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Michael Polydefkis, M.D. M.H.S. and Donna Westervelt
12-21-2010
- Diabetic Peripheral Neuropathy (DPN): The most common neuropathy in diabetes, DPN is a length-dependent, sensory predominant peripheral neuropathy in which symptoms begin at the distal ends of the longest peripheral nerves (those that extend to the feet).
- Neuropathy in a person with diabetes may not be due to diabetes alone (Gorson).
- DPN prevalence varies from ~25% when assessed with questionnaires or simple examination to ~70%, when assessed using peripheral nerve tests such as autonomic function testing, nerve conduction testing, and quantitative sensory testing (Laughlin).
- Risk factors for DPN include poor glycemic control, duration of diabetes and vascular risk factors such as hypertension, elevated cholesterol, tobacco use and hypertryglyceridemia. Height and BMI also increase risk.
- DPN can occur early in diabetes, can be a presenting symptom, and can be associated with IGT.
- DPN is an established risk factor for amputations.
- The diagnosis of DPN is made on the basis of patient history, physical examination and diagnostic testing (England).
- Neuropathy usually begins in the toes and feet and spreads in a caudal to rostral fashion.
- Bedside sensory examination tests include monofilament, vibratory threshold, proprioception and pin prick tests. These assess different populations of sensory nerves. Loss of sensation in the toes and feet can be detected by each of these measures though the exact sequence can vary among individual patients.
- Loss of monofilament sensation (called loss of protective sensation) is an established risk factor for diabetic foot ulceration and subsequent amputation.
- Electrophysiological changes associated with diabetic peripheral neuropathy are measured with the nerve conduction test. It assesses large, myelinated sensory nerve fibers. A reduction in conduction velocity represents demyelination of large sensory axons while a reduction in nerve amplitude represents axon loss. It is possible for patients to have DPN and show normal results to this test because the tested fibers comprise only 20% of sensory nerve fibers.
- Punch skin biopsy is a relatively non-invasive test that requires 3mm skin punches to be taken. After histological processing, nerve fibers can be viewed. This test assesses small unmyelinated sensory nerve fibers and is a more sensitive measure of DPN than NCV testing (Griffin).
- Patients with IGT-associated DPN typically have abnormal skin biopsies that gradually involve large myelinated nerve fibers.
- Other diagnostic tests include quantitative sensory testing and detailed autonomic testing.
- Symptoms of DPN are symmetric, sensory and follow the caudal to rostral (foot to head) pattern. They vary widely from pronounced neuropathic pain, to little or no symptoms.
- Sometimes, an absence of sensation (numbness) is the predominant symptom, while other patients experience pronounced neuropathic pain.
- The pain of DPN is often described as burning, which can be associated with electric-like shocks.
- Patients also complain of a 'pins and needles' tingling that can be painful and annoying. Symptoms often made worse by prolonged standing or walking, are typically worse at night, and can be associated with allodynia that interferes with sleep.
- When symptoms reach the level of the knee in the lower extremities, symptoms in the fingers also usually begin to develop. Similarly, patients can develop symptoms over the anterior chest and abdomen when symptoms extend to the level of the elbows in the upper extremities. It would not be typical, however, to have symptoms in the hands but not feet.
- Patients can develop little or no DPN despite years of poorly controlled diabetes, while others develop signs and symptoms very early.
- The best preventative treatment for DPN is improved glycemic control. This will result in a slower rate of progression, and can also stabilize existing peripheral neuropathy.
- Improved glycemic control is unlikely to result in reversal of DPN; peripheral nerve function will not usually improve, once lost, although many patients note reduced pain levels with improved glycemic control.
- There is no FDA approved agent for the treatment, reversal, or stabilization of DPN although as a class, aldose reductase inhibitors (ARI) have shown promise. Agents within this class have been withdrawn in some countries due to hepatic or renal toxicity, while another is actively used in Japan. There is a large trial of an ARI compound, ranaristat, underway in the US and Europe (Oates).
- Two FDA approved agents are available for treatment of DPN-associated neuropathic pain- duloxetine and pregabalin as well as several classes of agents such as tricyclic antidepressants and opiates that have consistently demonstrated efficacy. See treatment of neuropathic pain module.
- Follow up of a patient with DPN requires routine, detailed examinations as well as repeated counseling and education.
- Be aware of other causes of neuropathy, and other diseases that can affect people with diabetes and lead to rapid progression of neurologic disability. If rapid changes occur, consider vitamin deficiencies, toxic exposures or autoimmune neuropathies.
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Metformin has been implicated to interfere with vitamin B12 absorption and B12 levels should be checked (Bell) to rule out B12 deficiency as a cause of neuropathy.
- Diagnostic testing consisting of screening laboratory studies, NCV testing and/or punch skin biopsies are appropriate to confirm confirm the diagnosis of DPN and rule out other causes. Other conditions such as lumbar radiculopathy, focal nerve entrapments, intrinsic foot disorders (plantar fasciitis or arthropathies) can mimic DPN.
- Re-evaluate if distinct change of symptoms: development of weakness, changes in neuropathic pain, development of a non-length-dependent pattern.
- Focus on glycemic control as well as vascular risk factors, since hypertension and elevated cholesterol also contribute to DPN (Tesfaye).
- Studies have shown an association between statin-type medications and peripheral neuropathy, although there is not enough evidence to justify discontinuing use in patients with DM, given the cardiovascular benefits of statins.
- Surgical decompression of nerves has been proposed as a treatment for DPN. With proven focal demyelination due to compression, surgical decompression is clinically indicated; but it is not clear that surgical decompression of nerves improves symptoms of DPN itself.
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