Investigating Diabetes Surgery

Vetter thinks it’s possible that both hypotheses could play a role in diabetes resolution. “There’s actually pretty good evidence for both of them, and maybe, as an additive affect, that’s how gastric bypass improves diabetes,” she says.

Rubino’s theory also provides an explanation for the cause of type 2 diabetes. People with this disease, he says, may have excess anti-incretins that leads to insulin resistance. When the diabetes patients have the surgery, their incretin hormones are brought back into balance, and insulin acts normally. Although Rubino’s hypothesis goes against the current theory that fat is to blame for insulin resistance, his idea explains why not all diabetes patients are obese and why not all obese people have diabetes.

However, the jury is still out on Rubino’s theory. While many researchers feel that incretins play a role in diabetes remission, they are still not sure if imbalances in these hormones actually lead to diabetes.

It’s a “chicken or the egg kind of thing,” says Vetter, the diabetes researcher from the University of Pennsylvania. While it’s possible that defects in incretin levels may contribute to the cause of diabetes, she says, it’s not clear whether these defects are causing diabetes or whether they are a result of the disease.

Rubino thinks untangling this issue might help scientists learn more about what causes the disease. “We are looking to test this hypothesis, to understand not only why surgery improves diabetes but also why diabetes occurs altogether,” he says. “There might be an intestinal dysfunction which either causes diabetes or at the very least is involved in the determination of diabetes.”
All the Benefits of Surgery — Without the Surgery

An ideal situation for diabetes patients would be to have a treatment that mimics the surgery’s effect without having to go under the knife. With any surgical procedure, patients can experience complications such as infection or a reaction to the anesthesia. Gastric bypass surgery can also have other risks, including blood clots and fluid leaking from the gut. If there were non-surgical treatments that were able to produce the same results as the surgery, patients could avoid these risks. Not only might these treatments be possible, some are already in development.

One possibility is a “sleeve” for your intestine. Food would go through the sleeve instead of through part of your upper intestine, meaning that the sleeve would serve as a barrier between what you eat and what your intestine is able to absorb. Such a device would mimic bypass surgery, because if there is no contact between the intestine and the food, it is just as though the food is going around that portion of gut.

The Boston-based company, GI Dynamics, developed a device called Endobarrier that acts as a gastrointestinal sleeve. It can be put inside the gut with a tube-like device with a camera that guides the Endobarrier through the patient’s mouth into the intestine. So far, animal and human studies have shown that using the Endobarrier does indeed result in weight loss, although it is too early to tell how the results compare to gastric bypass surgery. The device is currently in clinical trials, and scientists plan to do more studies to specifically look at Endobarrier’s effects on type 2 diabetes, says Dr. Keith Gersin, a bariatric surgeon at Carolinas Medical Center in Charlotte, NC, who has worked on an Endobarrier study.

Another way to mimic the surgery could be with drugs. If it turns out that the surgical “cure” is due mostly to changes in the levels of gut hormones, then providing patients with medication that mimics these changes could result in diabetes remission.

“If there are hormones that we could give patients to kind of trick their body into thinking that the gut was functioning in a different way, that could actually … improve insulin secretion, [and] change metabolism in a positive manner so that the body can actually get healthier,” says Dr. Karen Herbst, a diabetes endocrinologist at the University of California, San Diego medical center.

In fact, there are two drugs already on the market that are intended to boost incretin levels in the body. The drugs, called Exenatide and Sitagliptin, increase the amount of one particular incretin called GPL-1. However, these drugs do not change GLP-1 levels in the body nearly as much as the surgery does.

“After patients have gastric bypass, they have extremely high levels of GLP-1,” says Vetter. “They’re higher than the levels that a normal lean person would have after eating.” While sitagliptin increases GLP-1 levels twofold to threefold, the surgery can boost the levels 10-fold, she adds.

Also, a drug regimen would most likely have to act on multiple hormones, not just GLP-1. “After the gastric bypass surgery, there are multiple changes in multiple hormones,” says Laferrère, the endocrinologist from St. Luke’s-Roosevelt Hospital. “So in order to reproduce that, we would have to administer multiple hormones together.” Future research looking at hormone levels after bariatric surgery could help scientists identify all the hormones that contribute to the surgery’s anti-diabetic effect. Scientists would first need to figure out how hormone levels, besides those of GLP-1, change following the surgery, and then look into ways to target those hormones with drugs. They also need to synthesize drugs that increase or decrease hormone levels to match the levels seen after surgery. The right drugs in the right combination may be able to treat the disease pharmacologically.

While gastric bypass surgery has shown some dramatic results, Rubino does not see it as the ultimate solution for everyone with diabetes. He hopes that future investigations into the surgery’s effects could help many more people who suffer from the disease. “Eventually, the entire diabetic population can benefit from further developing diabetes surgery — not only those who will actually undergo surgical procedures, but even those who will eventually undergo [endoscopic] procedures or drug therapies that we have learned [about during] this endeavor,” he says. “I think this is in fact the most fascinating part of everything — it’s not just the use of surgery per se, but what the future holds in terms of things that can be learned as we know and use [the] surgery more.”

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