Recognizing and Treating Diabetic Peripheral Neuropathy

LAS VEGAS, NV—Charles E. Argoff, MD, from Albany (NY) Medical Center, discussed diabetic peripheral neuropathy (DPN), at PAINWeek 2012, including how to recognize and treat it.

Among people with diabetes, DPN is the most common complication and greatest source of morbidity. While 60–70% of those with diabetes develop DPN, only one in four patients are diagnosed with the condition. The highest risk of developing DPN occurs in patients with poorly controlled diabetes, although other risk factors are unclear.

Quality of life is heavily impacted by DPN, which results in decreased activity, increased morbidity, increased medication usage and burden on the healthcare system, with a cost of up to $13.7 billion dollars annually. Many, but not all, DPN patients experience pain, explained Dr. Argoff. This pain is often described as a burning sensation, pins and needles, tingling, shooting, deep aching, jabbing, stabbing, or cold. Allodynia, which is pain in response to stimuli that is normally not painful, may also occur.

The nerve dysfunction of DPN is considered a microvascular complication of type 2 diabetes, similar to retinopathy and nephropathy. While the exact pathogenesis of DPN is unknown, its causes may include nerve hypoxia and ischemia, oxidative stress, and metabolic etiologies.

The most common form of DPN is distal symmetrical polyneuropathy, which can be sensory or sensorimotor, can involve large or small fibers, and has a stocking-glove pattern. Normally, sensory symptoms precede motor symptoms, and small-fiber dysfunction precedes large-fiber dysfunction.

Dr. Argoff said that large-fiber DPN is characterized by painless paresthesias, impairment of vibration, possible proprioceptive dysfunction, altered touch and pressure sensation, loss of ankle reflex, and abnormal nerve conduction studies. It is also associated with cardiovascular risk factors. The characteristics of small-fiber DPN include burning pain, loss of pain and temperature sensations, and normal nerve conduction studies. Emerging diagnostic tools include epidermal nerve fiber analysis and quantitative sensory testing. Dr. Argoff suggested that clinicians watch their patients walk at each visit to observe how their condition may be affecting their gait, along with inquiring about activities of daily living, sleep, depression, and obstacles to successful exercise.

When assessing patients with DPN, Dr. Argoff said to consider that DPN could co-occur with other causes of neuropathy, such as alcohol abuse, neurotoxic medication, vitamin deficiency, and renal failure. Assessment tools include monofilament testing and the use of a 128-Hz tuning fork on the bony prominence of the dorsal great toe. Assessment with a tuning fork can determine if the vibration feels normal, impaired, or absent to the patient. Further, nerve conduction studies, which are sensitive and specific for large-fiber dysfunction, typically reveal demyelination and the loss of axons.

Controlling A1c levels is critical in DPN, as a linear relationship exists between A1c levels and DPN. Also, tightly regulating blood pressure is effective at reducing microvascular aggregates.

Treatment for DPN must be individualized, considering that neuropathic pain is a heterogeneous condition. When treating DPN, the goals are to treat both symptoms and the underlying pathogenic mechanisms. No treatments for the underlying pathogenic mechanisms are FDA-approved, however, both alpha-lipoic acid and acetyl-L-carnitine have had promising results in clinical trials. Dr. Argoff advises his patients to take alpha-lipoic acid 600mg, and noted it has good tolerability with reasonable evidence to support its use.

To treat the symptoms of DPN, only duloxetine and pregabalin are FDA-approved. Pregabalin reduced pain by >50% in 395 of patients, which was favorable compared with 15% for placebo. Also, pregabalin improved the sleeplessness that is associated with DPN. Other agents that are effective, although not FDA-approved for DPN pain, include tricyclic antidepressants, gabapentin, topical lidocaine, certain opioids, topiramate, and other anticonvulsants. Treatments must be individualized, and patients may require a combination of several medications. Generally, when agents are combined, distinct pharmacologic classes should be represented.