Common variants in the TCF7L2 gene are strongly associated with risk of developing type 2 diabetes mellitus (T2DM) in multiethnic cohort.There are pronounced tissue-specific differences in the splicing of TCF7L2.The expression of TCF7L2 in islets of patients with T2DM is increased.Variants in the TCF7L2 gene are associated with impaired insulin secretion.The increased risk of T2DM conferred by variants in TCF7L2 may involve in impaired insulin secretion induced by incretin such as GLP-1,or impaired conversion of proinsulin to insulin,and/or Wnt signaling activation.So research in TCF7L2 gene as the strongest genetic contributor to risk of T2DM can yield novel insights into pathophysiology and pathogenesis of T2DM and exploration of new target in diabetic therapy.