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Diabetic peripheral neuropathy is a common complication of both type 1 and type 2 diabetes. The overall annual incidence of this condition is approximately 2%, according to the Diabetes Control and Complications Trial.1 Another study estimated that 7% of patients had neuropathy at the time they received a diagnosis of diabetes and that 50% of patients with diabetes for longer than 25 years had peripheral neuropathy.2  A later American study revealed similar findings, estimating that 47% of patients with diabetes eventually develop some sort of peripheral neuropathy.3

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Diabetic peripheral neuropathy is a significant source of morbidity and mortality and is implicated in approximately 50% to 75% of nontraumatic amputations.4 It has been defined as “the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes.”5 This article presents an overview of diabetic peripheral neuropathy, but it is important to remember that diabetes is not always the cause of nerve dysfunction in patients with diabetes in whom it develops. This article reviews the entities to be considered in the differential diagnosis when a patient with diabetes undergoes an evaluation for peripheral neuropathy; in addition, we review the risk factors for this condition, as well as pathophysiology, signs and symptoms, diagnosis, screening, and treatment of diabetic peripheral neuropathy.

Differential diagnosis

In making a diagnosis of diabetic peripheral neuropathy, it is important that the examiner consider a variety of entities because in 10% to 26% of patients with diabetes who experience peripheral neuropathy, another underlying cause may be present.6 Making the proper diagnosis requires a careful clinical evaluation and laboratory testing. Electrodiagnostic studies or nerve biopsy may be needed if the diagnosis remains unclear. Potential nondiabetic causes of peripheral neuropathy are listed in Table 1; however, this list is not exhaustive.

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Mechanisms underlying the development of diabetic peripheral neuropathy commonly cited in the literature include the polyol pathway, advanced glycation end products, and oxidative stress. In this section, each of these mechanisms is described briefly.

Which of the following do you most frequently recommend for managing chronic pain associated with diabetic peripheral neuropathy?

Polyol pathway. With prolonged hyperglycemia, excess glucose moves into the polyol pathway, where it is converted to sorbitol and fructose. The accumulation of sorbitol and fructose contributes to the structural breakdown of nerves, leading to the development of peripheral neuropathy.7

Advanced glycation end products. Also with prolonged hyperglycemia, the reaction of excess glucose with proteins, nucleotides, and lipids results in the production of advanced glycation end products. These play a role in disrupting nerve cell metabolism, leading to the development of peripheral neuropathy.8