Diabetic Autonomic Neuropathy

Aaron I. Vinik, MD, PhD.; Roy Freeman, MB, ChB.; Tomris Erbas, MD


Semin Neurol. 2003;23(4) 

In This Article


Hypotheses concerning the multiple etiologies of diabetic neuropathy include a metabolic insult to nerve fibers, neurovascular insufficiency, autoimmune damage, and neurohormonal growth factor deficiency.[1] Hyperglycemic activation of the polyol pathway leading to accumulation of sorbitol and potential changes in the NAD:NADH ratio may cause direct neuronal damage and/or decreased nerve blood flow.[11] Activation of protein kinase C induces vasoconstriction and reduces neuronal blood flow. Increased oxidative stress with increased free radical production causes vascular endothelium damage and reduces nitric oxide bioavailability.[12,13] Excess nitric oxide production may result in formation of peroxynitrite and damage endothelium and neurons, a process referred to as nitrosative stress.[14,15] In a subpopulation of individuals with neuropathy, immune mechanisms may also be involved.[16] Reduction in neurotrophic growth factors, deficiency of essential fatty acids, and formation of advanced glycosylation end products (localized in endoneurial blood vessels) also result in reduced endoneurial blood flow and nerve hypoxia with altered nerve function.[17,18,19] The result of this multifactorial process may be activation of polyadenosine diphosphate ribosylation depletion of adenosine triphosphate, resulting in cell necrosis and activation of genes involved in neuronal damage.[20,21]


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