Effect of Tight Glycemic Control on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes
Authors: McVean Jennifer , Forlenza Gregory P. , Beck Roy W. , Bauza Colleen , Bailey Ryan , Buckingham Bruce , DiMeglio Linda A. , Sherr Jennifer L. , Clements Mark , Neyman Anna , Evans-Molina Carmella , Sims Emily K. , Messer Laurel H. , Ekhlaspour Laya , McDonough Ryan , Van Name Michelle , Rojas Diana , Beasley Shannon , DuBose Stephanie , Kollman Craig , Moran Antoinette ,   CLVer Study Group, Moran Antoinette , McVean Jennifer , Beasley Shannon , Pappenfus Beth , Street Anne , Nelson Brittney , Leschyshyn Janice , Kennedy Jane , Rizky Ihsan , Forlenza Gregory , Cobry Erin , Messer Laurel , Slover Robert , Wadwa Paul , Towers Lindsey , Karami Angela , Fivekiller Emily , Boranian Emily , Escobar Estella , Jost Emily , Lange Samantha , Berget Cari , Geiser Luke , Clements Mark , Moore Wayne , McDonough Ryan , Paprocki Emily , Halpin Kelsee , Yan Yun , Livingston Erica , Howell Kelsye , Seuferling Barbara , Parish Susan , Orlich Stephen , Goff Rachel , Neyman Anna , DiMeglio Linda , Woerner Stephanie , Evans-Molina Carmella , Sims Emily , Kirchner Megan , Chatila Dana , Buckingham Bruce , Ekhlasour Laya , Norlander Lisa , Frank Eliana , Suh Bailey , Morgan Marci , Kingman Ryan , Hsu Liana , Sherr Jennifer , Weyman Kate , Tichy Eileen , Van Name Michelle , Brei Michelle , Steffen Amy , Carria Lori , Zgorski Melinda , Bauza Colleen , Beck Roy , Bailey Ryan , Kollman Craig , DuBose Stephanie , Rojas Diana , Cagnina Nicole , Reese Nicole , Strayer Heidi , Smith Emma , Frey Sarah , Vyas Shachi , Rosen Jonathan , Dutta Sanjoy , Janicek Robert , Gabrielson Deanna , Yu Liping , Stablein Donald , Klingensmith Georgeanna , Rodrigeuz Henry 
Published: February 2023

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