Briefly, an inverse correlation between IGF-1 (IGF-1/IGFBP-3 ratio) circulating levels and several markers for obesity, MetS, T2D, and CVD has been found; and thus, it could indicate that low circulating levels of IGF-1 can lead to MetS and raise the risk for CVD and T2D. This evidence concerns the gene IGFBP3 and obesity due to melanocortin 4 receptor deficiency.