Investigating Diabetes Surgery

To treat type 2 diabetes, doctors usually recommend lifestyle modifications such as dietary changes and more physical activity. But recently, the American Diabetes Association endorsed a new, more drastic treatment — bariatric surgery, also known as gastric bypass surgery. For this procedure, surgeons staple the stomach to make it into a small pouch and rearrange the gut so the middle portion of the intestines is connected to the stunted stomach. Not exactly non-invasive. Now when the patient eats, food will bypass part of the stomach and the small intestine, and go straight to the middle of the gastrointestinal tract. Why would scientists recommend such extreme measures for a disease traditionally treated with more subtle steps?

Doctors have performed bariatric surgery to help people lose weight since the 1950s, and for years they have observed that the operation has a beneficial side effect on patients’ blood sugar levels. Many patients with type 2 diabetes, a disease in which the body can no longer regulate blood sugar levels, saw their diabetes disappear. Because type 2 diabetes is highly correlated with obesity, doctors assumed that this outcome was due to the substantial weight loss patients experience after surgery. But recent studies show that many patients see their diabetes go away months before they lose the pounds. This paradox led some scientists to wonder if something intrinsic to the surgery itself was “curing” the diabetes.

Although scientists do not know what causes type 2 diabetes, figuring out why this surgery alleviates the disease could help them better understand it. The surgery focuses on an organ that has been somewhat neglected in diabetes research — the upper intestine — and suggests that the hormones secreted by this section of gut could contribute to the disease, and might even play a role in causing it. Investigating the mystery could also lead to new diabetes treatments that mimic the surgery’s effects, such as a device placed inside the intestine or drugs that target intestinal hormones. And scientists are taking this opportunity to reexamine what we know about this old disease.

“[The] surgical treatment of diabetes and obesity provides an opportunity to rethink these diseases at a different angle and maybe potentially lead to a better understanding of them,” says Dr. Francesco Rubino, chief of gastrointestinal metabolic surgery at Weill Cornell Medical College in New York City.

Type 2 diabetes is a complex disease in which cells in the body are deaf to the crucial insulin signal in a process known as insulin resistance. Insulin is a hormone produced by the pancreas that helps the cells of the body absorb glucose, which is their main energy source. In people with type 2 diabetes, the cells can’t use the insulin, and glucose builds up in the bloodstream. (This process is different from that of type 1 diabetes, in which the body fails to produce insulin.) Initially, the pancreas overcompensates by producing more insulin. Eventually, however, the pancreas can’t secrete enough insulin to overcome the resistance, and the body is left with a lot of glucose that can’t get inside the cells. Without the proper amount of glucose, cells do not get the energy they need. High levels of glucose in the bloodstream can also damage some organs, including the kidneys and the heart, and can lead to blindness. Patients try to control their glucose levels with diet and exercise, but some require insulin injections.

Many people see diabetes as a disease that worsens over a lifetime, but bariatric surgery is changing that view. The surgery appears to have a powerful anti-diabetic effect that has yet to be replicated with traditional treatment methods. This surgery has researchers all over the world turning to the gut for answers on what might cause or even cure the disease.

The Mysterious Cure

As a surgical resident, Rubino of Weill Cornell Medical College never planned to pursue a career in bariatric surgery. Although he was studying under a clinician with a large bariatric surgery practice, Rubino was more interested in adrenal diseases — disorders caused by the improper production of hormones from the adrenal gland, which secretes stress hormones, such as cortisol and adrenaline. But that was before one fateful afternoon in the library. “It was one of those things that in America you like to call serendipity,” says Rubino, who is originally from Italy.

In 1999, while trying to figure out ways to simplify a complicated procedure, Rubino came across some interesting literature in which the authors noted that their bariatric surgery patients’ diabetes seemed to disappear about a month after the operation. He thought back to the obese patient he had operated on that morning, “And in my mind, I say, well there’s no way this gentleman is going to be much leaner in a month,” Rubino recalls. This puzzling observation caused him to wonder, what was making the diabetes go away?

Soon afterward, Rubino started a series of experiments to tease out an answer. Performing operations on rats, he accumulated evidence that all pointed in one direction — the surgery was the cure. He first operated on rats that were diabetic, but not obese. In these rats, surgery to bypass part of the upper intestine caused a huge decrease in their blood sugar levels, meaning that the rodents were essentially cured of diabetes. However, rats that received a pretend operation, or simply a restriction in diet, did not see significant changes in their diabetes. Similarly, when Rubino performed a different type of gut surgery on the rats, one that did not bypass the upper intestine and still allowed nutrients to flow freely across this area, he saw that the diabetes remained the same. Then he set up a new set of experiments that strongly suggested that part of the upper intestine played a role in the disease remission. He once again performed a gastric bypass on rats and once again saw the diabetes disappear. Then he reversed the procedure, and the diabetes returned.