In cross-sectional studies in humans with insulin resistance of relatively short duration, increased hybrid receptor expression is not seen,10 whereas patients with type 2 diabetes have down-regulation of IR and increased expression of hybrids.11 The temporal relationship between expression of IR, IGF-1R and hybrids in obesity and their pathological correlates in the vasculature in vivo remains unclear. This evidence concerns the gene INSR and obesity due to melanocortin 4 receptor deficiency.