Peter Kador, PhD
Professor of Pharmaceutical Chemistry and Ophthalmology, University of Nebraska Medical Center
|ADA Research Funding|
Basic Science Award
Check just about any toothpaste tube, and you’ll see a scary word: gingivitis. It means gum disease, and it affects nearly three quarters of Americans at some point and is responsible for 70 percent of tooth loss in the United States.
Left untreated, the ugly result of gingivitis is periodontitis, an erosion of the bone that loosens teeth and destroys gums. For reasons doctors are just beginning to understand, people with diabetes are particularly threatened by periodontitis.
“Virtually everybody has the gingivitis part, but relatively few people have the progressive periodontitis part, which is bone loss and tooth loss,” says Richard Reinhardt, a professor of dentistry at the University of Nebraska–Lincoln. People with uncontrolled diabetes “tend to get periodontitis more often than the average person. People who are well controlled are just like everybody else in terms of their risk,” he adds.
Gum disease is caused by bacteria in the mouth, but not directly: When bacteria build up on and around your teeth, they produce waste. That’s what can give you bad breath. But when the bacteria get into your gums, the results are worse. The body’s reaction to the infection is an inflammation, which in turn interrupts the process of bone formation and maintenance around the roots of your teeth. “It’s really the inflammation the body produces, not the bacteria chewing away at the bone surface like Pac-Man,” says Reinhardt.
Reinhardt is helping Peter Kador, a diabetes researcher at the University of Nebraska Medical Center at Omaha, search for a better way to treat this gum disease. To start, they focused on an enzyme called aldose reductase. Usually, aldose reductase helps the body turn glucose into sorbitol, a sugar that’s harmless in small amounts. But the bodies of people with diabetes sometimes produce too much sorbitol as a result of aldose reductase activity—leading to complications, especially in the eye. In rats with diabetes, experiments have shown that the inflammation caused by gingivitis is also linked to aldose reductase activity in the gum tissue, or gingiva.
Kador has done decades of research into the link between aldose reductase and eye damage. With a grant from the American Diabetes Association, he is experimenting on diabetic rats to see if blocking the production of aldose reductase in and around the gums could help prevent gum disease.
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The researchers injected bacteria into the rats’ gums on one side to simulate gingivitis, and a sterile saline solution into those on the other side. The rats were fed a diet laced with an over-the-counter supplement called quercetin designed to reduce their aldose reductase levels. (“It’s awfully hard to get rats to take pills,” Reinhardt notes.) After two weeks, the rats’ jaws were measured for evidence of bone loss. “We used a very high dose and showed we can inhibit periodontal activity with a number of different aldose reductase inhibitors,” Kador says.
Kador’s experiment is essentially ignoring the infection and going straight to its consequences. “You have a cascade of events taking place that goes from infection to bone loss,” he says. “We’re not doing anything to the infection, but rather blocking the step in the cascade that leads to bone loss.”
Kador and Reinhardt say the ADA’s support has helped them establish some of the basics of how periodontitis works in diabetic rats—and show that quercetin can cut down on aldose reductase and help prevent periodontitis. “It’s an over-the-counter, safe supplement, and if it has a beneficial effect, it might be a cost-effective way to help people with diabetes control this,” Kador says.
The next step is to apply for a larger grant to test the treatment in humans. Instead of a pill that would deliver quercetin to the entire body in the hopes that some of it would affect the gum tissue, Kador thinks an ointment that could be applied to the gums by a dentist would work the best.
As a dentist, Reinhardt says the best way to avoid tooth loss from periodontitis is to make sure you never get it. Good control of blood glucose levels is one way to make sure gingivitis never develops into full-blown gum disease. The other will come as no surprise: “Regular cleanings and regular checkups to keep the gum area healthy are key,” Reinhardt says.