{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:39:30Z","timestamp":1792525170496,"version":"4.5.0"},"reference-count":23,"publisher":"American Diabetes Association","issue":"11","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"name":"NICHD"},{"name":"JDRF International"},{"name":"NIAID"},{"name":"NHGRI"},{"name":"McGill Faculty of Medicine and Health Sciences"},{"name":"NIDDK"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,11,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Among patients with young-onset type 1 diabetes, 10\u201315% are autoantibody (aAb) negative. How many of these are autoimmune versus nonautoimmune is unknown. To estimate this proportion, we used the only high-confidence evidence of autoimmunity in these cases, the presence of an aAb(+) sibling. In the 2,500 affected sibling pairs of the Type 1 Diabetes Genetics Consortium cohort, we compared the Type 1 Diabetes Genetic Risk Score (GRS2) between 379 aAb(\u2212) patients with an aAb(+) sibling (autoimmune cause) and 253 aAb(\u2212) patients with no aAb(+) siblings (unknown cause), under the assumption that siblings\u2019 diabetes must be of the same etiology. The GRS2 distribution for the unknown cause group showed a distinct minor mode, representing high-confidence nonautoimmune cases (1.2%). An increase in the frequency of scores &amp;lt;9.83 in the unknown cause group compared with the autoimmune cause group coincided with the peak in unaffected control individuals\u2019 scores. The difference between area under the curve over this range represented the maximum-likelihood proportion of nonautoimmune individuals (7.6%). These findings support aAb testing for type 1 diabetes and genetic testing for aAb(\u2212) individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>Accurate diagnosis of diabetes has important therapeutic consequences, yet 10\u201315% of individuals with type 1 diabetes are autoantibody negative, leaving the etiology of diabetes unconfirmed. We estimated what proportion of autoantibody-negative, clinically diagnosed type 1 diabetes is misdiagnosed nonautoimmune diabetes. Upwards of 7.6% of autoantibody-negative individuals are nonautoimmune. Our findings support the use of autoantibody screening and genetic testing of autoantibody-negative patients as standard of care for type 1 diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-1110","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:52:08Z","timestamp":1787579528000},"page":"2112-2116","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["What Proportion of Antibody-Negative Type 1 Diabetes Cases Have a Nonautoimmune Etiology? A Genetics-Based Estimate"],"prefix":"10.2337","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7240-7619","authenticated-orcid":false,"given":"Jacob L.","family":"Nicodemo","sequence":"first","affiliation":[{"name":"The Endocrine Genetics Laboratory, Research Institute of the McGill University Health Centre, Montreal 1 , Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1723-9731","authenticated-orcid":false,"given":"Angeliki","family":"Makri","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Departments of Pediatrics, Montreal Children\u2019s Hospital, Research Institute of the McGill University Health Centre 2 , Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7624-6635","authenticated-orcid":false,"given":"Constantin","family":"Polychronakos","sequence":"additional","affiliation":[{"name":"The Endocrine Genetics Laboratory, Research Institute of the McGill University Health Centre, Montreal 1 , Quebec, Canada"},{"name":"Division of Endocrinology and Metabolism, Departments of Pediatrics, Montreal Children\u2019s Hospital, Research Institute of the McGill University Health Centre 2 , Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"2026102014514080100_B1","doi-asserted-by":"crossref","first-page":"10012","DOI":"10.3390\/ijms241210012","article-title":"Anti-islet autoantibodies in type 1 diabetes","volume":"24","author":"Kawasaki","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2026102014514080100_B2","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.tem.2021.02.001","article-title":"Autoantibody-negative type 1 diabetes: a neglected subtype","volume":"32","author":"Patel","year":"2021","journal-title":"Trends Endocrinol 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