Original Investigation
February 24, 2023
Effect of Tight Glycemic Control on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial
Jennifer McVean, Gregory P. Forlenza, Roy W. Beck, et al
JAMA. 2023;329(12):980-989. doi:10.1001/jama.2023.2063
Question Does near normalization of glucose levels preserve pancreatic beta cell function in youth with newly diagnosed type 1 diabetes?
Findings In a randomized clinical trial including 113 youths aged 7 to 17 years with newly diagnosed type 1 diabetes, there was no significant difference in C-peptide levels measured during a mixed-meal tolerance test (a measure of pancreatic beta cell function) 52 weeks after diagnosis between intensive management and standard care groups. Mean time in the target range of 70 to 180 mg/dL, measured with continuous glucose monitoring, at 52 weeks was 78% with intensive management, which included automated insulin delivery, compared with 64% with standard care.
Meaning Intensive diabetes management with automated insulin delivery did not affect the decline in pancreatic C-peptide secretion at 52 weeks in youths with newly diagnosed type 1 diabetes.
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
