New Clues to How Gastric Bypass Surgery Combats Diabetes

Levels of amino acids linked to insulin resistance drop right after procedure

By Kathleen Doheny
HealthDay Reporter

WEDNESDAY, April 27 (HealthDay News) -- Gastric bypass surgery has been known to improve blood sugar control, often sending people with type 2 diabetes into remission, but experts have long wondered exactly how that happens.

Now, a new study provides some clues.

Circulating amino acids linked with insulin resistance decline dramatically in those who have the bypass surgery, the researchers discovered. They compared 10 obese people with diabetes who had the surgery with 11 who lost weight through dieting.

"Something happens after gastric bypass that does not happen as much after the diet-induced weight loss," said Dr. Blandine Laferrere, an associate professor of medicine at St. Luke's Roosevelt Hospital Center and Columbia University, both in New York City.

The study is published in the April 27 issue of Science Translational Medicine.

The surgery, which reduces the stomach to the size of a small pouch, also modifies the junction between the stomach and small intestine. It leads to a dramatic reduction in the level of circulating amino acids that have been linked with diabetes.

"The fact that gastric bypass results in the remission of diabetes in the majority of patients is not new," said Laferrere. According to background information in the study, 50 percent to 80 percent of diabetes cases go into remission after the surgery.

What doctors have been trying to figure out, she said, is why the bypass surgery is so good at making the diabetes disappear. "The diabetes improves almost immediately, before a significant amount of weight loss occurs," she said. "That points out it is something other than the weight loss."

In the new study, the researchers evaluated biochemical compounds involved in metabolic reactions in the participants. Each group had lost about 20 pounds.

The investigators found that the bypass patients had much lower levels of amino acids known as branched-chain amino acids, and the amino acids phenylalanine and tyrosine.

"Those changes in the amino acids could be implicated in the mechanism of diabetes remission after gastric bypass," Laferrere said.

Experts know the amino acids are linked with insulin resistance partly due to animal studies, she said. "If you supplement the diet of rats with branched-chain amino acids, you can induce more insulin resistance," she explained.

However, Laferrere said, the finding does not mean all obese people with diabetes should pick surgery over dieting. The surgery is highly invasive, she noted, and not everyone is a candidate.

While the findings are intriguing, she said, it's too early to apply them to diabetes treatment. Eventually, she added, after experts understand more about how the surgery affects the amino acids, it may be possible to apply the findings to develop better diabetes treatments or a less invasive surgery.

The new study adds weight to other research finding a link between the decline in branched-chain amino acids and the decline in insulin resistance, said Dr. Thomas J. Wang, associate professor of medicine at Harvard Medical School, and a coauthor of the perspective accompanying the study.

"It's known that gastric bypass rapidly reverses insulin resistance, which is one of the principal biochemical abnormalities that precedes diabetes," Wang said.

"This study really does help to confirm that hypothesis that branched-chain amino acids do go down more in people who have weight loss surgery," he said. While it lends support to the idea that there is a link between the reduction in the amino acids and the decline in insulin resistance, it does not yet prove cause and effect, Wang added.

"It shows people who get weight loss surgery have a bigger drop in their branched-chain amino acids. What is not yet proven is whether that reduction in branched-chain amino acids is the reason their insulin resistance declines," he pointed out.

Wang and his coauthor, Dr. Robert Gerszten, are co-inventors on patent applications related to metabolite predictors of diabetes.

Wang and Gerszten also pointed out that the number of obese people with type 2 diabetes was 171 million worldwide in 2000. By 2030, that number is expected to double. Therefore, they wrote, a detailed understanding of the role of the amino acids in diabetes would be valuable.

More information

To learn more about gastric bypass surgery, visit the U.S. National Library of Medicine.

SOURCES: Blandine Laferrere, M.D., associate professor, medicine, St. Luke's Roosevelt Hospital, Columbia University and New York Obesity Nutrition Research Center; Thomas J. Wang, M.D., associate professor of medicine, Harvard Medical School, Boston; April 27, 2011, Science Translational Medicine

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