Effect of Tight Glycemic Control on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial.
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  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.
JAMA : the journal of the American Medical Association
Female; Adolescent; Humans; Child; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Blood Glucose; Insulin-Secreting Cells; C-Peptide; Double-Blind Method; Glycemic Control; Blood Glucose Self-Monitoring; Glycated Hemoglobin; Insulin
Diabetes Mellitus, Type 1; Hypoglycemic Agents; Blood Glucose; Insulin-Secreting Cells; C-Peptide; Double-Blind Method; Glycemic Control; Blood Glucose Self-Monitoring; Glycated Hemoglobin; Insulin
McVean J, Forlenza GP, Beck RW, et al. Effect of Tight Glycemic Control on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial. JAMA. 2023;329(12):980-989. doi:10.1001/jama.2023.2063