The article discusses the Steno hypothesis, which suggests that albuminuria in Type 1 diabetes is not just an indicator of renal disease but also a new, independent risk marker for proliferative retinopathy and macroangiopathy. The authors propose that albuminuria reflects a widespread vascular process affecting the glomeruli, retina, and large vessel intima. They argue that this process is caused by genetically determined alterations in the composition of the extracellular matrix, particularly the loss of heparan sulfate proteoglycan, which is crucial for maintaining the integrity of the glomerular basement membrane and other vascular structures. The loss of heparan sulfate leads to increased vascular permeability and endothelial dysfunction, contributing to the development of albuminuria and its associated complications. The authors also highlight the role of genetic polymorphism in the enzymes involved in the metabolism of heparan sulfate proteoglycan, which may explain why only 35% of Type 1 diabetic patients develop albuminuria and why the prognosis is poor for those who do.The article discusses the Steno hypothesis, which suggests that albuminuria in Type 1 diabetes is not just an indicator of renal disease but also a new, independent risk marker for proliferative retinopathy and macroangiopathy. The authors propose that albuminuria reflects a widespread vascular process affecting the glomeruli, retina, and large vessel intima. They argue that this process is caused by genetically determined alterations in the composition of the extracellular matrix, particularly the loss of heparan sulfate proteoglycan, which is crucial for maintaining the integrity of the glomerular basement membrane and other vascular structures. The loss of heparan sulfate leads to increased vascular permeability and endothelial dysfunction, contributing to the development of albuminuria and its associated complications. The authors also highlight the role of genetic polymorphism in the enzymes involved in the metabolism of heparan sulfate proteoglycan, which may explain why only 35% of Type 1 diabetic patients develop albuminuria and why the prognosis is poor for those who do.