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Cited by 108Diabetes and associated disordersT-cell and B-cell ImmunologyPancreatic function and diabetes

Abatacept for Delay of Type 1 Diabetes Progression in Stage 1 Relatives at Risk: A Randomized, Double-Masked, Controlled Trial

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Russell, William E., Bundy, Brian N., Anderson, Mark S., Cooney, Laura A., Gitelman, Stephen E., Goland, Robin S., Gottlieb, Peter A., Greenbaum, Carla J. +18 more·2023·Diabetes Care
DOI 10.2337/dc22-2200PMC PMC10154649

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Abstract

OBJECTIVE: Previous studies showed that inhibiting lymphocyte costimulation reduces declining β-cell function in individuals newly diagnosed with type 1 diabetes. We tested whether abatacept would delay or prevent progression of type 1 diabetes from normal glucose tolerance (NGT) to abnormal glucose tolerance (AGT) or to diabetes and the effects of treatment on immune and metabolic responses. RESEARCH DESIGN AND METHODS: We conducted a phase 2, randomized, placebo-controlled, double-masked trial of abatacept in antibody-positive participants with NGT who received monthly abatacept/placebo infusions for 12 months. The end point was AGT or diabetes, assessed by oral glucose tolerance tests. RESULTS: A total of 101 participants received abatacept and 111 placebo. Of these, 81 (35 abatacept and 46 placebo) met the end point of AGT or type 1 diabetes diagnosis (hazard ratio 0.702; 95% CI 0.452, 1.09; P = 0.11) The C-peptide responses to oral glucose tolerance tests were higher in the abatacept arm (P < 0.03). Abatacept reduced the frequency of inducible T-cell costimulatory (ICOS)+ PD1+ T-follicular helper (Tfh) cells during treatment (P < 0.0001), increased naive CD4+ T cells, and also reduced the frequency of CD4+ regulatory T cells (Tregs) from the baseline (P = 0.0067). Twelve months after treatment, the frequency of ICOS+ Tfh, naive CD4+ T cells, and Tregs returned to baseline. CONCLUSIONS: Although abatacept treatment for 1 year did not significantly delay progression to glucose intolerance in at-risk individuals, it impacted immune cell subsets and preserved insulin secretion, suggesting that costimulation blockade may modify progression of type 1 diabetes.

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  • One year of abatacept treatment for children and adolescents with stage 1 type 1 diabetes did not significantly delay progression to stage 2 or 3 (HR 0.70; 95% CI 0.45-1.09), but it preserved insulin secretion and modified immune cell subsets.

    “Although 1 year of abatacept treatment for children and adolescents with stage 1 type 1 diabetes did not significantly delay progression to stage 2 or 3 (hazard ratio 0•70; 95% CI 0•45-1•09), it preserved insulin secretion and modified immune cell subsets.”

    From The future of type 1 diabetes therapy (2025) · cites this paper as [38]

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Authors
Russell, W. E., Bundy, B. N., Anderson, M. S., Cooney, L. A., Gitelman, S. E., Goland, R. S., Gottlieb, P. A., Greenbaum, C. J., Haller, M. J., Krischer, J. P., Libman, I. M., Linsley, P. S., Long, S. A., Lord, S. M., Moore, D. J., Moore, W. V., Moran, A. M., Muir, A. B., Raskin, P., Skyler, J. S., Wentworth, J. M., Wherrett, D. K., Wilson, D. M., Ziegler, A.-G., Herold, K. C., & Type 1 Diabetes TrialNet Study Group
Affiliations
  • Vanderbilt University Medical Center (US)
  • University of South Florida (US)
  • University of California, San Francisco (US)
  • Immune Tolerance Network (US)
  • Columbia University (US)
  • University of Colorado Anschutz (US)
  • Benaroya Research Institute (US)
  • University of Florida (US)
  • University of Pittsburgh (US)
  • Children's Mercy Hospital (US)
  • University of Minnesota (US)
  • Emory University (US)
  • The University of Texas Southwestern Medical Center (US)
  • University of Miami (US)
  • The Royal Melbourne Hospital (AU)
  • University of Toronto (CA)
  • Stanford University (US)
  • TUM Klinikum (DE)
  • Yale University (US)
Corresponding author
Russell, William E.
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2023-03-15
Volume
46
Issue
5
Pages
1005-1013
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/dc22-2200
PMC
PMC10154649
OpenAlex
W4324305894
Cited by
108
References
34
Citations by year
2026: 25 · 2025: 41 · 2024: 32 · 2023: 10
FWCI
17.93
Type
journal article
Language
en
Open access
Licence
www.diabetesjournals.org/journals/pages/license (vor)
Locations
  • Diabetes Care (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
  • PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
Funders
  • Juvenile Diabetes Research Foundation International (1-SRA-2020-900-M-X, 2-SRA-2018-609-Q-R, 2-SRA-2020-900-S-B, 3-SRA-2015-27-Q-R, 82-2013-652)
  • National Center for Research Resources (M01 RR00400, UL1 RR024131, UL1 RR024139, UL1 RR024153, UL1 RR024975, UL1 RR024982, UL1 RR025744, UL1 RR025761, UL1 RR025780, UL1 RR029890, UL1 RR031986, UL1 TR001872)
  • National Institute of Allergy and Infectious Diseases (UM1AI109565)
  • National Institute of Diabetes and Digestive and Kidney Diseases (U01 DK060782, U01 DK060916, U01 DK060987, U01 DK061010, U01 DK061016, U01 DK061029, U01 DK061030, U01 DK061034, U01 DK061035, U01 DK061036, U01 DK061037, U01 DK061040, U01 DK061041, U01 DK061042, U01 DK061055, U01 DK061058, U01 DK084565, U01 DK085453, U01 DK085461, U01 DK085463, U01 DK085465, U01 DK085476, U01 DK085499, U01 DK085504, U01 DK085505, U01 DK085509, U01 DK097835, U01 DK103153, U01 DK103180, U01 DK103266, U01 DK103282, U01 DK106984, U01 DK106994, U01 DK107013, U01 DK107014, UC4 DK085466, UC4 DK106993)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
abatacept, type 1 diabetes prevention, impaired glucose tolerance, C-peptide response, insulin secretion, PD-1, T follicular helper cells, regulatory T cells, naive CD4+ T cells, immune cell subsets
MeSH terms
Abatacept, Diabetes Mellitus, Type 1, Glucose, Humans, Immunosuppressive Agents, T-Lymphocytes, Regulatory

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