Assessing the efficacy, safety and utility of closed-loop insulin delivery compared with sensor-augmented pump therapy in very young children with type 1 diabetes (KidsAP02 study): an open-label, multicentre, multinational, randomised cross-over study protocol

Introduction: Diabetes management in very young children remains challenging. Glycaemic targets are achieved at the expense of high parental diabetes management burden and frequent hypoglycaemia, impacting quality of life for the whole family. Our objective is to assess whether automated insulin delivery can improve glycaemic control and alleviate the burden of diabetes management in this particular age group. Methods and analysis: The study adopts an open-label, multinational, multicentre, randomised, crossover design and aims to randomise 72 children aged 1-7 years with type 1 diabetes on insulin pump therapy. Following screening, participants will receive training on study insulin pump and study continuous glucose monitoring devices. Participants will be randomised to 16-week use of the hybrid closed-loop system (intervention period) or to 16-week use of sensor-augmented pump therapy (control period) with 1-4 weeks washout period before crossing over to the other arm. The order of the two study periods will be random. The primary endpoint is the between-group difference in time spent in the target glucose range from 3.9 to 10.0 mmol/L based on sensor glucose readings during the 16-week study periods. Analyses will be conducted on an intention-to-treat basis. Key secondary endpoints are between group differences in time spent above and below target glucose range, glycated haemoglobin and average sensor glucose. Participants' and caregivers' experiences will be evaluated using questionnaires and qualitative interviews, and sleep quality will be assessed. A health economic analysis will be performed. Ethics and dissemination: Ethics approval has been obtained from Cambridge East Research Ethics Committee (UK), Ethics Committees of the University of Innsbruck, the University of Vienna and the University of Graz (Austria), Ethics Committee of the Medical Faculty of the University of Leipzig (Germany) and Comité National d'Ethique de Recherche (Luxembourg). The results will be disseminated by peer-reviewed publications and conference presentations

Time spent in hypoglycemia according to age and time-of-day: Observations during closed-loop insulin delivery.

OBJECTIVE We aimed to assess whether percentage of time spent in hypoglycemia during closed-loop insulin delivery differs by age-group and time-of-day. METHODS We retrospectively analyzed data from hybrid closed-loop studies involving young children (2-7 years), children and adolescents (8-18 years), adults (19-59 years), and older adults (≥60 years) with type 1 diabetes. Main outcome was time spent in hypoglycemia <3.9mmol/l. Eight weeks of data for 88 participants were analyzed. RESULTS Median time spent in hypoglycemia over the 24-hour period was highest in children and adolescents (4.4%; [IQR 2.4-5.0]) and very young children (4.0% [3.4-5.2]), followed by adults (2.7% [1.7-4.0]), and older adults (1.8% [1.2-2.2]); p<0.001 for difference between age-groups. Time spent in hypoglycemia during nighttime (midnight-05:59) was lower than during daytime (06:00-23:59) across all age-groups. CONCLUSION Time in hypoglycemia was highest in the pediatric age-group during closed-loop insulin delivery. Hypoglycemia burden was lowest overnight across all age-groups

Psychological Well-Being of Parents of Very Young Children With Type 1 Diabetes – Baseline Assessment

Background: Type 1 diabetes in young children is a heavy parental burden. As part of pilot phase of the KIDSAP01 study, we conducted a baseline assessment in parents to study the association between hypoglycemia fear, parental well-being and child behavior. Methods: All parents were invited to fill in baseline questionnaires: hypoglycemia fear survey (HFS), WHO-5, Epworth Sleepiness Scale and Strength and Difficulties Questionnaire (SDQ). Results: 24 children (median age: 5-year, range 1-7 years, 63% male, mean diabetes duration: 3 ± 1.7 years) participated. 23/24 parents filled out the questionnaires. We found a higher score for the hypoglycemia fear behavior 33.9 ± 5.6 compared to hypoglycemia worry 34.6 ± 12.2. Median WHO-5 score was 16 (8 - 22) with poor well-being in two parents. Median daytime sleepiness score was high in five parents (>10). For six children a high total behavioral difficulty score (>16) was reported. Pro social behavior score was lower than normal in six children (<6). Parental well-being was negatively associated with HFS total (r = - 0.50, p <.05) and subscale scores (r = - 0.44, p <.05 for HFS-Worry and HFS-Behavior), child behavior (r = - 0.45, p = .05) and positively with child age and diabetes duration (r = 0.58, p <.01, r = 0.6, p <.01). HFS, parental well-being nor daytime sleepiness are associated with the HbA1c. Conclusion: Regular screening of parental well-being, hypoglycemia fear and child behavior should be part of routine care to target early intervention

Center Size and Glycemic Control: An International Study With 504 Centers From Seven Countries

The variance in glycemic control between different childhood diabetes centers is not fully understood. Although the International Society for Pediatric and Adolescent Diabetes guidelines from 2014 recommended center sizes of more than 150 patients (1), it has not been thoroughly investigated whether glycemic control is associated with center size (2–4). We have data from more than 500 childhood diabetes centers from seven different countries and thereby a unique opportunity to elaborate further on this association. Therefore, this study aims to investigate the relationship between center size and glycemic control in children with type 1 diabetes (T1D). Patient data have been described previously (5). Briefly, the population comprised children with T1D in the age-group 3 months from seven high-income countries during 2013–2014: Austria, Denmark, England, Germany, Norway, Sweden, and Wales. Data were anonymized and obtained from five national registries/audits on children with T1D (Austria and Germany use the same electronic health record and England and Wales have a common National Paediatric Diabetes Audit, while Denmark, Norway, and Sweden have national registries). Mean HbA1c was compared between groups after adjusting for sex, age (<6 years, 6 to <12 years, and 12–18 years), duration of diabetes (<2 years, 2 to <5 years, and ≥5 years), and minority status (yes/no) (HbA1c adj) before and after stratifying for treatment modality (insulin injection/pump). Center size was defined as the number of patients with diabetes reported to be cared for in a center. Center size groupings were 1) <20, 2) 20 to <50, 3) 50 to <100, 4) 100 to <200, and 5) ≥200 patients. In total 54,494 children (48% females) with T1D across 504 centers in seven countries were included in the study. The number of centers per country varied between 14 (Wales) and 219 (Germany). Mean (SD) for age was 12.5 (3.9) years, mean age at T1D onset was 7.5 (4.0) years, and mean T1D duration was 5.0 (3.7) years. A total of 21% of patients had minority status, which varied between 5% (Wales) and 28% (Austria). A total of 38.1% of patients were on pump treatment, and the percentage varied between 25% (England) and 69% (Denmark). National coverage of T1D patients was >95% in all countries, apart from Austria, which had ∼80% data coverage. Included patients had 100% data coverage for all of the following variables: sex, age, diabetes duration, minority status, and HbA1c. Data on treatment modality were not available for 2,428 patients (4.5%); of these, 2,130 were from England and 154 were from Sweden. A total of 23.2% of centers had 200 patients, representing 12.3% of all centers. The distribution of small and large centers in the seven countries varied. England and Sweden had few small centers (34%). HbA1c adj was significantly higher in the centers with 50 patients, in both pen users (P 50 patients managed equally well; therefore, centralizing to very-high-volume diabetes centers may not necessarily be an advantage. Future research should focus on identifying reasons leading to differences in glycemic control in T1D patients cared for in small and large centers, e.g., the lack or presence of an updated multidisciplinary diabetes team

Cambridge hybrid closed-loop system in very young children with type 1 diabetes reduces caregivers’ fear of hypoglycemia and improves their well-being

Objective To evaluate the impact of CamAPS FX hybrid closed-loop automated insulin delivery (HCL) in very young children with type 1 diabetes (T1D) on caregivers’ well-being, fear of hypoglycemia and sleepiness. Research Design Multinational, open label, randomized crossover study. Children (1-7years) with T1D received treatment for two 4-month periods in random order, comparing HCL with sensor augmented pump (SAP) (control). At baseline and after each treatment period, caregivers were invited to complete WHO-5, Hypoglycemia Fear Survey (HFS) and Epworth Sleepiness Scale (ESS). Results Caregivers of 74 children (mean±SD: age 5±2 years; 42% female, baseline HbA1c 7.3±0.7%) participated. Results revealed significantly lower scores for hypoglycemia fear (p<.001) and higher for well-being (p<.001) after HCL treatment. A trend towards a reduction in sleepiness score was observed (p=0.09). Conclusion Our results suggest a better well-being and less hypoglycemia fear in caregivers of very young children with T1D on CamAPS FX HCL

Psychological Well-Being of Parents of Very Young Children With Type 1 Diabetes – Baseline Assessment

Background: Type 1 diabetes in young children is a heavy parental burden. As part of pilot phase of the KIDSAP01 study, we conducted a baseline assessment in parents to study the association between hypoglycemia fear, parental well-being and child behavior. Methods: All parents were invited to fill in baseline questionnaires: hypoglycemia fear survey (HFS), WHO-5, Epworth Sleepiness Scale and Strength and Difficulties Questionnaire (SDQ). Results: 24 children (median age: 5-year, range 1-7 years, 63% male, mean diabetes duration: 3 ± 1.7 years) participated. 23/24 parents filled out the questionnaires. We found a higher score for the hypoglycemia fear behavior 33.9 ± 5.6 compared to hypoglycemia worry 34.6 ± 12.2. Median WHO-5 score was 16 (8 - 22) with poor well-being in two parents. Median daytime sleepiness score was high in five parents (>10). For six children a high total behavioral difficulty score (>16) was reported. Pro social behavior score was lower than normal in six children (<6). Parental well-being was negatively associated with HFS total (r = - 0.50, p <.05) and subscale scores (r = - 0.44, p <.05 for HFS-Worry and HFS-Behavior), child behavior (r = - 0.45, p = .05) and positively with child age and diabetes duration (r = 0.58, p <.01, r = 0.6, p <.01). HFS, parental well-being nor daytime sleepiness are associated with the HbA1c. Conclusion: Regular screening of parental well-being, hypoglycemia fear and child behavior should be part of routine care to target early intervention