ABSTRACT
Type 1 diabetes is perceived as a chronic immune-mediated disease with a subclinical prodrome of variable duration (1). The preclinical period is characterized by selective loss of insulin-producing b cells in the pancreatic islets in genetically susceptible subjects. The most important genes contributing to disease susceptibility are located in the HLA class II locus on the short arm of chromosome 6 (2). Only a relatively small proportion, i.e., less than 10%, of individuals with HLAconferred disease susceptibility progress, however, to clinical diabetes. This implies that additional factors are needed to trigger and drive b-cell destruction in genetically predisposed subjects. Environmental factors have been implicated in the pathogenesis of type 1 diabetes both as triggers and potentiators of b-cell destruction (3-5), although a critical role of any individual exogenous factor has not been definitely proven so far. In any case, a series of evidence support a crucial contribution of exogenous factors in the development of type 1 diabetes, such as (1) the fact that less than 10% of those with HLA-conferred diabetes susceptibility do progress to clinical disease, (2) a pair-wise concordance of type 1 diabetes of less than 40% among monozygotic twins, (3) a more than 10-fold difference in the disease incidence among Caucasians living in Europe, (4) a several fold increase in the incidence over the last 50 years in most developed countries, and (5) migration studies indicating that the disease incidence has increased in population groups who have moved from a low-incidence to a high-incidence region. This chapter discusses the role of viruses as potential triggers and potentiators of the diabetic disease process. In addition, we consider the standard of hygiene as a possible factor programming the immune system; a high standard favoring weak immune regulation resulting in either Th1 or Th2 polarization of the CD4þ T cells with autoimmune or allergic manifestations as the outcome.
