The activity of IGF-1 is regulated by IGF binding proteins (IGFBPs) which increase IGF-1 half life, and IGFBP-1 and IGFBP-2 are both decreased in obese subjects with hyperinsulinemia, increasing bioactive free IGF-1 which promotes cell growth and differentiation, thereby facilitating the development of hyperkeratosis and papillomatosis observed in AN [59]. This evidence concerns the gene IGF1 and Hyperinsulinemia.