Dimorphic histopathology of long-standing  childhood-onset diabetes.
OBJECTIVE
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
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.
Gianani
R
R
Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, 1775 Aurora Court, Aurora, CO 80055, USA. roberto.gianani@ucdenver.edu
Campbell-Thompson
M
M
Sarkar
S A
SA
Wasserfall
C
C
Pugliese
A
A
Solis
J M
JM
Kent
S C
SC
Hering
B J
BJ
West
E
E
Steck
A
A
Bonner-Weir
S
S
Atkinson
M A
MA
Coppieters
K
K
von Herrath
M
M
Eisenbarth
G S
GS
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood; D002096:C-Peptide / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology*; D005260:Female; D006684:HLA-DR Antigens; D006650:Histocompatibility Testing; D006801:Humans; D006946:Hyperinsulinism / Q000473:pathology; D050417:Insulin-Secreting Cells / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000473:pathology*; D012727:Sex Characteristics; D014019:Tissue Donors
D001323:Autoantibodies; D002096:C-Peptide; D006684:HLA-DR Antigens