Pathogenetic Mechanisms and Clinical Manifestations of Diabetic Peripheral Polyneuropathy in Type 2 Diabetes Mellitus Xaydarova Xilolaxon Ravshan qizi, Xolmatova Gulxayo Azimjonovna-

Аннотация

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that has become one of the leading global health challenges due to its rapidly increasing prevalence and numerous long-term complications. Among these complications, diabetic peripheral polyneuropathy (DPN) is the most common neurological disorder, affecting approximately one-third to one-half of patients with diabetes. DPN is characterized by progressive degeneration of peripheral nerves resulting from complex metabolic, vascular, inflammatory, and neurodegenerative processes initiated by persistent hyperglycemia. The pathogenesis of diabetic peripheral polyneuropathy involves multiple interconnected mechanisms, including activation of the polyol pathway, excessive formation of advanced glycation end products, oxidative stress, mitochondrial dysfunction, chronic inflammation, endothelial impairment, and microvascular ischemia. These pathological changes ultimately lead to axonal degeneration, segmental demyelination, impaired nerve conduction, and irreversible neuronal damage. Clinically, diabetic peripheral polyneuropathy presents with distal symmetric sensory loss, paresthesia, burning pain, numbness, muscle weakness, impaired proprioception, and reduced tendon reflexes. Disease progression significantly increases the risk of diabetic foot syndrome, recurrent ulceration, infection, lower-limb amputation, and reduced quality of life. Early diagnosis using neurological examination, quantitative sensory testing, nerve conduction studies, and validated clinical scoring systems remains crucial for preventing irreversible complications. Current treatment strategies combine strict glycemic control with pathogenetic therapies, antioxidant agents, symptomatic pain management, lifestyle modification, and comprehensive foot care. Emerging therapeutic approaches targeting oxidative stress, neuroinflammation, mitochondrial dysfunction, and nerve regeneration offer promising opportunities for improving long-term outcomes. This review summarizes current knowledge regarding the epidemiology, pathogenetic mechanisms, clinical manifestations, diagnostic approaches, and modern therapeutic strategies for diabetic peripheral polyneuropathy associated with type 2 diabetes mellitus.