Diabetes Forecast

Tackling Neuropathy in Type 2 Diabetes

Brian Callaghan, MD

Brian Callaghan, MD
Assistant Professor of Neurology, University of Michigan Medical School
ADA Research Funding
Junior Faculty Award

Think of the nerves in your body as telephone lines, running from the command center of the brain out to every part of your body. Some spots are close by, but others—the hands and feet in particular—require a very long wire.

The longer the wire, the more vulnerable it is to damage. And when those wires get damaged, it can cause neuropathy: a painful, and often dangerous, disconnect between the brain and the body's extremities.

Neuropathy's symptoms—including numbness, pain, tingling, and weakness in the fingers and toes—are well known. Less clear is what causes the condition. "There's a whole litany of problems that cause nerves to die," says Brian Callaghan, MD, a physician and researcher at the University of Michigan in Ann Arbor. "But there's more about it we don't know than we know."

The nerve damage has ripple effects that impact quality of life in a major way. "It can affect balance as well as cause falls. It's a very disabling condition—because of the pain, but also because it makes it harder to get around," Callaghan says.

Neuropathy can even claim limbs. "Neuropathy is one of the greatest risk factors for ulcerations that lead to amputations," says Callaghan. People with neuropathy may not be able to feel small cuts or injuries in their feet until it's too late to head off infections and sores that won't heal, trauma that may eventually lead to amputations.

For people with diabetes, this puzzling problem is a constant threat. Every other person with diabetes will develop neuropathy. That's four to six times the rate of the population at large.

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Until now, researchers haven't made much of a distinction between type 1 and type 2 diabetes when it comes to neuropathy. But Callaghan thinks that's a mistake. "Type 1 and type 2 are very different," he says. "If you improve sugar control in type 1 patients, you have a huge impact on neuropathy. In type 2, you don't. That shows there's something more than high sugars that's damaging the nerves."

What's missing, Callaghan says, is the rest of the picture: Type 2 rarely shows up alone. Says Callaghan: "Type 2 often goes hand in hand with metabolic syndrome," a set of connected ailments including diabetes, obesity, high blood pressure, low "good" cholesterol, and high "bad" cholesterol.

What Callaghan wants to know is whether people with metabolic syndrome and type 2 diabetes are more likely to have neuropathy than people with metabolic syndrome who do not have diabetes. With the help of a grant from the American Diabetes Association, he has enrolled 60 patients so far from a nearby obesity clinic for a study. Most of the participants have metabolic syndrome, but only half have diabetes or prediabetes. Thirty lean volunteers without metabolic syndrome serve as a control group.

As part of the study, Callaghan takes a set of baseline measurements of neuropathy, including skin biopsies and tests to see how well people can feel vibrations and small electric shocks. He then repeats the tests two years later to see how far any neuropathy has progressed. By seeing whose neuropathy gets worse, he hopes to isolate the elements of metabolic syndrome that contribute to the condition.

If Callaghan could show that high blood pressure or high "bad" cholesterol—together with type 2—play a big role in neuropathy, it would help doctors treat patients better and earlier. "Right now, we're really focused on people's sugar. That's the dominant factor, but not the only factor," he says.

More knowledge could also change how doctors treat their patients. "We have treatments for most of the different components of metabolic syndrome, but we don't emphasize them in neuropathy patients," Callaghan says.

Callaghan won't have conclusive data for a few more years. Until then, he encourages people at risk for neuropathy to concentrate on the basics, especially if they have diabetes. "Better sugar control may be something we aim for anyway, but it becomes even more important to patients with neuropathy," he says.



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