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Complications of Diabetes Mellitus: Neuropathy

Neuropathy is a particularly common diabetes complication, affecting approximately half of all diabetes patients. Distal symmetric polyneuropathy is the most common presentation. However, neuropathy can also involve the autonomic nervous system and individual nerves.

The disease may present with sensory loss, but also with paresthesia and dysesthesia in the affected areas. Pathogenesis may occur due to ischemia and metabolic factors, including advanced glycosylation end products. Progression is likely. If severe, neuropathy may lead to joint deformities and infections that ultimately require amputation.

Risk Factors

  • Poor blood glucose control. Good glycemic control helps prevent neuropathy, and improvement of previously poor glycemic control can improve neuropathic symptoms.10
  • Duration of diabetes.


The presence of distal symmetric polyneuropathy can be assessed with simple clinical tests. Altered sensation, whether vibration (128 Hz tuning fork), pain (pin–prick), temperature, or pressure (10–g monofilament at dorsal aspect of great toe), or absence of ankle reflexes suggests neuropathy. The use of more than one test increases diagnostic accuracy.1 Electrophysiologic studies such as nerve conduction tests can confirm the diagnosis.

The presence of autonomic neuropathy can be assessed by history and physical examination. Constipation, incontinence, erectile dysfunction, tachycardia, pupillary dysfunction, and orthostatic hypotension, among other abnormalities, suggest autonomic neuropathy.


Diabetes neuropathy is best addressed through primary prevention, which requires tight glycemic control. In cases of pre–existing neuropathy, symptoms may improve with diet and lifestyle changes, as noted below.

In addition to optimized glycemic control, foot care is essential. Properly fitted shoes, foot hygiene, daily foot inspection (special mirrors can help patients who have mobility problems), regular nail care (without cutting nails too short), and immediate consultation with a health care provider whenever an abnormality occurs are all important.

Medications also may help alleviate pain symptoms of diabetes neuropathy. Examples include:

  • Tricyclic antidepressants.
  • Capsaicin cream.
  • Anticonvulsants, such as carbamazepine and gabapentin. Phenytoin has shown inconsistent results, and other anticonvulsants are under study. Mexiletine may be substituted for carbamazepine, in consultation with a cardiologist, if pain persists. Pregabalin is structurally similar to gabapentin, but has a different mechanism of action.
  • Duloxetine, a dual serotonin and norepinephrine reuptake inhibitor.

Medications may treat autonomic symptoms, such as erectile dysfunction, gastric abnormalities, and incontinence. These treatments usually improve quality of life, but do not alter the disease course. 

Nutritional Considerations

A combination of a vegetarian diet and exercise may have particular value in treating neuropathy. In a study of 21 individuals with painful neuropathy, symptoms completely disappeared in 17 and improved in the remainder using a vegan diet along with regular walking.37 Evidence suggests that in addition to the effect of vegetarian diets on glycemic control, their effect on body weight, blood pressure, lipids, and blood rheology may be relevant to neuropathy.38,39 Future clinical trials are needed to determine the value of dietary modifications for this condition.

In addition to the benefits of a diet and exercise regimen, some nutritional supplements have shown potential benefit. Alpha–lipoic acid, in both intravenous and oral forms (≥600 mg/day), appears to be safe and effective for improving symptoms of diabetic neuropathy in clinical trials.40,41 Long–term safety and efficacy have yet to be established. Although an antioxidant action is presumed, alpha–lipoic acid also improves microcirculation.42 Other supplements under investigation for neuropathy treatment include gammalinolenic acid,43,44 carnitine,45, 46 and magnesium.47


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