{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:07:32Z","timestamp":1792102052831,"version":"4.4.0"},"reference-count":36,"publisher":"American Diabetes Association","issue":"2","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01DK121929, R01DK133881, R01-DK-093954, UC4-DK-12"],"award-info":[{"award-number":["R01DK121929, R01DK133881, R01-DK-093954, UC4-DK-12"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000901","name":"Juvenile Diabetes Research Foundation International","doi-asserted-by":"publisher","award":["3-SRA-2022-1186-S-B and 3-SRA-2023-1422-S-B"],"award-info":[{"award-number":["3-SRA-2022-1186-S-B and 3-SRA-2023-1422-S-B"]}],"id":[{"id":"10.13039\/100000901","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,2,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Abatacept, a cytotoxic T lymphocyte\u2013associated protein 4 immunoglobulin that inhibits T-cell costimulation, was evaluated for 12 months in stage 1 type 1 diabetes (T1D) to delay disease progression. Despite modest preservation of area under the curve C-peptide at 12 months, the primary end point was not met. We adopted the oral minimal model (OMM) to assess \u03b2-cell function over 48 months and explored how baseline insulin secretion (\u03d5total) modified treatment response. Using the OMM, \u03d5total was computed from oral glucose tolerance tests conducted at baseline and every 6 months. Participants were stratified into high- and low-secretor groups depending on baseline \u03d5total \u226533rd or &amp;lt;33rd centile, respectively. A sensitivity analysis was performed to validate threshold choice. Among 203 participants (abatacept n = 96; 107 placebo n = 107), 39% receiving abatacept and 47% receiving placebo experienced progression to stage 2 or 3 within 96 months. High secretors receiving abatacept gained 15.8 progression-free months (95% CI 4.85, 26.68; P = 0.005) and had a 54% lower hazard of progression versus those receiving placebo (hazard ratio [HR] 0.46; 95% CI 0.25, 0.84; P = 0.012). Treatment effect differed significantly by secretor status (interaction HR 2.92; 95% CI 1.23, 6.96; P = 0.015). A subgroup of responders to 12 months of abatacept was identified by \u03d5total, providing the first evidence that an immune intervention in stage 1 T1D may delay disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>We sought to investigate whether baseline insulin secretion (\u03d5total), quantified using the oral minimal model assessing \u03b2-cell function, could identify a subgroup of responders to abatacept (a cytotoxic T lymphocyte\u2013associated protein 4 immunoglobulin that inhibits T-cell costimulation) among those with stage 1 type 1 diabetes (T1D). Abatacept preserved \u03d5total during and up to 1 year after treatment cessation; high baseline secretors treated with abatacept gained \u223c16 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-0801","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T19:59:21Z","timestamp":1763150361000},"page":"229-240","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":4,"title":["Baseline Insulin Secretion Determines Response to Abatacept in Stage 1 Type 1 Diabetes"],"prefix":"10.2337","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8885-3056","authenticated-orcid":false,"given":"Alfonso","family":"Galderisi","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Yale University 1 , New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice L.J.","family":"Carr","sequence":"additional","affiliation":[{"name":"Alberta Diabetes Institute, University of Alberta 2 , Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Infection and Immunity, Cardiff University School of Medicine 3 , Cardiff, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacopo","family":"Bonet","sequence":"additional","affiliation":[{"name":"Department of Information Engineering, University of Padova 4 , Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Cuthbertson","sequence":"additional","affiliation":[{"name":"Health Informatics Institute, University of South Florida 5 , Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7204-8367","authenticated-orcid":false,"given":"Jay","family":"Sosenko","sequence":"additional","affiliation":[{"name":"University of Miami Miller School of Medicine 6 , Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily K.","family":"Sims","sequence":"additional","affiliation":[{"name":"Herman B. Wells Center for Pediatric Research, Department of Pediatrics, and Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine 7 , Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7764-8663","authenticated-orcid":false,"given":"Carmella","family":"Evans-Molina","sequence":"additional","affiliation":[{"name":"Herman B. Wells Center for Pediatric Research, Department of Pediatrics, and Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine 7 , Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Dalla Man","sequence":"additional","affiliation":[{"name":"Department of Information Engineering, University of Padova 4 , Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0102-0030","authenticated-orcid":false,"given":"Heba M.","family":"Ismail","sequence":"additional","affiliation":[{"name":"Herman B. Wells Center for Pediatric Research, Department of Pediatrics, and Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine 7 , Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Nathan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Minnesota 8 , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Petrelli","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, University of Milan 9 , Milan, Italy"},{"name":"Pio Albergo Trivulzio 10 , Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Senior","sequence":"additional","affiliation":[{"name":"Alberta Diabetes Institute, University of Alberta 2 , Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9301-3043","authenticated-orcid":false,"given":"Jennifer L.","family":"Sherr","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Yale University 1 , New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1534-6613","authenticated-orcid":false,"given":"Kevan C.","family":"Herold","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University 11 , New Haven, CT"},{"name":"Department of Internal Medicine, Yale University 12 , New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7609-0434","authenticated-orcid":false,"given":"William E.","family":"Russell","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Cell and Developmental Biology, Vanderbilt University Medical Center 13 , Nashville, 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