Type 2 diabetes develops as a conspiracy between the genetic background and the environment. The interaction between genes and environment may involve epigenetic factors, such as DNA methylation and histone modifications, to promote type 2 diabetes. The overall objective of our research is to identify the key epigenetic mechanisms influencing the pathogenesis of T2D. We are currently analysing DNA methylation and histone modifications in a number of human cohorts. Here, we examine if non-genetic and genetic factors as well as type 2 diabetes affect epigenetic variation in human tissues. We are further relating DNA methylation to gene expression, in vivo metabolism and type 2 diabetes. Furthermore, we are dissecting the role of epigenetic enzymes in development of type 2 diabetes.