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 journalArticlepeer-review

106 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

Bibliographical note

Funding Information:
Acknowledgements We gratefully acknowledge the JDRF-sponsored nPOD programme and the Brehm Coalition, which supported this study. Some of the experiments were performed by the Diabetes Endocrinology Research Center histology core (P30DK057516), NIH DK 32083. S. A. Sarkar is supported by NIH DK080193 and JDRF 1-2008-1021.

Keywords

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

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