title: Insulitis and β-Cell Mass in the Natural History of Type 1 Diabetes.
abstract: Descriptions of insulitis in human islets throughout the natural history of type 1 diabetes are limited. We determined insulitis frequency (the percent of islets displaying insulitis to total islets), infiltrating leukocyte subtypes, and β-cell and α-cell mass in pancreata recovered from organ donors with type 1 diabetes (n = 80), as well as from donors without diabetes, both with islet autoantibodies (AAb(+), n = 18) and without islet autoantibodies (AAb(-), n = 61). Insulitis was observed in four of four donors (100%) with type 1 diabetes duration of ≤1 year and two AAb(+) donors (2 of 18 donors, 11%). Insulitis frequency showed a significant but limited inverse correlation with diabetes duration (r = -0.58, P = 0.01) but not with age at disease onset. Residual β-cells were observed in all type 1 diabetes donors with insulitis, while β-cell area and mass were significantly higher in type 1 diabetes donors with insulitis compared with those without insulitis. Insulitis affected 33% of insulin(+) islets compared with 2% of insulin(-) islets in donors with type 1 diabetes. A significant correlation was observed between insulitis frequency and CD45(+), CD3(+), CD4(+), CD8(+), and CD20(+) cell numbers within the insulitis (r = 0.53-0.73, P = 0.004-0.04), but not CD68(+) or CD11c(+) cells. The presence of β-cells as well as insulitis several years after diagnosis in children and young adults suggests that the chronicity of islet autoimmunity extends well into the postdiagnosis period. This information should aid considerations of therapeutic strategies seeking type 1 diabetes prevention and reversal.
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL mct@ufl.edu.
authors.forename: Martha
authors.initials: M
authors.lastname: Campbell-Thompson
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL.
authors.forename: Ann
authors.initials: A
authors.lastname: Fu
authors.affiliation: City of Hope, Los Angeles, CA.
authors.forename: John S
authors.initials: JS
authors.lastname: Kaddis
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL.
authors.forename: Clive
authors.initials: C
authors.lastname: Wasserfall
authors.affiliation: Department of Pediatrics, University of Florida, Gainesville, FL.
authors.forename: Desmond A
authors.initials: DA
authors.lastname: Schatz
authors.affiliation: Diabetes Research Institute and Departments of Medicine and Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pugliese
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL Department of Pediatrics, University of Florida, Gainesville, FL.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Atkinson
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D050416:Glucagon-Secreting Cells / Q000276:immunology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D009929:Organ Size; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007328:Insulin