Abstract
OBJECTIVE: The aim of this study was to identify the distinct pathological changes on the endocrine and exocrine pancreas of slowly progressive insulin-dependent diabetes mellitus (SPIDDM) or latent autoimmune diabetes in adults. METHODS: The pancreases from 12 islet autoantibody-positive SPIDDM patients and 19 age-matched subjects with no diabetes were examined histologically for islet inflammation/insulitis, expressions of cytokines, and enterovirus VP1 protein, exocrine pancreatic inflammation, pancreatic ductal changes, major histocompatibility complex class I hyperexpression, and amylin-positive amyloid in the islets. RESULTS: Insulitis dominant for CD8 T-cells and CD68 macrophages was observed in all SPIDDM cases irrespective of duration of diabetes and weight of residual beta cells. Major histocompatibility complex class I hyperexpression on residual beta cells was observed in SPIDDM. All SPIDDM exocrine pancreases showed extensive inflammation, dilated pancreatic ducts, and periductal fibrosis. As many as 75% (9/12) of pancreases had pancreatic intraepithelial neoplasia, which is assumed to be associated with ductal obstruction/narrowing and exocrine pancreatic inflammation, in SPIDDM. Amylin-positive amyloid deposition was not detected in SPIDDM. CONCLUSIONS: Persistent insulitis with preserved beta cells and major histocompatibility complex class I hyperexpression and exocrine pancreatic inflammation with pancreatic intraepithelial neoplasia are distinct histological features of SPIDDM pancreas.