Speculation on prevention of type 1 diabetes

Abstract

The increasing incidence, decreasing age of onset, and the lowered threshold for developing type 1 diabetes make its prevention even more imperative and suggest changes over time in environmental etiologies contributing to the disease. A testable hypothesis is that these epidemiological changes are arising from defective development of or alteration in intestinal microbiome-induced immunoregulation in infancy and early childhood. Viruses contribute to the intestinal microbiome and the intestinal microbial flora may be altered by enteric infections. In addition, viruses may be contributing to the pathogenesis of type 1 diabetes by activation of innate immunity and/or infection of pancreatic beta cells or islets and the ensuing inflammatory response, which may lead to beta cell stress with modification of beta cell protein expression to generate beta cell protein neoepitopes that lead to breaking of immune tolerance to native beta cell antigens. Both primary and secondary prevention of childhood-onset type 1 diabetes should be pursued on a childhood population-wide basis. Primary prevention should focus on developing diabetes vaccines, including enteroviral vaccines if a restricted number of enteroviral serotypes account for a significant proportion of type 1 diabetes in different geographical regions and over time. Vaccine-based approaches to augment, accelerate, or induce robust microbiome-induced immunoregulation in childhood should be investigated.