Introduction: Glucose regulation in young children is complicated by higher glycemic variability, unpredictable behaviors, and low insulin needs. While the benefits of automated insulin delivery (AID) for this population are established, how to initiate and adjust pump settings still represents a challenging task for health care providers. In this study, we investigate the safety and efficacy of using algorithm-driven initiation and adjustments of AID parameters in children aged 2-6 years. Methods: Participants used AID at home for 8 weeks. Initial settings and periodic adjustments of therapy profiles (basal rates, insulin-to-carbohydrate ratios, insulin-correction factors, and sleep schedules) were provided through a cloud-based investigational software. Investigators reviewed therapy recommendations and could adjust if necessary. Primary safety endpoints included the percentage of time <54 mg/dL and >250 mg/dL, tested for noninferiority with respect to baseline. Primary efficacy endpoints (tested in a hierarchical manner) were the percentage of time in 70-180 mg/dL, mean glucose, the percentage of time >250 mg/dL, <70 mg/dL, and <54 mg/dL. Results: Thirty-two participants (age range: 2.0-5.9 years) were recruited for the study; 29 had sufficient data for the analysis. Investigators overrode 15% of software recommendations. The percentage of time <54 mg/dL and >250 mg/dL was noninferior in the 8-week follow-up with respect to baseline (P < 0.001). Statistically significant improvements were observed in the percentage of time in 70-180 mg/dL (P = 0.005), >250 mg/dL (P = 0.003), and mean glucose (P = 0.02). No difference was observed in the percentage of time <70 mg/dL (P = 0.34). Furthermore, no difference was observed with respect to a similar study cohort (same age range, n = 86) with expert pediatric endocrinologists modifying pump settings. Conclusions: Findings from this pilot study suggest that the use of AID with algorithm-driven initiation and adjustment of pump parameters is safe and effective in young children with type 1 diabetes. Further study of the algorithm in a larger cohort is indicated. Clinical Trials Registration number: NCT06017089.

Background: To evaluate the long-term safety and effectiveness of the Omnipod® 5 Automated Insulin Delivery (AID) System in very young children with type 1 diabetes with up to 2 years of use. Methods: Following a 13-week single-arm, multicenter, pivotal trial that took place after 14 days of standard therapy data collection, participating children (2-5.9 years of age at study enrollment) were provided the option to continue use of the AID system in an extension phase. HbA1c was measured every 3 months, up to 15 months of total use, and continuous glucose monitor metrics were collected through the completion of the extension study (for up to 2 years). Results: Participants (N = 80) completed 18.2 [17.4, 23.4] (median [interquartile range]) total months of AID, inclusive of the 3-month pivotal trial. During the pivotal trial, HbA1c decreased from 7.4% ± 1.0% (57 ± 10.9 mmol/mol) to 6.9% ± 0.7% (52 ± 7.7 mmol/mol, P < 0.0001) and was maintained at 7.0% ± 0.7% (53 ± 7.7 mmol/mol) after 15 months total use (P < 0.0001 from baseline). Time in target range (70-180 mg/dL) increased from 57.2% ± 15.3% during standard therapy to 68.1% ± 9.0% during the pivotal trial (P < 0.0001) and was maintained at 67.2% ± 9.3% during the extension phase (P < 0.0001 from standard therapy). Participants spent a median 97.1% of time in Automated Mode during the extension phase, with one episode of severe hypoglycemia and one episode of diabetic ketoacidosis. Conclusion: This evaluation of the Omnipod 5 AID System indicates that long-term use can safely maintain improvements in glycemic outcomes with up to 2 years of use in very young children with type 1 diabetes. Clinical Trials Registration Number: NCT04476472.

Objective: We evaluated a modified version of Control-IQ technology with a lower treatment range and a modified meal bolus module in adults, adolescents, children, and preschoolers with type 1 diabetes in a multicenter, randomized, and crossover trial. Research Design and Methods: After a 2-week run-in with Control-IQ technology v1.5, the modified system was evaluated for 2 weeks using treatment range of 112.5-160 mg/dL (standard range [SR]), and for 2 weeks using lower treatment range of 90-130 mg/dL (lower range, LR), at home in random order. Two late bolus meal challenges were performed in each 2-week period, bolusing 45 min after meals with and without a new late bolus feature. Results: Overall, 72 participants aged 3-57 years completed the study. There were no diabetic ketoacidosis or severe hypoglycemia events. All meal challenges were completed safely. Time in range (TIR) 70-180 mg/dL improved the most with LR to 68.0% (+3.1%, P < 0.001, for LR vs. run-in and +2.1%, P < 0.001, for LR vs. SR). Similar improvements were observed for time in tight range (TITR) 70-140 mg/dL (+3.3%, P < 0.001, for LR vs. run-in and +4.0%, P < 0.001, for LR vs. SR), time >180 mg/dL, and mean glucose. Participants with lower baseline hemoglobin A1c (HbA1c) achieved the highest TIR and TITR with LR use, while the greatest improvements in TIR and TITR were evident in those with higher baseline HbA1c. Conclusions: The lower treatment range and late bolus feature of the modified Control-IQ system were safe for use in all age-groups. TIR and TITR improved with LR regardless of baseline HbA1c.

Objective Examine patient-reported outcomes (PROs) after the use of t:slim X2 insulin pump with Control-IQ technology (CIQ) in young children with type 1 diabetes. Methods Children with type 1 diabetes, ages 2 to < 6 years (n = 102), were randomly assigned 2:1 to either CIQ or standard care (SC) with pump or multiple daily injections (MDI) plus continuous glucose monitoring (CGM) for 13 weeks. Both groups were offered to use CIQ for an additional 13 weeks after the randomized control trial's (RCT) completion. Guardians completed PRO questionnaires at baseline, 13-, and 26-weeks examining hypoglycemia concerns, quality of life, parenting stress, and sleep. At 26 weeks, 28 families participated in user-experience interviews. Repeated measures analyses compared PRO scores between systems used. Result Comparing CIQ vs SC, responses on all 5 PRO surveys favored the CIQ group, showing that CIQ was superior to SC at 26 weeks (p values < 0.05). User-experience interviews indicated significant benefits in optimized glycemic control overall and nighttime control (28 of 28 families endorsed). All but 2/28 families noted substantial reduction in management burden resulting in less mental burden and all but 4 stated that they wanted their children to continue using CIQ. Conclusions Families utilizing CIQ experienced glycemic benefits coupled with substantial benefits in PROs, documented in surveys and interviews. Families utilizing CIQ had reduced hypoglycemia concerns and parenting stress, and improved quality of life and sleep. These findings demonstrate the benefit of CIQ in young children with type 1 diabetes that goes beyond documented glycemic benefit.

The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This chapter builds on the 2022 ISPAD guidelines, and summarizes recent advances in the technology behind insulin administration, with special emphasis on insulin pump therapy, especially on glucose- responsive integrated technology that is feasible with the use of automated insulin delivery (AID) systems in children and adolescents. (c) 2024 The Author(s). Published by S. Karger AG, Basel

Aim: Automated insulin delivery (AID) systems have demonstrated improved glycaemic outcomes in people with type 1 diabetes (T1D), yet limited data exist on these systems in very young children and their impact on caregivers. We evaluated psycho- social outcomes following use of the tubeless Omnipod (R) (R) 5 AID System in caregivers of very young children. Materials and Methods: This 3-month single-arm, multicentre, pivotal clinical trial enrolled 80 children aged 2.0-5.9 years with T1D to use the Omnipod 5 AID System. Caregivers completed questionnaires assessing psychosocial outcomes-diabetes distress (Problem Areas in Diabetes), hypoglycaemia confidence (Hypoglycemia Confidence Scale), well-being (World Health Organization 5 Well-Being Index), sleep quality (Pittsburgh Sleep Quality Index), insulin delivery satisfaction (Insulin Delivery Satisfaction Survey) and system usability (System Usability Scale) at baseline with standard therapy and after 3 months of AID use. Results: Following 3 months of Omnipod 5 use, caregivers experienced significant improvements across all measures, including diabetes-related psychosocial outcomes (Problem Areas in Diabetes; p < 0.0001, Hypoglycemia Confidence Scale; p < 0.01), well-being (World Health Organization 5 Well-Being Index; p < 0.0001) and perceived system usability (System Usability Scale; p < 0.0001). Significant improvements were seen in the Pittsburgh Sleep Quality Index total score and the overall sleep quality, sleep duration and efficiency subscales (all p < 0.05). Insulin Delivery Satisfaction Survey scores improved on all subscales (greater satisfaction, reduced burden and reduced inconvenience; all p < 0.0001). Conclusions: Caregivers face unique challenges when managing T1D in very young children. While glycaemic metrics have unquestioned importance, these results evaluating psychosocial outcomes reveal additional meaningful benefits and suggest that the Omnipod 5 AID System alleviates some of the burdens caregivers face with diabetes management.

Children with type 1 diabetes and their caregivers face numerous challenges navigating the unpredictability of this complex disease. Although the burden of managing diabetes remains significant, new technology has eased some of the load and allowed children with type 1 diabetes to achieve tighter glycaemic management without fear of excess hypoglycaemia. Continuous glucose monitor use alone improves outcomes and is considered standard of care for paediatric type 1 diabetes management. Similarly, automated insulin delivery (AID) systems have proven to be safe and effective for children as young as 2 years of age. AID use improves not only blood glucose levels but also quality of life for children with type 1 diabetes and their caregivers and should be strongly considered for all youth with type 1 diabetes if available and affordable. Here, we review key data on the use of diabetes technology in the paediatric population and discuss management issues unique to children and adolescents.

Treatment of T1D in young children presents many challenges compared to other age groups. In a recent multicenter, randomized controlled trial, we showed significant glycemic improvements when using automated insulin delivery (AID, t:slim X2 insulin pump with Control-IQ technology) compared to standard care (SC) (+12.4% TIR, -0.42% HbA1c) over 13 weeks in N=102 young children (age 2-<6 yrs) with T1D. We focus here on the multiple daily injection (MDI) users at baseline. The cohort included 36 such participants, 10 in SC and 26 using AID. No difference between MDI participants and their pump-using peers was noted for age, gender, ethnicity, or household income; though they showed degraded glycemic control at baseline: TIR 49.7% vs 59.6%, p=0.004; TBR 2.4% vs 3.8%, p=0.016. MDI participants completed 94% of visits virtually and 19/26 were transitioned to AID virtually. Compared with SC, TIR improvement with AID was statistically similar for MDI (+11.6%) and pump (+12.3%) participants (see Figure). Comparable results were seen for other CGM outcomes. With increased TIR of approximately 3h/day, the studied AID system significantly improved glycemic control for prior MDI users, even with a transition almost exclusively performed online. Improvements were not associated with increased risk of hypoglycemia and indistinguishable from the effects observed for prior pump users. Disclosure M.D.Breton: Consultant; Dexcom, Inc., Tandem Diabetes Care, Inc., Roche Diabetes Care, Sanofi, Arecor, Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc., Novo Nordisk. Pedap trial study group: n/a. B.A.Buckingham: Advisory Panel; Medtronic, Novo Nordisk, Consultant; Lilly, Research Support; Medtronic, Insulet Corporation, Tandem Diabetes Care, Inc. M.D.Deboer: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc. L.Ekhlaspour: Consultant; Ypsomed AG, Tandem Diabetes Care, Inc., Other Relationship; NIH - National Institutes of Health, Research Support; MannKind Corporation, Tandem Diabetes Care, Inc., JDRF, Speaker's Bureau; Insulet Corporation. G.P.Forlenza: Advisory Panel; Medtronic, Consultant; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc., Lilly Diabetes, Research Support; Medtronic, Abbott, Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc. M.Schoelwer: Research Support; Tandem Diabetes Care, Inc., Insulet Corporation. R.Wadwa: Consultant; Eli Lilly and Company, Other Relationship; Dexcom, Inc., Eli Lilly and Company, Research Support; Dexcom, Inc., Eli Lilly and Company, Beta Bionics, Inc., Tandem Diabetes Care, Inc. J.W.Lum: None. R.Beck: Consultant; Eli Lilly and Company, Novo Nordisk, Diasome, Insulet Corporation, Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company, Novo Nordisk. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK127551); Tandem Diabetes Care, Inc.; Dexcom, Inc.

T1D management in children < age 6 yrs is challenging due to unpredictable food intake and activity. Efficacy of AID with the Tandem t:slim X2 insulin pump with Control-IQ technology (CIQ) in this age group has not been well studied. Data included 95 children with T1D age 2 to < 6 yrs (age 3.9±1.2 yrs, 46% male, 75 % non-Hispanic white, 34% on multiple daily injections) enrolled in a 13-week extended use phase of a randomized trial of closed loop control (CLC) with CIQ. In this phase, the group assigned to CLC for the initial 13 weeks continued on CLC (CLC-CLC) and those initially using standard care (SC) were placed on CLC (SC-CLC). CGM time in range 70-180 mg/dL (TIR) was the primary outcome. The SC-CLC group (n=33) increased TIR using CLC in the extension compared to the SC period (68±9% vs. 56±13%, p<0.001) with no significant change in hypoglycemia (%CGM < 54 mg/dL 0.4±0.3% vs. 0.5±0.6%, p=0.03). TIR increased within the first week of CLC use similar to the first 13 weeks of AID use for the CLC-CLC group (Figure). CLC training was completed virtually for 82% of the SC-CLC group. The CLC-CLC group (n=62) maintained TIR (71±11% vs. 70±10%, p=0.80) with slightly lower rates of hypoglycemia (%CGM < 54 mg/dL 0.5±0.4% vs. 0.6±0.5%, p=0.08). In conclusion, these data show that in young children age 2 to < 6, CLC with Control-IQ technology leads to increased TIR without an increase in time in hypoglycemia. Disclosure R.Wadwa: Consultant; Eli Lilly and Company, Other Relationship; Dexcom, Inc., Eli Lilly and Company, Research Support; Dexcom, Inc., Eli Lilly and Company, Beta Bionics, Inc., Tandem Diabetes Care, Inc. C.Kollman: Research Support; Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc. R.Beck: Consultant; Eli Lilly and Company, Novo Nordisk, Diasome, Insulet Corporation, Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company, Novo Nordisk. M.D.Breton: Consultant; Dexcom, Inc., Tandem Diabetes Care, Inc., Roche Diabetes Care, Sanofi, Arecor, Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc., Novo Nordisk. Pedap trial study group: n/a. Z.Reed: None. B.A.Buckingham: Advisory Panel; Medtronic, Novo Nordisk, Consultant; Lilly, Research Support; Medtronic, Insulet Corporation, Tandem Diabetes Care, Inc. M.D.Deboer: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc. L.Ekhlaspour: Consultant; Ypsomed AG, Tandem Diabetes Care, Inc., Other Relationship; NIH - National Institutes of Health, Research Support; MannKind Corporation, Tandem Diabetes Care, Inc., JDRF, Speaker's Bureau; Insulet Corporation. E.C.Cobry: None. M.Schoelwer: Research Support; Tandem Diabetes Care, Inc., Insulet Corporation. C.Berget: Consultant; Insulet Corporation, Dexcom, Inc., Other Relationship; Tandem Diabetes Care, Inc. J.W.Lum: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK127551); Tandem Diabetes Care, Inc.; Dexcom, Inc.

The objective was to examine PROs after use of t:slim X2 insulin pump with Control-IQ technology (CIQ) in young children. Children with T1D ages 2-<6 years (n=102) were randomized 2:1 to either CIQ or standard care (SC) with pump or MDI plus CGM for 13 wks. Both groups could use CIQ for an additional 13 wks. Parents completed PROs at baseline, 13-, and 26-wks examining hypoglycemia concerns, quality of life, parenting stress, and sleep (see table). At 26 wks, 28 families participated in focus groups about their experiences with CIQ. Repeated measures analysis with False Discovery Rate correction and accounting for baseline showed that all 5 PROs surveys moved in the positive direction. Four showed that CIQ was superior to SC at 26 wks (p values < 0.05). Focus group findings showed optimized glycemic control overall and nighttime control specifically (28 of 28 families endorsed). All but 2 families noted substantial reduction in management burden resulting in less mental burden and all but 4 stated that they wanted their kids to continue using CIQ. Families utilizing CIQ experienced glycemic benefit coupled with substantial benefit in PROs, documented on surveys and focus groups. Families utilizing CIQ had reduced hypoglycemia concerns and parenting stress, and improved quality of life and sleep. These findings demonstrate benefit of CIQ in young children with T1D that goes beyond documented glycemic benefit. Disclosure A.Schneider-utaka: None. C.Kollman: Research Support; Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc. R.Beck: Consultant; Eli Lilly and Company, Novo Nordisk, Diasome, Insulet Corporation, Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company, Novo Nordisk. M.D.Breton: Consultant; Dexcom, Inc., Tandem Diabetes Care, Inc., Roche Diabetes Care, Sanofi, Arecor, Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc., Novo Nordisk. K.K.Hood: Consultant; Cecelia Health. Pedap trial study group: n/a. Z.Reed: None. B.A.Buckingham: Advisory Panel; Medtronic, Novo Nordisk, Consultant; Lilly, Research Support; Medtronic, Insulet Corporation, Tandem Diabetes Care, Inc. E.C.Cobry: None. M.D.Deboer: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc. L.Ekhlaspour: Consultant; Ypsomed AG, Tandem Diabetes Care, Inc., Other Relationship; NIH - National Institutes of Health, Research Support; MannKind Corporation, Tandem Diabetes Care, Inc., JDRF, Speaker's Bureau; Insulet Corporation. M.Schoelwer: Research Support; Tandem Diabetes Care, Inc., Insulet Corporation. R.Wadwa: Consultant; Eli Lilly and Company, Other Relationship; Dexcom, Inc., Eli Lilly and Company, Research Support; Dexcom, Inc., Eli Lilly and Company, Beta Bionics, Inc., Tandem Diabetes Care, Inc. J.W.Lum: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK127551); Tandem Diabetes Care, Inc.; Dexcom, Inc.

BACKGROUND Closed-loop control systems of insulin delivery may improve glycemic outcomes in young children with type 1 diabetes. The efficacy and safety of initiating a closed-loop system virtually are unclear. METHODS In this 13-week, multicenter trial, we randomly assigned, in a 2:1 ratio, children who were at least 2 years of age but younger than 6 years of age who had type 1 diabetes to receive treatment with a closed-loop system of insulin delivery or standard care that included either an insulin pump or multiple daily injections of insulin plus a continuous glucose monitor. The primary outcome was the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter, as measured by continuous glucose monitoring. Secondary outcomes included the percentage of time that the glucose level was above 250 mg per deciliter or below 70 mg per deciliter, the mean glucose level, the glycated hemoglobin level, and safety outcomes. RESULTS A total of 102 children underwent randomization (68 to the closed-loop group and 34 to the standard-care group); the glycated hemoglobin levels at baseline ranged from 5.2 to 11.5%. Initiation of the closed-loop system was virtual in 55 patients (81%). The mean (±SD) percentage of time that the glucose level was within the target range increased from 56.7±18.0% at baseline to 69.3±11.1% during the 13-week follow-up period in the closed-loop group and from 54.9±14.7% to 55.9±12.6% in the standard-care group (mean adjusted difference, 12.4 percentage points [equivalent to approximately 3 hours per day]; 95% confidence interval, 9.5 to 15.3; P<0.001). We observed similar treatment effects (favoring the closed-loop system) on the percentage of time that the glucose level was above 250 mg per deciliter, on the mean glucose level, and on the glycated hemoglobin level, with no significant between-group difference in the percentage of time that the glucose level was below 70 mg per deciliter. There were two cases of severe hypoglycemia in the closed-loop group and one case in the standard-care group. One case of diabetic ketoacidosis occurred in the closed-loop group. CONCLUSIONS In this trial involving young children with type 1 diabetes, the glucose level was in the target range for a greater percentage of time with a closed-loop system than with standard care. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; PEDAP ClinicalTrials.gov number, NCT04796779.).

Automated insulin delivery improves glycemic control in young children with type 1 diabetes (T1D). We investigated the potential impact of baseline participant characteristics on glycemic improvements when using the Tandem t:slim X2 insulin pump with Control-IQ technology (CIQ). After a 13 wk randomized, multi-center, controlled trial comparing CIQ (CLC) to standard care insulin delivery plus CGM (SC) in 102 children with T1D age 2 to <6 years, 95 continued CLC for 13 wks (CLC-CLC, N=62) or transitioned to CLC (SC-CLC, N=33). We compared glycemic outcomes from the RCT to the extension phase in subgroups based on baseline characteristics. At baseline, participants were 3.9 ± 1.2 years old with 25% minority race/ethnicity; 48% household income <$100,000; 57% parents with bachelor’s degree or less; 21% public insurance; 69% baseline HbA1c ≥7%; and 34% used multiple daily injections. In the SC-CLC group, time 70-180 mg/dL (TIR) improved in all subgroups regardless of race/ethnicity, family income, education, health insurance type, baseline HbA1c, and experience with devices (Table 1). In the CLC-CLC group, TIR improvement with CLC during the RCT was maintained regardless of subgroup. Our results support the findings that young children with T1D benefit from using CIQ regardless of their baseline characteristics. The benefit is maintained over a 26-week period. Disclosure L.Ekhlaspour: Consultant; Ypsomed AG, Tandem Diabetes Care, Inc., Other Relationship; NIH - National Institutes of Health, Research Support; MannKind Corporation, Tandem Diabetes Care, Inc., JDRF, Speaker's Bureau; Insulet Corporation. C.Kollman: Research Support; Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc. R.Beck: Consultant; Eli Lilly and Company, Novo Nordisk, Diasome, Insulet Corporation, Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company, Novo Nordisk. M.D.Breton: Consultant; Dexcom, Inc., Tandem Diabetes Care, Inc., Roche Diabetes Care, Sanofi, Arecor, Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc., Novo Nordisk. Pedap trial study group: n/a. Z.Reed: None. B.A.Buckingham: Advisory Panel; Medtronic, Novo Nordisk, Consultant; Lilly, Research Support; Medtronic, Insulet Corporation, Tandem Diabetes Care, Inc. M.D.Deboer: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc. G.P.Forlenza: Advisory Panel; Medtronic, Consultant; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc., Lilly Diabetes, Research Support; Medtronic, Abbott, Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc. R.S.Kingman: None. M.Schoelwer: Research Support; Tandem Diabetes Care, Inc., Insulet Corporation. R.Wadwa: Consultant; Eli Lilly and Company, Other Relationship; Dexcom, Inc., Eli Lilly and Company, Research Support; Dexcom, Inc., Eli Lilly and Company, Beta Bionics, Inc., Tandem Diabetes Care, Inc. J.W.Lum: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK127551); Tandem Diabetes Care, Inc; Dexcom, Inc.

The Omnipod 5 AID System is a tubeless hybrid closed-loop system with on-body operation and customizable glucose targets. Safe and effective system use was demonstrated in children aged 2-5.9y with type 1 diabetes (T1D) during a 3-mo pivotal study. To evaluate durability of glycemic benefit, we analyzed results from 9mo of an ongoing extension study, totaling 12mo of system use. In the pivotal study, participants used the system for 3mo at home, after 14d of their standard therapy (ST, pump or multiple daily injections) . They were then invited to participate in the extension study. Safety endpoints were occurrence of severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) . Glycemic outcomes were A1C and percent time in ranges (TIR 70-180 mg/dL, TBR <70 mg/dL, TAR >180 mg/dL) during 3-mo AID intervals compared with ST. All pivotal trial participants (N=80) , aged (mean±SD) 4.7±1.0y with T1D duration 2.3±1.1y and total daily insulin of 14±4U (range: 5.3-27U) at baseline, enrolled in the extension. Improved outcomes were observed for up to 12mo, including lower A1C and greater TIR during each AID interval compared with ST (all p<0.05, Table) . There were no episodes of DKA or SH in the 12-mo study. The safety and improved glycemic outcomes from the initial 3mo pivotal study persisted for an additional 9mo, indicating the potential long-term benefit of the Omnipod 5 System in very young children with T1D. Disclosure D.Desalvo: Consultant; Dexcom, Inc., Insulet Corporation, Research Support; Insulet Corporation. D.W.Hansen: None. T.T.Ly: Employee; Insulet Corporation, Stock/Shareholder; Insulet Corporation. Omnipod 5 in preschoolers study group: n/a. B.W.Bode: Advisory Panel; CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Zealand Pharma A/S, Consultant; Bigfoot Biomedical, Inc., Research Support; Abbott, Beta Bionics, Inc., Dexcom, Inc., Diasome, Dompé, Eli Lilly and Company, Insulet Corporation, IQVIA Inc., Jaeb Center for Health Research, Medtronic, Novo Nordisk, Provention Bio, Inc., REMD Biotherapeutics, Sanvita Medical, Senseonics, ViaCyte, Inc., Speaker's Bureau; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Insulet Corporation, MannKind Corporation, Novo Nordisk, Sanofi, Xeris Pharmaceuticals, Inc., Stock/Shareholder; AgaMatrix, Glytec, LLC. G.P.Forlenza: Advisory Panel; Lilly, Medtronic, Consultant; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc., Research Support; Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care, Inc. L.M.Laffel: Advisory Panel; Medtronic, Roche Diabetes Care, Consultant; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompé, Insulet Corporation, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Provention Bio, Inc. B.A.Buckingham: Advisory Panel; Arecor, Lilly Diabetes, Medtronic, Other Relationship; Insulet Corporation, Research Support; Insulet Corporation, Lilly Diabetes, Medtronic. A.B.Criego: Advisory Panel; Insulet Corporation, Other Relationship; Medscape, Sanofi, Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Medtronic. M.Schoelwer: Other Relationship; Dexcom, Inc., Research Support; Insulet Corporation, Medtronic, Tandem Diabetes Care, Inc. S.A.Macleish: Advisory Panel; Insulet Corporation. J.Sherr: Advisory Panel; Bigfoot Biomedical, Inc., Cecelia Health, Insulet Corporation, Medtronic, Vertex Pharmaceuticals Incorporated, Consultant; Insulet Corporation, Lexicon Pharmaceuticals, Inc., Research Support; Dexcom, Inc., Insulet Corporation, Jaeb Center for Health Research, JDRF, Medtronic, National Institute of Diabetes and Digestive and Kidney Diseases, Speaker's Bureau; Lilly Diabetes. Funding Insulet Corporation

AID systems must accommodate a wide range of insulin requirements safely and effectively to apply to a broad population. We evaluated glycemic outcomes among people ages 2 to 70y with T1D and baseline A1C<10% during a 3-mo home trial with the Omnipod 5 AID System, stratified by their baseline total daily insulin dose (TDD) during a 14-day standard therapy phase (ST, multiple daily injections or pump therapy) before AID use. No minimum TDD or weight was required to enter the study. Glycemic outcomes (time in range (TIR) 70-180 mg/dL, time below range (TBR) <70 mg/dL, time above range (TAR) >180 mg/dL) and change in TDD were evaluated across 6 ST TDD ranges, from <10U to ≥65U, during AID compared with ST. Participants (N=320) had a ST TDD of (mean ± SD) 34.8±21.7U (range 5.3-166.0U) . TDD during AID ranged from 5.0 to 110.7U; TDD increased slightly for those using <30U per day. TIR increased during AID across all TDD ranges (p<0.05, Table) . TAR and TBR were reduced in groups with TDD ≥10U and TDD ≥20U, respectively. Multiple linear regression indicated that older age and higher TIR during ST (both p<0.05) were associated with higher TIR during AID, while no relationship was found between ST TDD and TIR during AID (p=0.29, r2=0.57) . The Omnipod 5 System was safe and effective for a large cohort of people with T1D ages 2 to 70y across a wide range of insulin needs. Disclosure M.Schoelwer: Other Relationship; Dexcom, Inc., Research Support; Insulet Corporation, Medtronic, Tandem Diabetes Care, Inc. L.M.Laffel: Advisory Panel; Medtronic, Roche Diabetes Care, Consultant; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompé, Insulet Corporation, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Provention Bio, Inc. J.Sherr: Advisory Panel; Bigfoot Biomedical, Inc., Cecelia Health, Insulet Corporation, Medtronic, Vertex Pharmaceuticals Incorporated, Consultant; Insulet Corporation, Lexicon Pharmaceuticals, Inc., Research Support; Dexcom, Inc., Insulet Corporation, Jaeb Center for Health Research, JDRF, Medtronic, National Institute of Diabetes and Digestive and Kidney Diseases, Speaker's Bureau; Lilly Diabetes. C.J.Levy: Advisory Panel; Dexcom, Inc., Eli Lilly and Company, Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, T1D Exchange, Tandem Diabetes Care, Inc. I.B.Hirsch: Consultant; Abbott Diabetes, Bigfoot Biomedical, Inc., GWave, Roche Diabetes Care, Research Support; Beta Bionics, Inc., Insulet Corporation, Medtronic. S.A.Macleish: Advisory Panel; Insulet Corporation. D.Desalvo: Consultant; Dexcom, Inc., Insulet Corporation, Research Support; Insulet Corporation. V.Shah: Advisory Panel; Medscape, Sanofi, Consultant; Dexcom, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk. A.Bhargava: Research Support; Abbott Diabetes, AbbVie Inc., Boehringer Ingelheim International GmbH, Boston Therapeutics, Inc., Covance, Dexcom, Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Insulet Corporation, Kowa Pharmaceuticals America, Inc., Lexicon Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Medtronic, Novo Nordisk, Poxel SA, Quintiles, Sanofi, Senseonics, Tolerion, Inc., Viking Therapeutics, vTv Therapeutics. T.C.Jones: None. G.Aleppo: Consultant; Insulet Corporation, Research Support; AstraZeneca, Dexcom, Inc., Eli Lilly and Company, Fractyl Health, Inc., Insulet Corporation, Novo Nordisk, Speaker's Bureau; Dexcom, Inc. B.W.Bode: Advisory Panel; CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Zealand Pharma A/S, Consultant; Bigfoot Biomedical, Inc., Research Support; Abbott, Beta Bionics, Inc., Dexcom, Inc., Diasome, Dompé, Eli Lilly and Company, Insulet Corporation, IQVIA Inc., Jaeb Center for Health Research, Medtronic, Novo Nordisk, Provention Bio, Inc., REMD Biotherapeutics, Sanvita Medical, Senseonics, ViaCyte, Inc., Speaker's Bureau; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Insulet Corporation, MannKind Corporation, Novo Nordisk, Sanofi, Xeris Pharmaceuticals, Inc., Stock/Shareholder; AgaMatrix, Glytec, LLC. R.E.Gurlin: Employee; Insulet Corporation. T.T.Ly: Employee; Insulet Corporation, Stock/Shareholder; Insulet Corporation. Omnipod 5 research group: n/a. A.L.Carlson: Advisory Panel; MannKind Corporation, Employee; Bright Health Group, Other Relationship; Medtronic, Research Support; Funding This study was funded by Insulet Corporation.

We assessed predictors of rising hemoglobin A1c (HbA1c) during long-term use of closed-loop control (CLC) in children aged 6-13 years with type 1 diabetes. Participants used a CLC system during a 16-week randomization phase followed by a 12-week extension phase. We compared an "Increased-HbA1c" group (n = 17, >= 0.5% rise in HbA1c between randomization and extension phases) to a "Maintained-Improvement" group (n = 18, had stable or improved HbA1c). The Increased-HbA1c group had higher pre-CLC HbA1c (8.42% +/- 0.80 vs. 7.45% +/- 0.93, P = 0.002). Contrary to a-priori hypotheses, there were no differences in Delta-height-for-age z-score, a surrogate for a pubertal growth spurt (+0.16 vs. -0.15, P = 0.113), or number of carbohydrate boluses per day, a surrogate for missed boluses (4.4 +/- 2.2 vs. 5.2 +/- 2.1, P = 0.263). Both groups maintained high rates in closed-loop. Thus, some children exhibit meaningful rise in HbA1c after initial CLC use, likely from multiple contributing factors, and may benefit from added encouragement during ongoing use.