Dimorphic histopathology of long-standing childhood-onset diabetes

Diabetologia. 2010 Apr;53(4):690-8. doi: 10.1007/s00125-009-1642-y. Epub 2010 Jan 9.


Aims/hypothesis: 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/interpretation: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Autoantibodies / blood
  • C-Peptide / blood
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / pathology*
  • Female
  • HLA-DR Antigens
  • Histocompatibility Testing
  • Humans
  • Hyperinsulinism / pathology
  • Insulin-Secreting Cells / pathology*
  • Male
  • Middle Aged
  • Pancreas / pathology*
  • Sex Characteristics*
  • Tissue Donors


  • Autoantibodies
  • C-Peptide
  • HLA-DR Antigens