The atherosclerotic process and its exacerbation by diabetes

The excess of glucose appears to play an important and specific role in the genesis of macroangiopathy in diabetics. Activation of protein kinase-C, t he sorbitol pathway, and AGE formation are thought to be the major pathways linking the degree of glycaemic compensation with the pathogenetic process of macrovascular disease. HSPG is likely to be a key element in this proce ss since it is a regulator of endothelial permeability, vascular antithromb otic capacity, insulin sensitivity (with respect to lipoprotein lipase avai libility), and vascular extracellular matrix content and smooth-muscle-cell activation. Loss of HSPG is suggested clinically by the presence of microa lbuminuria, to the development of which diabetic control also contributes s ignificantly. However, genetic factors also seem to be involved. Much more insight into the precise mechanismus is necessary to unravel the cellular a nd molecular chains of events for the premature and accelerated atheroscler osis in diabetic patients.