AGEs; Cytokines; Hexosamine pathway; Inflammation; Nephropathy; Nephropathy; Polyol pathway; Reductive stress; Retinopathy; Vascular complications
The distinctive characteristics of diabetes such as hyperglycemia, chronic oxidative stress, and inflammation contribute to the development of microvascular (neuropathy, retinopathy, and nephropathy) and macrovascular complications of this disease. Episodes of postprandial and persistent hyperglycemia drive several mechanisms conducting to endothelial dysfunction and vascular complications, including reductive/oxidative stress, activation of polyols and hexosamine pathways, protein kinase C activation, formation of advanced glycation end products (AGEs), and nitric oxide (NO) reduced availability. As a consequence, chemical modifications of macromolecules alter their functions, some toxic metabolites are accumulated (methylglyoxal, sorbitol), and pro-inflammatory (TNFa, IL-1ß, IL-6, cyclooxygenase-2, and monocyte chemoattractant protein 1), pro-fibrotic (TGFß and collagen), and pro-thrombotic (PAI-1) proteins are upregulated. These changes lead to endothelial dysfunction, cell death, fibrosis, altered vascularization, and tissue damage, which finally are associated with severe health problems (neuropathic pain, loss of extremities, retinal vascularization and blindness, glomerulosclerosis and renal failure, atherosclerosis, cardiomyopathy, and heart failure). Targeting some of these mechanisms may improve the strategies for the prevention and treatment of vascular complications. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2019, 2023.