Etiology of Type I diabetes mellitus: heterogeneity and immunological events leading to clinical onset.

Type I diabetes is a heterogeneous disorder and the causes of pancreatic beta-cell destruction are unknown. In 1-2% of all cases, viruses (e.g. coxsackie, rubella, mumps, or beta-cell poisons) have been implicated. Twin studies suggest at most 50% of genetic predisposition. In this review we describe the autoimmune components which, in association with inheritance of HLA-haplotypes in susceptible families, allow the future selection of predisposed sibs for possible preventive therapy to retard loss of insulin secretion. The known association of the endocrine autoimmune organ-specific disorders in 10% of Type I diabetics is the extreme expression of the other main genetic ingredient in the development of insulitis in this disease, irrespective of the triggering environmental components. In this "polyendocrine" subgroup and in the "juvenile-onset" cases there is a prolonged latency period during which pancreatic autoimmunity markers are present before clinical expression of the disease.