The hyperinsulinemia induced by insulin resistance is a hallmark of obesity and/or metabolic syndrome (167), and bioavailable IGF-I also increases in the obese state, possibly via hyperglycemia-induced suppression of IGFBP synthesis and/or hyperinsulinemia-induced promotion of hepatic GH receptor expression and IGF-I synthesis (168). This evidence concerns the gene IGF1 and obesity due to melanocortin 4 receptor deficiency.