Using the TODAY study, one of the largest studies on treatment and natural history of pediatric T2D to our knowledge, we chose to study 3 GH mediators: (1) IGF-1, the primary mediator of GH action; (2) GHR, a surrogate of GH bioavailability and action; and (3) IGFBP-1, a regulator of IGF-1 bioavailability and potential mediator of insulin sensitivity. The gene discussed is INS; the disease is type 2 diabetes mellitus.