The European Society for Paediatric Endocrinology (ESPE) e-Learning wesite is a free, globally accessible online resource to enhance learning in pediatric endocrinology and pediatric diabetes. The content is created by world-leading experts in pediatric endocrinology and pediatric diabetes and is closely aligned with published international consensus guidelines. In August 2022, 30 hours of e-learning courses received accreditation from the European Accreditation Council for Continuing Medical Education (CME). These CME courses cover three categories: (1) pediatric endocrinology, (2) pediatric diabetes, and (3) pediatric endocrinology in resource-limited settings. This study aimed to assess learners' demographics and feedback from mandatory surveys after completion of CME e-learning courses and to identify areas for improvement. The ESPE e-learning committee created a mandatory survey for each CME e-learning module. The survey includes baseline demographics and feedback on the quality of the learning content, assessed using a 5-point Likert scale. Data were extracted from the start of the CME modules in August 2022 until September 2025. A total of 567 surveys were completed: 286 (50.4%) in the category pediatric endocrinology, 225 (39.7%) in the category pediatric diabetes based on the International Society for Pediatric and Adolescent Diabetes guidelines, and 56 (9.9%) in the category pediatric endocrinology in resource-limited settings. There was global participation, with most learners practicing in Europe (n=333, 59%), followed by Asia (n=124, 22%), Africa (n=53, 9%), the Americas (North America, n=45, 8%; and South America, n=11, 2%), and Oceania (n=1, 0%). Most of the users indicated that they were medical experts (n=210, 37%), followed by fellows or residents (n=223, 39%), and medical students and nurses (n=29, 5% and n=32, 6%, respectively); overall, 10% (n=56) of learners practice in resource-limited countries. Overall, the learning content was well received for all modules regarding accessibility, organization, level of interest, improvement of learners' clinical practice, appropriateness of content, and provision of feedback (median Likert score 4, IQR 4-5). Learners' free-text feedback identified some areas for improvement, including reducing text-heavy content and providing more graphical content and more interactive case reports. Most learners' free-text feedback consisted of encouraging and thankful comments. The ESPE CME-accredited e-learning modules are well received, providing globally free CME education in pediatric endocrinology and pediatric diabetes. These findings support the continued development and promotion of open-access CME platforms, with the aim of improving global equity in specialist medical education and focusing on educational impact.
The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.
Type 1 diabetes mellitus (T1D) is one of the most common chronic diseases in childhood, with its incidence increasing globally. The coronavirus disease 2019 (COVID-19) pandemic has been associated with an increase in severity of cases of diabetic ketoacidosis. Type 1 diabetes mellitus (T1D) is one of the most common chronic diseases in childhood, with its incidence increasing globally. The coronavirus disease 2019 (COVID-19) pandemic has been associated with an increase in severity of cases of diabetic ketoacidosis. A retrospective cohort study was conducted, using patients' clinical records, between March 2016 and March 2024. The sample was divided in three groups: pre-pandemic (March 2016 to March 2020), pandemic (March 2020 to March 2021), and post-pandemic (March 2021 to March 2024). A retrospective cohort study was conducted, using patients' clinical records, between March 2016 and March 2024. The sample was divided in three groups: pre-pandemic (March 2016 to March 2020), pandemic (March 2020 to March 2021), and post-pandemic (March 2021 to March 2024). There was an improvement in the post-pandemic period, with a lower severity at presentation. However, the rate of ketoacidosis remained high, and the focus must remain on implementing preventative measures. Cukrzyca typu 1 jest jedną z najczęstszych chorób przewlekłych wieku dziecięcego, a jej częstość występowania wzrasta na całym świecie. Pandemia COVID-19 wiązała się ze zwiększoną częstością i ciężkością przypadków kwasicy ketonowej u dzieci z nowo rozpoznaną cukrzycą. Ocena ciężkości nowych przypadków cukrzycy typu 1 w szpitalu pediatrycznym po pandemii COVID-19 w porównaniu z okresem przed- i pandemicznym. Retrospektywne badanie kohortowe obejmowało pacjentów hospitalizowanych od marca 2016 r. do marca 2024 r., podzielonych na trzy grupy: przedpandemiczną (2016–2020), pandemiczną (2020–2021) i popandemiczną (2021–2024). Odnotowano 159 przypadków, z czego 79 w okresie przed pandemią, 26 w roku pandemii i 54 w okresie po pandemii. W grupie pandemicznej odnotowano znacznie niższe średnie pH (7,19 w porównaniu z 7,31 i 7,32 w grupach przed pandemią i po pandemii, p < 0,001 i p = 0,002) oraz niższe stężenie HCO3 (14,2 mmol/l w porównaniu z 19,3 i 20,5 mmol/l w grupach przedpandemicznej i popandemicznej, p < 0,001 i p = 0,011). Stężenie ketonów we krwi było wyższe w grupie pandemicznej (5,1 mmol/l w porównaniu z 3,0 i 3,1 w grupach przedpandemicznej i popandemicznej, p < 0,001 i p < 0,001). Średnia utrata masy ciała była większa w grupie pandemicznej w porównaniu z grupą przedpandemiczną (10,2% w porównaniu z 6,5%, p = 0,020). Nie stwierdzono żadnych innych różnic między trzema grupami. Po pandemii odnotowano łagodniejszy przebieg nowych przypadków cukrzycy typu 1, jednak odsetek kwasicy ketonowej pozostaje wysoki. Konieczne jest dalsze wzmacnianie działań profilaktycznych i edukacyjnych.
This retrospective chart review investigated the relationship between 25-hydroxyvitamin D levels and the initial clinical and biochemical presentation of type 1 diabetes mellitus (T1DM) in children under 18 years of age, specifically: (1) presence or absence of diabetic ketoacidosis and the severity of diabetic ketoacidosis (DKA) - among those with DKA, and (2) beta-cell function. This study included 99 children with new-onset Type 1 Diabetes Mellitus (T1DM). Patients were diagnosed at our pediatric endocrinology practice at Northwell Health between June 2023 and February 2025. A diagnosis of T1DM at the time of presentation was confirmed by the presence of at least one positive diabetes-specific autoantibody, and all included patients were required to have a 25-hydroxyvitamin D level measured within two days of presentation. Data extracted from the electronic health record included demographics, 25-hydroxyvitamin D levels at diagnosis, hemoglobin A1C, measures of DKA severity (pH, bicarbonate, beta-hydroxybutyrate, and DKA severity categorization), and beta-cell function (insulin and C-peptide levels). Statistical analyses included univariate tests, Spearman correlations, and multivariable logistic regression adjusting for race, ethnicity, and insurance status. Among 99 patients (mean age 10.3 ± 4.4 years, 50.5% female), 53.5% presented in DKA. After adjusting for race, ethnicity, and insurance status, higher 25-hydroxyvitamin D levels were significantly associated with less severe acidosis, showing moderate positive correlations with pH (rho=0.44, p<0.0001) and bicarbonate (rho=0.42, p<0.0001), and a weak negative correlation with beta-hydroxybutyrate (rho=-0.28, p=0.01), indicating higher 25-hydroxyvitamin D levels were associated with less severe acidosis. There was a significant association between 25-hydroxyvitamin D levels and presentation in DKA; each one-unit increase in 25-hydroxyvitamin D was associated with a 6% decrease in the odds of presenting in DKA (OR: 0.94, 95% CI: 0.89-0.99, p=0.03). 25-hydroxyvitamin D levels were significantly associated with DKA severity (p=0.01), with lower levels observed in patients with more severe DKA. No significant association was found between 25-hydroxyvitamin D levels and HbA1c or markers of beta-cell function. These findings suggest a potential protective role of 25-hydroxyvitamin D against severe metabolic decompensation at T1DM onset, specifically relating to DKA, but not beta-cell function. Further research is needed to confirm these findings and explore the potential mechanisms and clinical implications.
The incidence of type 2 diabetes (T2D) in children is rising rapidly, yet many cases remain undetected. Conventional diagnostic tools, including fasting glucose, HbA1c, and the gold-standard oral glucose tolerance test (OGTT), have limitations and often show low compliance in pediatric populations. This study aimed to evaluate a simplified OGTT (s-OGTT) with adjusted capillary glucose cut-off values as a novel approach for screening and diagnosing T2D in children and adolescents. A total of 468 children from four clinical centers in China underwent s-OGTT with capillary glucose testing. Capillary glucose values were compared with venous glucose levels using Bland-Altman analysis. Sensitivity and specificity for diagnosing diabetes and prediabetes were assessed using receiver operating characteristic (ROC) curves. Capillary glucose levels showed a strong correlation with venous measurements. Based on gold-standard criteria, 37 children were diagnosed with diabetes, 41 with impaired fasting glucose (IFG), and 74 with impaired glucose tolerance (IGT). Using optimized capillary cut-offs tailored for point-of-care testing, the s-OGTT demonstrated excellent diagnostic performance and improved specificity compared with applying conventional venous-based thresholds directly: for diabetes based on fasting glucose (sensitivity 97.56%, specificity 98.40%), diabetes based on 2 h postload glucose (sensitivity 100.00%, specificity 99.67%), IFG (sensitivity 97.60%, specificity 98.30%), and IGT (sensitivity 88.89%, specificity 92.04%). Validation analyses confirmed high agreement between s-OGTT and venous results. The s-OGTT provides a reliable, accurate, and child-friendly approach for diagnosing diabetes and abnormal glucose tolerance. These optimized thresholds enhance diagnostic specificity and support its use for large-scale pediatric screening.
Human endocrine cell differentiation and islet morphogenesis play critical roles in determining islet cell mass and function, but the events and timeline of these processes are incompletely defined. To better understand early human islet cell development and maturation, we collected 123 pediatric pancreata and mapped morphological and spatiotemporal changes from birth through the first ten years of life. Using quantitative analyses and a combination of complementary tissue imaging approaches, including confocal microscopy and whole-slide multiplex imaging, we developed an integrated model for endocrine cell formation and islet architecture, including endocrine cell type heterogeneity and abundance, endocrine cell proliferation, and islet vascularization and innervation. We also assessed insulin and glucagon secretory profiles in isolated islet preparations from pediatric donors aged 2 months to 10 years and found a temporal difference in the maturation of insulin secretion compared to glucagon secretion. This comprehensive summary of postnatal and pediatric pancreatic islet development provides a framework for future studies and for integrating emerging genetic and genomic data related to islet biology and diabetes risk.
Childhood obesity and youth-onset type 2 diabetes mellitus (T2DM) are increasing, highlighting the need for effective treatments beyond lifestyle intervention and metformin. This review systematically evaluated the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in children and adolescents with obesity or T2DM. PubMed-indexed studies published from 2000 to 2025 were reviewed, including seven pivotal randomized controlled trials and six meta-analyses involving 901 participants aged 6 to < 18 years. Semaglutide 2.4 mg/week produced the greatest BMI reduction in adolescents with obesity, followed by liraglutide 3.0 mg/day, which also improved BMI SDS in adolescents and younger children. In youth-onset T2DM, liraglutide 1.8 mg/day and dulaglutide significantly improved HbA1c compared with placebo. Weight-reducing agents also improved insulin resistance and modestly reduced triglycerides, while LDL-cholesterol changes were minimal. Gastrointestinal adverse events, mainly nausea and vomiting, were the most frequent and were generally transient and dose dependent. No significant adverse effects on linear growth or pubertal progression were reported. GLP-1 RAs are effective adjuncts for pediatric obesity and T2DM, but longer-term studies are needed to assess cardiovascular safety, bone health, and growth outcomes.
<p>Introduction: Obesity in childhood and adolescence represents one of the most challenging public health problems of our century and is associated with significant morbidity and mortality, as well as increased public health costs. To address the obesity epidemic more effectively, the World Health Organization suggests the development and implementation of reliable e-health systems (digital technologies, such as electronic health records, clinical decision support systems, and mobile health tools) that would monitor the daily behavior objectively. Our objective was to determine the effectiveness of BigO system in the prevention and management of childhood obesity. Our study was part of the 4-year European BigO project (<ext-link ext-link-type="uri" xlink:href="http://bigoprogram.eu" xmlns:xlink="http://www.w3.org/1999/xlink">http://bigoprogram.eu</ext-link>, Horizon2020, No. 727688). Overall, 1,727 (n = 1,727) children and adolescents (mean age ± SD: 12.6 ± 2.4; 898 males, 829 females) were studied prospectively following approval by the local Ethics Human Research Committee. The data collection system included the BigO technology platform, which interfaces with a Smartphone and Smartwatch and records data objectively (using inertial sensors and GPS) for each patient. Data were transmitted to BigO servers to extract behavioral indicators. Participants used the BigO system for at least 4 weeks. Subsequently, they entered a personalized lifestyle intervention program of diet, physical exercise, and sleep for 6 months and used the system again for 4 weeks. Subjects were classified as having obesity (n = 1,277, 73.9%), overweight (n = 413, 23.9%), or normal BMI (n = 37, 2.1%) according to WHO cutoff points. At the end of the study, the proportion of subjects with obesity decreased, while the proportion of subjects with overweight and normal BMI increased. The BigO system monitored the daily behavior of all subjects objectively and effectively and provided detailed information on their diet, physical activity, and sleep habits, as well as the availability of exercise facilities in their communities and their living conditions. These novel e-health applications and digital technologies were effective at collecting and analyzing objective data about the daily behavior of children and adolescents with overweight and obesity. Therefore, they may be useful to use in clinical practice and to design public health policies to address the epidemic of childhood obesity. </p>.
Metabolic and bariatric surgery (MBS) is an evidence-based intervention for adolescents with severe obesity, yet uptake remains low, especially among historically underrepresented populations. This study examined perceptions of MBS among youth and their caregivers referred to a tertiary care obesity center within a large urban safety-net hospital. Youth aged 12-18 years and their primary caregivers at a comprehensive obesity clinic completed a 22-item survey via REDCap assessing awareness, safety, perceptions, and willingness to consider surgery. Demographic and clinical data were extracted from electronic health records. Descriptive statistics, group comparisons, and multivariable regression identified factors linked to favorable MBS attitudes. Open-ended responses were analyzed using content analysis. A total of 109 youth (median age 15.2 years [IQR: 14.3-17.2]; 62.4% female; 89.9% Hispanic; median body mass index [BMI] 37.5 kg/m2 [IQR: 33.2-41.6]; median %BMIp95 127% [IQR:112-141%]) and 95 caregivers (median age 43.7 years [IQR: 41.2-55.3]; 93.7% female; 86.3% Hispanic; median BMI 32 kg/m2 [IQR: 28.2-42.2]) participated; 91 dyads completed all data. While 71% of caregivers and 56% of youth had heard of MBS as a treatment for obesity in adults, only 24% of caregivers and 15% of youth were aware of MBS as a treatment option for pediatric patients. Perceptions of safety were limited, with more than half of both caregivers and youth reporting uncertainty about the safety of MBS in children. Despite this, support for its availability was high: 79% of caregivers and 90% of youth believed that MBS should be an option for children with severe obesity when lifestyle interventions are unsuccessful. In adjusted models, caregiver history of MBS was associated with more favorable impressions of pediatric MBS among caregivers (OR = 2.86, 95% CI: 1.02-7.91, p = 0.01) and youth (OR = 2.43, 95% CI: 1.00-5.94, p < 0.05); youth impressions were also predicted by caregiver impressions (OR = 1.26, 95% CI: 1.03-1.54, p < 0.05). Among predominantly Hispanic, publicly insured families, awareness and safety perceptions of pediatric MBS were low despite high support. Caregiver MBS experience strongly influenced attitudes, highlighting the need for culturally informed, family-centered education to improve equitable access.
Anti-CD3 monoclonal antibody (aCD3) delays progression to stage 3 type 1 diabetes in high-risk individuals by modulating autoimmune activity. Nevertheless, responses remain variable and transient, with therapy providing only indirect beta cell protection. We investigated whether glucagon-like peptide-1-17ß-oestradiol conjugate (GLP1-E2), a beta cell-targeted fusion compound that enhances beta cell survival and function, could potentiate a short low-dose aCD3 course in preventing autoimmune diabetes in NOD mice. We hypothesised that co-targeting immune dysregulation and beta cell fragility would provide complementary and potentially synergistic benefits, resulting in more durable protection than either monotherapy. Female late-stage prediabetic NOD mice were randomised into four groups: untreated controls, aCD3 monotherapy, GLP1-E2 monotherapy and combination therapy. aCD3 was administered intravenously at 2.5 µg/day for 5 consecutive days, while GLP1-E2 was given subcutaneously at 100 nmol kg-1 day-1 for 18 weeks. Mice were monitored longitudinally for diabetes onset. The pancreas was analysed by spatial transcriptomics and immunostaining to assess immune infiltration, beta cell integrity and molecular pathway alterations. At 30 weeks of age, diabetes incidence was 77% in untreated controls, 66% in mono aCD3-treated mice and 61% in mono GLP1-E2-treated mice. Combination therapy significantly reduced diabetes incidence to 38% (p≤0.001) and delayed disease onset by 6 weeks, with sustained protection persisting for 5 weeks after treatment cessation. GLP1-E2 monotherapy reduced islet immune cell infiltration to a similar extent as aCD3 mono- and combination therapy, without affecting peripheral lymphocyte counts. Spatial transcriptomics showed increased gene responses linked to beta cell stress (Hspa5, Eif2ak3, Xbp1, Ddit3), dedifferentiation (Cd81), 'disallowed' genes (Oat, Igfbp4), antigen presentation (H2-K1, H2-Q6, H2-Ab1, H2-Eb1) and inflammation (Cxcl10, Cxcl9, Ccl5) during disease progression. These processes were attenuated by mono- and combination therapy, with aCD3 mostly restoring beta cell identity and GLP1-E2 reducing beta cell stress and immunogenicity. Staining for CD81 and TUNEL in 17-week-old treated mice revealed levels comparable to 12-week-old normoglycaemic NOD mice, while being increased in 17-week-old untreated mice. This reduced beta cell dedifferentiation and death was associated with improved beta cell protection and better preservation of beta cell mass at 26.5 weeks compared with new-onset (diabetic) mice. Low-dose aCD3 or GLP1-E2 monotherapy delayed diabetes onset and preserved beta cell mass in female NOD mice, while the combination provided substantially superior protection. Simultaneously targeting immune dysregulation and beta cell vulnerability highlights the potential of combination therapy to enhance and prolong immunotherapeutic efficacy in type 1 diabetes.
This study evaluated 6-month effectiveness and safety of automated insulin delivery (AID) in comparison with multiple daily injections (MDI) in pediatric and adult type 1 diabetes (T1D). Individuals with T1D, aged 2-80 years, were enrolled across 32 international centers (in the United States, Europe, Canada, and New Zealand) and randomized 1:1 to AID intervention (MiniMed™ 670G or 770G system) or MDI with or without continuous glucose monitoring. Primary endpoints were change in mean HbA1c for participants with a baseline HbA1c >8.0% (Group 1) and percentage of time spent below 70 mg/dL (%TBR <70 mg/dL [<3.9 mmol/L]) for participants with baseline HbA1c ≤8.0% (Group 2), to show superiority of AID intervention versus MDI. Safety endpoints including rates of severe hypoglycemia and diabetic ketoacidosis (DKA), and difference in diabetes treatment satisfaction score were assessed. For Group 1, N = 56 participants (aged 29.4 ± 17.0 years) were randomized to AID intervention and N = 54 participants (aged 36.8 ± 19.6 years) were randomized to MDI. For Group 2, N = 73 (aged 37.4 ± 21.0 years) and N = 69 (aged 39.2 ± 19.3 years), respectively, were randomized to AID and MDI. Change in HbA1c (mean [95% CI] difference of -0.7% [-1.1, -0.3], P = 0.0002) and difference in %TBR <70 mg/dL (4.8% [-6.4, -3.1], P<0.001) favored AID intervention versus MDI. Rates of severe hypoglycemia (AID: 1.82/100 patient-years) and DKA (MDI: 3.52/100 patient-years) were low and met preestablished success criteria for safety. This large, international, multicenter randomized controlled trial demonstrates safety of the MiniMed™ 670G/770G systems. AID significantly improved HbA1c and time spent in hypoglycemia when compared with MDI, in both youth and adults living with T1D. https://clinicaltrials.gov/, identifier NCT02748018.
South Asian individuals are at elevated diabetes risk attributed to insulin resistance, insulin deficiency, and ectopic fat. The CHARISMA study compared metabolic mechanisms in South Asian, White, and African American adolescents and young adults (AYAs) to investigate early diabetes risk in South Asian individuals. AYAs aged 12-21 years with a BMI ≥23 kg/m2 or ≥80 percentile underwent MRI/MRS to quantify fat; OGTT with minimal modeling to calculate insulin sensitivity (Si), AUC insulin secretory rate (ISR), and disposition index (DI); DXA; and glucose-potentiated arginine stimulation test. South Asian AYAs (n = 53, median [interquartile range] age 20.3 [18.9, 21.4] years) compared with White (n = 53, 19.1 [17.6, 20.8] years) and African American (n = 49, 18.8 [17.7, 20.5] years) AYAs (P = 0.02) of similar sex, pubertal stage, and BMI-Z had higher visceral fat on MRI (P < 0.001 vs. White; P = 0.009 vs. African American) and liver fat on MRS (P < 0.001 vs. both). South Asian AYAs had lower Si (P = 0.006) and higher dynamic AUC-ISR (P = 0.003) vs. White AYAs, higher total and static AUC-ISR vs. both White and African American AYAs (P < 0.001), and lower dynamic DI vs. African American AYAs (P = 0.039). South Asian AYAs had lower insulin clearance than White (P = 0.027) and African American (P = 0.007) AYAs. First-pass hepatic insulin extraction was lower in African American than South Asian (P < 0.0001) and White (P = 0.027) AYAs. Group differences in Si, dynamic AUC-ISR, and dynamic DI lost significance when visceral or liver fat was added to models, but higher total and static AUC-ISR in South Asian AYAs persisted. Compared with White and African American AYAs, South Asian AYAs have higher visceral and liver fat. These findings, along with lower Si and dynamic DI, suggest elevated metabolic risk in South Asian individuals, even at young ages. Higher total and static phase insulin secretion in South Asian AYAs may precede insulin deficiency, reported in adults.
Seasonal influenza causes morbidity and mortality in vulnerable communities. Narrative reminder recall (ie, digital stories using multimodal narratives that uplift community voices) may be scalable as an equity-promoting intervention to increase vaccination rates. To assess (1) the reach of texts with pediatric influenza vaccine digital stories among caregivers of young children and (2) associations of caregiver intervention assignment with time to child influenza vaccination. This pilot randomized clinical trial included caregivers and their children (aged 6 months to 5 years) from 2 safety-net clinics in historically Black neighborhoods in Denver, Colorado between September 16, 2024, and March 31, 2025. Caregivers aged 18 years and older who preferred English and their children, provided they had 1 well visit in the past 18 months and would be aged 6 to 71 months during the influenza season, were included. The digital storytelling intervention included texts with links to 5 stories (3 featuring caregivers who identified as Black or African American) sent in October 2024. Usual care included 1 message sent via an electronic health record messaging portal to caregivers of all children eligible for influenza vaccines. The primary outcome was digital story reach (ie, the proportion of caregivers viewing 1 or more digital stories for any length of time). Time to first influenza vaccination was recorded for children. Adjusted Cox proportional hazards modeling (with 95% CI) fit time to vaccination by group and baseline covariates. Kaplan-Meier curves analyzed the proportions of children remaining unvaccinated by group over time. Intention-to-treat analyses included 200 children (100 per group; mean [SD] age, 29.1 [16.1] months; 96 male [48%]; 77 Black or African American [39%]; 90 Hispanic or Latino/a [45%]; 54 White [27%]) and their 198 caregivers (100 usual care; 98 intervention; mean [SD] age, 30.5 [7.5] years; 176 mothers [89%]; 77 Black or African American [39%]; 87 Hispanic or Latino/a [44%]; 25 White [13%]). Overall, 686 of 686 texts (100%) were delivered; digital stories were viewed by 7 caregivers (7%). More children of intervention caregivers were vaccinated when influenza activity peaked on February 15, 2025, (percentage unvaccinated, 62% [95% CI, 53%-72%] in intervention vs 74% [95% CI, 66%-83%] in usual care; Z test, 1.82; P = .03). In adjusted analyses, children of intervention caregivers were 63% more likely to be vaccinated compared with children of caregivers receiving usual care (adjusted hazard ratio, 1.63; 95% CI, 1.01-2.64). In this pilot randomized clinical trial of a text message digital storytelling intervention centering Black families, intervention receipt was associated with improved pediatric influenza vaccination, although intervention reach was low. ClinicalTrials.gov Identifier: NCT06274359.
Automated insulin delivery (AID) systems have been shown to improve glycaemic outcomes in people with type 1 diabetes managed with insulin pump therapy. No randomised studies have evaluated the benefits of tubeless AID in both adults and children with suboptimal glycaemia compared with multiple daily injections. We aimed to evaluate the safety and efficacy of a tubeless AID system compared with multiple daily injections in this population. RADIANT was a multicentre, international, parallel-group, open-label, randomised, controlled trial done in 19 hospitals in the UK, Belgium, and France. Participants aged 4-70 years with type 1 diabetes managed with multiple daily injections and continuous glucose monitoring and who had HbA1c levels of 7·5-11% (58-97 mmol/mol) were randomly assigned (2:1) to tubeless AID or control (multiple daily injections) using a permuted-block design. Participant and study teams were not masked to group allocation. The primary outcome was the adjusted between-group difference in HbA1c at 13 weeks assessed for superiority. Primary and safety outcomes were assessed in the modified intention-to-treat population (all randomly assigned participants). The study is registered with ClinicalTrials.gov, NCT05923827, and has been completed. Between Sept 11, 2023, and April 26, 2024, 188 participants were randomly assigned to the AID group (n=125) or the control group (n=63). The AID group had a greater reduction in HbA1c, from 8·1% (SD 0·7; 65 mmol/mol [SD 7·7]) at baseline to 7·2% (0·6; 55 mmol/mol [6·6]) at 13 weeks, compared with the control group, from 8·1% (0·6; 65mmol/mol [6·6]) at baseline to 8·0% (0·7; 64 mmol/mol [7·7]) at 13 weeks, with an adjusted mean difference of -0·8% (95% CI -1·0 to -0·6; -8·7 mmol/mol [95% CI -10·9 to -6·6]; p<0·0001). During the 13-week trial, no episodes of severe hypoglycaemia or diabetic ketoacidosis occurred in either treatment group. 39 adverse events were reported among 28 participants in the AID group, and three adverse events among three participants in the control group. Two serious adverse events (Kawasaki disease and acute coronary syndrome) occurred in the AID group unrelated to the study device or procedure. Results from this trial show the clinical efficacy of direct transition from multiple daily injections to tubeless AID in adults and children with type 1 diabetes, with no safety concerns, supporting AID as a therapeutic option within standard of care for people with type 1 diabetes. Insulet Corporation.
Autism spectrum disorder (ASD) is more prevalent in transgender and gender-diverse (TGD) individuals than in the general population, yet the specific developmental pathways within and clinical outcomes of this intersection are insufficiently understood. This study examined how ASD and sex assigned at birth (SAAB) are associated with gender-related milestones, access to gender-affirming consultation and care (GACC), and psychiatric outcomes. We reviewed electronic medical records for 786 TGD children and adolescents (aged 4-19 years) presenting to a national referral clinic between 2013 and 2025. Demographic, developmental, and psychiatric variables were analyzed across four ASD-by-SAAB groups using generalized linear models and logistic regressions, with Bonferroni-adjusted post hoc comparisons (α = 0.0083). ASD was documented in 9.7% of the cohort, with referrals of autistic TGD patients increasing significantly over time. Autistic patients presented with a distinct profile, characterized by higher socioeconomic position (SEP), intellectual giftedness, non-binary gender identity, and an earlier stage of pubertal development at presentation. Crucially, while ages at gender-related milestones were largely comparable between neurotypes, autistic assigned female at birth (AFAB) adolescents were significantly less likely to initiate puberty suppression or gender-affirming hormones than their non-autistic peers. Furthermore, higher SEP was associated with earlier clinical presentation only for non-autistic youth. Autistic TGD patients exhibited a higher psychiatric burden, with an ASD diagnosis uniquely associated with elevated rates of anxiety, ADHD, and psychotropic medication use. These findings reveal a disparity between developmental synchrony and clinical access, underscoring the need for autism-informed protocols to support equitable gender-affirming care. The number of autistic transgender and gender‐diverse youth seeking gender‐affirming consultation and care has increased substantially in recent years. We found that autistic youth presenting at a national referral clinic had a distinct demographic and developmental profile, characterized by higher rates of intellectual giftedness, non‐binary gender identity, and an earlier stage of pubertal development at initial clinic presentation than their non‐autistic peers, alongside higher mental health challenges. While both groups realized they were gender diverse at similar ages, their healthcare experiences differed. Autistic youth, especially those assigned female at birth, were significantly less likely to start gender‐affirming medical care than their non‐autistic peers. We recommend that gender clinics adapt their services to better support the specific communication and mental health needs of autistic youth to ensure they receive fair and equitable care.
Optimizing Management of Endocrine Complications in Duchenne Muscular Dystrophy (OPTIMIZE DMD) is an international consortium of clinicians created to advance endocrine and bone clinical care in DMD. The aim of this study was to better understand current views and practices regarding investigation and management of growth and puberty concerns in individuals with DMD, relative to the 2018 Care Considerations and to inform updated guidance around endocrine care. A survey was created and sent to 47 OPTIMIZE DMD Consortium members and allied clinicians between September and November 2024. Areas surveyed included evaluation of growth, puberty, and arrested puberty/hypogonadism, and related management including use of vamorolone, growth hormone and testosterone. Survey responses were received from 37 clinicians (79%). Most individuals were referred to endocrinology for growth and puberty concerns, with referral patterns contingent upon the endocrinology/multidisciplinary clinic model. Management discussions for growth concerns involved continued monitoring (95% of clinicians), glucocorticoid adjustment (54%) including vamorolone (35%), and growth hormone (41%). For pubertal delay, 88% of endocrinologists offered testosterone for pubertal induction, most commonly intramuscular 4-weekly testosterone injections. Most endocrinologists (92%) offered testosterone supplementation for arrested puberty/hypogonadism, some (24%) on a case-by-case basis. Delivery routes were more varied, with subcutaneous injections prescribed by 52%. Compared with the 2018 Care Considerations, monitoring practices for growth and puberty remain largely consistent, while variability persists in management approaches. These findings provide important insights to inform future guidance and identify priorities for further education and research in endocrine management for individuals with DMD.
To compare changes in inflammatory biomarkers among youth with perinatally-acquired HIV (PHIV) and perinatal HIV-exposure without infection (PHEU), and to examine their associations with antiretroviral therapy (ART) and HIV disease status. A substudy within a longitudinal cohort study conducted across 14 U.S. sites. We measured inflammatory biomarkers at baseline and ~11 years later in 99 PHIV participants receiving ART and 59 PHEU participants. Univariable and multivariable linear regression models evaluated changes within and between groups and associations between biomarker concentrations at follow-up and ART regimens, CD4 + cell count, and viral loads (VL). At baseline, the median ages of PHIV and PHEU were 13 and 11 years. Median baseline concentrations of interleukin-18 (IL-18) and tumor necrosis factor alpha (TNF-α) were significantly higher in PHIV than PHEU. At follow-up, only the median sTNF-R2 concentration was significantly higher in PHIV than PHEU. In both groups, median biomarker concentrations decreased from baseline to follow-up except for TNF-α (increased in PHEU) and hsCRP (increased in both). A greater decrease in IL-10 in PHIV than PHEU was the only significant difference between groups. At follow-up, a nadir CD4 + <15% was associated with lower IL-8 concentrations; CD4 + cell count ≤500 cells/mm 3 was associated with higher IL-18 concentrations; and VL ≥400 copies/ml was associated with higher sTNF-R2 concentrations. Longer duration of integrase inhibitor (INSTI) use was associated with increases in IL-6, IL-8, and IL-10. Among PHIV on ART, inflammation decreases over time, associated with better HIV disease control, and likely reduces the risk of HIV-related comorbidities. However, inflammation may increase with INSTI exposure.
This study characterized the dose effect of whey protein isolate (WPI) ingestion on glucagon secretion, glycemia, and the underlying mechanisms in adults with type 1 diabetes. Twelve insulin pump-treated adults with type 1 diabetes (mean ± SD age 47.3 ± 16.4 years; BMI 26.1 ± 3.8 kg/m2) and six adults without diabetes (age 36.2 ± 20.9 years; BMI 27.3 ± 5.8 kg/m2) received 1) control (water), 2) low-dose WPI (0.25 g/kg), and/or 3) high-dose WPI (0.5 g/kg). Those with diabetes replaced subcutaneous insulin with fixed-rate i.v. insulin. [6,6-2H]glucose infusion was used to measure glucose flux. In participants with type 1 diabetes, low- and high-dose WPI raised plasma glucagon by approximately fivefold and approximately ninefold, respectively. Endogenous glucose production increased by ∼50% (peak) for both WPI doses, with the high dose producing more sustained stimulation. Plasma glucose decreased by a median (interquartile range) of ∼1.7 (2.0, 1.0) mmol/L for control but increased by 1.3 (1, 1.7) and 3.1 (2.5, 3.3) mmol/L for the low and high doses, respectively. Participants with and without diabetes had similar increases in amino acids, glucagon, glucagon-like peptide 1, and glucose-dependent insulinotropic polypeptide. This study highlights the substantial glucagon-stimulating and glycemic effects of WPI, which could be clinically useful for hypoglycemia management in type 1 diabetes. The effect of protein ingestion on glucagon and glycemic responses in individuals with type 1 diabetes is not well characterized. This study examined how ingestion of varying amounts of fast-absorbing whey protein (in the absence of other macronutrients) affected glucagon secretion, glucose levels, and associated metabolic hormone levels in adults with type 1 diabetes. Whey protein ingestion stimulated glucagon secretion and endogenous glucose production and increased blood glucose in adults with type 1 diabetes. Our findings highlight the potential of whey protein as a tool to support glycemic management and mitigate hypoglycemia in type 1 diabetes.
To determine the diagnostic performance of vibration-controlled transient elastography (VCTE) measured the same day as liver biopsy in screening and risk stratification of steatosis and fibrosis in children and adolescents. We compared VCTE measures of hepatic steatosis and fibrosis with liver biopsy histology as the reference standard. Sequential patients undergoing liver biopsy in a hospital-based pediatric gastroenterology practice were included. In primary analyses, we determined area under the receiver operating characteristic (AUC), sensitivity, and specificity for VCTE-derived measures of steatosis and fibrosis. In post hoc subgroup analyses, we examined VCTE measures of steatosis and fibrosis among patients according to metabolic dysfunction-associated steatotic liver disease (MASLD) diagnosis. Among 145 children, with mean age 13.6 years (SD: 5.1 years), VCTE measures of any steatosis (≥5%) showed AUC 0.89 (95% CI 0.83-0.94), sensitivity 0.90 (95% CI 0.79-0.97), and specificity 0.74 (95% CI 0.64-0.83). VCTE measures for fibrosis stage F2 or greater had AUC 0.71 (0.59-0.82), sensitivity 0.75 (0.53-0.90), and specificity 0.63 (0.54-0.72). In post hoc subgroup analyses among the subgroup of 37 patients with MASLD, VCTE had low ability to detect greater grades of steatosis (AUC 0.61 for S2 or greater) and low ability to detect clinically meaningful fibrosis (AUC 0.56 for F2 or greater). In the overall cohort, VCTE measurements on the same day as liver biopsy showed moderate ability to detect steatosis and limited ability to detect F2 fibrosis. Diagnostic discrimination for steatosis and fibrosis was low among the subgroup with MASLD. Disease-specific studies, rather than heterogeneous cohorts of mixed disease types, are needed to advance clinical implementation of noninvasive steatosis and fibrosis measures.
Graves' disease (GD) and autoimmune hepatitis (AIH) represent distinct autoimmune disorders affecting the thyroid and liver, respectively. This report discusses a case of a 13-year-old boy with rare coexistence of GD and AIH. The patient was admitted to the Department of Pediatric Endocrinology, presenting with suspected hyperthyroidism. Clinical manifestations included ocular exophthalmos, tachycardia, reduced exercise tolerance, and motor restlessness. Initial laboratory assessments revealed mildly elevated transaminases, prompting further investigation. A primary diagnosis of GD was confirmed by relevant laboratory parameters. Antithyroid drugs (ATD) were administered, resulting in proper control of thyroid dysfunction. However, despite the gradual reduction of ATD, a further increase in hepatic biomarkers was observed and required a comprehensive diagnostic investigation, culminating in a liver biopsy. The findings of the biopsy yielded a definitive diagnosis of AIH. In pediatric patients presenting with GD-associated liver dysfunction, AIH should be considered as a potential comorbidity, warranting vigilance in patients with hyperthyroidism and elevated transaminase levels. Choroba Gravesa (GD) i autoimmunologiczne zapalenie wątroby (AIH) to odrębne choroby autoimmunologiczne, które wpływają odpowiednio na funkcję tarczycy i wątroby. W pracy przedstawiono opis przypadku 13-letniego chłopca z rzadkim współwystępowaniem i jednoczasowym ujawnieniem GD i AIH. Pacjent został przyjęty do Oddziału Endokrynologii Dziecięcej z podejrzeniem nadczynności tarczycy. Objawy kliniczne obejmowały wytrzeszcz oczu, tachykardię, obniżoną tolerancję wysiłku oraz niepokój ruchowy. Na podstawie badań laboratoryjnych przy przyjęciu rozpoznano GD, ponadto zaobserwowano nieznacznie podwyższoną aktywność aminotransferaz, co wymagało dalszej diagnostyki. Do leczenia włączono tyreostatyk, uzyskując normalizacją funkcji tarczycy. Jednak pomimo stopniowego zmniejszania dawek tyreostatyku, widoczna była narastająca hipertransaminezemia. Do postawienia ostatecznego rozpoznania konieczna była biopsja wątroby, której wynik pozwolił na rozpoznanie AIH. U pacjentów pediatrycznych z zaburzeniami czynności wątroby w przebiegu choroby Gravesa, AIH może być jedną z chorób współwystępujących, co obliguje do zachowania czujności u pacjentów z nadczynnością tarczycy i podwyższonym stężeniem transaminaz.