Physician's Weekly Article - Diabetic Neuropathy: From Diagnosis to Treatment

       Physicians can significantly improve quality of life and prevent amputations, falls, and fractures in patients with diabetes by making greater efforts to catch diabetic neuropathy early. Therapies are also available to manage the complication.

      According to the American Diabetes Association (ADA), nearly 15 million people in the United States have been diagnosed with diabetes, and half of these patients will have symptomatic diabetic neuropathy. This figure may be substantially higher if sophisticated testing modalities, such as monofilament and vibration detection tests, are used more often. There are two common types of nerve damage: sensorimotor neuropathy and autonomic neuropathy. Sensorimotor neuropathy, also known as peripheral neuropathy, is quite common and can cause tingling, pain, numbness, or weakness in the feet and hands. Between 60% and 70% of people with the disease have mild to severe forms of neuropathy, resulting in impaired sensation or pain in the feet or hands, slowed digestion of food in the stomach, carpal tunnel syndrome, and other nerve problems. Almost 30% of people with diabetes over the age of 40 have impaired sensation in the feet. The disease causes more than just pain and discomfort; in severe cases, patients may eventually need their impaired extremity amputated. Neuropathy may be present in people with impaired glucose tolerance and impaired fasting glucose.

      Research has demonstrated that awareness of diabetic neuropathy among patients and providers is low (Table 1). “Despite the fact that many patients exhibit symptoms that are compatible with neuropathy,” explains Aaron I. Vinik, MD, PhD, FCP, MACP, “a large number of physicians fail to communicate with their patients that their symptoms may be related to neuropathy. There is a severe deficiency in the education of current healthcare providers about the nature of diabetic neuropathy. Physicians need a better understanding of the importance of identifying the symptoms, recognizing its presence on the physical examination, and treating the condition once it’s diagnosed.”

      Open the Dialogue

      Clinical investigations have established that the major causes of death in people with diabetes are heart attack and stroke. There are other complications to consider too, including neuropathy, hypertension, retinopathy, and nephropathy, among others. This can make it challenging for primary care physicians, says Dr. Vinik. “Most doctors have an average of just 7 minutes to spend with their patients so it can be overwhelming to tackle all of the complications associated with diabetes. However, the practices that are reasonably successful at managing these individuals tend to deal with complications one at a time, giving priority to any conditions that may be more severe or life threatening. One complication all physicians managing patients with diabetes should tackle is neuropathy because of its impact on disease-related outcomes.”

      The ADA has issued a simple questionnaire to identify symptoms related to diabetic neuropathy (Table 2). Dr. Vinik says it may help physicians open the lines of communication about the condition. “However, it will take more efforts by physicians to get the right diagnosis and provide treatment. The key is to create a behavioral change in both providers and patients. That requires additional surveillance efforts to monitor progression of neuropathy. A checklist can open dialogue with patients, but other interventions will be necessary. A key lesson learned from the Diabetes Control and Complications Trial is that constant one-on-one reminders for patients can have a great impact on outcomes. This lesson also needs to be applied to the management of diabetic neuropathy.”

      The Disease is Manageable

      To prevent further nerve damage in diabetic neuropathy, Dr. Vinik stresses that bringing blood glucose levels within the normal range is crucial. “Glucose monitoring, meal planning, exercise, and oral drugs or insulin injections are needed interventions to control glucose levels. Over time, maintaining lower glucose levels may lessen the impact of neuropathic symptoms while also helping prevent or delay the onset of further problems.”

      The FDA has approved two medications for the treatment of neuropathy within the past few years: duloxetine and pregabalin. While neither of these agents addresses the underlying mechanisms of the disease, Dr. Vinik says they do represent a significant advancement because they help manage pain symptoms. “In the past, physicians would ask themselves why they should make a diagnosis of diabetic neuropathy if all they can do is commiserate with their patients. Now, we have effective medications—the key is to educate physicians and their patients about appropriate use of these agents and how they can significantly improve quality of life.”

      A study presented at the ADA’s 67th Annual Scientific Sessions investigated two classes of lipid-lowering drugs—statins and fibrates—and their effects on the risk of diabetic neuropathy. Statins were found to reduce patients’ risk of developing peripheral neuropathy by 35%; use of fibrates correlated with a 48% risk reduction. Dr. Vinik noted that the benefits observed in the study were most likely class effects of these drugs, and their ability to reduce inflammation and oxidative stress likely played a role. “The findings were striking,” he says, “but it’s important to note that the mechanisms of these agents are still unknown. There was an association between use of these agents and a decreased risk of neuropathy, but we now need prospective, double-blinded, patient-controlled studies that further examine this association. Also, the agents used in the investigation were older medications, but the newer statins and fibrates as well as products that reduce oxidative and nitrosative stress may yield different results.”

      Dr. Vinik has indicated to Physician’s Weekly that he has or has had the following financial interest: Amgen, AstraZeneca, Athena, Boston Medical Technologies, Bristol-Myers Squibb, Eli Lilly, EMD Pharmaceuticals, Forest Laboratories, Fujisawa Healthcare, Genentech, GlaxoSmithKline, Guilford Pharmaceuticals, Knoll Pharmaceuticals, Medco, Merck, Mitsubishi Pharma America, NeurogesX, NEUROMetrix, Novartis, Paramount BioSciences, LLC, Pfizer, Recovexx, Regeneron Pharmaceuticals, Sankyo, Sanofi-Synthelabo, Sigma-Tau Pharmaceuticals, Synergy Biosciences, Takeda, TeraTechnologies, and Teva Pharmaceutical Industries.