{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T02:49:10Z","timestamp":1778122150538,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T00:00:00Z","timestamp":1595462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000361","name":"Diabetes UK","doi-asserted-by":"publisher","award":["16\/0005529"],"award-info":[{"award-number":["16\/0005529"]}],"id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI\u2010422388"],"award-info":[{"award-number":["AI\u2010422388"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["17\/0005624"],"award-info":[{"award-number":["17\/0005624"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000361","name":"Diabetes UK","doi-asserted-by":"publisher","award":["16\/0005480"],"award-info":[{"award-number":["16\/0005480"]}],"id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007028","name":"Leona M. and Harry B. Helmsley Charitable Trust","doi-asserted-by":"publisher","award":["#2018PG\u2010T1D053"],"award-info":[{"award-number":["#2018PG\u2010T1D053"]}],"id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabet. Med."],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Misclassification of diabetes is common due to an overlap in the clinical features of type 1 and type 2 diabetes. Combined diagnostic models incorporating clinical and biomarker information have recently been developed that can aid classification, but they have not been validated using pancreatic pathology. We evaluated a clinical diagnostic model against histologically defined type 1 diabetes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We classified cases from the Network for Pancreatic Organ donors with Diabetes (nPOD) biobank as type 1 (<jats:italic>n<\/jats:italic>\u00a0=\u00a0111) or non\u2010type 1 (<jats:italic>n<\/jats:italic>\u00a0=\u00a042) diabetes using histopathology. Type 1 diabetes was defined by lobular loss of insulin\u2010containing islets along with multiple insulin\u2010deficient islets. We assessed the discriminative performance of previously described type 1 diabetes diagnostic models, based on clinical features (age at diagnosis, BMI) and biomarker data [autoantibodies, type 1 diabetes genetic risk score (T1D\u2010GRS)], and singular features for identifying type 1 diabetes by the area under the curve of the receiver operator characteristic (AUC\u2010ROC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Diagnostic models validated well against histologically defined type 1 diabetes. The model combining clinical features, islet autoantibodies and T1D\u2010GRS was strongly discriminative of type 1 diabetes, and performed better than clinical features alone (AUC\u2010ROC 0.97 vs. 0.95; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.03). Histological classification of type 1 diabetes was concordant with serum C\u2010peptide [median &lt;\u00a017\u00a0pmol\/l (limit of detection) vs. 1037\u00a0pmol\/l in non\u2010type 1 diabetes; <jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.0001].<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study provides robust histological evidence that a clinical diagnostic model, combining clinical features and biomarkers, could improve diabetes classification. Our study also provides reassurance that a C\u2010peptide\u2010based definition of type 1 diabetes is an appropriate surrogate outcome that can be used in large clinical studies where histological definition is impossible.<\/jats:p><jats:p>Parts of this study were presented in abstract form at the Network for Pancreatic Organ Donors Conference, Florida, USA, 19\u201322 February 2019 and Diabetes UK Professional Conference, Liverpool, UK, 6\u20138 March 2019.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dme.14361","type":"journal-article","created":{"date-parts":[[2020,7,7]],"date-time":"2020-07-07T21:19:26Z","timestamp":1594156766000},"page":"2160-2168","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Histological validation of a type 1 diabetes clinical diagnostic model for classification of diabetes"],"prefix":"10.1111","volume":"37","author":[{"given":"A. L. J.","family":"Carr","sequence":"first","affiliation":[{"name":"Institute of Biomedical and Clinical Science University of Exeter Medical School Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. J.","family":"Perry","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine University of Florida Diabetes Institute Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. L.","family":"Lynam","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science University of Exeter Medical School Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Chamala","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine University of Florida Diabetes Institute Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. S.","family":"Flaxman","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science University of Exeter Medical School Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. A.","family":"Sharp","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science University of Exeter Medical School Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. A.","family":"Ferrat","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science University of Exeter Medical School Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0883-7599","authenticated-orcid":false,"given":"A. G.","family":"Jones","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science University of Exeter Medical School Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. L.","family":"Beery","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine University of Florida Diabetes Institute Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. M.","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics College of Medicine University of Florida Diabetes Institute Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. H.","family":"Wasserfall","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine University of Florida Diabetes Institute Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. L.","family":"Campbell\u2010Thompson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine University of Florida Diabetes Institute Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"Kusmartseva","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine University of Florida Diabetes Institute Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Posgai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine University of Florida Diabetes Institute Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. 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