Medicina de Família e Comunidade/economia , Glibureto/economia , Glibureto/uso terapêutico , Hipoglicemiantes/uso terapêutico , Insulina/economia , Insulina/uso terapêutico , Metformina/economia , Metformina/uso terapêutico , Estudos ProspectivosRESUMO
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.
Assuntos
Animais , Calophyllum , Diabetes Mellitus , Estreptozocina/uso terapêutico , Glibureto/uso terapêutico , GlucoseRESUMO
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.
Assuntos
Humanos , Feminino , Gravidez , Dieta para Diabéticos , Diabetes Gestacional/tratamento farmacológico , Diabetes Gestacional/terapia , Exercício Físico , Glibureto/uso terapêutico , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Insulina/uso terapêutico , Metformina/uso terapêutico , Cuidado Pré-Natal , Macrossomia Fetal/etiologiaRESUMO
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.
Assuntos
Animais , Ratos , Azadirachta/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Ilhotas Pancreáticas , Azadirachta/farmacologia , Diabetes Mellitus/tratamento farmacológico , Extratos Vegetais/farmacologia , Glibureto/uso terapêutico , Glicemia , Hipoglicemiantes , Ilhotas Pancreáticas/patologia , Peróxido de Hidrogênio/análise , Peróxidos Lipídicos/análise , Peso Corporal , Ratos Wistar , Superóxido Dismutase , Fatores de TempoRESUMO
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)
Assuntos
Humanos , Feminino , Gravidez , Diabetes Gestacional/tratamento farmacológico , /tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Bases de Dados Bibliográficas , Insulina/uso terapêutico , Administração Oral , Desenvolvimento Embrionário e Fetal , Glibureto/uso terapêutico , Metformina/uso terapêuticoRESUMO
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.