The Ecuadorian Laron and Brazilian Itabaianinha cohorts with congenital mutations in the GH and GHRH receptors, respectively, both provide a unique and arguably the purest examples to evaluate the effects of chronic severe IGF-I and both severe GH and IGF-I deficiency, respectively, with severe hypoinsulinemia being the common denominator in both cohorts (151, 152) (Table 1; Figures 1F, 3). Here, GH1 is linked to Hypoinsulinemia.