Exploring early DNA methylation alterations in type 1 diabetes: implications of glycemic control.

Background: Prolonged hyperglycemia causes diabetes-related micro- and macrovascular complications, which combined represent a significant burden for individuals living with diabetes. The growing scope of evidence indicates that hyperglycemia affects the development of vascular complications through DNA methylation. Methods: A genome-wide differential DNA methylation analysis was performed on pooled peripheral blood DNA samples from individuals with type 1 diabetes (T1D) with direct DNA sequencing. Strict selection criteria were used to ensure two age- and sex-matched groups with no clinical signs of chronic complications according to persistent mean glycated hemoglobin (HbA1c) values over 5 years: HbA1c<7% (N=10) and HbA1c>8% (N=10). Results: Between the two groups, 8385 differentially methylated CpG sites, annotated to 1802 genes, were identified. Genes annotated to hypomethylated CpG sites were enriched in 48 signaling pathways. Further analysis of key CpG sites revealed four specific regions, two of which were hypermethylated and two hypomethylated, associated with long non-coding RNA and processed pseudogenes. Conclusions: Prolonged hyperglycemia in individuals with T1D, who have no clinical manifestation of diabetes-related complications, is associated with multiple differentially methylated CpG sites in crucial genes and pathways known to be linked to chronic complications in T1D.

Case report: Fourth branchial cleft cyst: a case of acute suppurative thyroiditis.

This case report presents a 4 year-old-female patient with a neck mass who was diagnosed with an infected fourth branchial cleft cyst with left thyroid lobe involvement through fistulation. The case emphasizes the importance of considering uncommon etiologies, such as congenital anomalies, as a differential diagnosis when evaluating pediatric neck masses. The patient was prescribed broad-spectrum antibiotics, which led to the regression of the mass and inflammatory signs. Close follow-up in endocrinology and otorhinolaryngology appointments was maintained, and after 7 months, hypoplasia of the left lobe was observed. Thyroid function was reevaluated, and after two years, no recurrences were noted. The case highlights the significance of a comprehensive examination and assessment of corresponding clinical features, which can significantly reduce the rate of misdiagnoses and achieve an individualized diagnosis.

Insulin pump therapy in children with type 1 diabetes: analysis of data from the SWEET registry.

BACKGROUND: Intensified insulin delivery using multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) is recommended in children with type 1 diabetes (T1D) to achieve good metabolic control. OBJECTIVE: To examine the frequency of pump usage in T1D children treated in SWEET (Better control in Paediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference) centers and to compare metabolic control between patients treated with CSII vs MDI. METHODS: This study included 16 570 T1D children participating in the SWEET prospective, multicenter, standardized diabetes patient registry. Datasets were aggregated over the most recent year of treatment for each patient. Data were collected until March 2016. To assess the organization of pump therapy a survey was carried out. RESULTS: Overall, 44.4% of T1D children were treated with CSII. The proportion of patients with pump usage varied between centers and decreased with increasing age compared with children treated with MDI. In a logistic regression analysis adjusting for age, gender and diabetes duration, the use of pump was associated with both: center size [odd ratio 1.51 (1.47-1.55), P < .0001) and the diabetes-related expenditure per capita [odd ratio 1.55 (1.49-1.61), P < .0001]. Linear regression analysis, adjusted for age, gender, and diabetes duration showed that both HbA1c and daily insulin dose (U/kg/d) remained decreased in children treated with CSII compared to MDI (P < .0001). CONCLUSIONS: Insulin pump therapy is offered by most Sweet centers. The differences between centers affect the frequency of use of modern technology. Despite the heterogeneity of centers, T1D children achieve relatively good metabolic control, especially those treated with insulin pumps and those of younger age.

The Role of Haemoglobin A1c in Screening Obese Children and Adolescents for Glucose Intolerance and Type 2 Diabetes.

INTRODUCTION: In 2012, an international expert committee in diabetes wrote in favor of screening adult and paediatric patients for glucose intolerance and type 2 diabetes using glycated haemoglobin. The aim of this study was to evaluate glycated haemoglobin utility as a screening tool in a young obese mainly Caucasian population. MATERIAL AND METHODS: Children [(n = 266), body mass index z-score 3.35 ± 0.59, 90% Caucasian 90%, 55% female, median age 12.3 (range: 8.9 - 17.6) years old] recently referred to a tertiary hospital-based obesity clinic underwent a routine oral glicose tolerance test and glycated haemoglobin measurement. EXCLUSION CRITERIA: abnormal forms of haemoglobin and conditions linked to increased erythrocyte turnover. RESULTS: The oral glicose tolerance test diagnosed 13 (4.9%) subjects as prediabetic but none as diabetic. According to glycated haemoglobin, 32 would be prediabetic (29 false positives) and one would be diabetic (when he was only glucose intolerant). On the other hand, 10 prediabetic patients would not have been identified (false negatives). Glycated haemoglobin receiver operator characteristic analysis area under the curve was 0.59 (CI 95% 0.40 - 0.78), confirming its reduced capacity to identify prediabetes. Better results were achieved when calculating receiver operator characteristic analysis area under the curve for fasting glucose (0.76;CI 95% 0.66 - 0.87), homeostasis model assessment for insulin resistance (0.77; CI 95% 0.64 - 0.90) and triglycerides:HDL cholesterol ratio (0.81; CI 95% 0.66 - 0.96). DISCUSSION: In Paediatric populations, especially when mainly Caucasian, glycated haemoglobin does not seem to be a useful screening tool for prediabetes. CONCLUSION: For this reason, it would appear premature to advise it as a diagnostic tool until significantly more data is available. Homeostasis model assessment for insulin resistance and triglycerides: HDL cholesterol have higher precision and can be calculated using a fasting blood sample.

Introdução: Em 2012, um comité internacional de peritos em diabetes aconselhou a hemoglobina glicada como teste de rastreio de intolerância à glicose e diabetes mellitus tipo 2 no adulto e em idade pediátrica. O objetivo deste estudo foi avaliar a utilidade deste exame numa população de crianças e adolescentes obesos, maioritariamente de etnia caucasiana.Material e Métodos: Foram recrutados 226 doentes [índice de massa corporal z-score 3,35 ± 0,59, 90% caucasianos, 55% do sexo feminino, idade mediana de 12,3 (âmbito: 8,9 â 17,6) anos] referenciados à consulta de obesidade pediátrica de um hospital terciário, com critérios para rastreio de diabetes mellitus tipo 2. Situações de hemoglobinopatia ou de alteração da sobrevida eritrocitária foram excluídas. Todos os indivíduos foram submetidos a uma prova de tolerância à glicose oral e à medição da hemoglobina glicada.Resultados: Segundo a prova de tolerância à glicose oral, 13 (4,9%) eram pré-diabéticos e nenhum diabético. De acordo com a hemoglobina glicada, 32 seriam pré-diabéticos (29 falsos-positivos) e um diabético (falso positivo, sendo este, na realidade, apenas intolerante à glicose). Por outro lado, 10 pré-diabéticos não seriam identificados (falsos-negativos). A área sob a curva receiver operator characteristic analysis da hemoglobina glicada foi 0,59 (IC 95% 0,40 - 0,78), confirmando a sua reduzida capacidade de discriminação parapré-diabetes. Mais promissoras foram as áreas sob as curvas receiver operator characteristic analysis da glicemia em jejum (0,76; IC 95% 0,66 - 0,87), homeostasis model assessment for insulin resistance (0,77; IC 95% 0,64 - 0,90) e razão triglicerídeos:colesterol HDL (0,81; IC 95% 0,66 - 0,96).Discussão: Em Pediatria, particularmente em populações maioritariamente caucasianas, a hemoglobina glicada parece ser uma má ferramenta para diagnóstico de pré-diabetes.Conclusão: Pelo exposto, parece-nos prematura a utilização da hemoglobina glicada com fins diagnósticos até um maior número de estudos estar disponível. O homeostasis model assessment for insulin resistance e a razão triglicerídeos:colesterol HDL demonstraram uma maior exatidão diagnóstica, podendo ser calculados com base numa amostra única em jejum.

[New vaccines]. / Novas vacinas.

INTRODUCTION: Vaccines prevent more cases of diseases than any other medical treatment. However, information on new vaccines introduced in the market and not included in the National Vaccination Program (NVP) is often sparse, and their knowledge limited. OBJECTIVES: Evaluate general and specific knowledge of healthy children's parents on three vaccines not included in the NVP: pneumococcal (PCV7), varicella (Var) and rotavirus (RV). METHODS AND MATERIAL: Transversal descriptive study, in the format of a questionnaire applied randomly to parents of children that attended three Primary Care Centers of Portugal (Lisbon, Porto and Queluz), between March and April 2007. We analyzed sociodemographic parameters, level of knowledge (the existence and type of preventable disease by the three vaccines), its realization or intention of realization, and the availability of acquiring them by parents. Statistic analysis used Qui-Squares and T-Student tests (CI>95%), with p<0,05 considered statistically significant. RESULTS: We interviewed 187 children's parents with a median age of 13 months. Most (82%) had incomplete schooling and a mean monthly income of 1256€. In 83% of the interviews, the parents knew at least one of the vaccines: pneumococcal (72%), varicella (42%) and rotavirus (1,3%), and applying the same order, the type of disease each vaccine prevented: 118/135 (87%), 83/84 (99%) and 21/24 (87,5%). In 80% of cases, health care professionals provided the information to parents: pediatrician (67) and primary care doctor (49). Most (96%) parents considered the PCV7 the most important vaccine. Of the children evaluated, 93% had the NVS actualized, additionally, 39% had the pneumococcal vaccine, 0,5% varicella and 3% rotavirus vaccine. Knowledge about the varicella and rotavirus was associated with a higher academic level of the parents (40 vs 46,p = 0,018; 8 vs 16,p = 0,026) and the acquisition of the pneumococcal and rotavirus vaccine with a higher income (1506€ vs 1144€; p = 0,04) and (2283€ vs 1162€; p = 0,04). CONCLUSION: With exception of the PCV7 the remaining vaccines are still insufficiently known. It is up to health care professionals to disclose information and encourage families for vaccination.