Clinical diabetic nephropathy is characterized by an earlier functional phase in which hyperglycaemia is accompanied by an increased glomerular filtration rate and microalbuminuria; the persistence of this high-flow and high-pressure state, added to a poor control of hyperglycaemia, fosters renal damage and proteinuria, accompanied by a decline in glomerular filtration rate and progression to end-stage renal disease. In this review, we present glucose transporter 1 (GLUT-1) as a novel link that connects the glomerular hyperfiltration (hypertension) state and the complex cascade of events that leads to nephropathy. The interplay between angiotensin II and nitric oxide, and its interactions with reactive oxygen species, are also discussed, in an attempt to provide an integrated view of the pathophysiology of diabetic nephropathy.