Oxidative stress. Oxidative stress and the production of free radicals also are involved in the development of peripheral neuropathy. Free radicals may damage blood vessels, leading to ischemia in the nerve cells, and facilitate the production of advanced glycation end products, which in turn contribute to the development of peripheral neuropathy.9

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Signs and symptoms

The peripheral nervous system can be damaged by diabetes in numerous ways. Most commonly, patients with diabetes experience peripheral neuropathy. Symptoms typically include lower-extremity weakness, in addition to tingling, pain, burning, and electrical and stabbing sensations with or without numbness. Patients may describe a sensation that feels like socks bunching up in their shoes. These symptoms usually begin in the feet and move proximally (stocking-and-glove distribution). The symptoms present symmetrically and appear sensory in nature. Over time, allodynia (painful sensations in response to innocuous stimuli) and hyperalgesia (increased sensitivity to painful stimuli) may develop.10 Diabetic peripheral neuropathy is insidious in nature and can lead to foot ulceration. These ulcerations can be slow to heal, become infected, and lead to amputation. Unfortunately, patients with peripheral neuropathy may not report their symptoms, and often, fewer than half of patients are treated for their pain. Table 2 provides an overview of some of the common signs and symptoms of diabetic peripheral neuropathy.

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Risk factors

A variety of risk factors for the development of diabetic neuropathy are known (Table 3). According to the Diabetes Control and Complications Trial,1 hyperglycemia is one of the most significant risk factors. Others include a long duration of diabetes, large total exposure to hyperglycemia, male sex, advanced age, elevated lipid levels, elevated blood pressure, kidney disease, cigarette smoking, overweight, increased height, and a high level of exposure to other potentially neurotoxic agents, such as ethanol. Genetic factors, such as the HLA-DR3/4 phenotype and apolipoprotein E genotype, are also associated with a risk for diabetic peripheral neuropathy.

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