To understand the etiology of early changes in IS and insulin secretion with perturbations in energy balance it is important to investigate healthy non-obese subjects, because a chronic disturbance in energy balance may increase visceral and liver fat and thus lead to impaired hepatic insulin clearance [9], chronic low grade inflammation [10] and elevated FFA levels [11] associated with IR and pathological hyperinsulinemia. This evidence concerns the gene INS and hyperinsulinism.