INS and Insulin resistance: Undoubtedly, central accumulation of body fat is associated with insulin resistance [37], which has a role in the aetiology of biliary tract cancers (including GBC) [38]; insulin could stimulate the insulin receptor or the IGF-1R, activate their intrinsic tyrosine kinase activity, induce the production of lipid messengers by the phosphatidylinositol 3-kinase, and then trigger AKT-mammalian target of rapamycin pathway regulating cell growth and differentiation and the Ras-Raf-MEK-MAPK pathway inducing cell proliferation [39].