Current concepts in targeted therapies for the pathophysiology of diabetic microvascular complications.
Microvascular complications characterized by retinopathy, nephropathy, and neuropathy are highly prevalent among diabetics. Glycemic control has long been the mainstay for preventing progression of these complications; however, such control is not easily achieved. Currently, alternative adjunctive approaches to treating and preventing microvascular damage are being undertaken by targeting the molecular pathogenesis of diabetic complications. This review summarizes the specific pathogenic mechanisms of microvascular complications for which clinical therapies have been developed, including the polyol pathway, advanced glycation end products, protein kinase c, vascular epithelium growth factor, and the superoxide pathway. The review further focuses on therapies for these targets that are currently available or are undergoing late-stage clinical trials.
Cumbie
Brian C
BC
Division of Endocrinology, Diabetes & Medical Genetics, Department of Medicine, Medical University of South Carolina, Charleston 29425, USA.
Hermayer
Kathie L
KL
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D048909:Diabetes Complications / Q000503:physiopathology* / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors; D006801:Humans; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D017382:Reactive Oxygen Species; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors
D000975:Antioxidants; D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D042442:Vascular Endothelial Growth Factors; D000449:Aldehyde Reductase; D011493:Protein Kinase C