The use of an automated insulin delivery system is associated with a reduction in diabetes distress and improvement in quality of life in people with type 1 diabetes

Abstract

The need to address the emotional impact of diabetes has received growing attention over the last two decades and psychological care is now integrated into guidelines for diabetes management.1 As distinct from major depressive disorders, diabetes distress results from the interaction between the elevated mental load associated with the constraints and consequences of diabetes, the cognitive and psychological capacities of people living with diabetes to cope with multiple tasks, and concerns about their disease. A review focusing on people with type 1 diabetes (T1D) reported a prevalence of severe diabetes distress of 20%–30%,2 which impacted on self-care, management of diabetes, glycaemic control and quality of life (QoL). The development of hybrid closed-loop (HCL) systems offers the potential to improve glucose control but also to reduce diabetes burden thanks to the automation of multiple daily tasks. The present study was designed to assess, in a large cohort of people with T1D, the impact of an HCL system on diabetes distress, QoL and a panel of patient-reported outcome measures. IMPLIQUE was a multicentre longitudinal real-life study conducted in French university hospitals. Adults and adolescents were eligible if they had T1D treated by an insulin pump and a continuous glucose monitoring (CGM) system for at least 6 months, if they used the Tandem t:slim X2 insulin pump (Tandem Diabetes Care, USA) and Dexcom G6 CGM (Dexcom, USA) for at least 4 weeks before study inclusion and if Control-IQ initiation was planned by their diabetologist. Exclusion criteria were pregnancy, lactation, and severe retinopathy. At the end of a 3-week run-in period, the HCL system was activated and participants attended follow-up visits at 3 and 6 months, and received phone calls on Days 7, 14 and 42. The study was reviewed by an independent scientific board and approved by an institutional French Ethics Committee (CPP Ile de France X, 31 August 2021). Written informed consent was obtained as required. The trial was registered at ClinicalTrials.gov under NCT 04939766. Participants completed questionnaires assessing diabetes-related distress (Problem Areas in Diabetes questionnaire [PAID]-20 or PAID-5), QoL (Audit of Diabetes-Dependent Quality-of-Life [ADDQoL]), stress (Perceived Stress Scale [PSS]), anxiety (seven-item Generalized Anxiety Disorder questionnaire [GAD7]), depression (QSP9), fear of hypoglycaemia (Hypoglycaemia Fear Survey [HFS] II) including the behaviour (HFS-B) and worry (HFS-W) scales, physical activity (Godin), sleep (Pittsburgh Sleep Quality Index [PSQI]) and fatigue (Fatigue Severity Scale [FSS]; Appendix S1). The primary outcomes, PAID and ADDQoL scores, were assessed at baseline, 3 months (PAID-5) and 6 months during the study period. Secondary outcome scores were assessed at baseline and 6 months. Glycaemic outcomes were assessed at baseline and 6 months. Adverse events were reported throughout the study (Figure S1, Appendix S2). For statistical analyses, the population set included all enrolled participants with available baseline CGM data and completed questionnaires. Statistical analyses were run separately for adults and adolescents, and were considered significant if p values were <0.05. Missing data were minimal, therefore, only the results of analyses on complete cases are presented. Unless otherwise specified, results for quantitative data are expressed as mean ± SD. For the determination of differences in PAID and ADDQoL scores from inclusion until follow-up visit, paired Student tests were used. A total of 257 people with T1D were enrolled across 55 French centres. The participant characteristics are presented in Table 1. Of this study cohort, 250 participants completed the study (97%), while seven participants (five adults and two adolescents) withdrew. At baseline, 64% of adults had a PAID score above 40 indicating severe diabetes distress (Table 2). The most severe subscores (mean score >2/4) were obtained for concerns regarding serious diabetes complications, feelings of guilt, and anxiety regarding diabetes management, worry about hypoglycaemia, and mental and physical exhaustion caused by diabetes. In adults, PAID score decreased significantly after 3 months of HCL system use and remained stable at 6 months (p < 0.001), resulting in a 16% improvement in mean diabetes distress score. All subscores improved, with the exception of one, the feeling of being burned out by diabetes management. After 6 months of HCL system use, 50% of adults still had severe diabetes distress. Among adolescents, 40% had severe diabetes distress at baseline and the mean PAID score did not change significantly with HCL system use (Figure S2). Concerning QoL, ADDQoL global score improved rapidly in adults after 3 months of HCL system use (p < 0.001) and remained stable at 6 months. In adolescents, ADDQoL global score remained stable during the study (Figure S3). Concerning fear of hypoglycaemia, HFS-B score improved significantly in both adults (p < 0.001) and adolescents (p < 0.05) after 6 months of HCL system use, while HFS-W score improved only in adults (p < 0.001). The PSS global stress score also improved only in adults. GAD7 anxiety score improved in adults (p = 0.05) but remained stable in adolescents. In both adults and adolescents, neither QSP9 score nor PSQI score, nor FSS scores changed significantly. Godin physical activity score improved only in adolescents (p < 0.05). Outcomes for glucose control are summarized in Table S1. During the study period, one episode of severe hypoglycaemia and two episodes of ketoacidosis occurred in adolescents, while seven episodes of severe hypoglycaemia and one episode of ketoacidosis occurred in adults. Regarding device-related adverse events, five occurred in adolescents and 26 in adults, due to catheter occlusions (n = 8), sensor failures (n = 14), or pump failures (n = 9). In adults, severe diabetes distress at baseline was associated with female sex (p = 0.05), presence of retinopathy (p < 0.05), and neuropathy (p < 0.01). In adolescents, severe diabetes distress was associated with female sex (p < 0.01), low physical activity (p < 0.0) and pump use for fewer than 5 years (p < 0.05). No other variables were associated with severe diabetes distress. The psychosocial impact of HCL systems is now a matter of debate and worthy of clinical evaluation. In the present study, the main findings were a high prevalence of severe diabetes distress in adults and its improvement after 6 months of HCL system use. Importantly, despite the positive effect of HCL devices, half of the adults still exhibited severe diabetes distress scores and altered QoL at the study end, emphasizing that some of the difficulties in coping with diabetes burden are not modifiable by HCL technology. Previous studies have reported an improvement in diabetes distress with HCL devices,3-5 while others did not.6, 7 In contrast to adults, the HCL system did not modify the level of diabetes distress and QoL in adolescents, in accordance with some published studies6, 8 but not others.9, 10 HCL devices also improved QoL in adults only, in agreement with previous studies.3, 5 Concerning fear of hypoglycaemia, trials performed with second-generation HCL systems have shown improvements in both behaviour and worry about hypoglycaemia in children and their parents,11 as seen in the present study, while findings have been controversial in adults.6, 12 Other benefits of HCL systems were a reduction of anxiety and stress in adults and an improvement of physical activity level in adolescents. The strengths of the present study include the large panel of psychosocial outcomes investigated, the fact that most adults were using a sensor-augmented pump before the study and the 6-month duration of the study, while the main limitation was the lack of a control group. We conclude that HCL system use is associated with improvement in several psychosocial outcomes. The high percentage of residual distress despite HCL use suggests unmet needs which should be handled in an alternative way with psychotherapeutic approaches. Yves Reznik, Jean-Pierre Rivelin, Guy Fagherazzi and Mihaela Mihaileanu conceived the study. Yves Reznik wrote the manuscript. Yves Reznik, Elisabeth Bonnemaison, Guy Fagherazzi and Jean-Pierre Riveline interpreted the data. Guy Fagherazzi and Eric Renard reviewed the manuscript. Yves Reznik, Elisabeth Bonnemaison, Hélène Hanaire, Pauline Schaepelynck and Jean-Pierre Riveline provided the patient medical data. Yves Reznik is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The authors thank Dr Eric Leutenegger, freelance medical writer, for help with preparing the manuscript, and Cecile Caballol, VitalAire France, for her support. Editorial assistance was provided by Dr Ian Darby, Editingbiomed, Melbourne, Australia. The promoter of the study was VitalAire France. Study monitoring was conducted by Qualees, a contract research organization. Yves Reznik has received consultant/speaker fees from Medtronic, Insulet, Embecta, Abbott, Novo Nordisk, Eli-Lilly, Sanofi-Aventis, TIMKL, Vitalaire, ORKYN and Air Liquide Santé International. Elisabeth Bonnemaison has received consultant/speaker fees from Abbott, Eli-Lilly, Medtronic, Novo Nordisk, Sanofi-Aventis and Air Liquide Santé International. Guy Fagherazzi has received consultant/speaker fees from MSD, Eli-Lilly, Roche Diabetes Care, AstraZeneca, Danone Research, Diabeloop, Bristol Myers Squibb, L'Oréal R&D, AbbVie Pharmaceutical, Pfizer, Vitalaire and Sanofi-Aventis. Eric Renard has received consultant/speaker fees from A. Menarini Diagnostics, Abbott, Air Liquide SI, AstraZeneca, Becton-Dickinson, Boehringer-Ingelheim, Cellnovo, Dexcom Inc., Eli-Lilly, Hillo, Insulet Inc., Johnson & Johnson (Animas, LifeScan), Medtronic, Medirio, Novo Nordisk, Roche and Sanofi-Aventis and research support from Abbott, Dexcom Inc., Insulet Inc., Roche and Tandem Diabetes Care. Hélène Hanaire has received lecturer and scientific advisor fees from Insulet, Abbott, AstraZeneca, Novo Nordisk, Lilly, Sanofi A, Lifescan, Medtronic, and research grants from Novo Nordisk, Lifescan, Abbott, Sanofi-Aventis. Pauline Schaepelynck has received consultant/speaker fees from Medtronic, Abbott Diabetes Care, Novo Nordisk, Eli-Lilly, Sanofi-Aventis, TIMKL, Vitalaire and ORKYN. Mihaela Mihaileanu is an employee of VitalAire France. Jean-Pierre Riveline is an advisory panel member for Sanofi Aventis MSD, Eli Lilly, Novo Nordisk, AstraZeneca, Abbott, Dexcom, Alphadiab and Medtronic, and has received research funding from Abbott, Air Liquide Santé International, Sanofi-Aventis and Novo Nordisk. The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer-review/10.1111/dom.15462. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. TABLE S1. Glycaemic outcomes. FIGURE S1. Flow chart. FIGURE S2. PAID scores in adults and adolescents at baseline and 3 and 6 months after AID system use. Panel A: adults, panel B: adolescents. FIGURE S3. ADDQoL scores at baseline and 3 and 6 months after AID system use. APPENDIX S1. Descriptive of the psychosocial scales. APPENDIX S2. Descriptive of the Study sample calculation and statistical methods. DATA S1. STROBE statement—IMPLIQUE study. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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