Dimorphic histopathology of long-standing childhood-onset diabetes

作者：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

来源：Diabetologia, 2010, 53(4): 690-698.

DOI：10.1007/s00125-009-1642-y

• 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

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.
We evaluated 20 cadaveric organ donor pancreases of childhood-onset long-term patients for disease heterogeneity and obtained corresponding C-peptide measurements.
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.
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.

• 出版日期2010-4