Abatacept for Delay of Type 1 Diabetes Progression in Stage 1 Relatives at Risk: A Randomized, Double-Masked, Controlled Trial
- Author(s)
- Russell, WE; Bundy, BN; Anderson, MS; Cooney, LA; Gitelman, SE; Goland, RS; Gottlieb, PA; Greenbaum, CJ; Haller, MJ; Krischer, JP; Libman, IM; Linsley, PS; Long, SA; Lord, SM; Moore, DJ; Moore, WV; Moran, AM; Muir, AB; Raskin, P; Skyler, JS; Wentworth, JM; Wherrett, DK; Wilson, DM; ZIEGLER, AG; HEROLD, KC; Type 1 Diabetes TrailNET Study Group,;
- Journal Title
- Diabetes Care
- Publication Type
- epub ahead of print
- 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 naïve 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, naïve 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.
- Publisher
- American Diabetes Association
- Research Division(s)
- Population Health And Immunity
- PubMed ID
- 36920087
- Link To PubMed Central Version
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154649/
- Publisher's Version
- https://doi.org/10.2337/dc22-2200
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-03-29 08:34:09
Last Modified: 2023-06-13 11:40:02