Trends in Total Daily Dose and Variability of Insulin Requirements in Newly Diagnosed Children and Adolescents with Type 1 Diabetes over 48 Months.

Objective: To evaluate trends in insulin delivery and day-to-day variability of insulin requirements over 48 months of hybrid closed-loop use following diagnosis of type 1 diabetes (T1D) in individuals aged 10-16 years. Methods: A secondary analysis of the closed-loop arm of an open-label, multicenter, randomized, parallel hybrid closed-loop trial assessing closed-loop insulin delivery in newly diagnosed children and adolescents with T1D was conducted. Mean total daily dose (TDD) over 24 h and during the night, as well as mean total basal and bolus insulin over 24 h, were calculated. Day-to-day variability of insulin requirements was evaluated over 24 h and at night. Results: TDD increased from 27.2 ± 16.1 units/d (mean ± standard deviation) at 0-3 months following diagnosis to 65.7 ± 24.9 units/d at 42-48 months. The proportion of total daily insulin delivered as basal insulin rose from 41% to 61% over 48 months. Day-to-day variability of insulin requirements after diagnosis was high (coefficient of variation at 0-3 months: 23.3 ± 0.9%) and remained stable over 48 months. No clinically relevant sex-based differences were observed in insulin requirements. Conclusions: During the first 48 months after diagnosis of T1D, insulin requirements in children and adolescents more than double with hybrid closed-loop insulin delivery. Over time, a greater proportion of insulin is administered via the closed-loop algorithm, and the high day-to-day variability in insulin needs underscores the importance of initiating adaptive closed-loop systems from diagnosis.