EPO and diabetes mellitus: Erythropoietin (EPO) is produced by renal interstitial fibroblasts, and the regulation of EPO production by interstitial fibroblasts involves oxygen sensing through hypoxia-inducible factor (HIF).8 In patients with diabetes, excessive glucose reabsorption overtaxes the proximal tubules, which increases the oxygen requirement and causes tubulointerstitial hypoxia.