Encouraging Damaged Nerves to Regrow
Gordon Smith uses the “hot sauce” way of probing how weight loss can ease neuropathy
Gordon Smith, MD
Neurologist, University of Utah
ADA Research Funding
ADA-Ethicon Endo-Surgery/Covidien Research Award in Bariatric Surgery and Diabetes
Nerves are our connection to the outside world, relaying information about what’s around us to our brain. There might be a thousand or more nerve endings in a square inch of skin, all exposed to daily wear and tear. “The nerves in your skin are constantly being injured and regrowing,” says Gordon Smith, MD, a neurologist at the University of Utah. “They’re the foot soldiers of the nervous system, absorbing a great deal of the physical insult our bodies encounter every day.”
The nerves in the feet are the most vulnerable, because they have the farthest to travel: A single nerve fiber may stretch from your toe to your backbone, plugging into the spinal column not far from your belly button. “It’s like the Alaska oil pipeline—it’s a pretty big deal, and it takes a lot to maintain it. If there’s stress or injury, the part of the pipeline that’s farthest away absorbs the damage,” Smith says.
Under normal circumstances, nerve cells are surprisingly resilient. For people with diabetes, though, this resilience can decline or disappear, making nerve cells more fragile and less able to regrow when they’re damaged.
Accumulated nerve cell injury equals neuropathy, a common condition (about half of people with diabetes will have it at some point in their lives) with symptoms including pain, numbness, and loss of balance. It’s often part of a group of problems, including uncontrolled blood glucose and poor healing and circulation, that can escalate to the point where foot amputation is necessary. Diabetic neuropathy is one of the most common complications of diabetes, and one of the most costly and damaging. Estimates are that health care costs connected with neuropathy add up to well over $10 billion a year in the United States.
What is it about diabetes that makes neuropathy such a problem? Research has shown that hyperglycemia, or high blood sugar, causes nerves to degenerate. But hyperglycemia is not the only risk factor. “In the setting of diabetes, obesity seems to significantly increase one’s risk of neuropathy,” Smith says.
In recent experiments funded in part by the American Diabetes Association (ADA) involving people with type 2 diabetes, Smith has shown that exercise-related weight loss can temporarily slow neuropathy and encourage nerves to regrow, increasing the regeneration rate by 30 percent. “Those who lost weight or whose A1C got better are the ones who improved,” he says.
The cause and effect can be complex. Does obesity cause type 2 diabetes and thus neuropathy? Or does diabetes come first? One condition, after all, might contribute to the other. “If you have very bad foot pain and are unable to exercise, that might make you more likely to be overweight,” Smith points out.
To better understand how weight loss helps nerves stay in good shape, Smith is now working with patients about to undergo gastric bypass surgery. Other studies have shown that the weight-loss operation—which restructures the digestive system to bypass parts of the stomach and small intestine—leads not just to weight loss but to an almost immediate improvement in the body’s ability to produce and respond to insulin. In many cases, surgical patients with type 2 diabetes are able to immediately stop using or greatly reduce blood glucose–lowering medications. “It provides an ideal opportunity to look at the effects of weight loss and the correction of diabetes on nerve regeneration,” Smith says. “Our hope is that between that and looking at blood markers, we can understand the disease mechanism.”
Smith makes use of capsaicin, a compound familiar to any hot-sauce fan. It’s the stuff in chili peppers that “burns” the tongue. When applied to the skin, it damages nerve cells, causing them to retract from the skin surface.
With the help of another ADA grant, Smith is recruiting 50 people without neuropathy symptoms headed for weight-loss surgery—25 with diabetes, 25 without. In the time leading up to the operation, he takes a tiny sample of skin and underlying tissue from each patient’s thigh. Then he applies a capsaicin patch to the area, waits 48 hours, and takes another sample. The capsaicin simulates nerve damage that accompanies neuropathy. The biopsies can be repeated after the first and third months to determine the rate at which nerves regrow.
The patients go on to have gastric bypass surgery, and Smith monitors the impact on nerve function. Six months later, the nerve regeneration rate is measured again. The goal is to compare the progress of the patients with and without diabetes and to see if weight loss and metabolic improvement affect nerve regeneration.
One of Smith’s goals is to show that capsaicin is a tool that may be useful in future neuropathy research. But more important, understanding the relationship among obesity, diabetes, and nerve damage could help Smith and others treat or even prevent neuropathy in the future.
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