INS and Insulin resistance: As podocytes are insulin-sensitive cells, with both insulin resistance and excessive signalling activity being detrimental to cell function [26, 27, 43], it is plausible that the reduced glomerular IGFBP-1 observed early in type 2 DKD could also be a consequence of excessive insulin signalling, prior to the development of podocyte insulin resistance, in this regard mirroring the regulation of IGFBP-1 expression in the liver early in diabetes.