Cobry et al. [16] compared health-related QoL and emotional distress between CIQ and SAP therapy in a 16-week + 12-week extension phase RCT involving 101 children (aged 6–13 years) and their caregivers. The study utilized the Problem Areas In Diabetes (PAID) scale, the Pediatric QoL (PedsQL) survey, and the Insulin Delivery Systems: Perceptions, Ideas, Reflections, and Expectations (INSPIRE) questionnaire. No statistically significant improvement was observed between groups for either parents or children.

However, Bisio et al. [17] documented a significant improvement in emotional distress and depressive symptoms for parents in a single-arm clinical trial after transitioning to CIQ therapy. The study involved the completion of the PAID scale and the Center for Epidemiologic Studies Depression Scale—Revised (CESDR) by parents and the PAID scale and the Children's Depression Inventory, second version, Self-Reported Short version (CDI-2:SR[S]) by children.

Similarly, Cobry et al. [18] reported an increase in parents PAID and PedsQL scores after switching from MDI or SAP to CIQ in a 6-month, single-arm, prospective observational study. However, there were no significant changes in scores for children and adolescents, except for an improvement in PedsQL scores for children aged 5–7 years (p = 0.042). There were no significant changes for either the parent or child INSPIRE surveys.

Zuijdwijk et al. [19] reported that only parents experienced an improved QoL after their children transitioned from Tandem t:slim X2 pump to CIQ technology. The WHO-5 Well-Being Index (p = 0.003) and INSPIRE questionnaire (p <  0.04) were used.

Improved QoL associated with CIQ technology was also reported in Hood et al. [20] 13-week RCT of CIQ vs SAP/MDI therapy. This study enrolled 102 young children (aged 2–6 yrs), data were collected based exclusively on the guardian’s perspective since this particular population relies primarily on a caregiver for diabetes management. The PedsQL survey and the Pediatric Inventory for Parents (PIP) questionnaire were used, and both showed improvement in child QoL and parenting stress (p = 0.02 and p = 0.05, respectively).

More recently, Marks et al. [21] investigated the PROs in a single-arm prospective pilot study on 13 insulin pump-naïve non-Hispanic Black youth (6–21 years old) with type 1 diabetes and HbA1c ≥ 10%. QoL significantly increased among parents and youth, and diabetes distress decreased in both groups. The improvements in blood glucose control parameters affected none of these outcomes.

Fear of hypoglycemia, a significant distress factor for patients and families, was addressed in various studies using the Hypoglycemia Fear Survey (HFS), with varying results. Ng et al. [22], Cobry et al. [18], and Zuijdwijk et al. [19] documented a substantial improvement in both patients and caregivers thanks to CIQ technology. Bisio et al. [17], on the other hand, found a significant improvement in parents alone; Hood et al. [20] documented an improvement in parents of very young children and Cobry et al. [16, 23] only in parents identified as “poor” sleepers and their children.

Different questionnaires were used to assess technology acceptance and treatment satisfaction across studies. Forlenza et al. [24] found that using the CIQ system was associated with reduced time spent thinking about diabetes and decreased burden in managing it. Renard et al. [25] noted a significant increase in Artificial Pancreas Acceptance Questionnaire scores (p = 0.036). In contrast, Diabetes Impact and Device Satisfaction (DIDS) questionnaire scores improved significantly for parents and children in a study by Zuijdwijk et al. [19].

In the prospective clinical study by Mingorance Delgado et al. [26], the same survey improved parents’ subjective feelings about diabetes control. Contrarily, Cobry et al. [18] experienced no significant changes in the parent and child Diabetes Technology Questionnaire scores after 6 months of CIQ usage, and Bisio et al. [17] reported no substantial differences in the benefits and burdens that parents experienced during the CIQ study phase.

Table 2 shows psychological outcomes in youth with T1D and their caregivers.

Bisio et al. [17] conducted a single-arm clinical trial (4 weeks SAP + 4 weeks CIQ) using both questionnaires and an actigraphy watch to assess the sleep quality of parents and children. Parents reported a significant improvement in sleep quality and disturbances after switching to CIQ technology, as measured by the Pittsburgh Sleep Quality Index (PSQI). However, they did not observe a significant increase in their children's sleep quality and quantity, as measured by the Children's Sleep Habit Questionnaire-Abbreviated (CSHQ-A). Actigraphy data did not show any significant changes in sleep-related data for either parents or children, except for a decrease in parental awakenings lasting more than 5 min during the night (p = 0.036).

Cobry et al. [18], similarly, in their 6-month single-arm, prospective observational study, assessed sleep quality in children and adolescents and their parents. Participants' sleep was evaluated using questionnaires, wrist actigraphy, and sleep diaries. The Parent PSQI showed a significant improvement in subjective sleep quality after 3 months of AHCL use (p = 0.024), but this result was not confirmed at 6 months. The PROs Measurement Information System (PROMIS) scores showed significant improvements at 3 months only in the parent proxy for child sleep impairment subscale (p = 0.041); no improvement in PROMIS scores was seen at 6 months for either Child self-report (ages 8–17) or parent proxy for the child (children ages 5–17). Actigraphy watch measurements in children indicated no significant changes compared to baseline except for an increase in adolescents' sleep efficiency (ratio of the total sleep time and the time in bed) at 6 months (p = 0.03). Parents experienced a significant improvement in the total number of minutes awake after actigraphy sleep onset (WASO) at 3 (p = 0.004) and 6 months (p = 0.007).

Cobry et al. [16] also evaluated sleep quality in a RCT using the PSQI. Although there was no significant difference in PSQI scores between the two groups, parents in the CIQ group saw an improvement in sleep quality from “poor” (PSQI score > 5) to “adequate” over 16 weeks. A secondary analysis was conducted [23], focusing on parents identified as “poor” sleepers at baseline. At the end of the study, there was a significant improvement (p <  0.001) in PSQI scores, with 27 out of 49 poor sleepers becoming good sleepers. Hood et al. [20], in their RCT plus extension phase, reported improved PSQI scores in guardians of very young children on CIQ at 13 and 26 weeks compared to baseline.

Table 2 shows sleep quality outcomes in youth with T1D and their caregivers.

Data from different studies [22, 24, 25, 27,28,29,30,31,32,33,34,35,36,37] involving 1710 patients aged 0–18 were available regarding serious adverse events using the Tandem t:slim X2 insulin pump with CIQ technology. The follow-up duration varied considerably among the studies, ranging from 2 days to 12 months, with six studies lasting ≥ 6 months.

Messner et al. [27] conducted a prospective observational study in real-world conditions with 191 young people who began using the CIQ system for routine diabetes management. The follow-up period lasted for 6 months. At the 6-month mark, glycemic control improved compared to baseline. Additionally, two episodes of DKA were reported during the study period, one due to viral gastroenteritis and the other likely caused by an infusion set failure. There were no reports of severe hypoglycemic events in any of the participants.

Renard et al. [25] conducted a RCT with 122 free-living children with T1D aged between 6 and 12 years. The purpose of the study was to evaluate this system's safety over a 36-week period. During the initial phase of the study, which lasted 18 weeks, the authors compared the safety of using the CIQ technology only during the evening and night (E/N mode arm) when children were likely to be at home and under adult supervision with the safety of using it all day (24/7 arm). The study found that time in range (TIR) increased more in the 24/7 mode compared to the E/N mode (14.4% vs. 9.6%). Additionally, no severe adverse events such as SH or DKA were reported throughout the study when the CIQ software was activated. The authors concluded that this AHCL system is safe to use even when children are not under adult supervision, such as attending school, participating in physical activities, or eating without restrictions.

In a separate study conducted by Graham et al. [28], a single-arm, prospective, longitudinal study was carried out on individuals aged ≥ 6 years who started using the CIQ technology in a real-world setting. The trial enrolled 3157 participants with varying baseline HbA1c levels and previous therapy modalities. Participants were trained on the CIQ technology, and follow-up visits were conducted through their regular diabetes care provider without additional supervision. Data were collected over 12 months, and the rates of adverse events were compared to historical data from pediatrics [38]. It was found that the rates of SH and DKA were significantly lower in children compared to historical rates. The lower rates of adverse events were consistent regardless of baseline HbA1c levels, previous insulin delivery methods, or prior CGM experience.

Santova et al. [29] compared glycemic control and safety among Czech children with T1D using the 2022 annual report from the national pediatric diabetes registry, ČENDA. They collected data from all children < 19 years of age who had been using Medtronic MiniMed 780G (780G), Tandem t:slim X2 with CIQ, or do-it-yourself AndroidAPS (AAPS) HCL systems for > 12 months. The study included 512 patients, with 42.4% using 780G, 41.2% using CIQ, and 16.4% using AAPS. There were no statistically significant differences in the occurrence of DKA or SH events between the groups during the study period. In the CIQ group, DKA and SH events occurred at a rate of 2 per 100 patient-years.

All the other studies reported no serious adverse events [22, 24, 25, 30,31,32,33,34,35,36,37].

The CIQ system has also been proven safe during intense exercise in youth. Mameli et al. [37] evaluated the safety and performance of CIQ technology during 2-h outdoor physical activity in 24 children and adolescents aged 9–18 years. All participants took part in both endurance activities (1000-m run and a jump circuit; 60 min duration) and power activities (80-m run and long jump; 60 min duration). Lunch and self-administration of an insulin bolus reduced by 50% compared to the usual calculated meal dose that occurred 90 min before starting exercise. The “Exercise activity” mode was set 90 min before starting physical activity and maintained until dinner time, while the “sleep mode” function was turned on at bedtime. No severe hypoglycemic episodes were recorded during physical activity or until 7 a.m.

Ekhlaspour et al. [31] and Schoelwer et al. [32] tested this AHCL system during winter ski camps. High altitude, low temperature, prolonged intense activity, increased carbohydrate intake, stress, and excitement could challenge glycemic control. The first study [31] included both adolescents (n =   24, aged 13–18 years) and children (n =   24, aged 6–12 years) who took part in a 48-h ski camp (~ 5 h skiing/day); the second study [32] only included adolescents (n =   18, aged 12–18 years), and the ski camp lasted 60 h. No serious adverse events were recorded in either of these studies.