Pediatric Diabetes最新文献

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.

Background: Urologic complications, including urinary incontinence and urinary tract infections are commonly observed in the adult population with type 1 diabetes (T1D); however, there remains a paucity of data on the prevalence, associated risk factors and impact of bowel and bladder dysfunction (BBD) in the pediatric T1D population. Aim: This study aims to examine the prevalence of BBD in children with T1D compared to healthy pediatric controls and to explore clinical factors associated with childhood BBD. Methods: This cross-sectional, noninterventional, multicenter survey study involved children with TID and healthy controls aged 5-16 years across North America. Participants and their caregivers completed the Vancouver Symptom Score (VSS) to assess bowel and bladder symptoms. BBD was defined as a total VSS score of 11 or greater. Logistic regression was used to identify potential factors associated with BBD and bother with symptoms. Results: In a group of 242 participants with T1D and 86 controls, 46% were male, and the median age was 11.0 years. The prevalence of BBD was found to be higher in participants with T1D at 21.5%, compared to 10.5% in controls. While irritative symptoms were most commonly reported in the T1D group with BBD, urinary incontinence caused the most bother. In the T1D group, poorer glycemic control was linked to a greater likelihood of BBD, while male sex and more severe symptomatology (such as urinary incontinence) were associated with greater bother related to these symptoms. Conclusion: There is a high prevalence of BBD in children with T1D compared to healthy controls. These data highlight the need for early identification and intervention for BBD in T1D. Proactive measures, such as routine screening and comprehensive T1D management with strict attention to glycemic control, are crucial to address the significant burden of BBD and improve overall health outcomes for children with T1D and their families.

Objective: This study aimed to present a quantitative modeling and simulation approach for oral henagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor primarily metabolized by uridine diphosphate-glucuronosyltransferase (UGT) enzymes. Methods: A physiologically-based pharmacokinetic (PBPK) model for henagliflozin was developed using in vitro metabolism and clinical pharmacokinetic (PK) data, with validation across multiple contexts, including healthy adults, and hepatic impairment populations. Additionally, empirical pharmacodynamic (PD) modeling was employed to optimize pediatric dosing based on exposure-response relationships for urinary glucose excretion (UGE). Predicting henagliflozin exposure in pediatric patients poses challenges due to UGT enzyme ontogeny and the scarcity of clinical PK data in younger age groups. Using twofold acceptance criteria, model-predicted and observed drug exposures and PK parameters (area under the curve and peak concentration) were compared in diverse scenarios, including monotherapy in healthy adults (single/multiple doses), hepatic impairment, and extrapolation to pediatric age groups. Results: The PBPK model accurately captured observed exposures within a twofold range in both adults and adolescents, supporting the model's predictive utility. The verified PBPK and empirical PD models informed dosing recommendations in pediatric populations aged 1 month to 18 years, achieving henagliflozin exposures comparable to those in adult patients receiving a 5-10 mg dose. Conclusion: This study shows that PBPK and PD modeling effectively guide pediatric dosing of henagliflozin, reducing trial reliance and supporting real-world validation.

Objective: Children with type 1 diabetes (T1D) have an increased risk of developing additional autoimmune diseases. The risk of developing celiac disease (CD) is 3-4 times higher in children with T1D. Guidelines recommend regular screening for transglutaminase antibodies (TgAbs) in T1D children. CD could be an additional burden for T1D children as both diseases affect food intake. We describe the screening practice for CD during the last 25 years in our outpatient clinic in children with T1D. Methods: We retrospectively analyzed the development of CD-specific antibodies in our children with T1D (diabetes onset since 1998). We did not routinely recommend endoscopy when CD-specific antibodies (TgAb, endomysium [EAb], and gliadin) were positive and patients had no CD-specific symptoms. Results: We analyzed 304 patients. In total 122 had CD-specific antibodies. In 98 of them, they disappeared after a short time or had been only slightly elevated. The diagnosis of CD was confirmed in 12. All 12 showed CD-specific symptoms, such as failure to thrive, anemia, hypoglycemia, or gastrointestinal problems. In six patients, even severely elevated EAb and/or TgAb disappeared on average after 7.1 years (range 4.9-13.5 years) on gluten-containing diet. The remaining six had antibodies without CD-specific symptoms by the end of the observation period. In this group the duration of antibody-positivity was 4 years (range 1.8-11.6 years). Conclusion: We conclude that even highly elevated CD-specific antibodies can disappear in children with T1D and that screening for CD-specific antibodies is therefore only useful in symptomatic children with T1D.

Wolfram syndrome type 1 gene (WFS1), which encodes a transmembrane (TM) structural protein (wolframin), is essential for several biological processes. Mutations of WFS1, autosomal dominant or recessive inherited, are related to a broad clinical spectrum. Molecular genetic tests were performed, and clinical phenotypes of three WFS1-associated cases were evaluated. The expression of WFS1, viability, and endoplasmic reticulum (ER) stress of the MIN6 cell and structural analysis of the variant WFS1 protein were revealed. Furthermore, a total of 75 pathogenic WFS1 variants from ClinVar were included to analyze variant-phenotype association. Genetic testing revealed 3 mutations with unclear pathogenicity in WFS1 of the 3 patients with early-onset diabetes, including c.613G >A (p.G205S), c.2053C >T (p.R685C), and c.169G >A (p.A57T). Decreased expression, reduced β-cell viability and enhanced ER stress were found in all variants. Protein stability and structural analysis showed increased protein stability and molecule flexibility of variants p.R685C in the ER-lumenal domain and p.A57T in the ATP6VIA-interaction region, while destabilized protein and rigidificated structure by p.G205S variant in the EF-hand domain at the cytoplasm region. Remarkably, topology was found an independent risk factor with urological symptoms (USs) (p=0.007, odds ratio [OR] 4.768 [95% confidence interval (CI): 1.531-14.854]). Surprisingly, variants in the cytoplasm had the highest risk with US than ones in the ER-lumenal domain (p=0.008, OR 22.013 [95% CI: 2.270-213.428]). The functional analysis of the three variants of uncertain significance in WFS1 indicated a quantitative and qualitative damage to wolframin with proven pathogenicity. The topology of the WFS1 protein may play an important role in the pathogenesis of β-cell and urological defects in WFS1-associated disease.