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Insulitis in human diabetes: a histological evaluation of donor pancreases
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.ORCID iD: 0000-0002-8524-9547
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2017 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, no 2, p. 346-353Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2017. Vol. 60, no 2, p. 346-353
Keyword [en]
HLA, Inflammation, Insulin secretion, Insulitis, Islets, Macrophages, Tcells, Type 1 diabetes, Type 2 diabetes
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-315054DOI: 10.1007/s00125-016-4140-zISI: 000391359800016PubMedID: 27796420OAI: oai:DiVA.org:uu-315054DiVA, id: diva2:1079531
Funder
EU, FP7, Seventh Framework Programme, 261441 PEVNETNovo NordiskÅke Wiberg FoundationSwedish Diabetes Association
Available from: 2017-03-08 Created: 2017-03-08 Last updated: 2018-05-02Bibliographically approved
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