A proposal of three distinct subtypes of type 1 diabetes mellitus based on clinical and pathological evidence.
To better understand the pathogenesis of type 1 diabetes, our group performed a pathological examination on the pancreas tissue of recent-onset type 1 diabetics and analysed their clinical characteristics. These studies led us to speculate that there are three distinct subtypes of type 1 diabetes mellitus: autoimmune, nonautoimmune fulminant and nonautoimmune nonfulminant (or nonautoimmune chronic). The autoimmune type 1 diabetes mellitus comprises about 60% of the patients and is characterized by insulitis and over-expression of class I MHC molecules in the islet cells, a high prevalence of diabetes-related autoantibodies, and a progressive loss of beta-cell function after the onset of diabetes. The nonautoimmune nonfulminant type 1 diabetes mellitus includes about 30% of the patients, shows neither insulitis nor over-expression of class I MHC antigen in the islet cells, and has a low prevalence of diabetes-related autoantibodies and a relatively slow progression of beta-cell loss after the onset of diabetes. The nonautoimmune fulminant type 1 diabetes comprises about 10% of patients and shows neither insulitis nor over-expression of class I MHC molecules, but is characterized by lymphocytic infiltration in the exocrine pancreatic tissue, elevated serum pancreatic enzyme levels, absence of diabetes-related autoantibodies and a remarkably aggressive course of disease. The appropriate classification of type 1 diabetes would increase our understanding of the pathogenesis of the disease and would allow to develop therapeutic means based on this understanding.
Imagawa
A
A
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan. imagawa@imed2.med.osaka-u.ac.jp
Hanafusa
T
T
Miyagawa
J
J
Matsuzawa
Y
Y
D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000145:classification*; D003922:Diabetes Mellitus, Type 1 / Q000145:classification* / Q000276:immunology; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D008285:Major Histocompatibility Complex / Q000276:immunology
D001323:Autoantibodies