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
Julia Ware, Charlotte K. Boughton, Janet M. Allen, Malgorzata E. Wilinska, Sara Hartnell, Ajay Thankamony, Tabitha Randell, Atrayee Ghatak, Rachel Besser, Daniela Elleri, Nicola Trevelyan, Fiona Campbell, Judy Sibayan, Ryan Bailey, Peter Calhoun, Gareth Dunseath, Roman Hovorka, Tabitha Randell, Vreni Verhoeven, Roman Hovorka, Ajay Thankmonay, Carlo L. Acerini, David B. Dunger, Charlotte K. Boughton, Julia Ware, Martin Tauschmann, Rama Lakshman, Janet M. Allen, Malgorzata E. Wilinska, Sara Hartnell, Alina Cezar, Nicole Ashcroft, Mirela de Barros Tamarozzi, Meena Kolar Sridara Murthy, Atrayee Ghatak, Keith Thornborough, Jonathon Mimnagh, Joanne Shakeshaft, Karen Phelan, Rachel Besser, Rebecca M. Law, Clare Megson, Jane Haest, Alison C. West, Imogen Stamford, Daniela Elleri, Morag McDonald, Nicola Trevelyan, Helen Dewar, Rachel Brampton, Gabrielle Price, Gillian Crouch, Fiona Campbell, James Yong, Emily Metcalfe, Andrew M. Cameron, Julia Lawton, David Rankin, Judy Sibayan, Peter Calhoun, Ryan Bailey, Jessica Rusnak, Brian Bugielski, Gareth Dunseath, Stephen D. Luzio, Elisabeth Northam, John A. Todd, Stéphane Roze, Eleanor Scott, Tim Jones, C. C. Patterson, Peter Adolfsson, John W Gregory, Stephen J. Greene, Joanne Blair, A. P. Passmore
Abstract
OBJECTIVE: We evaluated the effect of long-term intensive metabolic control with hybrid closed-loop (CL) on residual C-peptide secretion and glucose control compared with 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 hybrid CL using the Cambridge algorithm or standard insulin therapy (control) until 48 months after diagnosis. Analysis was by intention-to-treat. RESULTS: At 24 months after 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 ± 14 pmol/L per mmol/L; mean adjusted difference -2 [95% CI -7, 4; P = 0.54]). Central laboratory HbA1c remained lower in the CL group by 0.9% (10 mmol/mol [95% CI 0.2, 1.5; 3, 17 mmol/mol); P = 0.009). Time in target range of 3.9 to 10.0 mmol/L was 12 percentage points (95% CI 3, 20; P = 0.008) higher in the CL group compared with control. There were 11 severe hypoglycemic events (6 CL, 5 control) and 7 diabetic ketoacidosis events (3 CL, 4 control) during the extension phase. CONCLUSIONS: Improved glycemic control was sustained over 48 months after diagnosis with CL insulin delivery compared with standard therapy in youth with type 1 diabetes. This did not appear to confer a protective effect on residual C-peptide secretion.