Smart Ways to Manage Neuropathy Neuropathy, a Common Complication of Diabetes, Was Once Thought to Be Untreatable

PAIN APRIL/MAY 2018 BY GINA SHAW Smart Ways to Manage Neuropathy Neuropathy, a common complication of diabetes, was once thought to be untreatable. Today, a variety of treatments and strategies are available to ease the discomfort.

By the time she was in her early fifties, Kathy Zimmerman knew she had to make a change. The computer software engineer in Springfield, VA, had steadily gained weight over the years until she was morbidly obese and had developed type 2 diabetes. "I had a number of other health problems, too, including arthritis and high blood pressure," says Zimmerman, now 67. Then she started noticing numbness, tingling, and burning in her feet and was told she had diabetic peripheral neuropathy—nerve damage caused by exposure to high blood sugar and the other metabolic consequences of diabetes. Although researchers are still investigating exactly how diabetes damages nerve cells, many believe it may be a result of metabolic changes that increase inflammation—changes that are also exacerbated by high cholesterol, high blood pressure, obesity, and smoking. Illustration by Jun Cen

All Too Common Nearly 60 percent of all people with diabetes have some form of neuropathy, most often in their feet. It affects people with both type 1 and type 2 diabetes: About 20 percent of type 1 patients develop it after 20 years, and about 50 percent of type 2 patients develop it after just 10 years. (In type 1 diabetes, the body's immune system destroys the cells needed to produce insulin, which means the pancreas cannot process the sugar, known as glucose, it needs to produce energy. In type 2, the pancreas isn't able to use insulin properly and may also produce less insulin over time.) Even as many as 30 percent of people with impaired glucose tolerance, known as prediabetes, may have neuropathy. It is more common in people who, like Zimmerman at the time, are overweight, over 40, and have high blood pressure.

In early 2005, Zimmerman underwent bariatric surgery and her diabetes went into remission. "Prior to the surgery, my hemoglobin A1C [a measurement of blood sugar] was averaging about 6.4, which is pretty low for someone with diabetes, but combined with my weight, it was a problem. After the surgery, the highest it's ever been is a 5, and most recently, it was a 4.2. And while the neuropathy still ﬂares up sometimes, I notice it much less often and I have found ways to control it." Normal A1C levels are below 5.7 percent over a period of three months; prediabetes is 5.7 to 6.4; and diabetes is 6.5 percent and above, according to the National Institute of Diabetes and Digestive and Kidney Diseases.

Prevent Progression Current medications cannot reverse the nerve damage of diabetic neuropathy once it is established. "But we do have effective prevention strategies for neuropathy, particularly for patients with type 1 diabetes, as well as symptomatic treatments to manage the pain," says Rodica Pop-Busui, MD, PhD, professor in the department of internal medicine, division of metabolism, endocrinology, and diabetes (MEND) and co-director of the Neuropathy Center at the University of Michigan. She's also the lead author of a new position statement on diabetic neuropathy from the American Diabetes Association (ADA).

For people with type 1 diabetes, research has consistently demonstrated that keeping hemoglobin A1C levels under tight control is the most important and most effective strategy for preventing diabetic neuropathy. "Large clinical trials have shown that intensive glucose control-targeting an A1C of under 7-reduces the risk of developing neuropathy by as much as 78 percent," says Dr. Pop-Busui. Once neuropathy has developed, glucose control is important to keep it from progressing.

But for people with type 2 diabetes, the research is less clear as to whether glycemic control by itself can help control neuropathy. "I personally believe that diabetic neuropathy is actually two diseases: one for type 1 patients and one for patients with prediabetes and type 2 diabetes," says Eva Feldman, MD, PhD, FAAN, an endowed professor of neurology at the University of Michigan and a co-author of the ADA statement. "For patients with prediabetes and type 2 diabetes, the clinical studies suggest that optimal glycemic control alone provides only a very small beneﬁt, if any beneﬁt at all," she says, adding that doctors need to address other factors as well, such as high cholesterol, obesity, hypertension, and smoking.

Manage Pain with Medication Currently, three drugs are approved by the US Food and Drug Administration to treat pain from diabetic peripheral neuropathy: duloxetine (Cymbalta), pregabalin (Lyrica), and tapentadol (Nucynta, Palexia, and Tapal). "The evidence suggests that other drugs not speciﬁcally approved for this indication, but commonly used, also may be effective," says Julie Waldfogel, PharmD, a clinical pharmacy specialist in pain and palliative care at Johns Hopkins Medicine in Baltimore, who co-authored a review of the available drug treatments for diabetic peripheral neuropathy that was published in Neurology in 2017. These other medications include tricyclic antidepressants, venlafaxine (Effexor), oxcarbazepine (Trileptal), tramadol (Ultram), and alpha-lipoic acid.

"None of these agents is a slam dunk," says A. Gordon Smith, MD, FAAN, professor of neurology and chair of the department of neurology at Virginia Commonwealth University. "None of them is effective in every patient, so there's a trial-and-error process for ﬁnding the right medication."

It's also important to ﬁnd a physician skilled in managing neuropathic pain, says Dr. Smith. "Doctors must be aware of other medical and psychosocial problems that can affect how we manage that pain, like sleep and mood disturbances," he says. "Most people with diabetes are primarily managed by a family physician or an endocrinologist, but this is an area of diabetes care where neurologists have a lot to offer, because many of them are familiar with managing neuropathic pain."

Adopt Healthy Habits Tight glycemic control and appropriate medication are only part of the puzzle of managing diabetic neuropathy and pain. The other part is following a balanced diet, exercising regularly, and quitting smoking. In patients with prediabetes, research has shown that a healthy diet and exercise can slow the progression of prediabetic neuropathy or even improve it.

"Multiple small studies suggest that lifestyle modiﬁcations like these are helpful in managing symptoms and potentially slowing the rate of progression in both types of diabetes," says Dr. Smith.

That's what Lisa Lake has found. The 50-year-old public relations professional and single mom from Greenbelt, MD, ﬁrst developed type 2 diabetes in her late thirties while pregnant with her son. After noticing sharp pain and stiffness in her feet over the last three to four years, she mentioned them to her doctor, who conﬁrmed she had diabetic neuropathy. Since then, Lake has found that exercise is one of her best weapons against it. "I always feel better when I'm walking," she says. "Sometimes I have to really put mind over matter when all I want to do is sit around and watch TV. I also try to go to yoga whenever I can. When I'm taking those classes regularly, even when I can barely do the moves, I don't notice a single thing hurting."

Kathy Zimmerman agrees. "I walk as much as I can, and I work a lot in my garden, digging out bamboo," she says. "I do shoulder, back, and leg exercises. And I've taken control of my eating, so when I have a craving for sweets, I eat fruit instead of bingeing on sugar. You can't completely reverse neuropathy—there are still days when the neuropathy ﬂares up, like when my feet get very cold—but I manage my health carefully and do my best to eliminate all the sources of pain that I can."

Don't Miss e Signs Of Neuropathy Diabetic peripheral neuropathy is easy to miss. As many as half of all people with neuropathy don't experience pain, so they don't realize their feet are numb. This increases the risk of infections and ulcers from missed cuts and blisters, as well as the risk of amputation. A comprehensive neurologic examination, performed by a health care practitioner at least once a year, is essential to check for peripheral neuropathy.

You should also talk with your doctor if you notice signs such as these: Numbness in hands or feet, or a tingling or burning sensation. Sudden shooting pains, or a feeling of cramping in hands or feet. Loss of balance or coordination, or noticing that you're dropping things more frequently. Dizziness when you change positions quickly. Changes in the way your feet look. Unexplained sores or blisters on hands or feet. Unusual responses to heat or cold, such as a warm cup of coffee feeling painfully hot. Your feet and hands might also feel inexplicably hot or cold.

Important Resources For Diabetic Neuropathy Looking for more information and guidance on preventing or managing diabetic neuropathy and neuropathic pain? Try these resources:

The American Academy of Neurology includes information on treatment, prognosis, research, and resources on this website, BrainandLife.org .

Read the American Diabetes Association's position statement on diabetic neuropathy. View a symptom checklist, links to articles from Diabetes Forecast, and a PSA, at diabetes.org.

The Foundation for Peripheral Neuropathy offers support groups and healthy lifestyle information at foundationforpn.org. For a directory of neurologists with expertise in managing neuropathic pain, visit foundationforpn.org.

The National Institute of Diabetes and Digestive and Kidney Diseases has a section on diabetic neuropathies.

The National Institute of Neurological Disorders and Stroke conducts and supports research on diabetic neuropathy. For more information, visit ninds.nih.gov.

The Neuropathy Action Foundation is an advocacy organization for patients with all types of neuropathies. For more information, visit neuropathyaction.org.

Enroll In A Clinical Trial Several clinical trials are currently recruiting people with diabetic peripheral neuropathy for new research studies. Some are studying new or already approved medications for the management of neuropathic pain while others are assessing prevention and management approaches. Here's an overview of two of them.

The Activity for Diabetic Polyneuropathy (ADAPT) study. Funded by the National Institutes of Health and located in Utah and Kansas, this trial will randomly assign participants either to generic annual counseling or to an integrated program of moderate supervised exercise and specialized counseling. The trial is actively recruiting patients, and more information is Research by Creative Stall from available at Clinicaltrials.gov. the Noun Project

The Topiramate for Cryptogenic Sensory Peripheral Neuropathy (TopCSPN) study. This nationwide trial, in collaboration with the National Institute of Neurological Disorders and Stroke, is the ﬁrst randomized, placebo-controlled study of topiramate (Topamax) for idiopathic (cause unknown) neuropathy and metabolic syndrome—the constellation of prediabetes, excess weight or obesity, high blood pressure, and abnormal cholesterol or triglycerides. Researchers will assess topiramate, which has been shown to cause weight loss and insulin sensitivity, in people with metabolic syndrome and neuropathy who do not yet have diabetes or another known cause for their neuropathy. "The goal of the study is not just pain management. It's also to slow the neuropathy based on [the drug's] effects on metabolism and weight," says A. Gordon Smith, MD, FAAN, professor of neurology at the University of Utah and one of the investigators involved with the study. More information is available at Clinicaltrials.gov.

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