While the above evidence suggests that loss of Tcf7l2 from the β cell is likely to impair insulin production, and hence increase T2D risk, adult Tcf7l2 knockout mice show reduced hepatic glucose production during fasting and improved glucose homeostasis when maintained on a high fat diet (31); loss of Tcf7l2 signalling in the liver is associated with lowered expression of genes involved in glucose metabolism in this tissue (31,39). This evidence concerns the gene TCF7L2 and type 2 diabetes mellitus.