Diabetes Forecast

A New Look at How Gastric Bypass "Cures" Type 2

By Andrew Curry , ,

David Bernlohr (left) and his research partner, surgeon Sayeed Ikramuddin.

David Bernlohr, PhD
Biochemist, University of Minnesota–Twin Cities College of Biological Sciences and Medical School
Type 2 Diabetes
ADA Research Funding
Clinical Translational Award

For years, scientists have marveled at the effects of gastric bypass surgery. The operation, which involves surgically removing part of the stomach and small intestine, physically restricts the amount of food people are able to consume and digest, leading to dramatic weight loss.

Even more remarkable, the procedure puts type 2 diabetes in remission for some people. The surgery restores the body's sensitivity to insulin and revives the pancreatic cells that produce it, even before any weight loss occurs.

Biologists studying the phenomenon say it has something to do with inflammation, caused by overactive immune cells that build up in fatty tissue. "One of the key observations in human biology is that when an individual transitions from lean to obese, there's an increase in inflammation," says David Bernlohr, PhD, a researcher at the University of Minnesota–Twin Cities.

That inflammation leads to things such as insulin resistance, which means the body needs to produce more and more insulin to control blood glucose levels. Eventually, the insulin-producing cells in the pancreas begin to give out, causing type 2 diabetes. After gastric bypass surgery, though, inflammation seems to decrease or disappear almost immediately. Tiny engines inside the cells called mitochondria that shut down as a result of inflammation grind to life again, increasing the body's sensitivity to insulin in the process. The surgery seems to reverse the course of type 2 diabetes in "just a couple of days," Bernlohr says.

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The big question, according to Bernlohr, is whether these changes deep in the cells are the result of the surgery itself, which rearranges the intestines in a way that bypasses part of the gut, or of the low-calorie life that follows. "It's been known for years that calorie restriction is very powerful in reducing hyperglycemia [high blood glucose]," says Sayeed Ikramuddin, MD, Bernlohr's research partner and a surgeon at the University of Minnesota. "Is this the way in which gastric bypass is exerting metabolic effect?"

Gastric bypass, after all, means a lifetime of enforced calorie restriction. After the surgery—formally known as Roux-en-Y gastric bypass—patients are able to eat only about 800 to 1,000 calories a day. In the week after the procedure, they may not eat at all. "Gastric bypass patients are just not hungry," Bernlohr says. "They can get by with zero calories that first week."

Bernlohr and Ikramuddin have set up an experiment to see what role a dramatic decrease in calorie consumption plays in reversing type 2 diabetes. They first approach patients already planning gastric bypass surgery. Volunteers are then divided into two groups. The first gets the surgery and is then monitored for a week afterward; the second is put on a diet of just a few hundred calories a day for a week before surgery and then tested to see the effects on their insulin resistance and inflammation levels before and after surgery.

As the researchers gather data—they hope to eventually have about two dozen participants in the study—they'll be looking to see if inflammation is reduced by about the same amount in both groups. That would suggest that it's calorie restriction, either as part of a controlled diet or as a result of surgery, that's causing changes in the cells. If, on the other hand, "inflammation is markedly less in the surgical group, that's a clue calorie restriction isn't so important," Ikramuddin says.

Ikramuddin has a hunch the data will show diet makes a big difference. "Is it caloric restriction or intestinal rearrangement? I think it's calorie restriction," he says. "This would be fairly eye-opening if we could demonstrate similar changes in the two groups."

From a research standpoint, the study—which is the first to look at patients just a few days after surgery, as opposed to months or even a year later—could go a long way toward illuminating why gastric bypass is so effective.

Oddly, it might also give doctors the information they need to offer people with type 2 diabetes an alternative to stomach surgery, which is an invasive procedure with potential complications and side effects. Says Bernlohr: "If you can achieve the same clinical efficacy simply by reducing caloric intake, that would have a broad impact on lots of patients."



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