Dimorphic histopathology of long-standing childhood-onset diabetes.
Gianani, R. 1; Campbell-Thompson, M. 2; Sarkar, S. A. 1; Wasserfall, C. 2; Pugliese, A. 3; Solis, J. M. 1; Kent, S. C. 4; Hering, B. J. 5; West, E. 1; Steck, A. 1; Bonner-Weir, S. 6; Atkinson, M. A. 2; Coppieters, K. 7; von Herrath, M. 7; Eisenbarth, G. S. 1
[Article] Diabetologia. 53(4):690-698, April 2010.

(Format: HTML, PDF)

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.

(C) 2010 Springer. Part of Springer Science Business Media