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The Bypass-Diabetes Link

Why does gastric bypass cure Type 2 diabetes? Dr. April Strader investigates.

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Written by Karen Carlson

Type 2 diabetes affects more than 40 million people in the United States. For morbidly obese people, gastric bypass surgery is an option for weight loss. But not only does the surgery cause massive weight loss, it has been found to immediately cure or “resolve” Type 2 diabetes in more than 85 percent of patients. This effect occurs sometimes even before patients are discharged from the hospital, but typically within a few weeks.

April D. Strader, Ph.D., assistant professor in the Department of Physiology in Carbondale, wondered, how exactly that happens. “It seemed that the improvements in metabolism were due to the effect of the surgery, independent of weight loss. It is unclear how this happens,” she says.

Dr. Strader decided to focus on one part of the gastric bypass surgery, a procedure that involves the ileum, the final section of the small intestine. In 2010, she received an American Recovery and Reinvestment Act Challenge Grant from the National Institutes of Health to study the role of the lower intestine in post-surgical metabolic improvement. More than 35,000 applications were received for these grants; only 300-400 were awarded.

Finding little scientific research on the ileum since the early 1990s, Dr. Strader resurrected the study of this section of the small intestine. “I wanted to study the actual effects of surgery independent of weight loss.” She is becoming the world expert in ileal interposition, a surgery that involves relocating a small segment of ileum to the upper intestine without shortening the small intestine and altering stomach anatomy. Ileal interposition isolates a component of gastric bypass: the premature stimulation of the lower intestine with relatively undigested nutrients.

The ileal interposition procedure doesn’t cause weight loss like gastric bypass, since the stimulation of lower intestine removes the other components of gastric bypass, like gastric restriction.

Using a new animal model, Dr. Strader examined bile salts and gene expression. She found an increase in hormone secretions following ileum interposition –– a change that could be responsible for the diabetes resolution. “We were the first to show that ileal interposition improves glucose levels and insulin sensitivity in rodents.”

She cited a hormone, GLP-1 as a major player. The ileum has the greatest population of cells that produce GLP-1 cells. “We think rapid delivery of nutrients and bile from the upper intestine to the lower intestine is stimulating GLP-1 cells to improve glucose metabolism.” One drug to treat diabetes, Byetta®, is a GLP-1 receptor agonist that improves glucose function.

Bile salts also play a role. Morbidly obese people have a different bacterial environment in their colon and small intestine than non-obese people. “Bacteria have enzymes that modify bile salts. Exposing the lower intestine to bile salts will improve Type 2 diabetes,” Dr. Strader says. “If we can determine which bile acid is changing metabolism, pharmacologists could make a pill that plausibly could mimic the effects of surgery without surgery.”
The hormone increases and bile salts alterations that change metabolism may be the keys to resolving diabetes. “Surgeons need to be educated in the hormones that are secreted by the ileum (and other parts of the small intestine) so they can tailor which surgery is right for their patients: gastric bypass or ileum interposition,” Dr. Strader advises.

And for diabetics of a normal weight with unmanageable Type 2 diabetes, “it may be possible to cure diabetes without bypass surgery, but they could benefit from a metabolic surgery such as ileal interposition.”

The Bypass-Brain Benefit
Another potential benefit of gastric bypass surgery previously unexamined is the reported cognitive improvements in patients undergoing obesity surgery. Dr. Strader is organizing ongoing collaborations with Dr. Greg Rose in the School of Medicine and hopes to look at the effect in rodents approximately two years post ileal interposition surgery to see if they improve in cognitive function. Recent human studies indicate a significant improvement following the gold standard, gastric bypass, at 3-5 years after surgery, but the mechanisms are unknown. Rodent studies will allow her research group to begin to understand how this is happening.