RESuMO tanto a bomba de infusão de insulina quanto a terapêutica de múltiplas doses de insulina (Mdi) são meios efetivos de implementar o manejo intensivo do diabetes melito tipo 1 (dM1), com o objetivo de chegar a níveis glicêmicos quase normais e obter-se um estilo de vida mais flexível. A terapia com bomba de infusão de insulina é tão segura quanto a Mdi e tem vantagens sobre ela, sobretudo em pacientes com hipoglicemias freqüentes, com um fenôme-no do alvorecer importante, com gastroparesia, na gravidez, em crianças e em pacientes com dM1 e com um estilo de vida errático. A terapia com bomba de infusão de insulina possibilita maior probabilidade de se alcançar melhor controle glicêmico com menos hipoglicemia, hipoglicemias assintomáticas e melhor qualidade de vida. Além disso, os riscos e os efeitos adversos da terapêutica insulínica em pacientes com dM1 em insulinização intensiva são menores nos pacientes usando esta terapia, quando comparados a pacientes em Mdi. Para tal, o ajuste cuidadoso das doses basais e de bólus e o seguimento adequado do paciente são vitais. Both continuous subcutaneous insulin infusion (csii) and Multiple daily injections (Mdi) are effective ways of implementing intensive management of dM1 to attain near normal glycemic levels and a more flexible lifestyle. csii is as safe as Mdi and has some advantages over it mostly in diabetic patients with frequent hypoglycemias with important dawn phenomenum, gastroparesia, during pregnancy, in children and in patients with an erratic way of living. csii allows a better chance to reach better glycemic control with less hypoglycemia, asymptomatic hypoglycemias and a better quality of life. Besides, risks are lower and adverse events are less frequent in dM1 patients under csii as compared to Mdi. to obtain results like this, a careful adjustment of basal and boluses insulin doses and an adequate patient follow-up are essential. (Arq Bras Endocrinol Metab 2008;52/2:340-348)

Consenso Brasileiro sobre antipsicóticos de segunda geração e distúrbios metabólicos Brazilian Consensus on second-generation antipsychotics and metabolic disorders

IntroductionStrict glucose control using multiple doses of insulin is the standard treatment for type 1 diabetes mellitus (T1DM), but increased risk of hypoglycemia is a frequent drawback. Regular insulin in multiple doses is important for achieving strict glycemic control for T1DM, but short-acting insulin analogues may be better in reducing hypoglycemia and postprandial glucose levels.ObjectiveWe conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effects of short-acting insulin analogues vs regular human insulin on hypoglycemia and postprandial glucose in patients with T1DM.MethodsSearches were run on the electronic databases MEDLINE, Cochrane-CENTRAL, EMBASE, ClinicalTrials.gov, LILACS, and DARE for RCTs published until August 2017. To be included in the study, the RCTs had to cover a minimum period of 4 weeks and had to assess the effects of short-acting insulin analogues vs regular human insulin on hypoglycemia and postprandial glucose levels in patients with T1DM. Two independent reviewers extracted the data and assessed the quality of the selected studies. The primary outcomes analyzed were hypoglycemia (total episodes, nocturnal hypoglycemia, and severe hypoglycemia) and postprandial glucose (at all times, after breakfast, after lunch, and after dinner). Glycated hemoglobin (HbA1c) levels and quality of life were considered secondary outcomes. The risk of bias of each RCT was assessed using the Cochrane Collaboration Risk of Bias table, while the quality of evidence for each outcome was assessed using the GRADEpro software. The pooled mean difference in the number of hypoglycemic episodes and postprandial glucose between short-acting insulin analogues vs. regular human insulin was calculated using the random-effects model.ResultsOf the 2897 articles retrieved, 22 (6235 patients) were included. Short-acting insulin analogues were associated with a decrease in total hypoglycemic episodes (risk rate 0.93, 95% CI 0.87–0.99; 6235 patients; I2 = 81%), nocturnal hypoglycemia (risk rate 0.55, 95% CI 0.40–0.76, 1995 patients, I2 = 84%), and severe hypoglycemia (risk rate 0.68, 95% CI 0.60–0.77; 5945 patients, I2 = 0%); and with lower postprandial glucose levels (mean difference/MD − 19.44 mg/dL; 95% CI − 21.49 to − 17.39; 5031 patients, I2 = 69%) and lower HbA1c (MD − 0,13%; IC 95% − 0.16 to − 0.10; 5204 patients; I2 = 73%) levels.ConclusionsShort-acting insulin analogues are superior to regular human insulin in T1DM patients for the following outcomes: total hypoglycemic episodes, nocturnal hypoglycemia, severe hypoglycemia, postprandial glucose, and HbA1c.Electronic supplementary materialThe online version of this article (10.1186/s13098-018-0397-3) contains supplementary material, which is available to authorized users.

RESUMOObjetivos: Avaliar o crescimento e a composição corporal de diabéti-cos tipo 1, pré-púberes, em relação à idade de início e tempo da doença, sexo, dose de insulina e hemoglobina glicada média. Pacientes e métodos: Foram incluídas no estudo 59 crianças diabéticas (30 M; 29 F), entre 1,2 e 11,5 anos, e 67 controles (36 M; 31 F), entre 1,2 e 11,7 anos. Peso, altura, IMC, perímetro braquial, pregas cutâneas e áreas de massa gorda e muscular braquial foram avaliados e transformados em escore z. Resultados: Verificou-se que entre os diabéticos a média de escore z de altura foi -0,13 (± 0,97), enquanto no grupo controle foi de 0,28 (± 0,86) (p= 0,013). A diferença entre os escores de altura inicial e atual mostrou perda estatural (p< 0,001) e a análise multivariada demonstrou associação com tempo de doença. Também observouse diferença na área de gordura braquial (p< 0,001). As médias de escore z de peso, IMC, soma de 3 dobras e área muscular braquial não diferiram entre os grupos. Conclusões: As crianças diabéticas apresentaram perda de estatura durante o período de acompanhamento e eram significativamente mais baixas que os controles, embora suas alturas ainda estivessem dentro dos padrões de normalidade. Também mostraram área de gordura braquial aumentada em relação aos controles. Objective: To evaluate the growth and body composition of pre-pubertal diabetic children, and to check for influence of the age of diabetes onset and length, sex, insulin requirement and glycosylated hemoglobin. Patients and methods: 59 diabetic children (39 M; 29 F), age 1.2-11.5 years, and 67 controls (36 M; 31 F), age 1.2-11.7 years were included. Weight, height, body mass index (BMI), arm circumference, skin folds, fat mass and muscle areas were evaluated and transformed into standard deviation scores (SDS). Results: Among the diabetic children the mean height SDS was -0.13 (± 0.97) while in the control group it was 0.28 (± 0.86) (p= 0.013). The difference between the first and the current height SDS showed that the height SDS decreased significantly (p< 0.001) and multiple regression analysis indicated correlation with the duration of the disease. The mean arm fat SDS also revealed difference (p< 0.001). The means for weight, BMI, addition of 3 skinfolds and muscle mass did not demonstrate difference between the groups. Conclusions: The diabetic children showed reduction of height SDS during the period studied and they were significantly shorter than the controls, even though their statures were within the population standards. The arm fat area also showed to be increased in relation with the controls.

BackgroundPermanent neonatal diabetes mellitus (PNDM) is a rare disorder, characterized by uncontrolled hyperglycemia diagnosed during the first 6 months of life. In general, PNDM has a genetic origin and most frequently it results from heterozygous mutations in KCNJ11, INS and ABCC8 genes. Homozygous or compound heterozygous inactivating mutations in GCK gene as cause of PNDM are rare. In contrast, heterozygosis for GCK inactivating mutations is frequent and results in the maturity-onset diabetes of young (MODY), manifested by a mild fasting hyperglycemia usually detected later in life. Therefore, as an autosomal recessive disorder, GCK-PNDM should be considered in families with history of glucose intolerance or MODY in first relatives, especially when consanguinity is suspected.ResultsHere we describe two patients born from non-consanguineous parents within a family. They presented low birth weight with persistent hyperglycemia during the first month of life. Molecular analyses for KCNJ11,INS, ABCC8 did not show any mutation. GCK gene sequencing, however, revealed that both patients were compound heterozygous for two missense combined in a novel GCK-PNDM genotype. The p.Asn254His and p.Arg447Gly mutations had been inherited from their mothers and fathers, respectively, as their mothers are sisters and their fathers are brothers. Parents had been later diagnosed as having GCK-MODY.ConclusionsMutations’ in silico analysis was carried out to elucidate the role of the amino acid changes on the enzyme structure. Both p.Asn254His and p.Arg447Gly mutations appeared to be quite damaging. This is the first report of GCK-PNDM in a Brazilian family.