Sep. 11, 1998 DURHAM, N.C. -- Researchers at Duke University Medical Center have shown they can reverse type 2 diabetes in mice simply by feeding them a very low-fat diet, and they believe the same potential exists in humans.
While doctors have long known that weight loss can control diabetes, the new research is the first scientific study to show that type 2 diabetes can be completely reversed in animals by lowering dietary fat, said Dr. Richard Surwit, professor and vice chairman in the department of psychiatry at Duke. Moreover, the findings suggest that reducing fat, not just weight, is a primary mechanism behind the reversal, Surwit said.
More than 14 million Americans have type 2 or non-insulin-dependent diabetes mellitus in which abnormally high blood sugar levels cause severe tissue damage. It is the leading cause of blindness in the country and causes kidney failure as well as irreparable nerve damage.
Results of the study, funded by the National Institute of Mental Health, are published in the September issue of Metabolism.
The research findings suggest that, while genetics determine which animals are at risk for developing diabetes, dietary changes can compensate for the genetic predisposition, Surwit said. If the same were proven true in humans, the potential for preventing the disease could be huge, he said.
"Certainly, there is evidence from the more radical diet programs like Pritikin or the Duke Rice Diet showing that reducing fat intake can control diabetes, but the evidence has all been anecdotal, and it hasn't illuminated the specific mechanism behind the improvement," he said. "Our animal research shows that, if you dramatically reduce the dietary fat, you can reverse the problem."
In the study of a genetic strain of diabetes-prone mice, the researchers found that cutting fat from 40 percent to 10 percent of their total caloric intake caused complete reversal of their diabetes, regardless of what stage in life the mice began the low-fat diet. And while the mice lost weight, the researchers found that weight loss alone could not account for the reversal, Surwit said.
That's because their insulin and glucose (blood sugar) levels began to decrease before their weight did, suggesting that fat reduction acts on insulin and glucose levels independent of weight loss.
"We have known that animals can develop diabetes before they develop obesity, so it stood to reason that animals could begin to reverse their diabetes before they lost weight," said Dr. Mark Feinglos, professor of endocrinology at Duke. "Weight-loss and nutrition certainly are connected, but they are not inseparable."
Feinglos emphasized that foods high in fat, not in sugar, are responsible for the onset of diabetes in the mice. In fact, sugar had no effect on the diabetes-prone mice -- it neither increased nor decreased their symptoms, a finding that's been shown in people as well.
"The only thing sugar has ever been shown to do is cause dental cavities. It's the fat that appears to be most detrimental," Feinglos said. Fats are metabolized quite differently from carbohydrates or pure sugars, he said. A small candy bar and a bagel may contain the same number of calories, but they are not necessarily metabolized and stored in the same way.
"All calories are not equal," Feinglos said. "Carbohydrates require burning of energy to convert to fat, whereas fat is directly converted to fat"
The distinction between carbohydrates and fat is an important one, because it distinguishes the unique role of fat in contributing to a inherited trait, researchers said. Without the fat, the diabetes does not occur, even in diabetes-prone mice. When the high-fat diet is stopped in mice that have been raised on it, the diabetes disappears.
Surwit said that the animal research provides a basis for further study of the role of a high-fat diet in adult Americans, 50 percent of whom are overweight and are, thus, at risk for developing the disease.
But even in the absence of weight loss in the mice, a low-fat diet can improve insulin and blood sugar control, the study showed. That improvement occurred regardless of how long the mice had previously eaten a high-fat diet, suggesting the disease process can be manipulated at various points of progression.
In humans, the disease is less malleable. Irreparable damage often occurs before it can be reversed, Feinglos said. But if you identify the disease early and make the appropriate dietary changes, then the disease could theoretically be modified or reversed.
"Our findings do point out that, at least in theory, it is doable," Feinglos said. "Our next step is to find pharmaceutical compounds to give animals a greater ability to eat normally, as would the mice without the genetic predisposition."
While reducing fat intake would be the safest and healthiest approach to controlling diabetes, experience has shown such reduction to be difficult to enforce and even harder to maintain, Feinglos said. Diabetics would theoretically have to reduce their fat intake to 10 percent of their total caloric intake, an extraordinarily low percentage, given that most Americans consume 30 percent of their calories through fat.
But even a more modest decrease in fat intake could have beneficial effects, the researchers believe. Cutting fat to 20 percent might not reverse the disease, but theoretically could reduce symptoms and the risk of serious tissue damage.
"It's not clear what the absolute limit of fat intake would be for people to derive some benefit," Surwit said. "We hope our ongoing studies will clarify that."
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