Cauchi et al [59]found that the expression of TCF7L2 gene was downregulated in obese subjects developing T2DM and they then brought forward a hypothesis of a potential interaction between TCF7L2 and Calpain-10 by a supporting material [114] that suggested that the Calpain system was involved in the constitutive regulation of β-catenin signaling functions. This evidence concerns the gene TCF7L2 and type 2 diabetes mellitus.