Patients with type 2 diabetes mellitus often experience microvascular complications, including diabetic retinopathy, nephropathy, and neuropathy. Despite advances in glucose-lowering treatments, these complications remain a significant clinical and financial burden worldwide. Their pathogenesis is influenced by genetic polymorphism and advanced glycation end products (AGEs). Chronic metabolic stress leads to the formation of AGEs via oxidative and nonenzymatic glycation. AGEs bind to the AGE receptor (RAGE) and actively cause microvascular damage. This occurs through endothelial dysfunction, amplification of oxidative stress, protein cross-linking, and inflammatory activation. Genes controlling AGE production, AGE-RAGE signaling, oxidative stress responses, endothelial nitric oxide bioavailability, and extracellular matrix remodeling affect individual susceptibility to AGE-mediated microvascular damage. Elevated AGE load and genetic polymorphisms influence metabolic memory, microvascular injury, and redox signaling. This review article outlines the molecular mechanisms involving AGEs, genetic polymorphisms, and microvascular complications. Understanding AGE biology and genetic risk analysis could support management of diabetic microvascular complications and foster personalized medicine and preventive approaches beyond traditional glucose-centric frameworks.
Sarangi et al. (Sat,) studied this question.