Abstract
Clinical and pathologic heterogeneity in type 1 diabetes is increasingly being recognized. Findings in the islets and pancreas of a 22-year-old male with 8 years of type 1 diabetes were discordant with expected results and clinical history (islet autoantibodies negative, A1C 11.9%) and led to comprehensive investigation to define the functional, molecular, genetic, and architectural features of the islets and pancreas in order to understand the cause of the donor’s diabetes. Examination of the donor’s pancreatic tissue found substantial, but reduced, β cell mass with some islets devoid of β cells (29.3% of 311 islets) while other islets had many β cells. Surprisingly, isolated islets from the donor pancreas had substantial insulin secretion that is uncommon for type 1 diabetes of this duration. Targeted and whole genome sequencing and analysis did not uncover monogenic causes of diabetes but did identify high-risk HLA haplotypes and a genetic risk score suggestive of type 1 diabetes. Further review of pancreatic tissue found islet inflammation and some previously described α cell molecular features seen in type 1 diabetes. By integrating analysis of isolated islets, histological evaluation of the pancreas, and genetic information, we concluded that the donor’s clinical insulin deficiency was most likely the result autoimmune-mediated β cell loss, but that the constellation of findings was not typical for type 1 diabetes. This report highlights the pathologic and functional heterogeneity that can be present in type 1 diabetes.
Retraction Note: Abstracts of the 50th Annual Meeting of the EASD, Vienna 2014. ‘Evaluation of DiaPep277® treatment in type 1 diabetes by integrated analysis’