The Challenges of Identifying Environmental Determinants of Type 1 Diabetes: In Search of the Holy Grail

Type 1 diabetes is the result of autoimmune-mediated destruction and inflammation of the insulin-producing β-cells of the pancreas. The excess morbidity and mortality from its complications coupled with its increasing incidence emphasize the importance to better understand the etiology of this condition. It has a strong genetic component, but a genetic predisposition is not the sole contributor to disease development as only 30% to 50% of identical twins both develop the disease. In addition, there are multiple lines of evidence to support that environmental factors contribute to the pathogenesis of type 1 diabetes. Environmental risk factors that have been proposed include infections, dietary factors, air pollution, vaccines, location of residence, childhood obesity, family environment and stress. Researchers have conducted many observational studies to identify and characterize these potential environmental factors, but findings have been inconsistent or inconclusive. Many studies have had inherent methodological issues in recruitment, participation, defining cases and exposures, and/or data analysis which may limit the interpretability of findings. Identifying and addressing these limitations may allow for greatly needed advances in our understanding of type 1 diabetes. As such, the purpose of this article is to review and discuss the limitations of observational studies that aim to determine environmental risk factors for type 1 diabetes and propose recommendations to overcome them.