Effect of 48 months of closed-loop insulin delivery on residual C-peptide secretion and glycemic control in newly diagnosed youth with type 1 diabetes: a randomized trial

Objective

We evaluated the effect of long-term intensive metabolic control with hybrid closed‑loop on residual C-peptide secretion and glucose control compared to standard insulin therapy in youth with type 1 diabetes over 48 months.

Research Design and Methods

Following the 24-month primary phase of a multicenter, randomized, parallel trial of 96 newly diagnosed youth aged 10 to 16.9 years, participants were invited to an extension phase using treatment allocated at randomization. They continued with either hybrid closed-loop using Cambridge algorithm (CL) or standard insulin therapy (control) until 48 months post-diagnosis. Analysis was by intention-to-treat.

Results

At 24-months post-diagnosis, 81 participants (mean±SD age 14±2 years) continued in the extension phase (47 CL, 34 control). There was no difference in fasting C-peptide corrected for fasting glucose at 48 months between groups (CL: 5±9 vs control: 6±14pmol/L per mmol/L; mean adjusted difference -2 [95% CI -7, 4; p=0.54]). Central lab HbA1c remained lower in the CL group by 0.9% [10mmol/mol] (95% CI 0.2, 1.5 [3, 17mmol/mol]; p=0.009). Time in target range 3.9 to 10.0mmol/L was 12 percentage points (95% CI 3, 20; p=0.008) higher in the CL group compared to control. Eleven severe hypoglycemic events (6 CL, 5 control) and seven DKA events (3 CL, 4 control) occurred during the extension phase.

Conclusions

Improved glycemic control was sustained over 48 months after diagnosis with closed‑loop insulin delivery compared to standard therapy in youth with type 1 diabetes. This did not appear to confer a protective effect on residual C-peptide secretion.