Dimorphic histopathology of long-standing childhood-onset diabetes

R. Gianani, M. Campbell-Thompson, S. A. Sarkar, C. Wasserfall, A. Pugliese, J. M. Solis, S. C. Kent, B. J. Hering, E. West, A. Steck, S. Bonner-Weir, M. A. Atkinson, K. Coppieters, M. Von Herrath, G. S. Eisenbarth

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)690-698
Number of pages9
JournalDiabetologia
Volume53
Issue number4
DOIs
StatePublished - Apr 2010

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Keywords

  • Autoimmune diabetes
  • Childhood diabetes
  • Heterogeneity of diabetes
  • HLA DR3
  • HLA DR4
  • Islet autoantibodies
  • Organ donors
  • Pathology of childhood diabetes
  • Patterns of beta cell loss
  • Type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Gianani, R., Campbell-Thompson, M., Sarkar, S. A., Wasserfall, C., Pugliese, A., Solis, J. M., Kent, S. C., Hering, B. J., West, E., Steck, A., Bonner-Weir, S., Atkinson, M. A., Coppieters, K., Von Herrath, M., & Eisenbarth, G. S. (2010). Dimorphic histopathology of long-standing childhood-onset diabetes. Diabetologia, 53(4), 690-698. https://doi.org/10.1007/s00125-009-1642-y