Celiac Disease (CD) occurs in patients with Type 1 Diabetes (T1D) ranging the prevalence of 4.4-11.1% versus 0.5% of the general population. The mechanism of association of these two diseases involves a shared genetic background: HLA genotype DR3-DQ2 and DR4-DQ8 are strongly associated with T1D, DR3-DQ2 with CD. The classical severe presentation of CD rarely occurs in T1D patients, but more often patients have few/mild symptoms of CD or are completely asymptomatic (silent CD). In fact diagnosis of CD is regularly performed by means of the screening in T1D patients. The effects of gluten-free diet (GFD) on the growth and T1D metabolic control in CD/T1D patient are controversial. Regarding of the GFD composition, there is a debate on the higher glycaemic index of gluten-free foods respect to gluten-containing foods; furthermore GFD could be poorer of fibers and richer of fat. The adherence to GFD by children with CD-T1D has been reported generally below 50%, lower respect to the 73% of CD patients, a lower compliance being more frequent among asymptomatic patients. The more severe problems of GFD adherence usually occur during adolescence when in GFD non compliant subjects the lowest quality of life is reported. A psychological and educational support should be provided for these patients.
Objective: Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features. Design: Retrospective analysis of the Italian data set of patients with TNDM. Methods: Clinical features and treatment of 22 KATP/ TNDM patients and 12 6q24/TNDM patients were compared. Results: Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; -2.27 SD) than those with KATP mutations (4.0 weeks; -1.04 SD) (p=0.009 and p=0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 vs 12 weeks) (p=0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy. Conclusions: If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.
We estimated perceived difficulty with physical tasks, lifestyle, and physical performance in 382 children and adolescents (163 obese, 54 overweight, and 165 normal-weight subjects) and the relationship between perceived physical difficulties and sports participation, sedentary behaviors, or physical performance. Perceived difficulty with physical tasks and lifestyle habits was assessed by interview using a structured questionnaire, while physical performance was assessed through the six-minute walking test (6MWT). Obese children had higher perceived difficulty with several activities of daily living, were less engaged in sports, and had lower physical performance than normal-weight or overweight children; on the contrary, they did not differ with regard to time spent in sedentary behaviors. Perceived difficulty in running and hopping negatively predicted sports participation (P < 0.05 and <0.01, resp.), while perceived difficulty in almost all physical activities negatively predicted the 6MWT, independently of BMI (P < 0.01). Our results indicate that perception of task's difficulty level may reflect an actual difficulty in obese children. These findings may have practical implications for approaching physical activity in obese children. Exploring both the perception of a task's difficulty level and physical performance may be useful to design exercise programs that allow safe and successful participation.
Type 1 diabetes is characterized by autoimmune destruction of pancreatic β-cells in genetically susceptible individuals. Triggers of islet autoimmunity, time course, and the precise mechanisms responsible for the progressive β-cell failure are not completely understood. The recent escalation of obesity in affluent countries has been suggested to contribute to the increased incidence of type 1 diabetes. Understanding the link between metabolism and immune tolerance could lead to the identification of new markers for the monitoring of disease onset and progression. We studied several immune cell subsets and factors with high metabolic impact as markers associated with disease progression in high-risk subjects and type 1 diabetic patients at onset and at 12 and 24 months after diagnosis. A multiple correlation matrix among different parameters was evaluated statistically and assessed visually on two-dimensional graphs. Markers to predict residual β-cell function up to 1 year after diagnosis were identified in multivariate logistic regression models. The meta-immunological profile changed significantly over time in patients, and a specific signature that was associated with worsening disease was identified. A multivariate logistic regression model measuring age, BMI, fasting C-peptide, number of circulating CD3+CD16+CD56+ cells, and the percentage of CD1c+CD19−CD14−CD303− type 1 myeloid dendritic cells at disease onset had a significant predictive value. The identification of a specific meta-immunological profile associated with disease status may contribute to our understanding of the basis of diabetes progression.
Purpose of review Non-diabetic hyperglycemia (NDHY) is a pathological condition that is not yet well known. The aim of this review is to examine approaches for management of this condition. Recent findings While it is well known that persistent hyperglycemia in diabetes affects immune response and risk for diabetesrelated micro-and macrovascular complications, little is known about the biological effects of transient NDHY, particularly in the pediatric age group. Summary Stress HY (SHY) is typically defined as blood glucose > 8.33 mmol/L (150 mg/dL) during physical stress, resolving spontaneously after dissipation of acute illness in patients without known diabetes. Based on the literature and clinical practice, two situations can be classified: (1) SHY1, which occurs during severe and prolonged illness and under serious life-threatening conditions, mainly in emergency situations and in resuscitation areas; and (2) SHY2, which occurs during acute illness, mainly in non-life-threatening conditions. Furthermore, (NDHY) among pediatric patients can be induced by drugs; the most frequent conditions are secondary to (1) steroid therapy and (2) antineoplastic/immunosuppressive therapy. Keywords Non-diabetic hyperglycemia . Stress hyperglycemia . Drug-induced hyperglycemia . Management This article is part of the Topical Collection on Pediatric Type 2 and Monogenic Diabetes * Enza Mozzillo
Cystic fibrosis (CF)-related diabetes mellitus is an unusual complication in very young pediatric patients with CF. It is generally associated with more severe clinical manifestations of CF. In this report, we describe a case of diabetes and CF starting in infancy. The patient manifested a form of intermittent diabetes without fasting hyperglycemia, which was exacerbated by steroid treatment during pulmonary disease and occasionally required insulin therapy. Insulin responses to oral and intravenous glucose challenge were low. The clinical and radiological status was stable during the 9-yr follow-up. Our patient demonstrates that diabetes may not only represent a complication of CF, as previously maintained, but can also be a co-morbid condition proceeding along with the exocrine disease. The early occurrence of hyperglycemia in this case may highlight an impairment of beta-cell function, which might be genetically determined. Careful monitoring of the glucose profile and of beta-cell function is indicated in patients with CF to avoid late recognition of diabetes.
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