Dimorphic histopathology of long-standing childhood-onset diabetes

R. Gianani, M. Campbell-Thompson, S. A. Sarkar, C. Wasserfall, Alberto 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

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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
Pages (from-to)690-698
Number of pages9
JournalDiabetologia
Volume53
Issue number4
DOIs
StatePublished - Apr 1 2010

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C-Peptide
Pancreas
Insulin
Tissue Donors
Type 1 Diabetes Mellitus
Autoantibodies
Cell Survival
Apoptosis

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., ... 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

Dimorphic histopathology of long-standing childhood-onset diabetes. / Gianani, R.; Campbell-Thompson, M.; Sarkar, S. A.; Wasserfall, C.; Pugliese, Alberto; 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.

In: Diabetologia, Vol. 53, No. 4, 01.04.2010, p. 690-698.

Research output: Contribution to journalArticle

Gianani, R, Campbell-Thompson, M, Sarkar, SA, Wasserfall, C, Pugliese, A, Solis, JM, Kent, SC, Hering, BJ, West, E, Steck, A, Bonner-Weir, S, Atkinson, MA, Coppieters, K, Von Herrath, M & Eisenbarth, GS 2010, 'Dimorphic histopathology of long-standing childhood-onset diabetes', Diabetologia, vol. 53, no. 4, pp. 690-698. https://doi.org/10.1007/s00125-009-1642-y
Gianani R, Campbell-Thompson M, Sarkar SA, Wasserfall C, Pugliese A, Solis JM et al. Dimorphic histopathology of long-standing childhood-onset diabetes. Diabetologia. 2010 Apr 1;53(4):690-698. https://doi.org/10.1007/s00125-009-1642-y
Gianani, R. ; Campbell-Thompson, M. ; Sarkar, S. A. ; Wasserfall, C. ; Pugliese, Alberto ; 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. / Dimorphic histopathology of long-standing childhood-onset diabetes. In: Diabetologia. 2010 ; Vol. 53, No. 4. pp. 690-698.
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AU - Solis, J. M.

AU - Kent, S. C.

AU - Hering, B. J.

AU - West, E.

AU - Steck, A.

AU - Bonner-Weir, S.

AU - Atkinson, M. A.

AU - Coppieters, K.

AU - Von Herrath, M.

AU - Eisenbarth, G. S.

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