In this study, we examine the association of genetic variants that abolish ANGPTL4 function with fasting glucose, oral glucose tolerance, and risk for type 2 diabetes in 58,124 individuals of European ancestry sampled from a large US health care population, and in 13 additional datasets comprising 82,766 type 2 diabetes cases and 498,761 controls. This evidence concerns the gene ANGPTL4 and type 2 diabetes mellitus.