{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:09:41Z","timestamp":1790104181559,"version":"4.0.1"},"reference-count":37,"publisher":"American Diabetes Association","issue":"1","license":[{"start":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T00:00:00Z","timestamp":1576800000000},"content-version":"vor","delay-in-days":85,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/100008871","name":"JDRF","doi-asserted-by":"publisher","award":["9-2011-253"],"award-info":[{"award-number":["9-2011-253"]}],"id":[{"id":"10.13039\/100008871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008871","name":"JDRF","doi-asserted-by":"publisher","award":["5-SRA-2015-130-A-N"],"award-info":[{"award-number":["5-SRA-2015-130-A-N"]}],"id":[{"id":"10.13039\/100008871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome","doi-asserted-by":"publisher","award":["091157"],"award-info":[{"award-number":["091157"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome","doi-asserted-by":"publisher","award":["107212"],"award-info":[{"award-number":["107212"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome","doi-asserted-by":"publisher","award":["076113"],"award-info":[{"award-number":["076113"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["U01-DK-062418"],"award-info":[{"award-number":["U01-DK-062418"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008871","name":"JDRF","doi-asserted-by":"publisher","award":["9-2011-530"],"award-info":[{"award-number":["9-2011-530"]}],"id":[{"id":"10.13039\/100008871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome","doi-asserted-by":"publisher","award":["203141\/Z\/16\/Z"],"award-info":[{"award-number":["203141\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>Immunohistological analyses of pancreata from patients with type 1 diabetes suggest distinct autoimmune islet \u03b2-cell pathology between those diagnosed at &amp;lt;7 years (&amp;lt;7 group) and those diagnosed at age \u226513 years (\u226513 group), with both B- and T-lymphocyte islet inflammation common in children in the &amp;lt;7 group, whereas B cells are rare in the \u226513 group. Based on these observations, we sought to identify differences in genetic susceptibility between these prespecified age-at-diagnosis groups to inform on the etiology of the most aggressive form of type 1 diabetes that initiates in the first years of life.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>Using multinomial logistic regression models, we tested if known type 1 diabetes loci (17 within the HLA and 55 non-HLA loci) had significantly stronger effect sizes in the &amp;lt;7 group compared with the \u226513 group, using genotype data from 27,071 individuals (18,485 control subjects and 3,121 case subjects diagnosed at &amp;lt;7 years, 3,757 at 7\u201313 years, and 1,708 at \u226513 years).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Six HLA haplotypes\/classical alleles and six non-HLA regions, one of which functions specifically in \u03b2-cells (GLIS3) and the other five likely affecting key T-cell (IL2RA, IL10, IKZF3, and THEMIS), thymus (THEMIS), and B-cell development\/functions (IKZF3 and IL10) or in both immune and \u03b2-cells (CTSH), showed evidence for stronger effects in the &amp;lt;7 group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>A subset of type 1 diabetes\u2013associated variants are more prevalent in children diagnosed under the age of 7 years and are near candidate genes that act in both pancreatic \u03b2- and immune cells.<\/jats:p>\n                  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