IGFBP1 and Hyperinsulinemia: Hyperinsulinemia has been shown to have a direct effect on the liver, inhibiting the production of insulin-like growth factor-binding proteins 1 and 2 (IGFBP-1,-2), while stimulating the production of insulin-like growth factor-1 (IGF-1) and increasing the bioavailability of IGF-1 (51–53).