[Slowly progressive IDDM].

Abstract

A prospective study over 10 years on the natural history of beta-cell function in islet cell antibody (ICA)-positive NIDDM disclosed a characteristic findings of slowly progressive IDDM distinct from those of acute onset IDDM. The characteristics includes: (1) the clinical phenotype at the onset of diabetes is non-insulin requiring, (2) the onset is late age, (3) beta-cell failure progresses slowly over several years with persistently positive low-titer ICA and high titer of GAD antibodies, (4) pathological study on autopsied pancreas demonstrated that beta-cell loss is incomplete, and exocrine pancreas is often atrophied with cell infiltration of CD8+ T lymphocytes, (5) higher family history of NIDDM, and (6) association with some genetic predisposition including HLA-DQA1*0301-DQB1*0401 and/or mitochondrial gene mutation at nucleotide pair 3243, and a lack of association with HLA-A24. These results are sharply contrast with acute onset IDDM, suggesting a presence of distinct subtype of IDDM in Japanese population. We also demonstrated that small dose of insulin therapy was effective for the suppression of immunological beta-cell failure.