title: Dimorphic histopathology of long-standing  childhood-onset diabetes.
abstract: OBJECTIVE
  Childhood diabetes is thought to usually result from autoimmune beta cell destruction (type 1A) with eventual total loss of beta cells. Analysis of C-peptide in children characterised at diabetes onset for autoantibodies shows heterogeneous preservation of insulin secretion in long-standing diabetes. The aim of this study was to characterise the pancreases of childhood-onset diabetes in order to define the pathological basis of this heterogeneity.
  
  
  METHODS
  We evaluated 20 cadaveric organ donor pancreases of childhood-onset long-term patients for disease heterogeneity and obtained corresponding C-peptide measurements.
  
  
  RESULTS
  Pancreases from the majority of cadaveric donors contained only insulin-deficient islets (14 of 20). The remaining six patients (30%) had numerous insulin-positive cells within at least some islets, with two different histological patterns. Pattern A (which we would associate with type 1A diabetes) had lobular retention of areas with 'abnormal' beta cells producing the apoptosis inhibitor survivin and HLA class I. In pattern B, 100% of all islets contained normal-appearing but quantitatively reduced beta cells without survivin or HLA class I.
  
  
  CONCLUSIONS
  Our data demonstrate that C-peptide secretion in long-standing diabetic patients can be explained by two different patterns of beta cell survival,possibly reflecting different subsets of type 1 diabetes.
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, 1775 Aurora Court, Aurora, CO 80055, USA. roberto.gianani@ucdenver.edu
authors.forename: R
authors.initials: R
authors.lastname: Gianani
authors.forename: M
authors.initials: M
authors.lastname: Campbell-Thompson
authors.forename: S A
authors.initials: SA
authors.lastname: Sarkar
authors.forename: C
authors.initials: C
authors.lastname: Wasserfall
authors.forename: A
authors.initials: A
authors.lastname: Pugliese
authors.forename: J M
authors.initials: JM
authors.lastname: Solis
authors.forename: S C
authors.initials: SC
authors.lastname: Kent
authors.forename: B J
authors.initials: BJ
authors.lastname: Hering
authors.forename: E
authors.initials: E
authors.lastname: West
authors.forename: A
authors.initials: A
authors.lastname: Steck
authors.forename: S
authors.initials: S
authors.lastname: Bonner-Weir
authors.forename: M A
authors.initials: MA
authors.lastname: Atkinson
authors.forename: K
authors.initials: K
authors.lastname: Coppieters
authors.forename: M
authors.initials: M
authors.lastname: von Herrath
authors.forename: G S
authors.initials: GS
authors.lastname: Eisenbarth
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood; D002096:C-Peptide / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology*; D005260:Female; D006684:HLA-DR Antigens; D006650:Histocompatibility Testing; D006801:Humans; D006946:Hyperinsulinism / Q000473:pathology; D050417:Insulin-Secreting Cells / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000473:pathology*; D012727:Sex Characteristics; D014019:Tissue Donors
chemical_list: D001323:Autoantibodies; D002096:C-Peptide; D006684:HLA-DR Antigens