It was suggested that hyperinsulinemia contributes to cancer development through direct effects of insulin on growth-promoting signaling, and indirectly through the effects of prolonged hyperinsulinemia that increase the availability of bioactive IGF-1 via the reduction of circulating levels of the proteins (IGF binding proteins) that normally bind IGF-1 and make it biologically unavailable. This evidence concerns the gene IGF1 and hyperinsulinism.