Histological validation of a type 1 diabetes clinical diagnostic model for classification of diabetes
dc.contributor.author | Carr, ALJ | |
dc.contributor.author | Perry, DJ | |
dc.contributor.author | Lynam, AL | |
dc.contributor.author | Chamala, S | |
dc.contributor.author | Flaxman, CS | |
dc.contributor.author | Sharp, SA | |
dc.contributor.author | Ferrat, LA | |
dc.contributor.author | Jones, AG | |
dc.contributor.author | Beery, ML | |
dc.contributor.author | Jacobsen, LM | |
dc.contributor.author | Wasserfall, CH | |
dc.contributor.author | Campbell-Thompson, ML | |
dc.contributor.author | Kusmartseva, I | |
dc.contributor.author | Posgai, A | |
dc.contributor.author | Schatz, DA | |
dc.contributor.author | Atkinson, MA | |
dc.contributor.author | Brusko, TM | |
dc.contributor.author | Richardson, SJ | |
dc.contributor.author | Shields, BM | |
dc.contributor.author | Oram, RA | |
dc.date.accessioned | 2020-09-18T09:01:30Z | |
dc.date.issued | 2020-07-07 | |
dc.description.abstract | Aims: 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. Methods: We classified cases from the Network for Pancreatic Organ donors with Diabetes (nPOD) biobank as type 1 (n = 111) or non-type 1 (n = 42) diabetes using histopathology. Type 1 diabetes was defined by lobular loss of insulin-containing islets along with multiple insulin-deficient 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-GRS)], and singular features for identifying type 1 diabetes by the area under the curve of the receiver operator characteristic (AUC-ROC). Results: Diagnostic models validated well against histologically defined type 1 diabetes. The model combining clinical features, islet autoantibodies and T1D-GRS was strongly discriminative of type 1 diabetes, and performed better than clinical features alone (AUC-ROC 0.97 vs. 0.95; P = 0.03). Histological classification of type 1 diabetes was concordant with serum C-peptide [median < 17 pmol/l (limit of detection) vs. 1037 pmol/l in non-type 1 diabetes; P < 0.0001]. Conclusions: 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-peptide-based definition of type 1 diabetes is an appropriate surrogate outcome that can be used in large clinical studies where histological definition is impossible. Parts of this study were presented in abstract form at the Network for Pancreatic Organ Donors Conference, Florida, USA, 19–22 February 2019 and Diabetes UK Professional Conference, Liverpool, UK, 6–8 March 2019. | en_GB |
dc.description.sponsorship | Diabetes UK | en_GB |
dc.description.sponsorship | National Institutes of Health (NIH) | en_GB |
dc.description.sponsorship | National Institute for Health Research (NIHR) | en_GB |
dc.description.sponsorship | JDRF | en_GB |
dc.description.sponsorship | Helmsley Charitable Trust | en_GB |
dc.identifier.citation | Published online 7 July 2020 | en_GB |
dc.identifier.doi | 10.1111/dme.14361 | |
dc.identifier.grantnumber | 16/0005529 | en_GB |
dc.identifier.grantnumber | AI‐422388 | en_GB |
dc.identifier.grantnumber | 17/0005624 | en_GB |
dc.identifier.grantnumber | 16/0005480 | en_GB |
dc.identifier.grantnumber | 5‐CDA‐2014‐221‐A‐N | en_GB |
dc.identifier.grantnumber | 2018PG‐T1D053 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/122908 | |
dc.language.iso | en | en_GB |
dc.publisher | Wiley / Diabetes UK | en_GB |
dc.rights | © 2020 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | en_GB |
dc.title | Histological validation of a type 1 diabetes clinical diagnostic model for classification of diabetes | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2020-09-18T09:01:30Z | |
dc.identifier.issn | 0742-3071 | |
dc.description | This is the final version. Available on open access from Wiley via the DOI in this record | en_GB |
dc.identifier.journal | Diabetic Medicine | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2020-07-01 | |
exeter.funder | ::Juvenile Diabetes Research Foundation International | en_GB |
exeter.funder | ::Diabetes UK | en_GB |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2020-07-01 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2020-09-18T08:53:20Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2020-09-18T09:01:37Z | |
refterms.panel | A | en_GB |
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Except where otherwise noted, this item's licence is described as © 2020 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.