Although tissue insensitivity to insulin is the main contributor to IR, changes in insulin secretion and degradation have also been established in CKD.9 In particular, a recent study using the gold standard high-dose hyperinsulinemic-euglycemic clamp to investigate peripheral insulin sensitivity showed disturbances in insulin clearance as a principle characteristic distinguishing patients with nondiabetic CKD to controls.10 This study demonstrated profound alterations in the plasma metabolome response to insulin in patients with CKD compared to controls. Here, INS is linked to chronic kidney disease.