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Background: An increased prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes in children was observed in various diabetes centres worldwide during the COVID-19 pandemic. We aimed to evaluate trends in the prevalence of diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes before and during the COVID-19 pandemic, and to identify potential predictors of changes in diabetic ketoacidosis prevalence during the pandemic. Methods: For this international multicentre study, we used data from 13 national diabetes registries (Australia, Austria, Czechia, Denmark, Germany, Italy, Luxembourg, New Zealand, Norway, Slovenia, Sweden, USA [Colorado], and Wales). The study population comprised 104 290 children and adolescents aged 6 months to younger than 18 years, who were diagnosed with type 1 diabetes between Jan 1, 2006, and Dec 31, 2021. The observed diabetic ketoacidosis prevalence in 2020 and 2021 was compared to predictions based on trends over the pre-pandemic years 2006–19. Associations between changes in diabetic ketoacidosis prevalence and the severity of the COVID-19 pandemic and containment measures were examined with excess all-cause mortality in the whole population and the Stringency Index from the Oxford COVID-19 Government Response Tracker. Findings: 87 228 children and adolescents were diagnosed with type 1 diabetes between 2006 and 2019, 8209 were diagnosed in 2020, and 8853 were diagnosed in 2021. From 2006 to 2019, diabetic ketoacidosis at diagnosis of type 1 diabetes was present in 23 775 (27·3%) of 87 228 individuals and the mean annual increase in the prevalence of diabetic ketoacidosis in the total cohort from 2006 to 2019 was 1·6% (95% CI 1·3 to 1·9). The adjusted observed prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes was 39·4% (95% CI 34·0 to 45·6) in 2020 and 38·9% (33·6 to 45·0) in 2021, significantly higher than the predicted prevalence of 32·5% (27·8 to 37·9) for 2020 and 33·0% (28·3 to 38·5) for 2021 (p

BACKGROUND: The possible advantage of hybrid closed-loop therapy (i.e., artificial pancreas) over sensor-augmented pump therapy in very young children with type 1 diabetes is unclear. METHODS: In this multicenter, randomized, crossover trial, we recruited children 1 to 7 years of age with type 1 diabetes who were receiving insulin-pump therapy at seven centers across Austria, Germany, Luxembourg, and the United Kingdom. Participants received treatment in two 16-week periods, in random order, in which the closed-loop system was compared with sensor-augmented pump therapy (control). The primary end point was the between-treatment difference in the percentage of time that the sensor glucose measurement was in the target range (70 to 180 mg per deciliter) during each 16-week period. The analysis was conducted according to the intention-to-treat principle. Key secondary end points included the percentage of time spent in a hyperglycemic state (glucose level, >180 mg per deciliter), the glycated hemoglobin level, the mean sensor glucose level, and the percentage of time spent in a hypoglycemic state (glucose level

Objective: The following report describes the evaluation of the ISPAD Science School for Physicians (ISSP) and for Healthcare Professionals (ISSHP) in terms of their efficiency and success. Methods: All past attendees from 2000–2019 ISSP and 2004–2019 ISSHP programs were invited to respond to an online survey to assess perceived outcomes of the programs on career development, scientific enhancement, scientific networking, and social opportunities. Results: One-third of the past ISSP (129/428), and approximately 43% of the past ISSHP attendees (105/245) responded to the surveys. Most of ISSP attendees reported that the programs supported their career (82%) by helping to achieve a research position (59%), being engaged with diabetes care (68%) or research (63%) or starting a research fellowship (59%). Responders indicated that ISSP was effective in increasing interest in diabetes research (87%) and enhancing the number (66%) and quality (83%) of scientific productions, and promotion of international collaborations (86%). After the ISSP, 34% of responders received research grants. From the first round of the ISSHP survey (2004–2013), responders reported have improved knowledge (60%), gained more confidence in research (69%), undertaken a research project (63%), and achieved a higher academic degree (27%). From the second round (2014–2019), participants indicated that the program was valuable/ useful in workplace (94%) through understanding (89%) and conducting (68%) research and establishing communication from other participants (64%) or from faculty (42%). After the ISSHP, 17% had received awards. Conclusions: From the participants' viewpoint, both programs were effective in improving engagement with diabetes research, supporting career opportunities, increasing scientific skills, and enhancing networking and research activities.

Objective: Many hybrid closed-loop (HCL) systems struggle to manage unusually high glucose levels as experienced with intercurrent illness or pre-menstrually. Manual correction boluses may be needed, increasing hypoglycemia risk with overcorrection. The Cambridge HCL system includes a user-initiated algorithm intensification mode (“Boost”), activation of which increases automated insulin delivery by approximately 35%, while remaining glucose-responsive. In this analysis, we assessed the safety of “Boost” mode. Methods: We retrospectively analyzed data from closed-loop studies involving young children (1-7 years, n = 24), children and adolescents (10-17 years, n = 19), adults (≥24 years, n = 13), and older adults (≥60 years, n = 20) with type 1 diabetes. Outcomes were calculated per participant for days with ≥30 minutes of “Boost” use versus days with no “Boost” use. Participants with Results: Eight weeks of data for 76 participants were analyzed. There was no difference in time spent 300 mg/dL was 1.39 percentage points (1.01 to 1.77; P < .001) higher on “Boost” days, with higher mean glucose and lower time in target range ( P < .001). Conclusions: Use of an algorithm intensification mode in HCL therapy is safe across all age groups with type 1 diabetes. The higher time in hyperglycemia observed on “Boost” days suggests that users are more likely to use algorithm intensification on days with extreme hyperglycemic excursions.

OBJECTIVE To evaluate the impact of CamAPS FX hybrid closed-loop (HCL) automated insulin delivery in very young children with type 1 diabetes (T1D) on caregivers’ well-being, fear of hypoglycemia, and sleepiness. RESEARCH DESIGN AND METHODS We conducted a multinational, open-label, randomized crossover study. Children (age 1–7 years) with T1D received treatment for two 4-month periods in random order, comparing HCL with sensor augmented pump (control). At baseline and after each treatment period, caregivers were invited to complete World Health Organization–Five Well-Being Index, Hypoglycemia Fear Survey, and Epworth Sleepiness Scale questionnaires. RESULTS Caregivers of 74 children (mean ± SD age 5 ± 2 years and baseline HbA1c 7.3 ± 0.7%; 42% female) participated. Results revealed significantly lower scores for hypoglycemia fear (P < 0.001) and higher scores for well-being (P < 0.001) after HCL treatment. A trend toward a reduction in sleepiness score was observed (P = 0.09). CONCLUSIONS Our results suggest better well-being and less hypoglycemia fear in caregivers of very young children with T1D on CamAPS FX HCL.

Available basal insulin regimes differ in pharmacokinetic profiles, which may be related to subsequent changes in anthropometry in patients with type 1 diabetes. This analysis elucidates the standardized height and body mass index development (height and BMI standard deviation score [height-SDS and BMI-SDS]) in pediatric type 1 diabetes patients depending on the choice of basal insulin.Longitudinal data of 10 338 German/Austrian patients from the Diabetes Prospective Follow-up (DPV, Diabetes Patienten Verlaufsdokumentation) database were analyzed. Patients aged 5.0 to 16.9 years were treated exclusively with neutral protamine Hagedorn (NPH), insulin detemir (IDet), insulin glargine (IGla), or continuous subcutaneous insulin infusion (CSII) for at least 3 years. Population-based German reference data were used to calculate height-SDS and BMI-SDS. Multiple linear regression was conducted.BMI-SDS increased significantly in all regimes (NPH P = .0365; IDet P = .0003; IGla P .0001; and CSII P .0001). Direct comparison of the therapies revealed a favorable association only for NPH vs IGla. A rise in BMI-SDS was observed for all insulins in females, but only for IGla in males. BMI-SDS increment was not observed before 8 years of age. Initially and at the end of the observation period, mean height was above the 50th percentile of the reference population. Across the cohort, height-SDS declined during the observation period, except for CSII. Apart from the 5.0- to 7.9-year-old subgroup, long-acting insulin analogues were associated with a significant loss of height-SDS.Choice of basal insulin regimen might influence height development. CSII appeared to have a favorable effect on growth trajectories. All therapies were associated with an increase of BMI-SDS, most evident in females.背景: 现有的基础胰岛素方案在药代动力学方面存在差异, 这可能与1型糖尿病患者后续的人体测量学变化有关。这项分析阐明了儿童1型糖尿病患者基于基础胰岛素的选择的标准化身高和体重指数BMI(身高和BMI标准差评分[身高-SDS和BMI-SDS])的发展。 方法: 对10338例德国/奥地利糖尿病进行前瞻性数据库中的纵向资料进行分析。年龄5.0~16.9岁的患者接受中性鱼精蛋白Hagedorn(NPH), 地特胰岛素(IDET), 甘精胰岛素(IGLA)或持续皮下胰岛素输注(CSII)治疗至少3年。以人群为基础的德国参考数据被用来计算身高-SDS和BMI-SDS。进行多元线性回归分析。 结果: BMI-SDS在所有方案中均显著升高(NPH P=.0365, IDET P=.0003, IGLA P.0001, CSII P.0001)。对这些疗法的直接比较显示, 仅对NPH和IGLA有有利的关联。在女性中观察到所有胰岛素的BMI-SDS升高, 但只在男性中观察到IGLA的升高。BMI-SDS在8岁前未见明显增加。 最初和在观察期结束时, 平均身高高于参考人口的第50个百分位数。在整个队列中, 除CSII外, 身高-SDS在观察期内均呈下降趋势。除了5.0到7.9岁的亚组外, 长效胰岛素类似物与身高-SDS显著降低相关。 结论: 基础胰岛素方案的选择可能影响身高发育。CSII似乎对增长轨迹有有利的影响。所有的治疗都与BMI-SDS的增加有关, 这在女性中最为明显。.

Background We present the results of the pilot study of a multinational “Diabetes Know‐Me” project investigating knowledge regarding diabetes of medical students. This is the first collaborative project of the ISPAD JENIOUS group. Methods Students of the final year of medical studies from six countries answered a 25‐question survey regarding basic knowledge concerning diabetes (1091 surveys handed out, response rate 86%). Results Among the responders (58% female) 90% confirmed attending diabetology classes; 11% planned to specialize in diabetology. There were significant differences between countries in the median score of correct answers ranging from 10/25 to 22/25. Attending diabetes classes (20 vs. 13/25, p

Objective: To examine the prevalence, time trends, and risk factors of diabetic retinopathy (DR) among youth with type 1 diabetes (T1D) from 11 countries (Australia, Austria, Denmark, England, Germany, Italy, Luxemburg, Netherlands, Slovenia, United States, and Wales). Subjects and Methods: Data on individuals aged 10–21 years with T1D for >1 year during the period 2000–2020 were analyzed. We used a cross-sectional design using the most recent year of visit to investigate the time trend. For datasets with longitudinal data, we aggregated the variables per participant and observational year, using data of the most recent year to take the longest observation period into account. DR screening was performed through quality assured national screening programs. Multiple logistic regression models adjusted for the year of the eye examination, age, gender, minority status, and duration of T1D were used to evaluate clinical characteristics and the risk of DR. Results: Data from 156,090 individuals (47.1% female, median age 15.7 years, median duration of diabetes 5.2 years) were included. Overall, the unadjusted prevalence of any DR was 5.8%, varying from 0.0% (0/276) to 16.2% between countries. The probability of DR increased with longer disease duration (aORper-1-year-increase = 1.04, 95% CI: 1.03–1.04, p < 0.0001), and decreased over time (aORper-1-year-increase = 0.99, 95% CI: 0.98–1.00, p = 0.0093). Evaluating possible modifiable risk factors in the exploratory analysis, the probability of DR increased with higher HbA1c (aORper-1-mmol/mol-increase-in-HbA1c = 1.03, 95% CI: 1.03–1.03, p < 0.0001) and was higher among individuals with hypertension (aOR = 1.24, 95% CI: 1.11–1.38, p < 0.0001) and smokers (aOR = 1.30, 95% CI: 1.17–1.44, p < 0.0001). Conclusions: The prevalence of DR in this large cohort of youth with T1D varied among countries, increased with diabetes duration, decreased over time, and was associated with higher HbA1c, hypertension, and smoking.

Background Telemedicine for routine care of people with diabetes (PwD) during the COVID‐19 pandemic rapidly increased in many countries, helping to address the several barriers usually seen. Objective This study aimed to describe healthcare professionals' (HCPs) experience on telemedicine use in diabetes care and investigate the changes and challenges associated with its implementation. Methods A cross‐sectional electronic survey was distributed through the global network of JENIOUS members of ISPAD. Respondents' professional and practice profiles, clinic sizes, their country of practice, and data regarding local telemedicine practices during COVID‐19 pandemic were investigated. Results Answers from 209 HCPs from 33 countries were analyzed. During the pandemic, the proportion of PwD receiving telemedicine visits increased from 50% (66.5%). There was an increase in specific privacy requirements for remote visits (37.3% to 75.6%), data protection policies (42.6% to 74.2%) and reimbursement for remote care (from 41.1% to 76.6%). Overall, 83.3% HCPs reported to be satisfied with the use of telemedicine. Some concerns (17.5%) about the complexity and heterogeneity of the digital platforms to be managed in everyday practice remain, feeding the need for unifying and making interoperable the tools for remote care. Also, 45.5% of professionals reported to feel stressed by the need for extra‐time for telemedicine consultations. Conclusions Telemedicine was rapidly and broadly adopted during the pandemic globally. Some issues related to its use were promptly addressed by local institutions. Challenges with the use of different platforms and for the need of extra‐time still remain to be solved.

ObjectiveTo compare glycemic control and treatment preference in children with type 1 diabetes (T1D) using sensor augmented pump (SAP) with predictive low glucose suspend (SmartGuard®) or pump with independent intermittent scanning continuous glucose monitoring (iscCGM, Freestyle libre ®).MethodsIn this open label, cross-over study, children 6 to 14 years of age, treated with insulin pump for at least 6 months, were randomized to insulin pump and iscCGM (A) or SAP with SmartGuard® (B) for 5 weeks followed by 5 additional weeks. The difference in percentages of time in glucose target (TIT), (3.9 – 8.0 mmol/l), 8 and 10 mmol/l, were analyzed using linear mixed models during the final week of each arm and were measured by blinded CGM (IPro2®).Results31 children (15 girls) finished the study. With sensor compliance > 60%, no difference in TIT was found, TIT: A 37.86%; 95% CI [33.21; 42.51]; B 37.20%; 95% CI [32.59; 41.82]; < 3 mmol/l A 2.27% 95% CI [0.71; 3.84] B 1.42% 95% CI [-0.13; 2.97]; > 8 mmol/l A 0.60% 95% CI [0.56, 0.67]; B 0.63% [0.56; 0.70]. One year after the study all participants were on CGM compared to 80.7% prior to the study, with a shift of 13/25 participants from iscCGM to SAP.ConclusionsIn this study, no significant difference in glycemic control was found whether treated with SAP (SmartGuard®) or pump with iscCGM. The decision of all families to continue with CGM after the study suggests a positive impact, with preference for SmartGuard®.Clinical Trial Registration[clinicaltrials.gov], identifier NCT03103867.

Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin-dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (ie, before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes.

Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin-dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (ie, before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes. ispartof: PEDIATRIC DIABETES vol:21 issue:8 pages:1375-1393 ispartof: location:Denmark status: published

Accurate data on type 1 diabetes prevalence, incidence, associated mortality and life expectancy are crucial to inform public health policy, but these data are scarce. We therefore developed a model based on available data to estimate these values for 201 countries for the year 2021 and estimate the projected prevalent cases in 2040.We fitted a discrete-time illness-death model (Markov model) to data on type 1 diabetes incidence and type 1 diabetes-associated mortality to produce type 1 diabetes prevalence, incidence, associated mortality and life expectancy in all countries. Type 1 diabetes incidence and mortality data were available from 97 and 37 countries respectively. Diagnosis rates were estimated using data from an expert survey. Mortality was modelled using random-forest regression of published type 1 diabetes mortality data, and life expectancy was calculated accordingly using life tables. Estimates were validated against observed prevalence data for 15 countries. We also estimated missing prevalence (the number of additional people who would be alive with type 1 diabetes if their mortality matched general population rates).In 2021, there were about 8·4 (95% uncertainty interval 8·1-8·8) million individuals worldwide with type 1 diabetes: of these 1·5 million (18%) were younger than 20 years, 5·4 million (64%) were aged 20-59 years, and 1·6 million (19%) were aged 60 years or older. In that year there were 0·5 million new cases diagnosed (median age of onset 39 years), about 35 000 non-diagnosed individuals died within 12 months of symptomatic onset. One fifth (1·8 million) of individuals with type 1 diabetes were in low-income and lower-middle-income countries. Remaining life expectancy of a 10-year-old diagnosed with type 1 diabetes in 2021 ranged from a mean of 13 years in low-income countries to 65 years in high-income countries. Missing prevalent cases in 2021 were estimated at 3·7 million. In 2040, we predict an increase in prevalent cases to 13·5-17·4 million (60-107% higher than in 2021) with the largest relative increase versus 2021 in low-income and lower-middle-income countries.The burden of type 1 diabetes in 2021 is vast and is expected to increase rapidly, especially in resource-limited countries. Most incident and prevalent cases are adults. The substantial missing prevalence highlights the premature mortality of type 1 diabetes and an opportunity to save and extend lives of people with type 1 diabetes. Our new model, which will be made publicly available as the Type 1 Diabetes Index model, will be an important tool to support health delivery, advocacy, and funding decisions for type 1 diabetes.JDRF International.

BACKGROUND The possible advantage of hybrid closed-loop therapy (i.e., artificial pancreas) over sensor-augmented pump therapy in very young children with type 1 diabetes is unclear. METHODS In this multicenter, randomized, crossover trial, we recruited children 1 to 7 years of age with type 1 diabetes who were receiving insulin-pump therapy at seven centers across Austria, Germany, Luxembourg, and the United Kingdom. Participants received treatment in two 16-week periods, in random order, in which the closed-loop system was compared with sensor-augmented pump therapy (control). The primary end point was the between-treatment difference in the percentage of time that the sensor glucose measurement was in the target range (70 to 180 mg per deciliter) during each 16-week period. The analysis was conducted according to the intention-to-treat principle. Key secondary end points included the percentage of time spent in a hyperglycemic state (glucose level, >180 mg per deciliter), the glycated hemoglobin level, the mean sensor glucose level, and the percentage of time spent in a hypoglycemic state (glucose level

Background CamAPS FX is a hybrid closed-loop smartphone app used to manage type one diabetes. The closed-loop algorithm has a default target glucose of 5.8 mmol/L (104.5 mg/dL), but users can select personal glucose targets (adjustable between 4.4 mmol/L and 11.0 mmol/L [79 mg/dL and 198 mg/dL, respectively]). Method In this post-hoc analysis, we evaluated the impact of personal glucose targets on glycemic control using data from participants in five randomized controlled trials. Results Personal glucose targets were widely used, with 20.3% of all days in the data set having a target outside the default target bin (5.5-6.0 mmol/L [99-108 mg/dL]). Personal glucose targets >6.5 mmol/L (117 mg/dL) were associated with significantly less time in target range (3.9-10.0 mmol/L [70-180 mg/dL]; 6.5-7.0 mmol/L [117-126 mg/dL]: mean difference = −3.2 percentage points [95% CI: −5.3 to −1.2; P < .001]; 7.0-7.5 mmol/L [126-135 mg/dL]: −10.8 percentage points [95% CI: −14.1 to −7.6; P < .001]). Personal targets >6.5 mmol/L (117 mg/dL) were associated with significantly lower time (Conclusions Discrete study populations showed differences in glucose control when applying similar personal targets.

Nutrition is crucial for maintaining normal growth, development, and glycemic control in young people with diabetes (PwD). Undue restrictions cause nutrient deficiencies as well as poor adherence to meal plans. Widespread availability of low-cost, ultra-processed, and hyperpalatable food is further damaging. Most families struggle to find ways to provide nutritious, yet attractive, food with a low glycemic index (GI). India is one of the oldest continuous civilizations with a rich and diverse cultural and culinary heritage. Traditional dietary practices, including the centuries-old ‘Thali’ (meaning plate) concept, emphasize combinations (grains, lentils, vegetables, dairy, spices, prebiotics and probiotics, and fats) of local, seasonal, and predominantly plant-based ingredients. These practices ensure that all of the necessary food groups are provided and fit well with current evidence-based recommendations, including the International Society for Pediatric and Adolescent Diabetes (ISPAD) 2018 Guidelines. Techniques for the preparation, cooking, and preservation of food further impact the GI and nutrient availability. These practices benefit nutrient density, diet diversity, and palatability and thus improve adherence to meal plans and glycemic control. This narrative review describes the ancient wisdom, food composition, and culinary practices from across India which are still valuable today. These may be of benefit worldwide to improve glycemic control as well as quality of life, especially in PwD.

IntroductionFamilial hypercholesterolaemia (FH) is a frequent (1:300) autosomal dominantly inherited condition which causes premature (women Methods and analysisIn this cross-sectional study, all children (n=3200) between 7 and 12 years, attending primary school in the city of Luxembourg and invited for their mandatory medical school examinations between 2021 and 2023 are invited to participate. A study nurse performs a capillary blood test to analyse the lipid profile. Families receive the result including an interpretation and invitation to seek medical advice if indicated. If FH is confirmed, a reverse cascade screening in that family will be proposed. The child will receive standard care. Primary outcome is the occurrence of confirmed FH in the study population. Secondary outcomes include the percentage of children screened, percentage of children with abnormal lipid values, percentage of families screened and percentage of families with additionally identified members suffering from hypercholesterolaemia. A health economic analysis will be performed.Ethics and disseminationEthics approval (reference number 202108/01) has been obtained from the National Research Ethics Committee (CNER (Luxembourg)) and was authorised by the ministry of health in Luxembourg. Families receive written information with an informed consent form. Participation requires an informed consent form signed by the parents. The results will be disseminated in peer-reviewed publications, conference presentations and by public media to the general public.Trial registration numberNCT05271305.

OBJECTIVE: To quantify age-related variability of insulin needs during day and night closed-loop insulin delivery. RESEARCH DESIGN AND METHODS: We retrospectively analyzed data from hybrid closed-loop studies involving young children (1-6 years old, n = 20), children (7-12 years, n = 21), adolescents (13-17 years, n = 15), and adults (>18 years, n = 58) with type 1 diabetes. The coefficient of variation quantified variability of insulin needs during 3 weeks of unrestricted-living hybrid closed-loop use. RESULTS: Data from 2,365 nights and 2,367 days in 114 participants were analyzed. The coefficient of variation of insulin delivery was higher in young children compared with adults (mean difference at nighttime 10.7 percentage points [95% CI 2.9-18.4], P = 0.003; daytime 6.4 percentage points [95% CI 2.0-10.9], P = 0.002) and compared with adolescents (mean difference at nighttime 10.2 percentage points [95% CI 0.0-20.4], P = 0.049; daytime 7.0 percentage points [95% CI 1.1-12.8], P = 0.014). CONCLUSIONS: Diabetes management in young children is complicated by higher variability in insulin requirements, supporting fast-track clinical practice adoption of closed-loop in this vulnerable population. With increasing application of insulin pump therapy and continuous glucose monitors, hybrid closed-loop has become a feasible treatment modality for people with type 1 diabetes (1,2). Apart from manual meal-time boluses, insulin delivery is autonomously modulated by a control algorithm based on real-time sensor glucose values. Insulin delivery may vary considerably from day to day and night to night due to varying activity levels, insulin set-changes, meal timings and composition, and other factors(3,4).Todate,theassociationbetweenageandinsulinvariabilityhasnotbeen assessed.Inthepresentanalysis,weinvestigatewhetherinsulinrequirementsmaybe more variable in younger age.

Caesarean section delivery (CSD) disrupts mother-to-neonate transmission of specific microbial strains and functional repertoires as well as linked immune system priming. Here we investigate whether differences in microbiome composition and impacts on host physiology persist at 1 year of age. We perform high-resolution, quantitative metagenomic analyses of the gut microbiomes of infants born by vaginal delivery (VD) or by CSD, from immediately after birth through to 1 year of life. Several microbial populations show distinct enrichments in CSD-born infants at 1 year of age including strains of Bacteroides caccae, Bifidobacterium bifidum and Ruminococcus gnavus, whereas others are present at higher levels in the VD group including Faecalibacterium prausnitizii, Bifidobacterium breve and Bifidobacterium kashiwanohense. The stimulation of healthy donor-derived primary human immune cells with LPS isolated from neonatal stool samples results in higher levels of tumour necrosis factor alpha (TNF-α) in the case of CSD extracts over time, compared to extracts from VD infants for which no such changes were observed during the first year of life. Functional analyses of the VD metagenomes at 1 year of age demonstrate a significant increase in the biosynthesis of the natural antibiotics, carbapenem and phenazine. Concurrently, we find antimicrobial resistance (AMR) genes against several classes of antibiotics in both VD and CSD. The abundance of AMR genes against synthetic (including semi-synthetic) agents such as phenicol, pleuromutilin and diaminopyrimidine are increased in CSD children at day 5 after birth. In addition, we find that mobile genetic elements, including phages, encode AMR genes such as glycopeptide, diaminopyrimidine and multidrug resistance genes. Our results demonstrate persistent effects at 1 year of life resulting from birth mode-dependent differences in earliest gut microbiome colonisation.

CamAPS FX (CamDiab, Cambridge, U.K.) is a hybrid closed-loop app hosting the Cambridge closed-loop algorithm on an Android smartphone, and it is approved in the European Union for use in children ≥1 year and adults (including during pregnancy) with type 1 diabetes (T1D). The interoperable CamAPS FX app receives glucose data from a compatible continuous glucose monitoring system (Dexcom G6; Dexcom, San Diego, CA), connects to a compatible insulin pump (Dana Diabecare RS and DANA-i; Sooil, Seoul, South Korea) to direct glucose-responsive insulin delivery every 8–12 min, includes a bolus calculator allowing discrete bolusing via the app, and streams data in real time to cloud-based diabetes data repositories (Diasend/Glooko, Gothenburg, Sweden). It is currently unknown how much time different user cohorts spend interacting with hybrid closed-loop systems. We aimed to investigate usage patterns of the CamAPS FX app across different populations by considering the amount of time a person spends using the app over a 24-h period. We noted time spent within the CamAPS FX app over an 11-week period from February to May 2020 in 134 individuals from six ongoing clinical studies. Each study involved a different demo graphic cohort: very young children (1–7 years) in which caregivers use the app (NCT03784027, ClinicalTrials.gov), children and adolescents (6–19 years) (NCT02925299), adolescents (10–17 years) using the closed-loop system from diagnosis of T1D (NCT02871089), adults (≥18 years) (NCT04055480), pregnant women (≥18 years) (ISRCTN56898625, www.isrctn.org), and older adults (≥60 years) (NCT04025762). All studies received regulatory and ethical approval; participants/guardians signed informed consent. User engagement is the duration of time that users have the application active and in the foreground, as calculated by an analytics cloud platform (Firebase; …

BACKGROUND: Wolfram Syndrome is a very rare genetic disease causing diabetes mellitus, blindness, deafness, diabetes insipidus, and progressive brainstem degeneration. Neurologic symptoms of affected patients include ataxia, sleep apnea, loss of bladder control, dysphagia, loss of taste, and accompanying psychiatric symptoms as a sign of progressive neurodegeneration. Its genetic cause is mainly biallelic mutations of the Wolframin endoplasmatic reticulum transmembrane glycoprotein gene Wfs1. These result in increased ER stress, which in turn induces apoptosis and leads to the depletion of the corresponding cells and a loss of their physiological functions. Though diabetes mellitus is mostly treated by insulin, there is still no proven cure for the disease in general. It leads to premature death in affected individuals-usually within the 4th decade of live. CURRENT RESEARCH AND TREATMENT TRIALS: Clinical studies are currently being conducted at various locations worldwide to test a therapy for the disease using various approaches. POTENTAIL OF VIRTUAL NETOWRKING: As rare diseases in general represent a major challenge for individual clinicians and researchers due to the rarity of diagnosis, the lack of evidence and of value of existing research, international cooperation, coordination and networking leading to an alignment of different stakeholders is necessary to support patients and increase knowledge about these diseases, like wolfram syndrome. CONCLUSION: ENDO-ERN and EURRECA are two EU-funded networks that aim to promote knowledge sharing, education and research on rare endocrine diseases.

We thank Dr Yardley and Dr Sigal for their comments on the position statement pertaining to the use of continuous glucose monitoring (CGM) systems around exercise in type 1 diabetes.

BACKGROUND Electronic learning (e-learning) is a widely accessible, low-cost option for learning remotely in various settings that allows interaction between an instructor and a learner. OBJECTIVE We describe the development of a free and globally accessible multilingual e-learning module that provides education material on topics in pediatric endocrinology and diabetes and that is intended for first-line physicians and health workers but also trainees or medical specialists in resource-limited countries. METHODS As complements to concise chapters, interactive vignettes were constructed, exemplifying clinical issues and pitfalls, with specific attention to the 3 levels of medical health care in resource-limited countries. The module is part of a large e-learning portal, ESPE e-learning, which is based on ILIAS (Integriertes Lern-, Informations- und Arbeitskooperations-System), an open-source web-based learning management system. Following a review by global experts, the content was translated by native French, Spanish, Swahili, and Chinese–speaking colleagues into their respective languages using a commercial web-based translation tool (SDL Trados Studio). RESULTS Preliminary data suggest that the module is well received, particularly in targeted parts of the world and that active promotion to inform target users is warranted. CONCLUSIONS The e-learning module is a free globally accessible multilingual up-to-date tool for use in resource-limited countries that has been utilized thus far with success. Widespread use will require dissemination of the tool on a global scale.

Background Electronic learning (e-learning) is a widely accessible, low-cost option for learning remotely in various settings that allows interaction between an instructor and a learner. Objective We describe the development of a free and globally accessible multilingual e-learning module that provides education material on topics in pediatric endocrinology and diabetes and that is intended for first-line physicians and health workers but also trainees or medical specialists in resource-limited countries. Methods As complements to concise chapters, interactive vignettes were constructed, exemplifying clinical issues and pitfalls, with specific attention to the 3 levels of medical health care in resource-limited countries. The module is part of a large e-learning portal, ESPE e-learning, which is based on ILIAS (Integriertes Lern-, Informations- und Arbeitskooperations-System), an open-source web-based learning management system. Following a review by global experts, the content was translated by native French, Spanish, Swahili, and Chinese–speaking colleagues into their respective languages using a commercial web-based translation tool (SDL Trados Studio). Results Preliminary data suggest that the module is well received, particularly in targeted parts of the world and that active promotion to inform target users is warranted. Conclusions The e-learning module is a free globally accessible multilingual up-to-date tool for use in resource-limited countries that has been utilized thus far with success. Widespread use will require dissemination of the tool on a global scale.