{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T16:13:44Z","timestamp":1785255224017,"version":"3.55.0"},"reference-count":39,"publisher":"American Diabetes Association","issue":"9","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["RO1 DK132406"],"award-info":[{"award-number":["RO1 DK132406"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,9,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>To explore if oral insulin could delay onset of stage 3 type 1 diabetes (T1D) among patients with stage 1\/2 who carry HLA DR4-DQ8 and\/or have elevated levels of IA-2 autoantibodies (IA-2As).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH AND METHODS<\/jats:title>\n                  <jats:p>Next-generation targeted sequencing technology was used to genotype eight HLA class II genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, and DPB1) in 546 participants in the TrialNet oral insulin preventative trial (TN07). Baseline levels of autoantibodies against insulin (IAA), GAD65 (GADA), and IA-2A were determined prior to treatment assignment. Available clinical and demographic covariables from TN07 were used in this post hoc analysis with the Cox regression model to quantify the preventive efficacy of oral insulin.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Oral insulin reduced the frequency of T1D onset among participants with elevated IA-2A levels (HR 0.62; P = 0.012) but had no preventive effect among those with low IA-2A levels (HR 1.03; P = 0.91). High IA-2A levels were positively associated with the HLA DR4-DQ8 haplotype (OR 1.63; P = 6.37 \u00d7 10\u22126) and negatively associated with the HLA DR7\u2013containing DRB1*07:01-DRB4*01:01-DQA1*02:01-DQB1*02:02 extended haplotype (OR 0.49; P = 0.037). Among DR4-DQ8 carriers, oral insulin delayed the progression toward stage 3 T1D onset (HR 0.59; P = 0.027), especially if participants also had high IA-2A level (HR 0.50; P = 0.028).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>These results suggest the presence of a T1D endotype characterized by HLA DR4-DQ8 and\/or elevated IA-2A levels; for those patients with stage 1\/2 disease with such an endotype, oral insulin delays the clinical T1D onset.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc24-0573","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T15:34:08Z","timestamp":1719848048000},"page":"1608-1616","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":21,"title":["Oral Insulin Delay of Stage 3 Type 1 Diabetes Revisited in <i>HLA DR4-DQ8<\/i> Participants in the TrialNet Oral Insulin Prevention Trial (TN07)"],"prefix":"10.2337","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4817-4969","authenticated-orcid":false,"given":"Lue Ping","family":"Zhao","sequence":"first","affiliation":[{"name":"1Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA"},{"name":"2School of Public Health, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6944-6591","authenticated-orcid":false,"given":"George K.","family":"Papadopoulos","sequence":"additional","affiliation":[{"name":"3Laboratory of Biophysics, Biochemistry, Biomaterials and Bioprocessing, Faculty of Agricultural Technology, Technological Educational Institute of Epirus, Arta, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1136-8110","authenticated-orcid":false,"given":"Jay 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