Search

Introduction: The impact of ETI therapy on pulmonary function and nutritional status has been widely studied; the literature on the possible outcomes on glycemic control and insulin requirement in patients affected by CFRD is controversial. Aim: The main objective of our study was to evaluate HbA1c levels in patients with cystic fibrosis-related diabetes (CFRD) after one year of therapy with elexacaftor/tezacaftor/ivacaftor (ETI). The secondary objective was to study the changes in the total daily insulin dose (TDD), pulmonary function and metabolism in this population. Materials and methods: A retrospective single-center observational study was conducted at the Regional Cystic Fibrosis Centre and Diabetology Centre of IRCCS Istituto Giannina Gaslini. The observation period was divided into four different time points: initiation (T0), 3 months (T3mo), 6 months (T6mo) and 12 months (T12mo) of ETI therapy. Demographic and clinical data were collected. The results were then stratified by genotype (homozygous or heterozygous F508del). Results: Twenty-eight patients with CFRD undergoing insulin therapy were included. TDD (IU) significantly decreased at T3mo and T6mo, but not at T12mo, whereas HbA1c decreased significantly at all three times. The number of hospitalizations and pulmonary exacerbations decreased significantly. Conclusion: We demonstrated both improvement in glycemic control (by means of HbA1c) and insulin requirement in insulin-dependent CFRD patients after one year of ETI treatment. [ABSTRACT FROM AUTHOR]

The case report shows the safety and efficacy of insulin treatment with Advanced Hybrid Closed Loop (AHCL) system in a young patient affected by permanent neonatal diabetes mellitus (PNDM) due to chromosome 8 deletion syndrome involving the GATA4 gene. In the first days of life, he presented hyperglycaemia and started an intravenous insulin infusion therapy, replaced by a continuous subcutaneous insulin infusion (CSII) with Medtronic Minimed 780G® insulin pump (Medtronic, Northridge, CA, USA). At the age of 2 years, the off-label activation of SmartGuard® automated insulin delivery mode led to a great improvement in glycaemic control, reaching all recommended targets. At the 1-month follow-up visit, Time in Range (TIR) increased from 66% to 79%, with a Time in Tight Range (TTIR) of 55% and a reduction of 11% in time in hyperglycaemia and of 2% in time in hypoglycaemia. During the entire follow-up, no episodes of ketoacidosis or severe hypoglycaemia were observed and the patient maintained the glycaemic recommended targets reached at 1 month. Maintaining optimal glycaemic control and reducing hyperglycaemia are essential for brain growth and neurocognitive development in young patients. AHCL use should be considered to ensure good glycaemic control in patients affected by neonatal diabetes. [ABSTRACT FROM AUTHOR]

Context In the last decade the Sanger method of DNA sequencing has been replaced by next-generation sequencing (NGS). NGS is valuable in conditions characterized by high genetic heterogeneity such as neonatal diabetes mellitus (NDM). Objective To compare results of genetic analysis of patients with NDM and congenital severe insulin resistance (c.SIR) identified in Italy in 2003-2012 (Sanger) vs 2013-2022 (NGS). Methods We reviewed clinical and genetic records of 104 cases with diabetes onset before 6 months of age (NDM + c.SIR) of the Italian dataset. Results Fifty-five patients (50 NDM + 5 c.SIR) were identified during 2003-2012 and 49 (46 NDM + 3 c.SIR) in 2013-2022. Twenty-year incidence was 1:103 340 (NDM) and 1:1 240 082 (c.SIR) live births. Frequent NDM/c.SIR genetic defects (KCNJ11 , INS , ABCC8 , 6q24, INSR) were detected in 41 and 34 probands during 2003-2012 and 2013-2022, respectively. We identified a pathogenic variant in rare genes in a single proband (GATA4) (1/42 or 2.4%) during 2003-2012 and in 8 infants (RFX6 , PDX1 , GATA6 , HNF1B , FOXP3 , IL2RA , LRBA , BSCL2) during 2013-2022 (8/42 or 19%, P =.034 vs 2003-2012). Notably, among rare genes 5 were recessive. Swift and accurate genetic diagnosis led to appropriate treatment: patients with autoimmune NDM (FOXP3 , IL2RA , LRBA) were subjected to bone marrow transplant; patients with pancreas agenesis/hypoplasia (RFX6 , PDX1) were supplemented with pancreatic enzymes, and the individual with lipodystrophy caused by BSCL2 was started on metreleptin. Conclusion NGS substantially improved diagnosis and precision therapy of monogenic forms of neonatal diabetes and c.SIR in Italy. [ABSTRACT FROM AUTHOR]

Background and aims: Cystic fibrosis related diabetes (CFRD) is correlated with worsening of nutritional status and greater deterioration of lung function. The role of new technologies for the treatment of CFRD is little explored. The aim of the study was to evaluate the efficacy of Advanced Hybrid Closed Loop (AHCL) systems on glycemic control in CF patients. Methods: A single-center retrospective study on CFRD patients using AHCL systems was performed. Glycated hemoglobin (HbA1c) values and Continuous Glucose Monitoring (CGM) metrics were collected at T0 (AHCL placement), T1 (1-month), T2 (6-months) and T3 (1-year) to evaluate glycemic control. Results: 10 patients were included in the study. Data showed a reduction of HbA1c value (7.31 ± 0.34 to 6.35 ± 1.00; p=0.03), glycemic variability (p=0.05) and insulin requirement (p=0.03). The study population reached American Diabetes Association (ADA) recommended glycemic targets at 1-year. An increase in the Time in Range (TIR) and a reduction in time in hyperglycemia were also observed, although not statistically significant. Conclusions: In patients with CFRD, the use of AHCL leads to an improvement in glycemic control in terms of HbA1c and glycemic variability. The increase in TIR and the reduction of time in hyperglycemia, although not statistically significant, are extremely encouraging from a clinical point of view. Further studies with a larger population and a longer follow-up are needed. The results of this study demonstrate the importance of proposing the use of AHCL even in CF patients, who could benefit from glycemic improvement also in terms of nutritional status and respiratory function. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) has been frequently associated with an impaired immune response against infectious agents, making affected patients at risk for more severe disease and sometimes causing worse outcomes. The recent COVID-19 pandemic has seriously affected patients with both diabetes, in particular those carrying comorbidities or with poor glycemic control. As regards pediatric diabetes mellitus, the availability of more accurate and technological tools for glycemic management and the improved markers of metabolic control might mitigate the negative impact of infections. Notably, good metabolic control of diabetes since its diagnosis reduces not only the risk of microangiopathic complications but also of impaired immune response to infectious diseases. Therefore, vaccinations are strongly recommended. Our paper aims to provide the most updated evidence regarding infectious diseases in type 1 pediatric DM. [ABSTRACT FROM AUTHOR]

Monogenic diabetes is a rare form of diabetes, accounting for approximately 1% to 6% of pediatric diabetes patients. Some types of monogenic diabetes can be misdiagnosed as type 1 diabetes in children or adolescents because of similar clinical features. Identification of the correct etiology of diabetes is crucial for clinical, therapeutic, and prognostic issues. Our main objective was to determine the prevalence of monogenic diabetes in patients with diabetes mellitus, diagnosed in childhood or in adolescence, and negative autoimmunity. We retrospectively analyzed clinical data of 275 patients diagnosed with insulin-dependent diabetes at age <18yr in the last 10 years. 8.4% of subjects has negative autoimmunity. Their DNA was sequenced by NGS custom panel composed by 45 candidate genes involved in glucose metabolism disorder. Two novel heterozygous pathogenic or likely pathogenic variants (10,5% of autoantibody negative subjects) were detected: the frameshift variant c.617_618insA in NEUROD1 exon 2 and the missense change c.116T>C in INS exon 2. Our study corroborates previous results of other reports in literature. NGS assays are useful methods for a correct diagnosis of monogenic diabetes, even of rarest forms, highlighting mechanisms of pediatric diabetes pathogenesis. [ABSTRACT FROM AUTHOR]

Aim: To ascertain whether the prevalence of retinopathy has declined over the last 2 decades in individuals with childhood‐onset type 1 diabetes and whether this might be explained by changes in lifetime HbA1c. Materials and Methods: A multicentre, retrospective, observational study, comparing 128 subjects with diabetes onset in 2000‐2003 assessed for retinopathy in 2016‐2019, with a previous cohort of 115 individuals diagnosed in 1990‐1993 and assessed for retinopathy in 2007‐2009, was conducted. The two cohorts had both a similar diabetes duration and age at diagnosis. Retinal photographs were centrally graded. Lifetime HbA1c and its variability, estimated as the ratio between intrapersonal mean and standard deviation of HbA1c, were evaluated. Results: The prevalence of any retinopathy in the new and old cohort was 24.2% and 43.5% (P <.003), respectively, and that of severe retinopathy was 1.7% and 9.6% (P =.018). Lifetime HbA1c was lower in the new cohort (7.8% ± 0.8% vs. 8.1% ± 0.8%; P =.002) during all periods following the first 5 years after diagnosis. Patients without retinopathy in the two cohorts had similar levels of HbA1c. Compared with patients without retinopathy, those with retinopathy had higher lifetime HbA1c and long‐term HbA1c variability. However, on multiple regression analysis, only lifetime HbA1c was independently associated with retinopathy (P =.0018). Conclusions: The risk of developing retinopathy was nearly halved in children who developed type 1 diabetes in the new millennium compared with previous cohorts. These results confirm that maintaining the lowest possible levels of HbA1c throughout lifetime protects from diabetic retinopathy. [ABSTRACT FROM AUTHOR]

OBJECTIVE-- Wolfram syndrome is an autosomal recessive neurodegenerative disorder characterized by diabetes insipidus, diabetes (nonautoimmune), optic atrophy, and deafness (a set of conditions referred to as DIDMOAD). The WFS1 gene is located on the short arm of chromosome 4. Wolfram syndrome prevalence is 1 in 770,000 live births, with a 1 in 354 carrier frequency. RESEARCH DESIGN AND METHODS-- We evaluated six Italian children from five unrelated families. Genetic analysis for Wolfram syndrome was performed by PCR amplification and direct sequencing. RESULTS-- Mutation screening revealed five distinct variants, one novel mutation (c.1346C>T; p.T449I) and four previously described, all located in exon 8. CONCLUSIONS-- Phenotype-genotype correlation is difficult, and the same mutation gives very different phenotypes. Severely inactivating mutations result in a more severe phenotype than mildly inactivating ones. Clinical follow-up showed the progressive syndrome's seriousness. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article on strong epidemiologic association between type 1 diabetes and epilepsy by D. McCorry and colleagues.