Visceral adiposity, hepatic insulin resistance and chronic inflammation in obesity and type 2 diabetes have an impact on the IGF system that reflects the heterogeneity of these disorders and includes an altered relationship between IGFBP-1 and insulin, leading to IGFBP-1 concentrations that are inappropriately normal or elevated. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.