This model can explain the insulin resistance and frequent T2D seen in conditions such as acromegaly, where GH levels are persistently raised due to a functional somatotrope tumor,44 and the striking protection from T2D seen in patients with Laron dwarfism, whose markedly reduced circulating IGF-1 levels are due to biallelic loss-of-function (LoF) mutations in the GH receptor.45 This evidence concerns the gene GHR and type 2 diabetes mellitus.