The role of intermittent continuous glucose monitoring in a successful outpatient transition from insulin to glibenclamide in a patient with transient neonatal diabetes

SUMMARY Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes occurring mainly in the first 6 months of life. Approximately 30% of transient NDM (TNDM) cases will have an activating mutation in the KATP channel genes ABCC8 and KCNJ11. The majority of the patients with KCNJ11 mutations who are receiving insulin treatment can be transferred to treatment with sulfonylurea (SU), with an improvement in metabolic control and quality of life. Intermittent continuous glucose monitoring (iCGM) is used to assess the current and retrospective interstitial glucose, providing information such as hypo/hyperglycemia tendency and time on target. This case report describes the use of iCGM in the transition from insulin treatment to glibenclamide in a patient with TNDM caused by a pathogenic variant of KCNJ11. This is the first report of a successful outpatient transition from insulin to glibenclamide, in a Brazilian child with TNDM using iCGM (FreeStyle Libre@). The remote monitoring and online management allowed the patient to safely stay at home during the transition from insulin to SU, especially important in the context of the COVID-19 pandemic. We conclude that iCGM is a helpful tool in cases of NDM and should be used to increase safety and speed up dose adjustments in outpatient transition from insulin to glibenclamide.

The role of intermittent continuous glucose monitoring in a successful outpatient transition from insulin to glibenclamide in a patient with transient neonatal diabetes.

Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes occurring mainly in the first 6 months of life. Approximately 30% of transient NDM (TNDM) cases will have an activating mutation in the KATP channel genes ABCC8 and KCNJ11. The majority of the patients with KCNJ11 mutations who are receiving insulin treatment can be transferred to treatment with sulfonylurea (SU), with an improvement in metabolic control and quality of life. Intermittent continuous glucose monitoring (iCGM) is used to assess the current and retrospective interstitial glucose, providing information such as hypo/hyperglycemia tendency and time on target. This case report describes the use of iCGM in the transition from insulin treatment to glibenclamide in a patient with TNDM caused by a pathogenic variant of KCNJ11. This is the first report of a successful outpatient transition from insulin to glibenclamide, in a Brazilian child with TNDM using iCGM (FreeStyle Libre@). The remote monitoring and online management allowed the patient to safely stay at home during the transition from insulin to SU, especially important in the context of the COVID-19 pandemic. We conclude that iCGM is a helpful tool in cases of NDM and should be used to increase safety and speed up dose adjustments in outpatient transition from insulin to glibenclamide.

Delayed Puberty Phenotype Observed in Noonan Syndrome Is More Pronounced in Girls than Boys.

INTRODUCTION: Pubertal delay is described as one of the clinical features in Noonan syndrome (NS) and it may be one of the factors causing short adult height in those patients. The present study aimed at characterizing pubertal development in NS and identifying pubertal delay predictors. METHODS: We analyzed 133 individuals with a molecular diagnosis of NS and clinical puberty evaluation. We characterized delayed puberty as pubertal onset after 12 years in girls and 13.5 years in boys, according to parameters of the Brazilian population. To investigate its predictors, we correlated the age at onset of puberty with several characteristics and genotype in a multilevel regression model. For comprehending pubertal development in NS, we assessed age and anthropometric measures at each Tanner stage and adult age. RESULTS: The mean age at puberty onset for girls was 11.9 ± 1.9 years and for boys, 12.5 ± 1.7 years, significantly later than the Brazilian population (p = 0.025; p < 0.001). Girls (49.1%) presented delayed puberty more frequently than boys (27.9%, p = 0.031). Body mass index standard deviation scores (SDS) and insulin growth factor 1 SDS at puberty onset significantly predicted later puberty entry. Height gain from the onset of puberty to adult height was lower in children with pubertal delay. CONCLUSION: Pubertal delay is characteristically found in children with NS, more frequently in females. The low weight of patients with NS could modulate the age of puberty, just as the increase in overweight/obesity in the general population has shown an effect on reducing the age of onset of puberty.

Characteristics of type 1 diabetes mellitus in children and adolescents with Down's syndrome in an admixed population.

OBJECTIVE: People with Down's syndrome (DS) have a higher risk of developing type 1 diabetes mellitus (T1D) and may have specific clinical features compared to T1D patients without DS. This study evaluated the clinical and laboratory aspects of T1D in children and adolescents with DS in an admixed population. METHODS: A case-control study comparing patients with T1D and DS (T1D+DS) to patients with T1D without DS (T1D controls) from two tertiary academic Hospitals in São Paulo, Brazil. RESULTS: The sample consisted of 9 patients with T1D+DS and 18 T1D age and sex-matched controls. Anti-glutamic acid decarboxylase 65 antibodies were positive in 7/7 of the 9 T1D+DS patients, confirming the presence of diabetes autoimmunity in this group. Mean age at diagnosis of T1D was 4.9 ± 3.9 years in the T1D+DS group and 6.4 years ± 3 in the T1D control group; early diagnosis (<2 years old) occurred in three T1D+DS patients but only in one T1D control patients, both suggesting lower age of diagnosis in T1D+DS group, although without statistical significance (p = 0.282 and p = 0.093, respectively). The T1D+DS group presented lower total insulin dose (0.7 IU/kg/day ± 0.2) and HbA1c (7.2% ± 0.6) than the control group (1.0 IU/kg/day ± 0.3 and 9.1% ± 0.7, respectively) (p = 0.022 and p = 0.047, respectively). CONCLUSION: We confirmed the autoimmune etiology of diabetes in people with DS in this admixed population. T1D+DS patients developed diabetes earlier and achieved better metabolic control with a lower insulin dose than T1D controls. These findings are in agreement with previous studies in Caucasian populations.

Characteristics of type 1 diabetes mellitus in children and adolescents with Down's syndrome in an admixed population

ABSTRACT Objective: People with Down's syndrome (DS) have a higher risk of developing type 1 diabetes mellitus (T1D) and may have specific clinical features compared to T1D patients without DS. This study evaluated the clinical and laboratory aspects of T1D in children and adolescents with DS in an admixed population. Subjects and methods: A case-control study comparing patients with T1D and DS (T1D+DS) to patients with T1D without DS (T1D controls) from two tertiary academic Hospitals in São Paulo, Brazil. Results: The sample consisted of 9 patients with T1D+DS and 18 T1D age and sex-matched controls. Anti-glutamic acid decarboxylase 65 antibodies were positive in 7/7 of the 9 T1D+DS patients, confirming the presence of diabetes autoimmunity in this group. Mean age at diagnosis of T1D was 4.9 ± 3.9 years in the T1D+DS group and 6.4 years ± 3 in the T1D control group; early diagnosis (<2 years old) occurred in three T1D+DS patients but only in one T1D control patients, both suggesting lower age of diagnosis in T1D+DS group, although without statistical significance (p = 0.282 and p = 0.093, respectively). The T1D+DS group presented lower total insulin dose (0.7 IU/kg/day ± 0.2) and HbA1c (7.2% ± 0.6) than the control group (1.0 IU/kg/day ± 0.3 and 9.1% ± 0.7, respectively) (p = 0.022 and p = 0.047, respectively). Conclusion: We confirmed the autoimmune etiology of diabetes in people with DS in this admixed population. T1D+DS patients developed diabetes earlier and achieved better metabolic control with a lower insulin dose than T1D controls. These findings are in agreement with previous studies in Caucasian populations.

Infections in children with diabetes / Infecções na criança com diabetes

Abstract Objective The association between diabetes mellitus and infections is very common. These infections, even when mild, interfere with blood glucose control. The aim of this review is to describe infections that occur in children and adolescents with DM, as well as to provide recommendations on glycemia management during these episodes. Source of data A non-systematic review was carried out in the PubMed database, using the terms "diabetes mellitus," "infection," "children," and "adolescents." The most relevant publications were selected. Synthesis of data In addition to the usual community diseases, some infections may occur predominantly in diabetic patients, especially when there is inadequate glycemic control, and common infections can be more severe in these patients. Alterations caused by the disease itself and the immune response are responsible for the risk of higher frequency and severity of infections. During infections, an increase in blood glucose occurs and usually an increase in insulin dose is required. Conclusions Pediatric patients with diabetes have some immune system disorders that, when associated with high glycemia, increase the risk of infections and their severity, and should be promptly identified and treated. The presence of an infectious condition, in turn, raises blood glucose and increases the risk of decompensation, and pediatricians should be cautioned to intensify monitoring and insulin therapy, and to avoid the risk of DKA. It should also be noted that many infections are preventable and can be avoided with adequate vaccine coverage.

Resumo Objetivo A associação entre diabetes mellitus e infecções é muito frequente. Essas infecções, mesmo quando leves, interferem no controle da glicemia. O objetivo desta revisão é descrever as infecções que ocorrem em crianças e adolescentes com DM, bem como orientar o manejo glicêmico nestes episódios. Fonte dos dados Foi feita uma revisão não sistemática na base de dados PubMed, com os termos "diabetes mellitus", "infecção", "crianças" e "adolescentes". Foram selecionadas as publicações mais relevantes. Síntese dos dados Além de infecções comunitárias habituais, algumas infecções ocorrem predominantemente no paciente com diabetes, principalmente quando não há um controle glicêmico adequado, e infecções comuns podem ser mais graves nesse paciente. Alterações da própria doença e da resposta imune, em conjunto com alterações do microbioma, são responsáveis pela maior frequência e gravidade das infecções. Durante as infecções, ocorre um aumento da glicemia e habitualmente é necessário o aumento da dose de insulina. Conclusões O paciente pediátrico com diabetes apresenta algumas desordens imunes que, quando associadas a elevaçao da glicemia, aumentam o risco de infecção e sua gravidade. A presença da infecção, por sua vez, eleva a glicemia e aumenta o risco de descompensação. Desta forma, a monitorização da glicemia, bem como o aumento da dose de insulina, são fundamentais para evitar o risco de cetoacidose diabética. Destaca-se ainda que muitas infecções são imunopreveníveis e podem ser evitadas com uma cobertura vacinal adequada.

Infections in children with diabetes.

OBJECTIVE: The association between diabetes mellitus and infections is very common. These infections, even when mild, interfere with blood glucose control. The aim of this review is to describe infections that occur in children and adolescents with DM, as well as to provide recommendations on glycemia management during these episodes. SOURCE OF DATA: A non-systematic review was carried out in the PubMed database, using the terms "diabetes mellitus," "infection," "children," and "adolescents." The most relevant publications were selected. SYNTHESIS OF DATA: In addition to the usual community diseases, some infections may occur predominantly in diabetic patients, especially when there is inadequate glycemic control, and common infections can be more severe in these patients. Alterations caused by the disease itself and the immune response are responsible for the risk of higher frequency and severity of infections. During infections, an increase in blood glucose occurs and usually an increase in insulin dose is required. CONCLUSIONS: Pediatric patients with diabetes have some immune system disorders that, when associated with high glycemia, increase the risk of infections and their severity, and should be promptly identified and treated. The presence of an infectious condition, in turn, raises blood glucose and increases the risk of decompensation, and pediatricians should be cautioned to intensify monitoring and insulin therapy, and to avoid the risk of DKA. It should also be noted that many infections are preventable and can be avoided with adequate vaccine coverage.

Health-related quality of life in patients with type 1 diabetes mellitus in the different geographical regions of Brazil: data from the Brazilian Type 1 Diabetes Study Group.

BACKGROUND: In type 1 diabetes mellitus (T1DM) management, enhancing health-related quality of life (HRQoL) is as important as good metabolic control and prevention of secondary complications. This study aims to evaluate possible regional differences in HRQoL, demographic features and clinical characteristics of patients with T1DM in Brazil, a country of continental proportions, as well as investigate which variables could influence the HRQoL of these individuals and contribute to these regional disparities. METHODS: This was a retrospective, cross-sectional, multicenter study performed by the Brazilian Type 1 Diabetes Study Group (BrazDiab1SG), by analyzing EuroQol scores from 3005 participants with T1DM, in 28 public clinics, among all geographical regions of Brazil. Data on demography, economic status, chronic complications, glycemic control and lipid profile were also collected. RESULTS: We have found that the North-Northeast region presents a higher index in the assessment of the overall health status (EQ-VAS) compared to the Southeast (74.6 ± 30 and 70.4 ± 19, respectively; p < 0.05). In addition, North-Northeast presented a lower frequency of self-reported anxiety-depression compared to all regions of the country (North-Northeast: 1.53 ± 0.6; Southeast: 1.65 ± 0.7; South: 1.72 ± 0.7; Midwest: 1.67 ± 0.7; p < 0.05). These findings could not be entirely explained by the HbA1c levels or the other variables examined. CONCLUSIONS: Our study points to the existence of additional factors not yet evaluated that could be determinant in the HRQoL of people with T1DM and contribute to these regional disparities.

Thyroid function and autoimmunity in children and adolescents with Type 1 Diabetes Mellitus.

We evaluated 233 children and adolescents with T1 Diabetes to analyze the prevalence and characteristics of Autoimmune Thyroid Disease. AITD was found in 23%, the majority being female and patients older than 5 years of age. Screening is mandatory, and the best approach could be guided by gender and age.

Dyslipidemia in young patients with type 1 diabetes mellitus.

OBJECTIVE: The association between type 1 diabetes mellitus (T1D) and dyslipidemia (DLP) increases the risk of cardiovascular disease (CVD). The aim of this study was to evaluate the presence of dyslipidemia in young T1D patients. MATERIALS AND METHODS: The study design was cross-sectional and descriptive. We reviewed medical records of T1D patients followed at an endocrinology service, from 1998-2012. DATA COLLECTED: gender, actual age and age at diagnosis, duration of T1D since diagnosis, body mass index (BMI), pubertal stage, glycemic control (GC) determined by glycated hemoglobin (HbA1c), total cholesterol (TC), HDL, LDL, triglycerides (TG). To analyze lipid profile and metabolic control, we used the Brazilian Society of Diabetes Guidelines. RESULTS: Were included 239 T1D patients, 136 (56.9%) females; mean ± SD: actual age 15.7 ± 5.0 years and at T1D diagnosis 7.3 ± 3.9; T1D duration 10.6 ± 6.4 years, 86.6% puberty, 15.1% overweight. The prevalence of DLP was 72.5%, 63.3% females, 86.6% puberty, mean ± SD: actual age 15.4 ± 4.8 years and at T1D diagnosis 7.2 ± 4.1 years, duration of T1D 10.7 ± 6.1 years. We found high-CT in 56.7%, low-HDL = 21.7%, high LDL = 44.0%, high-TG = 11.8%. Between females with DLP, 83.5% was in puberty. We find correlation between the presence of DLP, a poor GC and BMC. CONCLUSION: We found a high prevalence of DLP in young patients with T1D, particularly in puberty females. Programs targeting the prevention of dyslipidemia should be adopted, especially for this group, in order to prevent/delay chronic complications and cardiovascular disease.

Dyslipidemia in young patients with type 1 diabetes mellitus

Objective The association between type 1 diabetes mellitus (T1D) and dyslipidemia (DLP) increases the risk of cardiovascular disease (CVD). The aim of this study was to evaluate the presence of dyslipidemia in young T1D patients.Materials and methods The study design was cross-sectional and descriptive. We reviewed medical records of T1D patients followed at an endocrinology service, from 1998-2012. Data collected: gender, actual age and age at diagnosis, duration of T1D since diagnosis, body mass index (BMI), pubertal stage, glycemic control (GC) determined by glycated hemoglobin (HbA1c), total cholesterol (TC), HDL, LDL, triglycerides (TG). To analyze lipid profile and metabolic control, we used the Brazilian Society of Diabetes Guidelines.Results Were included 239 T1D patients, 136 (56.9%) females; mean ± SD: actual age 15.7 ± 5.0 years and at T1D diagnosis 7.3 ± 3.9; T1D duration 10.6 ± 6.4 years, 86.6% puberty, 15.1% overweight. The prevalence of DLP was 72.5%, 63.3% females, 86.6% puberty, mean ± SD: actual age 15.4 ± 4.8 years and at T1D diagnosis 7.2 ± 4.1 years, duration of T1D 10.7 ± 6.1 years. We found high-CT in 56.7%, low-HDL = 21.7%, high LDL = 44.0%, high-TG = 11.8%. Between females with DLP, 83.5% was in puberty. We find correlation between the presence of DLP, a poor GC and BMC.Conclusion We found a high prevalence of DLP in young patients with T1D, particularly in puberty females. Programs targeting the prevention of dyslipidemia should be adopted, especially for this group, in order to prevent/delay chronic complications and cardiovascular disease. Arch Endocrinol Metab. 2015;59(3):215-9.

Importance of screening with oral glucose tolerance test for early diagnosis of cystic fibrosis-related diabetes mellitus.

OBJECTIVES: To evaluate (a) the prevalence of cystic fibrosis-related diabetes mellitus (CFRD) in a non-Caucasian population treated in a University Hospital in São Paulo, Brazil; and (b) if annual screening of patients with cystic fibrosis (CF) ≥ 10 yr of age, with oral glucose tolerance test (OGTT), resulted in early detection of CFRD. SUBJECTS AND METHODS: A cross-sectional study was performed with retrospective/prospective analysis of CF patients ≥10 yr of age. Various parameters were analyzed. Patients previously diagnosed with CFRD had their parameters collected at the time of diabetes diagnosis; others were submitted to annual OGTTs, with the parameters collected at the time of their last OGTT. RESULTS: A total of 60 subjects [29 females/31 males; mean age 19.1 yr (±7.6)] were analyzed. In our group of CF patients, we found that 30% had CFRD, 26.7% had altered response to OGTT, and 43.3% had normal glucose tolerance. Analysis of those patients with CFRD showed that the mean age at the time of diagnosis of CFRD, in patients diagnosed by OGTT screening, was 13.5 yr (±2.9) vs. 22.3 yr (±5.4) among those previously diagnosed by clinical suspicion (p < 0.001). CONCLUSIONS: The prevalence of CFRD in our patients is high, similar to the data from Caucasian populations, and significantly higher than previously reported in Brazil. Screening with OGTT resulted in earlier diagnosis of CFRD by 8 yr. These data may help convince national CF centers that CFRD is frequent, and that screening should be mandatory.

Update on diagnosis and monitoring of cystic fibrosis-related diabetes mellitus (CFRD) / Atualização no diagnóstico e acompanhamento do diabetes melito relacionado à fibrose cística (DRFC)

Cystic fibrosis (CF) is the most common recessive autosomal disease among Caucasian. Children with CF have benefitted from advances in medical and nutritional treatments, and this can be gleaned from the improvement in the survival of these patients. The increase in the survival rate brought with it the appearance of co-morbidities related to CF. Nowadays cystic fibrosis-related diabetes (CFRD) is considered the most common complication associated with CF. It can appear as early as infancy or adolescence, and its prevalence can be as high as 50 percent in adult patients. Because of its high prevalence, difficulties in early detection and the risks involved, in recent years several studies and consensuses have focused on this condition, adding information about the epidemiology, pathophysiology, prognosis and treatment of CFRD. The main aspects of these new concepts, as well as the current recommendations for its diagnosis and follow-up, will be presented in this study.

Fibrose cística (FC) é a doença autossômica recessiva mais comum nos caucasianos. Avanços no tratamento da FC acarretaram aumento na sobrevida dos pacientes, que trouxe o aparecimento de comorbidades relacionadas à doença. Atualmente, o diabetes relacionado à fibrose cística (DRFC) é considerado a complicação mais comum associada à FC, podendo aparecer já na infância ou adolescência, chegando a atingir até 50 por cento dos pacientes adultos. Em virtude da alta prevalência, das dificuldades de diagnosticar precocemente e das graves consequências para os pacientes, nos últimos anos vem crescendo a preocupação com a detecção e o tratamento precoces do DRFC. Vários grupos têm se dedicado a procurar evidências e desenvolver consensos com o objetivo de orientar o diagnóstico e o acompanhamento dessa comorbidade. Neste artigo apresentamos os principais aspectos dessa evolução, bem como as atuais recomendações no acompanhamento de pacientes com DRFC.

Update on diagnosis and monitoring of cystic fibrosis-related diabetes mellitus (CFRD).

Cystic fibrosis (CF) is the most common recessive autosomal disease among Caucasian. Children with CF have benefitted from advances in medical and nutritional treatments, and this can be gleaned from the improvement in the survival of these patients. The increase in the survival rate brought with it the appearance of co-morbidities related to CF. Nowadays cystic fibrosis-related diabetes (CFRD) is considered the most common complication associated with CF. It can appear as early as infancy or adolescence, and its prevalence can be as high as 50% in adult patients. Because of its high prevalence, difficulties in early detection and the risks involved, in recent years several studies and consensuses have focused on this condition, adding information about the epidemiology, pathophysiology, prognosis and treatment of CFRD. The main aspects of these new concepts, as well as the current recommendations for its diagnosis and follow-up, will be presented in this study.

Evaluation of AC(n) and C(-106)T polymorphisms of the aldose reductase gene in Brazilian patients with DM1 and susceptibility to diabetic retinopathy.

PURPOSE: Diabetic retinopathy (DR) is one of the most important microvascular complications in both type 1 and type 2 diabetes. In Brazil, its proliferative form is the second cause of irreversible blindness among adults of working age. Despite the strong association of DR with disease duration and degree of chronic hyperglycemia, genetic predisposition has been recognized as a possible trigger in the development of this complication. Recent studies have demonstrated that the development of DR in patients with type 1 diabetes is associated with the occurrence of polymorphisms at the 5'-end of the aldose reductase gene (ALR2). There are no reports investigating these polymorphisms in type 1 diabetes Brazilian patients. The aim of this study was to investigate the relationship between the AC(n) repeat and C(-106)T polymorphisms of the ALR2 gene with the susceptibility to the development of DR in Brazilian patients with type 1 diabetes. METHODS: We selected 64 patients who had diabetes for at least 10 years from Santa Casa de São Paulo and State University of Campinas. The study group was divided into the following: Group 1, patients with no evidence of diabetic retinopathy; group 2, patients with nonproliferative diabetic retinopathy (NPDR); and group 3, patients with proliferative diabetic retinopathy (PDR), confirmed by fundoscopy. The AC(n) microsatellite region was evaluated through polymerase chain reaction (PCR) and automated genotyping and the C(-106)T substitution through polymerase chain reaction/restriction fragment length polymorphism (RFLP). RESULTS: When each allele of the AC(n) polymorphism was evaluated, the Z allele (24 repeats) was significantly associated with the development of PDR (p=0.014). The C allele of the C(-106)T substitution wasn't associated with the susceptibility to this microvascular complication (p=0.153). When the Z and C allele were concomitantly evaluated regarding their presence or absence a positive correlation was observed for the presence of both alleles and the development of PDR. CONCLUSIONS: In our sample of Brazilian patients with type 1 diabetes, the presence of the AC(n) polymorphism Z allele may be considered a risk factor for the development of PDR. The C allele of the C(-106)T polymorphism, in association with the Z allele, also increased the risk for the development of PDR, but when it was analyzed by itself there was no association with the complication.