INS and obesity due to melanocortin 4 receptor deficiency: It is possible that this is due to the presence of obesity rather than the primary hyperinsulinaemia described by Federici et al.23 An additional explanation could be the use of different tissues – muscle samples as studied by Federici et al may show more sensitivity to hybrid formation following perturbations in insulin and glucose, whereas vascular tissue as in this study may be more sensitive to changes in IGF-1 levels.