C3 and Insulin resistance: Our focused investigation of early and late-stage human biopsy data confirmed consistent regulation of multiple “insulin-resistance-associated genes” in human DKD, including C3, CXCL1, CTSS, NRBF2, PFKFB3 and TFPI2. We provide further evidence that kidney inflammation, ER stress and glycoprotein metabolism are enhanced in DKD, which may be driven by cellular insulin resistance and highlight a previously under-appreciated discordance in the regulation of mitochondrial proteins vs. transcripts in the kidney.