Decoding diabetic peripheral neuropathy: pathogenesis, diagnostic breakthroughs, and emerging therapeutics- a comprehensive review
Abstract
Diabetic Peripheral Neuropathy (DPN) is a common and debilitating complication of diabetes, characterized by peripheral nerve dysfunction after excluding other potential causes. Diabetic distal symmetric polyneuropathy (DSPN) is the most prevalent form, affecting 10-15% of newly diagnosed Type 2 Diabetes Mellitus (T2DM) patients, with prevalence rates exceeding 50% in those with more than 10 years of diabetes. The primary symptoms include bilateral limb pain, numbness, and paresthesia, which in severe cases can lead to foot ulcers and even amputation. Although the precise pathogenesis remains incompletely understood, hyperglycemia, lipid metabolism disturbances, and insulin signaling abnormalities are recognized as key contributors, initiating a cascade of pathophysiological changes that affect myelinated and unmyelinated nerve fibers, perikaryon, neurovascular structures, and glial cells. Moreover, impaired insulin signaling inhibits axonal repair and promotes neuronal apoptosis. Recent studies have uncovered several mechanisms underlying DPN, including oxidative stress, microvascular damage, neuroinflammation, mitochondrial dysfunction, and cellular oxidative damage. Additionally, a reduced oxygen supply through vasa nervorum and inflammatory processes further exacerbate nerve injury. The most common clinical presentation is symmetrical painful neuropathy, especially affecting the lower limbs. Understanding the interactions between these mechanisms is crucial for advancing diagnostic and therapeutic strategies. This review synthesizes the latest research on DPN’s pathophysiology and diagnostic challenges, offering novel insights into the disease’s underlying mechanisms and the potential for targeted interventions to improve patient outcomes.
Keywords:
Apoptosis, Diabetic Peripheral Neuropathy, Foot ulcers, Neuroinflammation, Type 2 Diabetes MellitusDOI
https://doi.org/10.70604//ijzels.v1i2.15References
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