Non-genetic factors in the pathogenesis of type 1 diabetes

Abstract

Type 1 diabetes is an autoimmune disease characterised by immune-cell-mediated destruction of the pancreatic islet cells leading to insufficient insulin production and consequent clinical manifestations of hyperglycaemia. Many genetic variants have been identified through GWAS to detect common variants in alleles that are disease-associated; some of these variants are associated with protection from virus infection by interferon-releasing factors. Migration studies support a role for environmental factors causing a change in disease incidence. Extensive epidemiological, histological and immunological data have indicated a role for viruses in the pathogenesis of type 1 diabetes although it has proven difficult to find a causal relationship. Increasing wealth and industrialisation in developed countries may also contribute to the rising incidence of type 1 diabetes. Disproportionate maternal influences on risk of type 1 diabetes suggest that critical disease-inducing environmental events operate very early, even in utero. Early infant diet can affect the appearance of diabetes-associated autoantibodies. Disproportionate maternal influences on risk of type 1 diabetes suggest that critical disease-inducing events operate very early, even in utero. Identification of relevant disease-causing non-genetic effects, especially if they are environmental in origin, could point the way towards disease modulation or even prevention.