Environmental risk factors for type 1 diabetes

Abstract

The incidence of type 1 diabetes has risen considerably in the past 30 years due to changes in the environment that have been only partially identified. In this Series paper, we critically discuss candidate triggers of islet autoimmunity and factors thought to promote progression from autoimmunity to overt type 1 diabetes. We revisit previously proposed hypotheses to explain the growth in the incidence of type 1 diabetes in light of current data. Finally, we suggest a unified model in which immune tolerance to β cells can be broken by several environmental exposures that induce generation of hybrid peptides acting as neoautoantigens.

Figure 1

Environmental triggers and protective factors for islet autoimmunity and promoters of progression to type 1 diabetes for which an association has been suggested Triggers and factors with the strongest evidence base are shown in blue.

Figure 2

A unified model of the relationship between environmental factors, β-cell endoplasmic reticulum stress, generation of neoautoantigens (HIPs), and loss of immune tolerance that triggers islet autoimmunity HIP=hybrid insulin peptide.