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.

Supplementation of Vitamin D in the Postdelivery Period of Women with Previous Gestational Diabetes Mellitus: Systematic Review and Meta-Analysis of Randomized Trials / Suplementacão da vitamina D no período pós-parto de mulheres com diabetes mellitus gestacional anterior: revisão sistemática de ensaios clínicos randomizados

Abstract Objective To evaluate the effects of vitamin D supplementation in the postpartum period of women with previous gestational diabetes mellitus (GDM). Methods Randomized clinical trials of pregnant women with GDM of any chronological, gestational age and parity, with no history of previous disease who received vitamin D supplementation in the prenatal and/or postpartum period and were evaluated in the postpartum period were included. The PubMed, EMBASE, Cochrane, and LILACS databases were consulted until July 2019. Serum vitamin D concentration (25- hydroxyvitamin D in nmol/L), fasting blood glucose, glycated hemoglobin, serum calcium concentration, homeostatic model assessment of insulin resistance (HOMAIR), quantitative insulin sensitivity check index (QUICKI), parathyroid hormone (PTH) and body mass index (BMI) were evaluated. Similar results in at least two trials were plotted using the RevMan 5; Cochrane Collaboration, Oxford, Reino Unido. The quality of the evidence was generated according to the classification, development, and evaluation of the classification of the recommendations. Results Four studies were included in the present review (200 women). The findings indicate that there is no difference in the postpartum period in women diagnosed with previous GDM who received vitamin D supplementation in the prenatal and/or in the postpartum period, showing only that there was a significant increase in the concentration of vitamin D (relative risk [RR]: 1.85; 95% confidence interval [CI]: 1.02-2.68). Conclusion This increase in the concentration of vitamin D should be interpreted with caution, since the assessment of the quality of the evidence was very low. For the other analyzed outcomes, there was no significance between the intervention and control groups, and the outcomes, when analyzed in their strength of evidence, were considered very low and low in their evaluation.

Resumo Objetivo Avaliar os efeitos da suplementação de vitamina D no pós-parto de mulheres com diabetes mellitus gestacional (DGM) anterior. Métodos Foram incluídos ensaios clínicos randomizados com gestantes com GDM de qualquer idade cronológica, gestacional e paridade, sem história de doença prévia, que receberam suplementação de vitamina D no pré-natal e/ou no pós-parto e foram avaliadas no pós-parto. As bases de dados consultadas foram PubMed, EMBASE, Cochrane e LILACS, até julho de 2019. Foram avaliados concentração sérica da vitamina D (25-hidroxivitamina D em nmol/L), glicemia de jejum, hemoglobina glicada, concentração sérica de cálcio, modelo de avaliação da homeostase de resistência à insulina (HOMA-IR, na sigla em inglês), índice qualitativo de verificação da sensibilidade à insulina (QUICKI, na sigla em inglês), hormônio da paratireoide (PTH) e índice de massa corpórea (IMC). Resultados semelhantes em pelo menos dois ensaios foram plotados no software RevMan 5; Cochrane Collaboration, Oxford, Reino Unido. A qualidade das evidências foi gerada de acordo com a classificação, o desenvolvimento e a avaliação da classificação das recomendações. Resultados Quatro estudos foram incluídos na presente revisão (200 mulheres). Os achados indicam que não há diferença no período pós-parto em mulheres com diagnóstico prévio de DMG que receberam suplementação de vitamina D no período pré-natal e/ou pós-parto, mostrando apenas que houve um aumento significativo na concentração de vitamina D (risco relativo [RR]: 1,85; IC [intervalo de confiança] 95%: 1,02-2,68). Conclusão Este aumento na concentração de vitamina D deve ser interpretado com cautela, uma vez que a avaliação da qualidade das evidências foi muito baixa. Para os demais desfechos analisados, não houve significância entre os grupos intervenção e controle, e os desfechos, quando analisados em sua força da evidência, foram considerados muito baixa e baixa em sua avaliação. PROSPERO CRD42018110729

Hyperglycemia in pregnancy: sleep alterations, comorbidities and pharmacotherapy

SUMMARY OBJECTIVE: To investigate sleep alterations and associated factors in pregnant diabetic women (n=141). METHODS: Sleep profile, sociodemographics and clinical information were collected. Poor sleep quality (Pittsburgh Sleep Quality Index >5) and excessive daytime sleepiness (Epworth Sleepiness Scale ≥10), sleep duration (h), sleep latency (min), frequent sleep interruption and short sleep (≤6 h) were assessed in type 1 diabetes mellitus (16.3%), type 2 diabetes mellitus (25.5%) and gestational diabetes mellitus (58.2%). RESULTS: Poor sleep quality was found in 58.8% of patients and daytime sleepiness in 25.7%, regardless of hyperglycemia etiology. No correlation existed between daytime sleepiness and poor sleep quality (Pearson correlation r=0.02, p=0.84). Short sleep duration occurred in 1/3 of patients (31.2%). Sleep interruptions due to frequent urination affected 72% of all and sleep interruptions due to any cause 71.2%. Metformin was used by 65.7% of type 2 diabetes mellitus and 28.7% of gestational diabetes mellitus. In gestational diabetes mellitus, parity number was independently associated with poor sleep quality (p=0.02; OR=1.90; 95%CI 1.07-3.36) and metformin use was also independently associated with poor sleep quality (p=0.03; OR=2.36; 95%CI 1.05-5.29). CONCLUSIONS: Our study originally shows that poor sleep quality and excessive daytime sleepiness are frequent in diabetic pregnancy due to different etiologies. Interestingly, only in gestational diabetes mellitus, metformin therapy and higher parity were associated with poor sleep quality.

Research Progress of the Effects of Vitamin D Supplementation on Glycemic Control and Adverse Maternal-neonatal Outcomes in Gestational Diabetes Mellitus Patients / 中国医学科学院学报

Gestational diabetes mellitus(GDM)can cause blood glucose disorders in pregnant women and result in adverse maternal-neonatal outcomes.Vitamin D(VD)can improve glucose tolerance and insulin sensitivity,and thus theoretically,VD supplementation during pregnancy could improve glycemic control as well as maternal-neonatal outcomes in GDM patients.Although studies have shown that VD deficiency is associated with poor maternal-neonatal outcomes in GDM patients,no solid conclusion has been drawn with regard to the effects of VD supplementation on these patients.Therefore,here we summarized the research progress of the effects of VD supplementation on glycemic control and adverse maternal-neonatal outcomes in GDM patients,in an effort to guide the clinical VD supplementation during pregnancy.

Effects of Vitamin D Supplementation on Serum Lipid Profiles and Neonatal Outcomes in Gestational Diabetes Mellitus:a Meta-analysis / 中国医学科学院学报

Objective To evaluate the effects of vitamin D supplementation on serum lipid profiles and neonatal prognosis in gestational diabetes mellitus(GDM)patients.Methods The electronic databases including PubMed,Web of Science,Embase,CNKI,and Wanfang Data were searched from inception to February 1,2020.All randomized controlled trials that compared vitamin D supplementation with placebo or without supplementation for GDM women were included.Paper selection,data extraction,meta-analysis and sensitivity analysis were conducted independently by two authors.Risk of bias was assessed using the Cochrane Risk of Bias Tool.The data were analyzed in RevMan 5.3 software and Stata 12.0.Results Totally 17 randomized controlled trials involving 1432 patients(704 in the intervention group and 728 in the control group)were included in the meta-analysis.The results showed that vitamin D supplementation significantly reduced serum total cholesterol [MD=-6.11,95% CI=(-7.17,-5.04)],low-density lipoprotein cholesterol [MD=-10.80,95% CI=(-14.72,-6.89)],and triglyceride [MD=-8.11,95% CI=(-10.09,-6.13)],while significantly increased serum 25-hydroxyvitamin D3 level [MD=45.45,95% CI=(41.98,48.92)] and high-density lipoprotein cholesterol [MD=2.77,95% CI=(1.59,3.96)].In addition,vitamin D supplementation significantly reduced the incidence rate of hyperbilirubinemia [RR=0.49,95% CI=(0.35,0.68)],premature birth [RR=0.44,95% CI=(0.27,0.72)],and neonatal hospitalization [RR=0.44,95% CI=(0.29,0.67)].Conclusions Vitamin D supplementation may regulate the serum lipid profiles in patients with GDM and reduce the incidence of adverse neonatal outcomes.More high-quality RCTs are needed to confirm the findings in our study.

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)

Factors associated with the need for insulin as a complementary treatment to metformin in gestational diabetes mellitus / Fatores associados à necessidade de insulina como tratamento complementar à metformina na diabetes mellitus gestacional

Abstract Objective To evaluate the factors associated with the need for insulin as a complementary treatment to metformin in pregnant women with gestational diabetes mellitus (GDM). Methods A case-control study was performed from April 2011 to February 2016 with pregnant women with GDM who needed complementary treatments besides diet and physical exercise. Those treated with metformin were compared with those who, in addition to metformin, also needed the combination with insulin. Maternal characteristics and glycemic control were evaluated. Multinomial logistic regression models were developed to evaluate the influence of different therapies on neonatal outcomes. Results A total of 475 pregnant women who needed pharmacological therapy were evaluated. Of these, 366 (77.05%) were submitted to single therapy with metformin, and 109 (22.94%) needed insulin as a complementary treatment. In the analysis of the odds ratio (OR), fasting glucose (FG)<90 mg/dL reduced the odds of needing the combination (OR: 0.438 [0.235-0.815]; p=0.009], as well as primiparity (OR: 0.280 [0.111-0.704]; p=0.007]. In obese pregnant women, an increased chance of needing the combination was observed (OR: 2,072 [1,063-4,039]; p=0,032). Conclusion Obesity resulted in an increased chance of the mother needing insulin as a complementary treatment to metformin, while FG<90 mg/dL and primiparity were protective factors.

Resumo Objetivo Avaliar os fatores associados à necessidade de insulina como tratamento complementar à metformina em gestantes com diabetes mellitus gestacional (DMG). Métodos Um estudo caso-controle foi realizado de abril de 2011 a fevereiro de 2016 comgestantes portadoras de DMG que necessitaram de tratamentos complementares além de dieta e exercícios físicos. Aquelas tratadas commetformina foram comparadas com aquelas que, além da metformina, também precisaram de combinação com insulina. Foram avaliadas as características maternas e de controle glicêmico. Modelos de regressão logística multinomial foram construídos para avaliar a influência das diferentes terapias nos desfechos neonatais. Resultados Foram avaliadas 475 gestantes que necessitaram de terapia farmacológica. Destas, 366 (77,05%) utilizaram terapia única com metformina, e 109 (22,95%) necessitaram de insulina como tratamento complementar. Na análise da razão de possibilidades (RP), a glicemia de jejum (GJ)<90mg/dL reduziu as chances de necessidade da combinação (RP: 0,438 [0,235-0,815]; p=0,009), bem como a primiparidade (RP: 0,280 [0,111-0,704]; p=0,007). Em gestantes obesas, foi observada uma chance maior de necessidade da combinação (RP: 2.072 [1.063-4.039]; p=0,032). Conclusão A obesidade resultou em um aumento na chance de a mãe precisar de insulina como tratamento complementar à metformina, enquanto a GJ<90 mg/dL e a primiparidade foram fatores de proteção.

Adherencia terapéutica y control glucémico en pacientes con diabetes gestacional bajo dos esquemas de tratamiento / Gestational diabetes adherence to treatment and metabolic control

Background: Adherence to treatment is a large obstacle in the management of chronic diseases. Aim: To evaluate therapeutic adherence and its relationship with glycemic control in patients with gestational diabetes using two types of treatment. Material and Methods: The Measurement of Treatment Adherence (MAT) questionnaire was applied to 93 patients with gestational diabetes. Fifty-two used metformin 41 were treated with insulin. Obstetric and socio-demographic data were collected. Results: A higher therapeutic adherence was associated with a better glycemic control. Women with a higher education level had a better adherence to treatment. The adherence and metabolic control were higher in women treated with metformin. Conclusions: Therapeutic adherence is an important factor for adequate glycemic control.

Effectiveness of insulin analogs compared with human insulins in pregnant women with diabetes mellitus: systematic review and meta-analysis / Efetividade dos análogos da insulina comparados às insulinas humanas em gestantes com diabetes mellitus: Revisão sistemática com metanálise

Abstract Diabetes during pregnancy has been linked to unfavorable maternal-fetal outcomes. Human insulins are the first drug of choice because of the proven safety in their use. However, there are still questions about the use of insulin analogs during pregnancy. The objective of the present study was to determine the effectiveness of insulin analogs compared withhuman insulin in the treatment of pregnant women with diabetes througha systematic review withmeta-analysis. The search comprised the period since the inception of each database until July 2017, and the following databases were used:MEDLINE, CINAHL, EMBASE, ISIWeb of Science, LILACS, Scopus, SIGLE andGoogle Scholar.We have selected 29 original articles: 11 were randomized clinical trials and 18 were observational studies.We have explored data from 6,382 participants. All of the articles were classified as having an intermediate to high risk of bias. The variable that showed favorable results for the use of insulin analogs was gestational age, with a mean difference of - 0.26 (95 % confidence interval [CI]: 0.03-0.49; p = 0.02), but with significant heterogeneity (Higgins test [I2] = 38%; chi-squared test [χ2] = 16.24; degree of freedom [DF] = 10; p = 0.09). This result, in the clinical practice, does not compromise the fetal well-being, since all babies were born at term. There was publication bias in the gestational age and neonatal weight variables. To date, the evidence analyzed has a moderate-to-high risk of bias and does not allow the conclusion that insulin analogs are more effective when compared with human insulin to treat diabetic pregnant women.

Resumo Diabetes durante a gestação tem sido relacionado a desfechos materno-fetais desfavoráveis. As insulinas humanas são a primeira escolha medicamentosa, devido à comprovada segurança no seu uso. Entretanto, ainda há questionamentos sobre o uso dos análogos da insulina na gestação. O objetivo do presente estudo foi determinar a efetividade dos análogos da insulina comparados às insulinas humanas no tratamento de gestantes com diabetes por meio de uma revisão sistemática com metanálise. A busca compreendeu desde o início de cada base de dados até julho de 2017, e foi realizada nos seguintes bancos de dados: MEDLINE, CINAHL, EMBASE, ISI Web of Science, LILACS, Scopus, SIGLE e Google Scholar. Selecionamos 29 artigos originais, sendo 11 ensaios clínicos randomizados e 18 estudos observacionais. Exploramos dados de 6.382 participantes. Todos os artigos foram classificados como sendo de intermediário a alto risco de viés. A variável que demonstrou resultado favorável ao uso dos análogos da insulina foi idade gestacional, com uma diferençamédia de - 0.26 (95% índice de confiança [IC]: 0.03-0.49; p = 0.02), porém com heterogeneidade significativa (teste de Higgins [I2] = 38%; teste do qui quadrado [χ2] =16.24; graus de liberdade [GL] =10; p = 0.09). Esse resultado, na prática clínica, não compromete o bem-estar fetal, uma vez que todos os bebês nasceram a termo. Houve viés de publicação nas variáveis idade gestacional e peso neonatal. Até o momento, as evidências analisadas possuem um risco de viés moderado a elevado e não permitem concluir que os análogos da insulina sejam mais efetivos em comparação às insulinas humanas para tratar gestantes diabéticas.

Insulinoterapia en situaciones especiales / Insulin therapy in special conditions

La hiperglucemia durante la internación es una condición frecuente que se asocia al aumento de complicaciones y resulta en un mal pronóstico para quienes la padecen. La estrategia para su tratamiento es la insulinoterapia. Un adecuado control glucémico se asocia a mejor evolución y pronóstico. Sin embargo, el nivel adecuado de glucemia se encuentra aún en debate, ya que aquellos ensayos en los cuales se fijaron metas estrictas demostraron incrementar las tasas de hipoglucemia y eventos clínicos adversos. La diabetes mellitus es la principal causa de enfermedad renal crónica en nuestro país. El tratamiento en ese contexto merece un análisis especial, ya que la vida media de la insulina puede resultar prolongada. Las opciones de insulinización en pacientes con enfermedad renal crónica e insuficiencia asociada provienen de recomendaciones de expertos en las cuales se jerarquizan esquemas que utilizan insulina de acción intermedia o prolongada asociadas a insulina regular o análogos de acción rápida. Durante el embarazo, las insulinas NPH y regular han demostrado seguridad y eficacia. Sin embargo, el desarrollo de nuevas moléculas de acción lenta y rápida permitió reducir la variabilidad glucémica, mejorar el control de la glucemia postprandial y reducir la tasa de hipoglucemias. El objetivo del presente trabajo es proporcionar una revisión sobre el adecuado uso de insulina en estas tres situaciones especiales.

Hyperglycemia during hospitalization is a common condition associated with poor prognosis. To date, insulin is the best strategy to treat hyperglycemia in these patients. An adequate glycemic control is associated with better clinical results. Nevertheless, glycemic goals are still controversial due to the increase of hypoglycemia and other adverse events. Diabetes mellitus is still the main cause of chronic renal failure in our country and its treatment deserves a special analysis considering that insulin pharmacokinetics is altered. Recommendations in this setting are based in expert panel opinions, focusing mainly in intermediate or long acting insulins combined with regular insulin and/or rapid acting analogues. During pregnancy, NPH and regular insulin are safe and effective. It is worth mentioning that the development of new long and rapid acting molecules yielded lower glycemic variability, better post-prandial control and less hypoglycemia. The aim of this study is to provide a review of the proper use of insulin in these special conditions.

Resultados maternos y perinatales en gestantes diabéticas que requirieron tratamiento insulínico / Maternal and Perinatal Outcomes in Diabetic Pregnant Women Who Required Insulin Treatment

Introducción: la diabetes mellitus representa un factor de riesgo para la mujer embarazada y un problema de salud para el producto. Objetivos: identificar los resultados maternos y perinatales en gestantes diabéticas que recibieron tratamiento insulínico. Métodos: se realizó una investigación de desarrollo, descriptiva, transversal en el Hospital Ginecobstétrico Mariana Grajales de Villa Clara, Cuba desde enero de 2013 hasta diciembre de 2014. La muestra quedó conformada de manera no probabilística por 111 pacientes diabéticas gestacionales y pregestacionales con tratamiento insulínico. Resultados: predominó la diabetes gestacional (58 por ciento de los casos) respecto a la pregestacional (42 por ciento). El primer grupo alcanzó un buen control metabólico. La mayoría de las pacientes tuvo recién nacidos con peso de 2 500 gr a 4 199 gr, presentándose la macrosomía fetal solo en 17,1 por ciento del total de pacientes. Los trastornos hipertensivos y la infección vaginal fueron las complicaciones maternas de más representatividad. La complicación perinatal con mayor incidencia fue el parto pretérmino, aunque sin significación estadística. Conclusiones: hubo predominio de la diabetes mellitus gestacional en más de la mitad de la muestra. Este grupo resultó ser el de mejor control metabólico respecto a la pregestacional. Los trastornos hipertensivos y la infección vaginal fueron las complicaciones más representativas y el parto pretermino resulto de mayor incidencia en la muestra. Predominaron los recién nacidos de peso adecuado(AU)

Introduction: Diabetes mellitus represents a risk factor for pregnant women and a health problem for the offspring. Objectives: Identify maternal and perinatal outcomes in diabetic pregnant women who received insulin treatment. Methods: A descriptive, cross-sectional research was conducted at Mariana Grajales Gyneco-Obstetric Hospital in Villa Clara, Cuba from January 2013 to December 2014. A hundred-eleven (11) gestational and pre-gestational diabetic patients with insulin treatment non-probabilistically formed the sample. Results: Gestational diabetes predominated (58 percent of cases) compared to pre-gestational diabetes (42 percent). The first group achieved good metabolic control. The majority of the patients had newborns weighing 2 500 g to 4 199 g, with fetal macrosomia only in 17.1 percent of the total patients. Hypertensive disorders and vaginal infection were the most representative maternal complications. The most frequent perinatal complication was preterm delivery, although there was no statistical significance. Conclusions: There was a predominance of gestational diabetes mellitus in more than half of the sample. This group turned out to be the one with the best metabolic control with respect to pre-gestational control. Hypertensive disorders and vaginal infection were the most representative complications and preterm birth resulted in a higher incidence in the sample. The newborns of adequate weight predominated(AU)

Neonatal outcomes according to different therapies for gestational diabetes mellitus / Desfechos neonatais de acordo com diferentes terapêuticas do diabetes mellitus gestacional

Abstract: Objectives: To compare different neonatal outcomes according to the different types of treatments used in the management of gestational diabetes mellitus. Methods: This was a retrospective cohort study. The study population comprised pregnant women with gestational diabetes treated at a public maternity hospital from July 2010 to August 2014. The study included women aged at least 18 years, with a singleton pregnancy, who met the criteria for gestational diabetes mellitus. Blood glucose levels, fetal abdominal circumference, body mass index and gestational age were considered for treatment decision-making. The evaluated neonatal outcomes were: type of delivery, prematurity, weight in relation to gestational age, Apgar at 1 and 5 min, and need for intensive care unit admission. Results: The sample consisted of 705 pregnant women. The neonatal outcomes were analyzed based on the treatment received. Women treated with metformin were less likely to have children who were small for gestational age (95% CI: 0.09-0.66) and more likely to have a newborn adequate for gestational age (95% CI: 1.12-3.94). Those women treated with insulin had a lower chance of having a preterm child (95% CI: 0.02-0.78). The combined treatment with insulin and metformin resulted in higher chance for a neonate to be born large for gestational age (95% CI: 1.14-11.15) and lower chance to be born preterm (95% CI: 0.01-0.71). The type of treatment did not affect the mode of delivery, Apgar score, and intensive care unit admission. Conclusions: The pediatrician in the delivery room can expect different outcomes for diabetic mothers based on the treatment received.

Resumo: Objetivos: Comparar diferentes desfechos neonatais de acordo com as diferentes modalidades de tratamento do diabetes mellitus gestacional. Métodos: Trata-se de uma coorte retrospectiva. A população do estudo foi composta por gestantes com diabetes gestacional atendidas em uma maternidade pública de julho de 2010 a agosto de 2014. Foram incluídas mulheres com idade mínima de 18 anos, gestação única e com critérios para diabetes mellitus gestacional. Para decisão terapêutica foram considerados glicemias, circunferência abdominal fetal, índice de massa corporal e idade gestacional. Os desfechos neonatais avaliados foram: via de parto, prematuridade, relação do peso com idade gestacional, Apgar no 1º e 5º minuto e necessidade de internação em unidade de terapia intensiva. Resultados: A amostra foi composta por 705 gestantes. Os desfechos neonatais foram analisados com base na terapêutica recebida. Mulheres tratadas com metformina tiveram menor chance de ter filhos pequenos para a idade gestacional (IC 95%: 0,09-0,66) e maior chance de ter um filho adequado para a idade gestacional (IC 95%: 1,12-3,94). A gestante tratada com insulina teve menor chance de ter um filho prematuro (IC 95%: 0,02-0,78). O tratamento feito com a associação de insulina e metformina resultou em maior chance de um recém-nascido grande para a idade gestacional (IC 95%: 1,14-11,15) e menor chance de prematuridade (IC 95%: 0,01-0,71). A modalidade de tratamento não interferiu na via de parto, Apgar e internação em terapia intensiva. Conclusões: O pediatra na sala de parto pode esperar diferentes desfechos para o filho de mãe diabética, com base no tratamento recebido.

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)

Uso de hipoglicemiantes orales durante la lactancia / Use of oral hypoglycemic agents during breastfeeding

Antecedentes: Los hipoglicemiantes orales son una alternativa emergente en el tratamiento de la diabetes mellitus gestacional (DMG), pero existe poca información acerca de su uso durante la lactancia. Objetivo: Revisar la evidencia respecto a la seguridad del uso de los hipoglicemiantes orales durante la lactancia. Resultados: Encontramos 3 trabajos que evaluaron el paso de metformina a la leche materna: hubo traspaso de metformina a leche materna en todos los casos. La concentración de metformina excretada a la leche fue en promedio 48 por ciento de la concentración plasmática materna. Las dosis calculadas que recibieron los lactantes en promedio fue 0,38 por ciento de la dosis materna, ajustada por peso. La concentración promedio de metformina en los lactantes fue de 0,025 mg/L. No se reportaron efectos adversos en los lactantes, incluso en el seguimiento a 6 meses de vida. Se encontró sólo un trabajo en relación a glibenclamida y lactancia materna, en el que no se detectó excreción del fármaco a la leche materna. Conclusiones: Los hipoglicemiantes orales parecen ser medicamentos seguros durante la lactancia, sin embargo, la evidencia es escasa. Sugerimos el uso de la glibenclamida por sobre metformina, por su nulo paso a la leche materna.

Background: Oral hypoglycemic agents are an emergent therapy for the treatment of gestational diabetes mellitus (GDM), but there is little information about its use during breastfeeding. Objectives: To review the available evidence regarding the use and safety of oral hypoglycemic agents during breastfeeding. Results: We found 3 studies that described the transfer of metformin to breast milk; there was transfer of metformin to breast milk in all cases. The concentration of metformin in breast milk was 48 percent of the maternal plasma concentration. The calculated dose for the infants was 0.38 percent of the maternal weight adjusted dose. The mean concentration of metformin in the infant's plasma was 0.025 mg/L. No adverse effects were reported in the infants, including 6 months of follow-up. Only one study investigated glyburide and breastfeeding, showing no excretion to breast milk. Conclusion: Oral hypoglycemic agents seem to be safe during breastfeeding; however, the available data is scarce. We suggest the use of glyburide over metformin because of its null excretion to breast milk.

Preditores de sucesso da metformina no tratamento do diabetes mellitus gestacional / Predictors of success of metformin treatment of diabetes mellitus in pregnancy

Identificar características maternas relacionadas à falha no tratamento do diabetes mellitus gestacional (DMG) com metformina. MÉTODOS: estudo retrospectivo observacional (julho/2008-setembro/ 2010), com 104 gestantes com DMG que necessitaram de terapêutica complementar a dietoterapia e utilizaram metformina. Dividiram-se em dois grupos: sucesso terapêutico (n=82), onde a droga foi mantida até o parto; outro com falha terapêutica (n=22) onde a droga foi substituída por insulina. Variáveis maternas estudadas: idade, número de partos, ganho de peso na gestação, glicemia de jejum (GJ) e 2h no OGTT75g, idade gestacional de diagnóstico de DMG (IGDMG). Variáveis do recém nascido: incidência de RNs GIG e hipoglicemia neonatal. Foram comparadas as características clínico-metabólicas maternas e os resultados perinatais, o nível de significância utilizado foi de 5 por cento. RESULTADOS: apresentaram diferença na IGDMG (27,5 vs 24,3 semanas; p=0,02), no índice de massa corporal (IMC) (27,5 vs 31,6 kg/m²; p=0,01), e GJ no OGTT75g (91,5 vs 108 mg/dL; p=0,02), nos grupos de sucesso e falha respectivamente. A falha terapêutica aumentou o índice ponderal dos RNs (2,8 vs 3 g/cm³; p=0,05), incidência de RNs GIG (4,9 vs 22,7 por cento; p=0,02) e hipoglicemia neonatal (6,1 vs 18,2 por cento; p=0,04). Os dados dos RNs foram objetivos secundários. CONCLUSÕES: o diagnóstico precoce, o maior IMC e maior GJ OGTT75g estiveram mais relacionados a falha terapêutica...

To identify characteristics of the mother related to failure of treatment of diabetes mellitus in pregnancy using metformin. METHODS: an observational retrospective study (July 2008- September 2010), with 104 pregnant women with pregnancy-related diabetes mellitus needing therapy to complement dietary treatment and using metformin. The women were divided into two groups: successful treatment (n=82), where the drug was maintained up to delivery; treatment failure (n=22) where the drug was replaced by insulin. The maternal variables studied were age, number of deliveries, weight gain during pregnancy, fasting glycaemia and two hours after OGTT75g, gestational age on diagnosis of diabetes mellitus. Variables relating to the newborn were incidence of GIG and neonatal hypoglycaemia. The clinical and metabolic characteristics of the mother and perinatal results were compared. The level of significance used was 5 percent. RESULTS: there were diferences in the gestational age on diagnosis of diabetes melittus (27.5 vs 24.3 weeks; p=0.02), body mass index (BMI) (27.5 vs 31.6 kg/m²; p=0.01), and fasting glycaemia on OGTT75g (91.5 vs 108 mg/dL; p=0.02), in the treatment success and failure groups, respectively. Treatment failure increased the weight index of newborns (2.8 vs 3 g/cm³; p=0.05), the incidence of GIG in RNs (4.9 vs 22.7 percent; p=0.02) and neonatal hypoglycaemia (6.1 vs 18.2 percent; p=0.04). The data on newborns were secondary objectives. CONCLUSIONS: early diagnosis, higher BMI and higher fasting glycaemia OGTT75g were more related to treatment failure...

Frequency of fear of needles and impact of a multidisciplinary educational approach towards pregnant women with diabetes / Frequência de medo de agulhas e impacto de uma abordagem educacional multidisciplinar em gestantes com diabetes

PURPOSE: To evaluate the frequency of fear of needles and the impact of a multidisciplinary educational program in women with pre-gestational and gestational diabetes taking insulin during pregnancy. METHODS: The short Diabetes Fear of Injecting and Self-testing Questionnaire (D-FISQ), composed by two subscales that access fear of self injection (FSI) and fear of self testing (FST), was administered twice during pregnancy to 65 pregnant women with pre-gestational and gestational diabetes: at the first endocrine consult and within the last two weeks of pregnancy or postpartum. An organized multidisciplinary program provided diabetes education during pregnancy. Statistical analysis was carried out by Wilcoxon and McNemar tests and Spearman correlation. A p<0.05 was considered to be significant. RESULTS: Data from the short D-FISQ questionnaire shows that 43.1% of pregnant women were afraid of needles in the first evaluation. There was a significant reduction in scores for FSI and FST subscales between the first and second assessments (first FSI 38.5% compared with second 12.7%, p=0.001; first FST 27.7% compared with second FST 14.3%, p=0.012). CONCLUSIONS: The fear of needles is common in pregnant women on insulin therapy and an organized multidisciplinary educational diabetes program applied during pregnancy reduces scores of such fear.

OBJETIVO: Avaliar a frequência do medo de agulhas e o impacto de um programa educacional multidisciplinar em mulheres com diabetes pré-gestacional e gestacional em uso de insulinas durante a gravidez. MÉTODOS: O questionário Diabetes Fear of Injecting and Self-testing Questionnaire (D-FISQ) resumido, composto por duas subescalas que acessam o medo de injeções (FSI) e o medo da automonitoração (FST), foi administrado duas vezes durante a gestação de 65 mulheres com diabetes pré-gestacional e gestacional: na primeira consulta endocrinológica e dentro das últimas duas semanas de gestação ou pós-parto. Durante a gravidez, as gestantes foram submetidas a um programa multidisciplinar sistematizado para prover educação em diabetes. A análise estatística foi realizada por meio dos testes de Wilcoxon e McNemar e a correlação de Spearman. Valor p<0,05 foi considerado como significativo. RESULTADOS: A aplicação do questionário D-FISQ resumido indicou que 43,1% das gestantes apresentavam medo de agulhas na primeira avaliação. Houve significativa redução nos escores das subescalas FSI e FST entre a primeira e segunda avaliação (primeiro FSI 38,5% comparado com o segundo 12,7%, p=0,001; primeiro FST 27,7% comparado com segundo FST 14,3%, p=0,012). CONCLUSÃO: O medo de agulhas é frequente em gestantes em uso de terapia com insulina, e um organizado programa multidisciplinar educacional em diabetes aplicado durante a gestação reduz os escores do medo.