Can exposure to environmental chemicals increase the risk of diabetes type 1 development?

Abstract

Type 1 diabetes mellitus (T1DM) is an autoimmune disease, where destruction of beta-cells causes insulin deficiency. The incidence of T1DM has increased in the last decades and cannot entirely be explained by genetic predisposition. Several environmental factors are suggested to promote T1DM, like early childhood enteroviral infections and nutritional factors, but the evidence is inconclusive. Prenatal and early life exposure to environmental pollutants like phthalates, bisphenol A, perfluorinated compounds, PCBs, dioxins, toxicants, and air pollutants can have negative effects on the developing immune system, resulting in asthma-like symptoms and increased susceptibility to childhood infections. In this review the associations between environmental chemical exposure and T1DM development is summarized. Although information on environmental chemicals as possible triggers for T1DM is sparse, we conclude that it is plausible that environmental chemicals can contribute to T1DM development via impaired pancreatic beta-cell and immune-cell functions and immunomodulation. Several environmental factors and chemicals could act together to trigger T1DM development in genetically susceptible individuals, possibly via hormonal or epigenetic alterations. Further observational T1DM cohort studies and animal exposure experiments are encouraged.

Figure 1

Mechanisms suggested to be involved in pathways of T1DM development after exposure to environmental chemicals via food/gut, air/lungs, and skin. Chemicals can act directly on beta or immune cells, by binding to receptors (X and Y-receptors could, for instance, be adrenergic-, purinergic-, or scavenger receptors) or after uptake in the cells by pinocytosis, endocytosis, or diffusion. Chemicals can also affect factors like mucosal permeability, the microbiome, or the hormone balance, all shown to interact with the immune system. Several chemicals have been shown to induce epigenetic changes. Chemical exposures can further lead to apoptosis or cell death, increased oxidative stress, impaired insulin response, altered immune function or immunosuppression, molecular mimicry, and posttranslational modifications.