IGFBP1 and hyperinsulinism: Under conditions of IR, hyperinsulinemia leads to decreased hepatic production of IGF-binding proteins 1 and 2 (IGFBP1/2) and increased tissue bioavailability of free IGF-1 and IGF-2, thus enhancing the activation of intracellular mitogenic signaling pathways at the expense of essential metabolic pathways in pre-malignant and malignant cells [72,73,74].