SUMMARY Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic forms of diabetes mellitus with distinct clinical features. Clinical dermatological phenotypes in MODY patients are very rare in literature. This report describes a patient with HNF1A-MODY presenting with necrobiosis lipoidica (NL) and granuloma annulare (GA). A 39-year-old asymptomatic woman, with atypical diabetes diagnosed at age 17, has a confirmed HNF1A mutation on exon 2 (c.392G>A, p.R131Q), classified as Pathogenic by the ACMG guidelines. She has reasonable metabolic control using oral anti-diabetic medications and has no chronic diabetic complications. Clinical and histologic diagnoses of both NL and GA were made. We discuss these conditions and their association with MODY.

RESUMO O objetivo deste estudo foi comparar resinas compostas bulk- -fill de baixa e alta viscosidade quanto à microdureza Knoop (KHN), resistência de união a microtração (MTBS) em cavidades oclusais e carga à fratura (FS) em molares com restauração mesio-oclusal-distal. Amostras em forma de disco com diferentes espessuras (2 ou 4 mm) de resinas bulk-fill de baixa viscosidade (SDR Flow, Dentsply) e alta viscosidade (Filtek BulkFill, 3M ESPE; e Tetric-N Ceram Bulk Fill, Ivoclar Vivadent) foram obtidas para análise de KHN no topo e na base (n = 10). A MTBS em dentina e o padrão de fratura foram avaliados em molares humanos com cavidades oclusais restauradas com (n = 10): resina composta nanoparticulada convencional (Z350XT, 3M ESPE), resinas bulk-fill de baixa viscosidade (Filtek Bulk-fill Flow, 3M ESPE) ou alta viscosidade (Filtek BulkFill). Foram investigados a FS e o padrão de fratura de molares humanos em restaurações mesial-ocluso-distais sub metidas ou não à ciclagem termomecânica (n = 10), sendo: dente íntegro (controle), e restaurações baseadas em resina composta microhíbrida convencional (Z250, 3M ESPE); resinas bulk-fill de baixa viscosidade (SDR Flow) ou alta viscosidade (Filtek BulkFill). Os dados foram submetidos a split-plot ANOVA (KHN), one-way ANOVA (MTBS), two-way ANOVA (FS) seguidos do teste de Tukey (α = 0,05). Para KHN, não houve diferença significativa entre o topo e a base para as resinas compostas. Para MTBS, não foram detectadas diferenças significativas entre os materiais; entretanto, a resina bulk-fill de baixa viscosidade apresentou menor frequência de falhas adesivas. Para FS, não houve diferença significativa entre os materiais e o dente íntegro, independentemente da ciclagem termomecânica. As resinas bulk-fill de baixa e alta viscosidade têm microdureza e resistência à microtração comparáveis quando usados em restaurações oclusais. Da mesma forma, as resinas bulk-fill apresentam resistência à fratura semelhante em molares com restaurações mesio-oclusal-distais.

ABSTRACT The aim of this study was to compare low- and high-viscosity bulk-fill composites for Knoop microhardness (KHN), microtensile bond strength (MTBS) to dentin in occlusal cavities, and fracture strength (FS) in molars with mesialocclusal- distal restoration. Disk-shaped samples with different thicknesses (2 or 4 mm) of low-viscosity (SDR Flow, Dentsply) and high-viscosity bulk-fill composites (Filtek BulkFill, 3M ESPE; and Tetric-N Ceram Bulk Fill, Ivoclar Vivadent) were prepared for top and bottom KHN analysis (n=10). MTBS to dentin and fracture pattern was evaluated in human molars with occlusal cavities restored with (n=10): conventional nanocomposite (Z350XT, 3M ESPE), low-viscosity (Filtek Bulk-fill Flow, 3M ESPE) or high-viscosity bulk-fill composites (Filtek BulkFill). The FS and fracture pattern of human molar with mesial-occlusal-distal restorations submitted or not to thermomechanical cycling were investigated (n=10) using: intact tooth (control), and restoration based on conventional microhybrid composite (Z250, 3M ESPE), low-viscosity (SDR Flow) or high-viscosity bulk-fill composites (Filtek BulkFill). The data were submitted to split-plot ANOVA (KHN), one-way ANOVA (MTBS), two-way ANOVA (FS) followed by Tukey’s test (α=0.05). For KHN, there was no significant difference for the resin composites between the top and bottom. For MTBS, no significant differences among the materials were detected; however, the low-viscosity composite presented lower frequency of adhesive failures. For FS, there was no significant difference between composites and intact tooth regardless of thermomechanical cycling. Low- and high-viscosity bulk-fill composites have comparable microhardness and microtensile bond strength when used in occlusal restorations. Likewise, the bulk-fill composites present similar fracture strength in molars with mesio-occlusal-distal restorations.

ABSTRACT Objective To verify the presence of variants in HNF1B in a sample of the Brazilian population selected according to the presence of renal cysts associated with hyperglycemia. Subjects and methods We evaluated 28 unrelated patients with clinical suspicion of HNF1B mutation because of the concomitant presence of diabetes mellitus (DM) or prediabetes and renal cysts. Genotyping was accomplished using Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA). In positive cases, available relatives were recruited. Results We found two patients with HNF1B mutations. The first presented the variant p.Pro328Leufs*48(c.983delC) and had DM, renal cysts, and hypomagnesemia. The second presented a heterozygous whole gene deletion in HNF1B, DM, renal cysts, body and tail pancreatic agenesis, and hypomagnesemia; this alteration was also found in his two siblings and his father. Conclusion The recruitment of suspected cases of HNF1B gene mutations in Brazilians due to hyperglycemia and renal cysts presents two positive cases. Our cases contribute to the annotation of clinical and biochemical phenotypes of this rare form of maturity-onset diabetes of the young (MODY).

ABSTRACT Elevated hepatic glucose production, impaired insulin secretion, and insulin resistance - abnormalities of glucose metabolism typically found in subjects with obesity - are major factors underlying the pathogenesis of type 2 diabetes (DM2) and the metabolic syndrome (MS). Adiponectin is a major regulator of glucose and lipid homeostasis via its insulin-sensitizing properties, and lower levels seems to be associated with the development of DM2 and MS. The purpose of this review is to clarify the mechanisms whereby adiponectin relates to the development of DM2 and MS and the association between polymorphisms of the adiponectin gene, circulating levels of the hormone, and its relationships with DM2. In addition, the impact of dietary lipids in the circulating levels of adiponectin will be addressed. According to the literature, circulating adiponectin levels seem to decrease as the number of MS components increases. Lower adiponectin concentrations are associated with higher intra-abdominal fat content. Therefore, adiponectin could link intra-abdominal fat with insulin resistance and development of MS. Therapeutic strategies that target the MS and its components, such as lifestyle modification through physical activity and weight loss, have been shown to increase adiponectin concentrations. Possible roles of diets containing either low or high amounts of fat, or different types of fat, have been analyzed in several studies, with heterogeneous results. Supplementation with n-3 PUFA modestly increases adiponectin levels, whereas conjugated linoleic acid supplementation appears to reduce concentrations when compared with unsaturated fatty acid supplementation used as an active placebo.

Introduction Undiagnosed hyperglycemia is common in high cardiovascular risk individuals, especially in those with coronary artery disease (CAD). There is no consensus about the optimal method for the screening of hyperglycemia in this population.Subjects and methods Five hundred and fourteen Brazilian individuals undergoing coronary angiography, without previously known diabetes mellitus (DM), had their glycemic status evaluated by both fasting plasma glucose (FPG) and HbA1c, being classified in normal (N), prediabetes (PD), and DM according to American Diabetes Association criteria. Concordance between both methods was assessed by Cohen’s κ. Accuracy of FPG and HbA1c to diagnose CAD was evaluated as proof-of-concept.Results Among individuals screened by FPG, 41.2% had PD and 6% had DM. Among those screened by HbA1c, 52.7% had PD and 12.7% had DM. Concordance for a positive screening of PD occurred in 125 individuals (κ = 0.084). Eighteen individuals had a concordant positive screening of DM (κ = 0.310). As a predictor of CAD, accuracy of FPG was 0.554 (p = 0.009) and of HbA1c 0.557 (p = 0.006).Conclusion a high frequency of hyperglycemia, between 47 and 65%, was found in individuals submitted to coronary angiography without previously known glucose disturbances, using FPG and HbA1c as screening methods respectively.HbA1c detected significantly more individuals with both PD and DM than FPG. Concordance between both methods is low. The question of which is the gold-standard method to diagnose hyperglycemia in this population is still open.

OBJETIVO: Avaliar a efetividade de uma intervenção não farmacológica no manejo do ganho de peso para pacientes com transtornos mentais graves. MÉTODO: Foi realizado um estudo aberto multicêntrico longitudinal em 93 serviços de saúde. Pacientes preocupados com o peso foram incluídos e participaram de uma intervenção em grupo de uma hora de duração durante 12 semanas com foco em educação alimentar, atividade física e autoestima. Peso, circunferência da cintura e pressão arterial foram avaliados antes e após a intervenção. RESULTADOS: 1071 pacientes foram incluídos no estudo, 73,9% completaram a intervenção. Foram observados diminuição de peso e índice de massa corporal significativos (peso: diferença da média: 0,41, IC 95%: 0,18-0,64, p = 0,001; índice de massa corporal: diferença da média: 0,13, IC 95%: 0,04-0,22, p = 0,006). Após a intervenção, 37 (4,4%) pacientes perderam mais que 7% do peso inicial, 780 (92,5%) mantiveram o peso e 26 (3,1%) dos pacientes apresentaram ganho de peso acima de 7%. Houve aumento da proporção de pacientes que praticavam atividade física (70,8%, p < 0,001). CONCLUSÃO: Encontramos uma pequena redução de peso e cinturae aumento de atividade física, sugerindo uma tendência à melhora no perfil antropométrico. Ensaios clínicos controlados e randomizados são necessários para avaliar a eficácia e a relevância clínica dessa intervenção.

OBJECTIVE: To evaluate the effectiveness of a non-pharmacological intervention for weight gain management in severe mental disorders. METHOD: An open, multicentre interventional study was conducted in 93 mental health services. Patients concerned with weight gain were included in this study and received a 12-week 1-hour group intervention focused on nutrition counseling, lifestyle, physical activity and self-esteem. Weight, waist circumference and blood pressure were measured before and after the intervention. RESULTS: 1,071 patients were enrolled in the study, and 73.9% completed the 12-week intervention. Significant weight loss (Mean difference: 0.41, CI 95%: 0.18 to 0.64, p = 0.001) and a significant BMI reduction (Mean difference: 0.13, CI 95%: 0.04 to 0.22, p = 0.006) were observed. During the intervention 37 (4.4%) patients lost > 7% of their initial weight, 780 (92.5%) maintained their weight, and 26 (3.1%) of the patients had a meaningful weight gain (> 7%). There was a significant increase in the proportion of patients undertaking physical activity after the intervention (70.8%, p < 0.001). CONCLUSION: In this 3-month open study we found a small weight and waist reduction, and increased physical activity practice, suggesting a trend towards anthropometric profile improvement. However, further randomized-controlled trials are necessary to evaluate the efficacy and clinical relevance of this psychosocial intervention for weight gain.

INTRODUÇÃO: Pacientes com esquizofrenia têm maior prevalência de obesidade em comparação à população geral. Esse fato está relacionado a uma alimentação inadequada, ao sedentarismo e ao uso de antipsicóticos. O aumento da obesidade associa-se a diversos distúrbios metabólicos, como o diabetes melito. As intervenções para prevenção e controle do ganho de peso são necessárias nessa população, em especial as intervenções não farmacológicas. OBJETIVO: Revisar os estudos sobre intervenções não farmacológicas para prevenção e controle do ganho de peso em pacientes com esquizofrenia. MÉTODOS: Foram encontrados oito estudos controlados e quatro não controlados sobre intervenções não farmacológicas. Foi feita uma revisãosobre a metodologia e os fatores positivos e limitações dos estudos. CONCLUSÕES: As intervenções não farmacológicas parecem ter um efeito importante em termos de prevenção e controle do ganho de peso e, portanto, devem ser incentivadas e adaptadas à realidade dos pacientes e serviços de saúde.

INTRODUCTION: Schizophrenic patients have a higher prevalence of obesity than the general population. There are several factors implicated in weight gain, including poor dietary conditions, sedentary lifestyle and antipsychotic drugs use. Obesity is also associated with metabolic disturbances such as diabetes mellitus. Weight gain interventions are necessary in this population, especially non-pharmacological interventions. OBJECTIVE: To review the non-pharmacological interventions for weight gain management in patients with schizophrenia. METHODS: Eight clinical trials and four open-label studies using these interventions were found. The methodology, strength and limitations of the studies were reviewed. CONCLUSIONS: Non-pharmacological interventions seem to have an important effect on weight gain prevention and control, and should be encouraged and adapted to patients and in mental health institution's reality.

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.

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.

Os pacientes com diabetes apresentam risco três vezes maior de desenvolverem aterosclerose e suas complicações quando comparados a indivíduos sem hiperglicemia. Parte desse risco associado ao diabetes é provavelmente relacionado a determinantes genéticos que influenciam tanto a homeostase glicídica quanto o desenvolvimento da aterosclerose. Entretanto, o diabetes tipo 2 freqüentemente coexiste com outros fatores de risco cardiovascular, tais como hipertensão arterial, obesidade central e dislipidemia. A variabilidade genética interfere em várias áreas tais como o metabolismo lipídico, o metabolismo energético, hipertensão, mecanismos hemodinâmicos, mecanismos de coagulação, inflamação e na formação da matriz na parede vascular, que podem estar envolvidos nas complicações macrovasculares dos pacientes com diabetes. A adiponectina é secretada com abundância pelos adipócitos. Apresenta importante papel no metabolismo lipídico e glicídico, tendo ação direta tanto antiinflamatória quanto anti-aterogênica. Na atual revisão, nós resumimos os dados recentes da literatura que sugerem uma implicação de variantes alélicas do gene da adiponectina (ADIPOQ) que podem estar envolvidos na determinação genética da doença cardiovascular em indivíduos com diabetes.

Diabetic patients have a 3-fold higher risk of developing atherosclerosis and its clinical complications as compared to non-diabetic individuals. Part of the cardiovascular risk associated with diabetes is probably due to genetic determinants influencing both glucose homeostasis and the development of atherosclerosis. However, type 2 diabetes frequently coexists with other cardiovascular risk factors like arterial hypertension, central obesity and dyslipidemia. Genetic variability affecting many areas such as lipid and energy metabolisms, hypertension and haemodynamic mechanisms, blood clotting homeostasis, inflammation, and matrix turnover in the vascular wall will have an impact on the development of macrovascular complications in diabetic patients. Adiponectin is abundantly secreted by adipocytes. It plays important roles in lipid and glucose metabolisms and has direct anti-inflammatory and anti-atherogenic effects. In this review, we summarize recent data from the literature suggesting an implication of allelic variations of the adiponectin gene (ADIPOQ) in the genetic determinants of cardiovascular disease in diabetic subjects.

INTRODUÇÃO: Baseado no conhecimento atual sobre o diabetes tipo 2 (DM), considerado como um estado de doença cardiovascular, várias diretrizes surgem no intuito de sugerir uma avaliação cardiovascular rotineira nesses indivíduos, na tentativa de se detectar precocemente a doença arterial coronariana (DAC). Neste trabalho, objetivamos descrever qual avaliação cardiovascular basal fora realizada em um período de seguimento dos mesmos, dentro de um centro universitário especializado no tratamento de diabetes, adequado para a realidade brasileira. SUJEITOS E MÉTODOS: Anotamos dados clínicos do prontuário de 121 pacientes portadores de DM tipo 2 atendidos no Centro de Diabetes da Universidade Federal de São Paulo e confrontamos com o tipo de avaliação cardiovascular a que os mesmos haviam sido submetidos no ano que precedia a consulta. RESULTADOS: Observamos que na população estudada havia uma alta prevalência de outros fatores de risco cardiovasculares associados. Quanto às avaliações cardiovasculares realizadas no período, cerca de 36% dos pacientes não realizaram nenhum teste cardiológico, 17% foram submetidos ao eletrocardiograma de repouso e 27% dos pacientes foram submetidos ao teste ergométrico. Exames como ecocardiograma em repouso ou sob stress farmacológico, cintilografia de perfusão do miocárdio e cinecoronariografia foram realizados em menor proporção. CONCLUSÃO: Nossos dados mostraram a variabilidade e limitações na forma de abordagem diagnóstica de DAC de pacientes acompanhados em ambiente universitário e nos apontam para a necessidade de construir diretrizes mais bem definidas e dirigidas para as peculiaridades da população e sistema de saúde brasileiros.

INTRODUCTION: Type 2 diabetes is a cardiovascular disease. The morbidity and mortality among these patients are primarily due to cardiovascular diseases. There are many guidelines regarding clinical evaluation of cardiovascular disease in those patients. Implementation of these guidelines has been an argued subject. Our objective in this paper is to describe what basal cardiovascular evaluation has been carried out at a specialized university Diabetes Center. SUBJECTS AND METHODS: Data were collected from February to October 2006 of 121 type 2 diabetes individuals who were enrolled at the Diabetes Center of Federal University of São Paulo. We analyzed the type of cardiovascular disease evaluation that they had been submitted in the year that preceded the consultation. RESULTS: We have observed a high prevalence of several other cardiovascular risk factors in this population. The cardiovascular evaluations during this period has shown 36% of the patients had not been submitted to any cardiovascular test, 17% had been submitted to resting electrocardiogram and 27% of the patients had been submitted to exercise test. Rest echocardiogram, pharmacologic stress echocardiogram, myocardial perfusion scintigraphy, and coronary angiography have been carried out in a much lesser ratio. CONCLUSION: Our data has shown the variability and limitations on boarding diagnosing of DAC in university environment patients and point us the necessity of constructing defined and directed directives for the peculiarities of the Brazilian population and health system.

A avaliação do controle glicêmico no diabetes mellitus (DM) envolve tradicionalmente a observação das taxas de glicemia e hemoglobina glicada. Recentemente o Fleury - Centro de Medicina Diagnóstica implantou o exame de monitorização contínua de glicose (MCG) (Medtronic Minimed - CGMS® System GoldTM) e, neste trabalho, objetivamos descrever a experiência relacionada à realização deste exame durante o ano de 2004. Realizaram-se 141 exames neste período. Do total, 88% (n= 124) pacientes eram diabéticos, sendo 99 usuários de insulina. Encontramos forte correlação entre os valores de glicose obtidos com a MCG e no sangue capilar (r= 0,926; p< 0,005). Nos diabéticos, identificou-se hipoglicemia noturna (< 50mg/dL) em ~35% (n= 44), padrões hiperglicêmicos (> 220mg/dL) em períodos determinados do dia em ~44% e hiperglicemia sustentada ao longo de toda monitorização em treze casos (10%). Doze exames foram realizados para investigação de hipoglicemias em não diabéticos. Dois exames foram sugestivos de "dumping" e em um caso a MCG reforçou a hipótese de insulinoma. Ocorreram interrupções parciais das monitorizações em 15% dos exames. Concluímos que a MCG é uma metodologia útil para investigação das oscilações glicêmicas, sendo uma importante ferramenta para ajuste terapêutico em pacientes com DM.

Conventional assessment of glycemic control in diabetes mellitus (DM) includes blood glucose attention to glycemia and glycated hemoglobin levels. Recently, we introduced the continuous glucose-monitoring test (CGM) (Medtronic Minimed - CGMS® System GoldTM). Here we describe our experience with this methodology over the year 2004. A total of 141 CGM tests were performed over this period of time. Overall, 88% (n= 124) patients were diabetics (DM), 99 of them were insulin users. We found a strong correlation between glucose values obtained by CGM and capillary glucose measures (r= 0.926; p< 0.005). In diabetic patients, nocturnal hypoglycemia (< 50mg/dL) was identified in ~35% (n= 44), hyperglycemic patterns (> 220mg/dL) at specific times of day in ~44% and sustained hyperglycemia throughout the whole monitoring period in thirteen cases (10%). Twelve tests were performed to investigate the occurrence of hypoglycemia in non-diabetic subjects. Two tests came out very suggestive of "dumping", and in one case the CGMS supported the hypothesis of insulinoma. Partial monitoring interruptions have occurred in 15% of all tests. We concluded that CGMS is a useful methodology to investigate glycemic fluctuations, and it is also an important tool to adjust therapy in diabetic patients.