title: Insulitis in human diabetes: a histological evaluation of donor pancreases.
abstract: 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.
  
  
  
  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, HbA1cor autoantibody positivity were examined.
  
  
  
  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 HbA1c.
  
  
  
  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.
authors: Department of Immunology, Genetics and Pathology, The Rudbeck Laboratory C11, Clinical Immunology, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden. marcus.lundberg@igp.uu.se.
authors: Marcus
authors: M
authors: Lundberg
authors: Department of Immunology, Genetics and Pathology, The Rudbeck Laboratory C11, Clinical Immunology, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.
authors: Peter
authors: P
authors: Seiron
authors: Department of Immunology, Genetics and Pathology, The Rudbeck Laboratory C11, Clinical Immunology, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.
authors: Sofie
authors: S
authors: Ingvast
authors: Department of Immunology, Genetics and Pathology, The Rudbeck Laboratory C11, Clinical Immunology, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.
authors: Olle
authors: O
authors: Korsgren
authors: Department of Immunology, Genetics and Pathology, The Rudbeck Laboratory C11, Clinical Immunology, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.
authors: Oskar
authors: O
authors: Skog
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology*; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D007328:Insulin; D017493:Leukocyte Common Antigens
keywords: HLA; Inflammation; Insulin secretion; Insulitis; Islets; Macrophages; T cells; Type 1 diabetes; Type 2 diabetes