Reduced burden of diabetes and improved quality of life: Experiences from unrestricted day‐and‐night hybrid closed‐loop use in very young children with type 1 diabetes

Abstract Objective To evaluate the experiences of families with very young children aged 1 to 7 years (inclusive) with type 1 diabetes using day‐and‐night hybrid closed‐loop insulin delivery. Methods Parents/caregivers of 20 children aged 1 to 7 years with type 1 diabetes completed a closed‐loop experience survey following two 3‐week periods of unrestricted day‐and‐night hybrid closed‐loop insulin therapy using Cambridge FlorenceM system at home. Benefits, limitations, and improvements of closed‐loop technology were explored. Results Responders reported reduced burden of diabetes management, less time spent managing diabetes, and improved quality of sleep with closed‐loop. Ninety percent of the responders felt less worried about their child's glucose control using closed‐loop. Size of study devices, battery performance and connectivity issues were identified as areas for improvement. Parents/caregivers wished for more options to input information to the system such as temporary glucose targets. Conclusions Parents/caregivers of very young children reported important quality of life benefits associated with using closed‐loop, supporting adoption of this technology in this population.


Funding information
Results: Responders reported reduced burden of diabetes management, less time spent managing diabetes, and improved quality of sleep with closed-loop. Ninety percent of the responders felt less worried about their child's glucose control using closed-loop. Size of study devices, battery performance and connectivity issues were identified as areas for improvement. Parents/caregivers wished for more options to input information to the system such as temporary glucose targets.
Conclusions: Parents/caregivers of very young children reported important quality of life benefits associated with using closed-loop, supporting adoption of this technology in this population.
artificial pancreas, closed-loop insulin delivery, type 1 diabetes, very young children

| INTRODUCTION
The burden of diabetes management in very young children is a significant challenge for caregivers. In this vulnerable population glycemic control is particularly demanding, with unpredictable eating habits, irregular bouts of physical activity, erratic behavior, and significant fear of hypoglycemia. The incidence of hypoglycemia is high in children <6 years of age, with most cases occurring during the night. 1 Caregivers of very young children with type 1 diabetes often routinely monitor blood glucose levels overnight, with consequent sleep disruption and anxiety. 2 Significant fear of hypoglycemia leads to reduced quality of life and sub-optimal glycemic control. 3 Closed-loop systems, which automatically and continuously adjust insulin delivery according to real-time sensor glucose levels, may reduce burden of diabetes management. A recent trial involving very young children aged 1 to 7 years demonstrated that unrestricted home use of day-and-night closed-loop is feasible and safe in managing glucose control. 4 The psychosocial benefits of closed-loop have been explored in older children, adolescents, and adults 5-7 but the impact of closed-loop use in very young children with type 1 diabetes is yet to be assessed.
The aim of this study was to evaluate the experience of families with very young children with type 1 diabetes using day-and-night hybrid closed-loop system during unrestricted living.

| METHODS
Twenty-four children aged 1 to 7 years (inclusive), with type 1 diabetes for at least 6 months, using insulin pump therapy for at least 3 months and with glycated hemoglobin (HbA1c) ≤ 97 mmol/mol (11%) were rec- At the end of the study, caregivers were asked to complete the Closed-loop Experience Questionnaire (Table S1), consisting of two parts. Part A lists six questions about closed-loop experience during the study using a numerical scale from 1 to 5, from "Strongly Agree" to "Strongly Disagree." For each answer a mean score was calculated.
Questions are reverse scored (except for question 3), so a higher score denotes more satisfaction with the closed-loop system. Part B con- sists of three open questions regarding perceived benefits and limitations of the system with space for suggestions for additional features.
Quotes in French and German were translated in English prior to analysis. Trial registration NCT03101865 (ClinicalTrials.gov)

| RESULTS
Completed surveys were available for 20 of 24 enrolled participants: seven from Austria, two from Germany, four from Luxembourg, and seven from UK (

| Overall experience
Ninety percent of caregivers would strongly recommend the system to others. After just 6 weeks of use, 95% of responders were satisfied with their child's glucose levels being controlled automatically by the system, suggesting rapid gain of trust in the closed-loop.

| Reducing the burden of diabetes
Caregivers acknowledged closed-loop reduced the burden of diabetes management. Eighty-five percent of the responders reported spending less time managing their child's diabetes (finger-pricks, insulin therapy adjustment, regular data review) with closed-loop. One caregiver (5%) felt that closed-loop took more time and work than it was worth.

| Reduced stress levels
Ninety percent of responders reported that they were less worried about their child's glucose control when using closed-loop. Eighteen out of 20 (90%) caregivers reported having less trouble sleeping whilst their child was using the system.

| Perceived benefits
Responders identified several clinical benefits of closed-loop regarding reduced hypoglycemic events ("…safe system with little hypoglycemia," "…no hypos at night") and more stable glycemic control ("more sugar stability," "…Values more stable throughout the day"), especially during night-time ("…little fluctuation especially at night," "The overnight control was excellent," "We have had issues with overnight and the system helped").
Caregivers were positive about the system's responsiveness with its "automatic basal rate adjustment for high and low glucose levels" and "automatic shutdown in case of hypoglycemia." They also felt reassured by the ability of the closed-loop system to "give the exact amount of insulin which is required." These features reduced the burden of disease management as caregivers spent less time performing diabetes-related activities ("less 'visual inspection' on pump + less BG measurements"). Real-time visualization of data ("to see the pattern on a big screen" and the "amount of data for analysis/decision making") was highlighted as a very useful benefit.
Responders emphasized the improvement in quality of sleep with closed-loop ("the quieter nights") both for caregivers ("first time we as parents were able to sleep the night straight since diagnosis") and users ("Also…our child…was able to sleep undisturbed").
Many caregivers felt reassured ("Having the system working at school also for us was reassuring") and less stressed ("Less worry, better quality of life," "I was less worried about blood sugar"). Some caregivers suggested that closed-loop had a positive impact on their child's wellbeing ("Overall we noticed the effect on our child's life: he had a significant improvement in developing his walking & talking," "It has made a massive difference to the last few months. My son was a lot more confident, less angry and generally happier").

| Limitations of the closed-loop system
Several caregivers highlighted limitations of the system relating to the size of the study devices ("The device was bulky," "phone handset a little too large"), battery performance ("phones need to be charged a lot"), and connectivity issues ("the systems…would lose connection even when they were within a reasonable range e.g. in the same room").
While alarms were perceived as intrusive ("a curse") by some users, and seemed to create some "anxiety" due to the "noise from the phone" and "warning vibration from the pump," for others they were considered reassuring ("The alarms were…a blessing…and created… reassurance to ourselves").

| Features to be implemented
Responders were invited to suggest additional features for the system. These included mostly technical improvements: "a longer range," "the closed-loop system incorporated into the pump," "be able to access blood sugars from different phones," or "bolusing without having to touch the pump." Some participants also suggested more user-adjustable settings and the option to be able to override the closed-loop system: "ability to suggest change of closed-loop action if desired," "more variable control, like OpenAPS e.g. temp targets, micro bolus for food, ability to change settings throughout the trial." Some caregivers also wanted an option to incorporate into the system additional information regarding food types in order to improve its effectiveness ("Use phone to input food type, e.g. spaghetti, pizza etc."). has not yet been validated. Given the very good glycemic control of the participants enrolled (Table S3), it is possible that the study population is not representative of the broader population of young children with type 1 diabetes. We need to verify if the reported benefits would result in similar findings in a less selective population. We aim to address these issues in a longer duration follow-up study (NCT03784027, ClinicalTrials.gov). As part of the planned study caregivers will take part in semi-structured interviews in order to gather their experiences using the closed-loop system and the quality of life impact.

| DISCUSSION
There is significant interest in automated insulin delivery systems for caregivers of children with type 1 diabetes. One expression of this is the growing patient-designed and -driven artificial pancreas systems, the so-called DIY (Do-it-Yourself) community. 9 The desire from some caregivers to be more involved in interacting with the system was evident in some responses to the questionnaire. Future developments of this technology should provide users with a wider range of adjustable settings to improve user experience.
Psychosocial perspectives of closed-loop system use from both users and caregivers are vital. User feedback is instructive to help the manufacturers and the researchers improve the systems and develop additional features to be implemented. If closed-loop is to be widely adopted as standard management of type 1 diabetes in the future, it is essential for healthcare providers to explore users' real-life experience using this technology in order to meet their expectations properly.
In conclusion, results from our survey undertaken by caregivers of very young children with type 1 diabetes demonstrated overall satisfaction with unrestricted hybrid closed-loop use. Future closedloop systems may address some of the identified limitations. Further studies of longer duration are required to better understand closedloop experience in this age group.