RALEIGH, N.C. — As the prevalence of diabetes has doubled in the U.S. over the past decade, doctors are beginning to unravel the complex cellular events that cause some people to develop the chronic disease while others remain healthy.

New findings by North Carolina researchers are pointing to additional targets for drug therapies.

In a paper published yesterday, Duke University researchers conclude that diabetes could be affected by protein — not the usual suspects of sugary carbohydrates that are most associated as dietary taboos.

The Duke team found that obese people metabolize protein differently than lean people, particularly when it's part of a high-fat diet.

Diabetes, once considered a fairly straightforward problem, results when the body does not properly produce or effectively use insulin, a hormone produced in the pancreas that helps cells absorb sugars for energy. Too much food and too little physical activity can burn out the body's ability to manage insulin.

"It's almost like it's a social problem as much as a disease," said Dr. John Buse, director of the Diabetes Care Unit at the University of North Carolina-Chapel Hill.

But not everybody who is overweight develops diabetes, and not every person with diabetes is overweight.

Some research is focusing on the metabolic processes that involve food — often with surprising results.

PROTEIN OVERLOAD

When people eat too much protein and fat — think double cheeseburger — the metabolic byproducts can't be fully absorbed, and they flood the bloodstream. Among those byproducts is an enzyme that affects insulin sensitivity. So a diet heavy on cheeseburgers creates a whole new way for the body to become insulin-resistant.

"Correctly, protein is viewed as a good nutrient, and it certainly is in people who exercise and eat in moderation," said study lead author Christopher Newgard, director of Duke's nutrition and metabolism center. "That's not what we're talking about here. We're talking about a dietary pattern that is typical in the U.S. and Western society, where 65 percent of people are overweight. And they get that way by ingesting too many calories and not exercising."

Another curious discovery about metabolism has scientists at East Carolina University pursuing a molecule that re-creates the effects of gastric bypass surgery. Doctors at the university who helped pioneer the weight-loss surgery reported that many patients were cured of their diabetes within days of having a gastric bypass — before they even lost weight.

Dr. Walter Pories, who founded ECU's bariatric surgery unit, said the procedure reroutes food around a whole section of gut and, in the process, likely blocks a signal to the pancreas that triggers insulin production. Because many people with diabetes produce too much insulin, and the body becomes resistant to it, this signal interruption appears to cure diabetes in more than half of patients.

"We're trying to figure out what are the signals coming from the gut," Pories said. "Once you identify the abnormal signal, then you could make a molecule to stop the signals. That molecule would then be the treatment for diabetes. Sweet, huh?"

'MAJOR TURNAROUND'

But it's not that easy to pinpoint, and there remains the question of why diabetes persists in up to 40 percent of patients after weight-loss surgery.

"It is complex," Pories said. "But there has been a major turnaround. Here's a disease that has doubled in prevalence in the last 10 years, not just in the U.S. but around the world. But it is no longer hopeless."

Buse, at UNC, agreed. "It's like having a loaded handgun at home: If it's not dealt with appropriately, it can kill. But the truth of the matter is, just like many, many people are able to own weapons and nothing happens ... the vast majority of people can live a full lifespan without disabling complications."