Effect of Tight Glycemic Control on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial

JAMA. 2023 Mar 28;329(12):980-989. doi: 10.1001/jama.2023.2063.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Blood Glucose / drug effects
  • Blood Glucose Self-Monitoring
  • C-Peptide / pharmacology
  • C-Peptide / therapeutic use
  • Child
  • Diabetes Mellitus, Type 1* / drug therapy
  • Double-Blind Method
  • Female
  • Glycated Hemoglobin
  • Glycemic Control
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Insulin / administration & dosage
  • Insulin / adverse effects
  • Insulin-Secreting Cells* / drug effects

Substances

  • Hypoglycemic Agents
  • Blood Glucose
  • C-Peptide
  • Glycated Hemoglobin
  • Insulin

Associated data

  • ClinicalTrials.gov/NCT04233034