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

Document Type

Article

Publication Date

5-1-2023

Identifier

DOI: 10.2337/dc22-2200; PMCID: PMC10154649

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.

Journal Title

Diabetes care

Volume

46

Issue

5

First Page

1005

Last Page

1013

MeSH Keywords

Humans; Abatacept; Diabetes Mellitus, Type 1; Immunosuppressive Agents; T-Lymphocytes, Regulatory; Glucose

Keywords

Abatacept; Diabetes Mellitus, Type 1; Immunosuppressive Agents; Regulatory T-Lymphocytes; Glucose

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