Baseline Insulin Secretion Determines Response to Abatacept in Stage 1 Type 1 Diabetes
We sought to investigate whether baseline insulin secretion (ϕtotal), quantified using the oral minimal model assessing β-cell function, could identify a subgroup of responders to abatacept (a cytotoxic T lymphocyte-associated protein 4 immunoglobulin that inhibits T-cell costimulation) among those with stage 1 type 1 diabetes (T1D). Abatacept preserved ϕtotal during and up to 1 year after treatment cessation; high baseline secretors treated with abatacept gained ∼16 months of progression-free survival and had a 54% lower hazard of progression versus those receiving placebo, whereas no benefit was observed in low secretors. This is the first evidence of an immune intervention delaying disease progression in those with stage 1 T1D. Continued treatment may result in a greater delay in progression.
Authors
- William E. Russell (ORCID: https://orcid.org/0000-0001-7609-0434)
- Antoinette Moran (ORCID: https://orcid.org/0000-0002-2694-5147)
- Peter Senior (ORCID: https://orcid.org/0000-0003-1033-8673)
- Colin Mark Dayan (ORCID: https://orcid.org/0000-0002-6557-3462)
- Kevan C. Herold (ORCID: https://orcid.org/0000-0003-1534-6613)
- Emily K. Sims (ORCID: https://orcid.org/0000-0002-4393-954X)
- Jacopo Bonet (ORCID: https://orcid.org/0000-0003-4097-7943)
- Heba M. Ismail (ORCID: https://orcid.org/0000-0003-0102-0030)
- Jay M. Sosenko (ORCID: https://orcid.org/0000-0002-7204-8367)
- Peter Nicholas Taylor (ORCID: https://orcid.org/0000-0002-3436-422X)
- Carmella Evans‐Molina (ORCID: https://orcid.org/0000-0001-7764-8663)
- Alessandra Petrelli (ORCID: https://orcid.org/0000-0002-5639-9415)
- Chiara Dalla Man (ORCID: https://orcid.org/0000-0002-4908-0596)
- Brandon M. Nathan (ORCID: https://orcid.org/0000-0001-6405-3994)
- Alice L. J. Carr (ORCID: https://orcid.org/0000-0003-0704-8843)
- Jennifer L. Sherr (ORCID: https://orcid.org/0000-0001-9301-3043)
- Alfonso Galderisi (ORCID: https://orcid.org/0000-0001-8885-3056)
- David Cuthbertson
Institutions
- University of Minnesota (US)
- University of Padua (IT)
- University of Miami (US)
- University of Alberta (CA)
- University of Milan (IT)
- IULM University (IT)
- University of South Florida (US)
- Yale University (US)
- MNGI Digestive Health (US)
- Institute of Infection and Immunity (CA)
- Indiana University – Purdue University Indianapolis (US)
- Cardiff University (GB)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Diabetes
- Published
- 2025-11-14
- DOI
- https://doi.org/10.2337/db25-0801
- Primary Topic
- Diabetes and associated disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00