These seemingly contradictory associations between IGF-1 levels and CVD (risk factors) can be explained by a phenomenon called ‘IGF-1 resistance’, which is observed in dysmetabolic states like obesity, hypertension and chronic kidney failure [44], and is characterized by a diminished maximal response to IGF-1 (with or without additional changes in receptor sensitivity) [45, 46]. This evidence concerns the gene IGF1 and obesity due to melanocortin 4 receptor deficiency.