Diabetic Neuropathy: Mechanisms, Emerging Treatments, and Subtypes

摘要: Diabetic neuropathies (DNs) differ in clinical course, distribution, fiber involvement (type and size), pathophysiology, the most typical type being a length-dependent distal symmetric polyneuropathy (DSP) with differing degrees of autonomic involvement. The pathogenesis diabetic DSP is multifactorial, including increased mitochondrial production free radicals due to hyperglycemia-induced oxidative stress. Mechanisms that impact neuronal activity, function, membrane permeability, endothelial function include formation advanced glycosylation end products, activation polyol aldose reductase signaling, poly(ADP ribose) polymerase, altered Na+/K+-ATPase pump. Hyperglycemia-induced endoplasmic reticulum stress triggers several apoptotic processes. Additional mechanisms impaired nerve perfusion, dyslipidemia, redox status, low-grade inflammation, perturbation calcium balance. Successful therapies require an integrated approach targeting these mechanisms. Intensive glycemic control essential but insufficient prevent onset or progression DSP, disease-modifying treatments for have been disappointing. Atypical forms DN subacute-onset sensory (symmetric) motor (asymmetric) predominant conditions are frequently painful generally self-limited. DNs major cause disability, associated reduced quality life mortality.