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.