Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Mar 28;329(12):980-989.
doi: 10.1001/jama.2023.2063.

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

Jennifer McVean  1   2 , Gregory P Forlenza  3 , Roy W Beck  4 , Colleen Bauza  4 , Ryan Bailey  4 , Bruce Buckingham  5 , Linda A DiMeglio  6 , Jennifer L Sherr  7 , Mark Clements  8 , Anna Neyman  6 , Carmella Evans-Molina  6 , Emily K Sims  6 , Laurel H Messer  3   9 , Laya Ekhlaspour  5   10 , Ryan McDonough  8 , Michelle Van Name  7 , Diana Rojas  4 , Shannon Beasley  1 , Stephanie DuBose  4   11 , Craig Kollman  4 , Antoinette Moran  1 ; CLVer Study Group
Collaborators, Affiliations

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

Jennifer McVean et al. JAMA. .

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr McVean reported being an employee of Medtronic. Dr Forlenza reported serving as a consultant, speaker, or advisory board member for Medtronic, Dexcom, Abbott, Tandem Diabetes Care, Insulet, Lilly, and Beta Bionics and reported that his institution has received funding on his behalf for research grants from Medtronic, Dexcom, Abbott, Tandem Diabetes Care, Insulet, Lilly, and Beta Bionics. Dr Beck reported his institution has received funding on his behalf as follows: grant funding and study supplies from Tandem Diabetes Care, Beta Bionics, and Dexcom; grant funding from Bigfoot Biomedical; study supplies from Medtronic, Ascencia, and Roche; consulting fees and study supplies from Lilly and Novo Nordisk; and consulting fees from Insulet and Zucara Therapeutics. Dr Buckingham reported receiving grants, personal fees, and/or nonfinancial support from Medtronic, Tandem Diabetes Care, Insulet, Novo Nordisk, and Lilly and reported his institution has received research funding from Medtronic, Tandem Diabetes Care, Beta Bionics, and Insulet. Dr DiMeglio reported receiving consulting or advisory fees from Abata Therapeutics, MannKind, Provention Bio, and Zealand Pharma and study supplies from Dexcom. Dr Sherr reported receiving speaking honoraria from Lilly, Insulet, Medtronic, and Zealand Pharma; serving on advisory boards for Bigfoot Biomedical, Cecelia Health, Insulet, Medtronic Diabetes, JDRF (formerly the Juvenile Diabetes Research Foundation) T1D Fund, StartUp Health T1D Moonshot, and Vertex Pharmaceuticals; receiving consultant fees from Insulet and Medtronic; and reported that her institution has received research grant support from Medtronic and Insulet. Dr Clements reported receiving personal fees from Glooko Inc and nonfinancial support from Dexcom and Abbott Diabetes Care. Dr Evans-Molina reported serving on advisory boards for ProventionBio, Isla Technologies, MaiCell Therapeutics, Avotres Inc, DiogenX, and Neurodon; receiving in-kind research support from Bristol Myers Squibb and Nimbus Therapeutics; receiving investigator-initiated grants from Lilly and Astellas Pharma; and having a patent for extracellular vesicle RNA cargo as a biomarker of hyperglycemia and type 1 diabetes and a provisional patent for a biomarker of type 1 diabetes (PDIA1 as a biomarker of beta cell stress). Dr Sims reported receiving compensation for educational lectures on type 1 diabetes screening from Medscape and the American Diabetes Association. Dr Messer reported receiving speaking or consulting fees from Dexcom, Tandem Diabetes Care, Capillary Biomedical (now owned by Tandem Diabetes Care), and Lilly; receiving grants from Insulet, Beta Bionics, and Tandem Diabetes; and being a current employee of Tandem Diabetes Care. Dr Ekhlaspour reported receiving consulting fees from Tandem Diabetes Care and Ypsomed Holding AG; receiving speaking fees from Insulet; and receiving research support from Medtronic and MannKind. Dr Van Name reported receiving research support from ProventionBio. Dr Kollman reported receiving grants from Dexcom and Tandem Diabetes Care. Dr Moran reported serving on advisory boards for Dompé Farmaceutici SpA, ProventionBio, and Abata Therapeutics; serving on a data and safety monitoring board for Novo Nordisk; and reported that her institution has received grant funding on her behalf from Abbott Diabetes, ProventionBio, Intrexon (now Precigen), and Caladrius Biosciences and study supplies from Novo Nordisk, Medtronic, and Abbott Diabetes. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Participant Recruitment, Randomization, and Follow-up in a Trial of Intensive Diabetes Management vs Standard Care Diabetes Management for Preservation of Beta Cell Function in Newly Diagnosed Pediatric Diabetes
aRandomization was stratified by site with a permuted block design and used a 2:1 ratio to intensive diabetes management for participants weighing less than 30 kg and a 1:1 ratio for those 30 kg or more. bParticipants assigned to the intensive management group received 1 of 2 automated insulin delivery systems along with frequent contacts by study staff and nutrition management; participants in the standard care group received continuous glucose monitoring with either daily injections or a pump and management by their personal health care team. cAll randomized participants with at least 1 analyzable C-peptide area under the curve measurement from a mixed-meal tolerance test were included in the primary analysis. One participant in the standard care group who dropped out immediately following randomization without completing the baseline mixed-meal tolerance test was not included in the primary analysis.
Figure 2.
Figure 2.. Time in Target Glucose Range of 70 to 180 mg/dL and C-Peptide Results
Panel A descriptively shows the cumulative distribution plot for each treatment group of C-peptide area under the curve (AUC) values obtained from a mixed-meal tolerance test at 52 weeks from diagnosis of type 1 diabetes. For any given C-peptide AUC level, the percentage of participants in each treatment group with a value at that level or higher can be determined from the figure. Panels B and C, In each box and whisker plot, a black dot represents the mean of the outcome measure, the horizontal line represents the median, the ends of the box represent the 25th and 75th percentiles, the whiskers represent the lowest or highest values within 1.5 × the IQR, and the dots represent outlier values. The AUC value is computed using the trapezoidal rule as a weighted sum of the C-peptide measurements obtained during a mixed-meal tolerance test at time 0 and after 15, 30, 60, 90, and 120 minutes. The numbers beneath the x-axis reflect the number of participants in each group at each time point. Panel D shows for each treatment group, box and whisker plots of time in the target glucose range of 70 to 180 mg/dL, measured with continuous glucose monitoring, at each time point timed from diagnosis of type 1 diabetes, except for 6 weeks, which is timed from randomization (data were not collected at baseline). aSix weeks from randomization.
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Foster NC, Beck RW, Miller KM, et al. . State of type 1 diabetes management and outcomes from the T1D Exchange in 2016-2018. Diabetes Technol Ther. 2019;21(2):66-72. doi:10.1089/dia.2018.0384 - DOI - PMC - PubMed
    1. Steffes MW, Sibley S, Jackson M, Thomas W. Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial. Diabetes Care. 2003;26(3):832-836. doi:10.2337/diacare.26.3.832 - DOI - PubMed
    1. Bowman MA, Campbell L, Darrow BL, Ellis TM, Suresh A, Atkinson MA. Immunological and metabolic effects of prophylactic insulin therapy in the NOD-scid/scid adoptive transfer model of IDDM. Diabetes. 1996;45(2):205-208. doi:10.2337/diab.45.2.205 - DOI - PubMed
    1. Gotfredsen CF, Buschard K, Frandsen EK. Reduction of diabetes incidence of BB Wistar rats by early prophylactic insulin treatment of diabetes-prone animals. Diabetologia. 1985;28(12):933-935. doi:10.1007/BF00703140 - DOI - PubMed
    1. Shah SC, Malone JI, Simpson NE. A randomized trial of intensive insulin therapy in newly diagnosed insulin-dependent diabetes mellitus. N Engl J Med. 1989;320(9):550-554. doi:10.1056/NEJM198903023200902 - DOI - PubMed

Publication types

Associated data