Insulindependent Diabetes Mellitus Human

Andrew Muir and Noel Maclaren, Department of Pathology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida, USA

Copyright © 1998 Elsevier Ltd. All Rights Reserved.

Contemporary management of insulin-dependent diabetes mellitus (IDDM) is intrusive and cannot guarantee complication-free survival. Improved understanding of the pathogenesis of IDDM has, however, provided optimism that this autoimmune disease will soon become either preventable or curable. While determined by multiple genes, the predisposition to destruction of the insulin-producing (3 cells in the pancreatic islets of Langerhans is transmitted predominantly through the class II human leukocyte antigen (HLA) DR and DQ loci. These predispositions involve the failure of multiple regulatory mechanisms and breakdown of immunological tolerance to self, probably induced by exposure to one or more incompletely identified environmental triggers. Particular attention has focused on the identification of specific islet autoantigens, soluble mediators of cytotoxicity (e.g. cytokines, superoxides), the balance between antigen-specific CD4J T,|l and T,,2 cells, and the cytotoxic effects of macrophages and CD 84 T lymphocytes. Future treatments will focus on preservation of pancreatic (3 cells and/or provision of permanent and physiological insulin replacement.

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