Environmental factors in the pathogenesis of type 1 diabetes mellitus

Type 1 diabetes mellitus is perceived as a chronic autoimmune disease with a subclinical prodrome characterized by selective loss of insulin producing beta cells in the pancreatic islets in genetically predisposed subjects. Less than 10% of those with increased genetic susceptibility progress to clinical disease suggesting a strong environmental modification of the prediabetic process. Various exogenous triggers, such as certain dietary factors and viruses, are thought to induce the autoimmune process leading in some individuals to extensive beta-cell destruction and ultimately to the clinical manifestation of type 1 diabetes. In addition to their role as triggers, environmental factors are also likely affecting the outcome of the process and the rate of progression to clinical disease in those who do develop Type 1 diabetes. The present review focuses on relatively recent data on environmental factors potentially involved in the pathogenesis of Type 1 diabetes with an emphasis on dietary factors, and cow's milk (CM) proteins in particular. The CM hypothesis has remained controversial for a decade, and therefore an intervention trial should be performed to settle the issue. Recent prospective studies have indicated that enterovirus infections may induce beta-cell autoimmunity and potentiate the humoral immune response to beta-cell antigens in subjects with an ongoing process. There are also very preliminary data suggesting a similar role for rotavirus infections. Although there may be a single trigger of beta-cell autoimmunity in a given individual, it is highly unlikely that there is only one exogenous determinant of Type 1 diabetes. Rather we have a complicated interaction between a series of environmental factors and between environmental factors and genetic disease predisposition resulting in progression to clinical Type 1 diabetes in those genetically susceptible individuals who experience an unfortunate timing and/or clustering of diabetogenic exogenous culprits and/or a lack of protective environmental modifiers. Ongoing prospective studies starting from birth provide an optimal setting for the identification of environmental factors affecting the risk of progression to clinical Type 1 diabetes.