Globally, the incidence of diabetes has grown rapidly. The prevalence of diabetes in China was 11.6% in 2010. Diabetes has become a huge challenge for public health. The cause of diabetes is not yet completely clear. Potential risk factors include genetic factors, environmental factors, and interactions between the two. Genome-wide association studies have found a series of genetic variants that are closely related to diabetes. Several environmental factors, such as excessive energy intake and lack of physical activity, have been associated with increased risk of diabetes. In the meanwhile, genetic and environmental factors could modify each other’s effect on diabetes risk. With the advent of molecular techniques, post-genomics research, gut microbiota, and trans-omics have provided novel perspectives for the study of diabetes risk factors.