Do gene-environment interactions have implications for the precision prevention of type 2 diabetes?

ABSTRACT

The past decades have seen a rapid global rise in the incidence of type 2 diabetes. This surge has been driven by diabetogenic environmental changes that may act together with a genetic predisposition to type 2 diabetes. It is possible that there is a synergistic gene-environment interaction, where the effects of the diabetogenic environment depend on the genetic predisposition to type 2 diabetes. Randomised trials have shown that it is possible to delay, or even prevent the development of type 2 diabetes in individuals at elevated risk through behavioural modification, focusing on weight loss, physical activity and diet. There is wide heterogeneity between individuals regarding the effectiveness of these interventions, which could, in part, be due to genetic differences. However, the studies of gene-environment interactions performed thus far suggest that behavioural modifications appear equally effective in reducing the incidence of type 2 diabetes from the stage of impaired glucose tolerance, regardless of the known underlying genetic predisposition. Recent studies suggest that there may be several subtypes of type 2 diabetes, which give new opportunities for gaining insight into gene-environment interactions. At present, the role of gene-environment interactions in the development of type 2 diabetes remains unclear. With many puzzle pieces missing in the general picture of type 2 diabetes development, the available evidence of gene-environment interactions is not ready for translation to individualised type 2 diabetes prevention based on genetic profiling.