Effect of Tight Glycemic Control on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes
Jennifer McVean, Gregory P. Forlenza, Roy W. Beck, Colleen Bauza, Ryan Bailey, Bruce A. Buckingham, Linda A. DiMeglio, Jennifer L. Sherr, Mark A. Clements, Anna Neyman, Carmella Evans‐Molina, Emily K. Sims, Laurel H. Messer, Laya Ekhlaspour, Ryan McDonough, Michelle Van Name, Diana Rojas, Shannon Beasley, Shannon Beasley, Craig Kollman, Craig Kollman, Antoinette Moran, CLVer Study Group, Jennifer McVean, Shannon Beasley, Beth Pappenfus, Anne Street, Brittney Nelson, Janice Leschyshyn, Jane Kennedy, Ihsan Rizky, Gregory P. Forlenza, Erin Cobry, Laurel H. Messer, Robert Slover, Paul Wadwa, Lindsey Towers, ANGELA J. KARAMI, Emily Fivekiller, Emily Boranian, Estella Escobar, Emily Jost, Samantha Lange, Cari Berget, Luke Geiser, Mark A. Clements, Wayne D. Moore, Ryan McDonough, Emily Paprocki, Kelsee Halpin, Yun Yan, Erica Livingston, Kelsye Howell, Barbara Seuferling, Susan Parish, Stephen Orlich, Rachel Goff, Rachel Goff, Linda A. DiMeglio, Stéphanie Woerner, Carmella Evans‐Molina, Emily K. Sims, Megan Kirchner, Dana Chatila, Bruce A. Buckingham, Laya Ekhlasour, Lisa Norlander, Eliana Frank, Bailey Suh, Marci Morgan, Ryan Kingman, Liana Hsu, Jennifer L. Sherr, Kate Weyman, Eileen Tichy, Michelle Van Name, Michelle Brei, Amy Steffen, Lori Carria, Melinda Zgorski, Colleen Bauza, Roy W. Beck, Ryan Bailey, Roy Beck, Ryan Bailey, Diana Rojas, Nicole Cagnina, Nicole Reese, Heidi Strayer, Emma Smith, Sarah Frey, Shachi Vyas, Jonathan Rosen, Sanjoy Dutta, Robert Janicek, Deanna Gabrielson, Liping Yu, Donald Stablein, Georgeanna J. Klingensmith, Henry Rodrigeuz
Abstract
Importance: Near normalization of glucose levels instituted immediately after diagnosis of type 1 diabetes has been postulated to preserve pancreatic beta cell function by reducing glucotoxicity. Previous studies have been hampered by an inability to achieve tight glycemic goals. Objective: To determine the effectiveness of intensive diabetes management to achieve near normalization of glucose levels on preservation of pancreatic beta cell function in youth with newly diagnosed type 1 diabetes. Design, Setting, and Participants: This randomized, double-blind, clinical trial was conducted at 6 centers in the US (randomizations from July 20, 2020, to October 13, 2021; follow-up completed September 15, 2022) and included youths with newly diagnosed type 1 diabetes aged 7 to 17 years. Interventions: Random assignment to intensive diabetes management, which included use of an automated insulin delivery system (n = 61), or standard care, which included use of a continuous glucose monitor (n = 52), as part of a factorial design in which participants weighing 30 kg or more also were assigned to receive either oral verapamil or placebo. Main Outcomes and Measures: The primary outcome was mixed-meal tolerance test-stimulated C-peptide area under the curve (a measure of pancreatic beta cell function) 52 weeks from diagnosis. Results: Among 113 participants (mean [SD] age, 11.8 [2.8] years; 49 females [43%]; mean [SD] time from diagnosis to randomization, 24 [5] days), 108 (96%) completed the trial. The mean C-peptide area under the curve decreased from 0.57 pmol/mL at baseline to 0.45 pmol/mL at 52 weeks in the intensive management group, and from 0.60 to 0.50 pmol/mL in the standard care group (treatment group difference, -0.01 [95% CI, -0.11 to 0.10]; P = .89). The mean time in the target range of 70 to 180 mg/dL, measured with continuous glucose monitoring, at 52 weeks was 78% in the intensive management group vs 64% in the standard care group (adjusted difference, 16% [95% CI, 10% to 22%]). One severe hypoglycemia event and 1 diabetic ketoacidosis event occurred in each group. Conclusions and Relevance: In youths with newly diagnosed type 1 diabetes, intensive diabetes management, which included automated insulin delivery, achieved excellent glucose control but did not affect the decline in pancreatic C-peptide secretion at 52 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT04233034.