Etiopathology of diabetes mellitus

Available evidence suggests a multifactorial etiology (especially genetic, immunologic and environmental) for IDDM. Genetic factors appear to be related to certain HLA types, which in turn might be associated with abnormal immunologic responses directed against pancreatic beta cells. Environmental agents, particularly diabetogenic chemicals or viruses, or both, might actually trigger an autoimmune response leading to cumulative damage to beta cells and development of diabetes mellitus in genetically predisposed persons. Much attention is being directed toward the elucidation of the immunologic and environmental factors in IDDM. Islet cell antibodies (either against the cytoplasmic components (ICA) or surface determinants (ICSA)) are found in 90% of IDDM and inflammation of the islets (insulitis) consistent with either a viral infection and/or autoimmune response can be found at autopsy, particularly in children. Virus-induced diabetes has been accepted as one of the animal models for the study of IDDM in humans. Moreover, viruses diabetogenic for the animal model have been recovered from persons with IDDM. It has also been observed that viruses may damage beta cells during fatal infections. The identification of possible environmental triggers such as viruses that damage human beta cells in vivo and the elucidation of the events that follow the infection may represent one of the first steps toward eventual prevention (e.g., vaccination) or therapeutic intervention (e.g., immunosuppression) of IDDM.