Weyer et al, showed that serum adiponectin concentrations were more closely related to fasting insulinemia and to the rate of insulin-stimulated glucose disposal, a direct measure of insulin sensitivity, than to percent body fat and the 2-hr glucose concentration suggesting that hyperinsulinaemia and/or insulin resistance might be a major determinants of the hypoadiponectinemia in obesity and type 2 diabetes. This evidence concerns the gene ADIPOQ and obesity due to melanocortin 4 receptor deficiency.