Pediatric Diabetes最新文献

Objective: Wolfram Syndrome Type 1 (WS1) is a rare neurodegenerative disorder characterized by diabetes insipidus (DI), diabetes mellitus (DM), optic atrophy (OA), and deafness (D) due to biallelic mutations in the WFS1 gene. As the cardinal symptoms of DI, polyuria and polydipsia, overlap with those of DM, DI might be underdiagnosed or delayed in the early stages of WS1. In the present study, we assessed whether DI could be an early sign of WS1 and analyzed genotype-phenotype correlations in a group of Turkish patients with Type 1 DM. Patients and Methods: We applied a polyuria/polydipsia questionnaire to 1278 children with Type 1 DM. Patients with suggestive symptoms of DI were further evaluated for other clinical features of WS1 and molecular genetic analysis of the WFS1 gene. Clinical, laboratory, and genetic characteristics of cases identified using questionnaires were compared with a historical case series of seven children with WS1 and previously published literature data. Results: Eighteen patients were considered to have a diagnosis of DI, thereby being eligible for genetic analysis of WFS1 variants. Of those, six had biallelic variations (four missense variants, one in-frame duplication, and three frameshift variants) in the WFS1 gene, and a diagnosis of WS1 was confirmed. The age of admission for DM was younger in the historical cases (5.1 ± 2.0 vs. 8.7 ± 3.4; p=0.04). There was no statistically significant difference between the ages for the diagnosis of WS1 (12.9 ± 5.0 vs. 9.6 ± 2.7; p=0.191), though the diagnostic delay from DM onset to WS1 diagnosis was significantly shorter in the screened group (median 1.8 vs. 6.9 years; p ≈ 0.015). Conclusion: Our findings suggest that DI may present before OA in WS1. Enriching the diagnosis of DI using a simple polyuria/polydipsia questionnaire may provide an earlier diagnosis of WS1 in patients followed with Type 1 DM. Screening and early genetic testing of these patients enhances the diagnosis, follow-up, and management strategies of patients with WS1.

Introduction: Type 1 diabetes is commonly associated with microvascular complications. Sublingual microcirculation examination using sidestream dark-field (SDF) imaging can reflect the situation in visceral microcirculation. The main goals of this observational study were to assess the feasibility of SDF imaging in children with compensated type 1 diabetes, determine selected sublingual microcirculation parameters, and compare them with parameters obtained in healthy children.

Methods: In total 30 children with stable type 1 diabetes without clinical or laboratory signs of microvascular complications were included in the study, 15 males and 15 females in three age categories. Three video clips were recorded using an SDF probe from different parts of the sublingual area and analyzed by software-aided offline analysis.

Results: Videoclips were successfully recorded in all children. Compared with healthy children, the De Backer score (DeBS) in females and total vessel density (TVD), small vessel density (SVD), perfused vessel density (PVD), and perfused SVD (PSVD) in both genders were significantly lower in children with T1D. There were no differences in TVD, SVD, PVD, PSVD, and DeBS between age or gender categories. DeBS correlated with ketonemia; otherwise, no significant relationship was observed between microcirculatory and other recorded parameters.

Conslusions: Sublingual microcirculation examination using SDF imaging is feasible in children with type 1 diabetes. Alteration of sublingual microcirculatory parameters is detectable in children with type 1 diabetes before they show clinical or laboratory signs of any microvascular complication.

Trial registration: ClinicalTrials.gov identifier: NCT05958264.

Aims: This study aimed to identify age-related peripheral immune endotypes in pediatric patients with type 1 diabetes (T1D) at disease onset and assess their metabolic control 1 year post-diagnosis. Methods: Immune cell subpopulations (T and B lymphocytes, myeloid cells, and natural killer [NK] cells) were analyzed via multicolor flow cytometry in pediatric T1D patients and age- and sex-matched controls, grouped as <7 years, 7-12 years, and >12 years. Sociodemographic, clinical, and metabolic data were collected, including autoantibodies, bicarbonate (HCO₃), C-peptide, HbA1c, and time in range (TIR), with follow-up for 1 year to evaluate partial remission (PR) likelihood and metabolic control. Results: Patients <7 years showed reduced regulatory immune cells (memory/activated regulatory T lymphocytes (Tregs), regulatory B cells, and Th17) and more severe disease onset (shorter symptoms, greater acidosis, and lower C-peptide). Ages 7-12 exhibited increased memory B cells, particularly the unswitched ones. Myeloid cells showed no significant variation in T1D, despite age trends in controls. Anti-insulinoma-antigen 2 (IA2) titers were lower in patients >12 years, while anti-glutamic acid decarboxylase 65 (GAD65) positivity remained constant. Younger patients had lower PR rates and poorer glycemic control at 1 year. Conclusions: Younger patients face greater immune dysregulation and β-cell loss, while older patients show better immune maturity and metabolic outcomes. These differences underline the need for age-specific T1D therapies.

Aim: To examine the impact of adding an intensive, integrated telehealth intervention on glycemic control in children and adolescents with type 1 diabetes using continuous glucose monitoring (CGM) and multiple daily injections (MDIs) of insulin. Materials and Methods: In this randomized, two-period crossover trial conducted between May 2023 and June 2024, 105 children and adolescents with type 1 diabetes using FreeStyle Libre 2 CGM were randomized to receive intensive telehealth weekly over 12 weeks first followed by routine care (n = 50) or routine care over 12 weeks first followed by intensive telehealth weekly (n = 55), with a 2-week washout. Intensive telehealth was intensified follow-up with weekly teleconsultation (20 min, by telephone) and digital support from a trained diabetes educator delivering structured support, including review of the latest ambulatory glucose profile. The primary outcome measures were HbA1c and GCM metrics. Results: The average (SD) age of the study cohort (n = 105) was 11.8 (4.2) years, 48.6% were female, with an average diabetes duration of 3.5 (3.0) years and suboptimally controlled diabetes in terms of HbA1c levels (9.4 (1.6) %, target < 6.5%), and other 14-day CGM metrics. Compared with routine care, intensified follow-up with weekly intensive telehealth was associated with a decrease in HbA1c (-0.29 (0.60) %, 95%CIs -0.41 to -0.17, p  < 0.001), significantly increased time in range (TIR), and decreased time above range (TAR), average glucose level, glucose variability, glucose management indicator (GMI), and frequency of low glucose events. Teleconsultation did not affect time below range (TBR), which was already within target. Conclusion: This randomized, controlled, and crossover study shows that intensified follow-up with a weekly telehealth intervention results in small but significant improvements in glycemic control metrics in children and adolescents. The clinical impact of these changes requires prospective study.

Objective: To design a dynamic prediction model for estimating the time of progression from a single glutamic acid decarboxylase autoantibody (GADA) to multiple islet autoantibodies and type 1 diabetes in children, exploring different longitudinally measured risk variables. Research Design and Methods: GADA-positive children (n = 379) participating in The Environmental Determinants of Diabetes in the Young (TEDDY) study were followed for the appearance of additional autoantibodies against either insulin autoantibody (IAA), insulinoma-like 2 autoantibody (IA-2A), or zinc transporter 8 antibody (ZnT8A) and type 1 diabetes. A dynamic prediction model was designed, including trajectories of longitudinal risk variables, autoantibody titers, and metabolic variables (C-peptide, glucose, and HbA1c) together with time-invariant variables (gender, age at GADA positivity, and high-risk HLA genotypes). Results: Transition risk from GADA to multiple autoantibodies was increased by lower age (p < 0.001) and by increased GADA titers during follow-up (p < 0.001), and was less likely in children with HLA DQ2/X but not DQ2/8 (p=0.004). The transition risk from multiple autoantibodies without IA-2A to IA-2A positivity was associated with increased levels of 2 h glucose following oral glucose tolerance test (OGTT) (p < 0.001) and increased ZnT8A titers (p < 0.001). Increasing HbA1c (p < 0.001) and GADA titers (p < 0.001) were associated with an increased risk of transition from GADA only to type 1 diabetes; while increasing HbA1c (p < 0.001) was associated with the transition from multiple autoantibodies to type 1 diabetes. Risk of transition from multiple autoantibodies, including IA-2A to type 1 diabetes was also associated with 2 h glucose level (p < 0.001). Conclusion: The dynamic prediction model presented an individual time-specific risk of transition from a single GADA to multiple autoantibodies and type 1 diabetes.

Aims: To establish the current prevalence of type 2 diabetes in children and adolescents aged under 16 years in the Republic of Ireland, to identify modes of presentation, patient characteristics, comorbidities, management, and outcomes. Methods: We conducted a cross-sectional study of children and adolescents aged under 16 years with a diagnosis of type 2 diabetes in September 2023 using a standardized proforma. This was circulated to all clinicians providing care to children with diabetes in all 19 centers in the Republic of Ireland. Results: Thirty-two cases of type 2 diabetes were identified, giving an estimated prevalence in children and adolescents under 16 years of 3/100,000 population, a significant increase from 1.2/100,000 population in 2015 (p  < 0.004). This was due to increased prevalence rates in, both White and Asian populations, as well as an increase in the size of the Asian population under 16. Nineteen (59%) were girls. Median duration of diabetes was 1.2 (0.1-4.9) years. Median body mass index (BMI) z-score at diagnosis was identical to the 2015 study (+2.3). Sixteen (50%) achieved the target HbA1c specified by the International Society for Pediatric and Adolescent Diabetes (ISPAD) of 48 mmol/mol (6.5%) or less. Completion of screening for comorbidities and complications of type 2 diabetes were not in accordance with guidelines. Conclusion: There has been a significant increase in the prevalence of type 2 diabetes in under 16's in a short timeframe. Establishment of a National Diabetes Register will facilitate ongoing monitoring of disease epidemiology in this and other age cohorts.

Objective: Seasonal variation in type 1 diabetes (T1D) incidence has long been a focus of epidemiological research, with viral infections among the proposed contributing factors. Our aim was to examine the seasonal pattern of T1D onset in Poland and to assess how viral infections-including COVID-19-may influence this seasonality. Methods: We analyzed data from 2381 children with newly diagnosed T1D admitted to two pediatric diabetes centers in the Masovian Voivodeship between 2015 and 2023 and compared them with epidemiological data on COVID-19 and influenza cases during the same period. Results: Our analysis revealed a 30% increase in T1D cases over the study period, with a pronounced seasonal pattern: the highest number of diagnoses occurred in February and the lowest was noted in June. Children under 4 years of age exhibited a distinct pattern with a peak in October, suggesting age-specific differences in T1D pathogenesis. Overall, T1D onset was more frequent in autumn-winter than in spring-summer, with 1294 (54%) vs. 1087 (46%) cases, respectively (p  < 0.0001). The influence of COVID-19 on T1D incidence was limited to the first wave of the pandemic. During this period, a strong association was observed (r = 0.96, p  < 0.001), whereas no correlation was found during the second wave (r = 0.086, p = 0.87). The seasonality of T1D diagnoses closely correlated with that of influenza infections (r = 0.79, p = 0.002). However, the overall trends differed, suggesting that other viruses with similar transmission patterns may contribute to the seasonality of T1D onset. Conclusion: These findings underline the complex interplay between viral infections and T1D seasonality and suggest that public health strategies aimed at mitigating severe viral infections, including vaccination, warrant further investigation for their potential role in modulating T1D onset in susceptible individuals.

Objective: Mauriac syndrome (MS) is a rare condition linked to inadequate glycemic control in type 1 diabetes mellitus (T1DM) and has also rarely been reported in patients with neonatal diabetes. MS manifests as growth failure, delayed puberty, cushingoid features, and hepatomegaly. The condition can be associated with complications like dyslipidemia, retinopathy, and nephropathy. The main objective of this study was to describe the magnitude of the condition, clinical features, management, and outcome of Sudanese children and adolescents with MS due to inadequate control of diabetes in our center. Study Design and Methods: This is a cross-sectional hospital-based study. All medical records of patients with MS were reviewed. Data, including demographics, clinical features, investigations, management, and outcome, were obtained. Patients were re-educated and management intensified then followed up. Results: Thirty-seven MS patients were enrolled in this study, with a male predominance of 59.5%. Neonatal diabetes was diagnosed in 5.4% of the patients, while others had T1DM. The median age at diagnosis of MS was 12 years. The diagnosis was based solely on clinical findings, including a history of prolonged unsatisfactory glycemic control, short stature, and hepatomegaly. Regarding the outcome, eight children (21.6%) were lost to follow-up, one patient died (2.7%), seven (18.9%) had a static condition, and those who showed improvement were 21 (56.8%). Signs of improvement were a decrease in liver size with or without an increase in growth velocity. Nephropathy was the most common associated complication; it was seen in 33.3% of our cohort. Some got it at a very young age. Conclusions: Despite many efforts that have been made to achieve better glycemic control in children with T1DM, MS still exists in our setting. Though liver biopsy is the gold standard for diagnosis, being invasive, the diagnosis could be made conservatively, based on clinical features and response to treatment. The condition can be reversed with good metabolic control.

[This corrects the article DOI: 10.1111/pedi.13409.].

Objective: To expand the effective local Stuttgart childhood diabetic ketoacidosis (DKA) prevention campaign to the federal state of Baden-Württemberg (BW) in Germany. Research Design and Methods: All public health departments (PHDs) in BW were invited to participate. The DKA-incidence at diabetes onset was compared between participating and nonparticipating districts, prior (2015-2020) and during the campaign (2021-2023). Results: A total of 3038 children and adolescents were newly diagnosed with type 1 diabetes in BW during the observation period. DKA was present in 990 children (32.6%), severe DKA in 346 (11.4%). In total 14 of 38 PHD (37%) participated. DKA rates increased both in participating (29.9%-36.3%) and in nonparticipating districts (27.0%-41.0%; p < 0.0001 for time-trend). However, there was a significant interaction between time-interval and the groups of districts (p < 0.03) reflecting a significant treatment effect in the intervention group. Conclusions: The expansion of our local awareness campaign was possible and successful.