Hyperglycemia and vascular outcome. Hyperglycemia activates multiple and complex pathogenetically relevant pathways. Inflammatory processes lead to a thickening of the basal membrane of microvessels and perivascular fibrosis resulting in microvascular endpoints in the most susceptible organs, such as renal insufficiency and retinopathy. The structural changes also result in functional impairment and a reduction in blood flow regulation, which in turn reduces macrovascular endothelial function ("Micro/Macro Interaction"). The loss of endothelial protection may lead to the subsequent development of atherosclerosis. The structural changes within the microcirculation may account for building up a "metabolic memory".