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Insulitis in human diabetes: a histological evaluation of donor pancreases
AIMS/HYPOTHESIS: According to the consensus criteria developed for type 1 diabetes, an individual can be diagnosed with insulitis when ≥ 15 CD45(+) cells are found within the parenchyma or in the islet–exocrine interface in ≥ 3 islets. The aim of this study was to determine the frequency of individu...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518093/ https://www.ncbi.nlm.nih.gov/pubmed/27796420 http://dx.doi.org/10.1007/s00125-016-4140-z |
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author | Lundberg, Marcus Seiron, Peter Ingvast, Sofie Korsgren, Olle Skog, Oskar |
author_facet | Lundberg, Marcus Seiron, Peter Ingvast, Sofie Korsgren, Olle Skog, Oskar |
author_sort | Lundberg, Marcus |
collection | PubMed |
description | AIMS/HYPOTHESIS: According to the consensus criteria developed for type 1 diabetes, an individual can be diagnosed with insulitis when ≥ 15 CD45(+) cells are found within the parenchyma or in the islet–exocrine interface in ≥ 3 islets. The aim of this study was to determine the frequency of individuals with type 2 diabetes fulfilling these criteria with reference to non-diabetic and type 1 diabetic individuals. METHODS: Insulitis was determined by examining CD45(+) cells in the pancreases of 50, 13 and 44 organ donors with type 2 diabetes, type 1 diabetes and no diabetes, respectively. CD3(+) cells (T cells) infiltrating the islets were evaluated in insulitic donors. In insulitic donors with type 2 diabetes, the pancreases were characterised according to the presence of CD68 (macrophages), myeloperoxidase (MPO; neutrophils), CD3, CD20 (B cells) and HLA class I hyperstained islets. In all type 2 diabetic donors, potential correlations of insulitis with dynamic glucose-stimulated insulin secretion in vitro or age, BMI, HbA(1c) or autoantibody positivity were examined. RESULTS: Overall, 28% of the type 2 diabetic donors fulfilled the consensus criteria for insulitis developed for type 1 diabetes. Of the type 1 diabetic donors, 31% fulfilled the criteria. None of the non-diabetic donors met the criteria. Only type 1 diabetic donors had ≥ 15 CD3(+) cells in ≥ 3 islets. Type 2 diabetic donors with insulitis also had a substantial number of CD45(+) cells in the exocrine parenchyma. Macrophages constituted the largest fraction of CD45(+) cells, followed by neutrophils and T cells. Of type 2 diabetic pancreases with insulitis, 36% contained islets that hyperstained for HLA class I. Isolated islets from type 2 diabetic donors secreted less insulin than controls, although with preserved dynamics. Insulitis in the type 2 diabetic donors did not correlate with glucose-stimulated insulin secretion, the presence of autoantibodies, BMI or HbA(1c). CONCLUSIONS/INTERPRETATION: The current definition of insulitis cannot be used to distinguish pancreases retrieved from individuals with type 1 diabetes from those with type 2 diabetes. On the basis of our findings, we propose a revised definition of insulitis, with a positive diagnosis when ≥ 15 CD3(+) cells, not CD45(+) cells, are found in ≥ 3 islets. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-016-4140-z) contains peer-reviewed but unedited supplementary material, which is available to authorised users. |
format | Online Article Text |
id | pubmed-6518093 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-65180932019-06-05 Insulitis in human diabetes: a histological evaluation of donor pancreases Lundberg, Marcus Seiron, Peter Ingvast, Sofie Korsgren, Olle Skog, Oskar Diabetologia Article AIMS/HYPOTHESIS: According to the consensus criteria developed for type 1 diabetes, an individual can be diagnosed with insulitis when ≥ 15 CD45(+) cells are found within the parenchyma or in the islet–exocrine interface in ≥ 3 islets. The aim of this study was to determine the frequency of individuals with type 2 diabetes fulfilling these criteria with reference to non-diabetic and type 1 diabetic individuals. METHODS: Insulitis was determined by examining CD45(+) cells in the pancreases of 50, 13 and 44 organ donors with type 2 diabetes, type 1 diabetes and no diabetes, respectively. CD3(+) cells (T cells) infiltrating the islets were evaluated in insulitic donors. In insulitic donors with type 2 diabetes, the pancreases were characterised according to the presence of CD68 (macrophages), myeloperoxidase (MPO; neutrophils), CD3, CD20 (B cells) and HLA class I hyperstained islets. In all type 2 diabetic donors, potential correlations of insulitis with dynamic glucose-stimulated insulin secretion in vitro or age, BMI, HbA(1c) or autoantibody positivity were examined. RESULTS: Overall, 28% of the type 2 diabetic donors fulfilled the consensus criteria for insulitis developed for type 1 diabetes. Of the type 1 diabetic donors, 31% fulfilled the criteria. None of the non-diabetic donors met the criteria. Only type 1 diabetic donors had ≥ 15 CD3(+) cells in ≥ 3 islets. Type 2 diabetic donors with insulitis also had a substantial number of CD45(+) cells in the exocrine parenchyma. Macrophages constituted the largest fraction of CD45(+) cells, followed by neutrophils and T cells. Of type 2 diabetic pancreases with insulitis, 36% contained islets that hyperstained for HLA class I. Isolated islets from type 2 diabetic donors secreted less insulin than controls, although with preserved dynamics. Insulitis in the type 2 diabetic donors did not correlate with glucose-stimulated insulin secretion, the presence of autoantibodies, BMI or HbA(1c). CONCLUSIONS/INTERPRETATION: The current definition of insulitis cannot be used to distinguish pancreases retrieved from individuals with type 1 diabetes from those with type 2 diabetes. On the basis of our findings, we propose a revised definition of insulitis, with a positive diagnosis when ≥ 15 CD3(+) cells, not CD45(+) cells, are found in ≥ 3 islets. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-016-4140-z) contains peer-reviewed but unedited supplementary material, which is available to authorised users. Springer Berlin Heidelberg 2016-10-28 2017 /pmc/articles/PMC6518093/ /pubmed/27796420 http://dx.doi.org/10.1007/s00125-016-4140-z Text en © The Author(s) 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Article Lundberg, Marcus Seiron, Peter Ingvast, Sofie Korsgren, Olle Skog, Oskar Insulitis in human diabetes: a histological evaluation of donor pancreases |
title | Insulitis in human diabetes: a histological evaluation of donor pancreases |
title_full | Insulitis in human diabetes: a histological evaluation of donor pancreases |
title_fullStr | Insulitis in human diabetes: a histological evaluation of donor pancreases |
title_full_unstemmed | Insulitis in human diabetes: a histological evaluation of donor pancreases |
title_short | Insulitis in human diabetes: a histological evaluation of donor pancreases |
title_sort | insulitis in human diabetes: a histological evaluation of donor pancreases |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518093/ https://www.ncbi.nlm.nih.gov/pubmed/27796420 http://dx.doi.org/10.1007/s00125-016-4140-z |
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