Investigating Diabetes Surgery

By the time Rubino published his findings in 2004 and 2006, others in the medical community were investigating the effects of bariatric surgery on people with type 2 diabetes, and they saw similarly encouraging results. The surgery has gained popularity in recent years, increasing nine-fold from 13,386 total surgeries in 1998 to 121,055 in 2004, according to the Agency for Healthcare Research and Quality. As the number of surgeries increased, says Rubino, more people began to notice the dramatic effects on type 2 diabetes. A 1995 study was one of the first to note the link between bariatric surgery and diabetes remission, commenting that the surgery was the most effective way to control type 2 diabetes. In 2004, an analysis that examined data from 136 studies and over 22,000 patients found that around 80 percent of diabetics who underwent bariatric surgery saw complete remission of their diabetes. And a larger study conducted over 10 years, known as the Swedish Obesity Study, also showed a significant improvement in diabetes following the surgery. Some began to wonder if this surgery should be an option for all diabetics, even those who are not obese.

To address this question and set rules for the potential new therapy, Rubino organized the international Diabetes Surgery Summit in 2007 in Rome. The purpose of the meeting was not only to raise awareness about the surgery as a potential treatment for the right candidates, but to set guidelines. It made sure the surgery was, for the moment, only recommended for morbidly obese individuals — people with a Body Mass Index, or BMI, over 35 — the only population it has been sufficiently tested in so far. BMI, is an approximation of how much body fat a person has, calculated from height and weight. A person with a BMI greater than 30 is considered overweight.

Then, in September 2008, Rubino organized another conference, the 1st World Congress on Interventional Therapies for Type 2 Diabetes held in New York City. This time, the meeting was not just for doctors and surgeons, but also for policy makers and health care providers.

The conference established that more studies with the right design are needed to examine the impact of bariatric surgery on diabetes, says Dr. Marion Vetter, a diabetes researcher at the University of Pennsylvania. The studies that have taken place so far, she says, have not been properly controlled. As a result, the benefit from the surgery may not be as large as it seems. Future studies — such as analyses comparing the effects of surgery to those of more traditional diabetes treatments — should help quantify the benefit and determine the right candidates for this surgery.

The Chicken or the Egg

As obesity has become more prevalent in the US, so has diabetes — about 80 percent of patients with the disease are overweight. Between 1991 and 2002, the number of people considered obese in this country increased by 74 percent and the number of diabetes cases increased 61 percent, according to the Centers for Disease Control and Prevention, or CDC. This strong correlation has led to the hypothesis that excess fat causes type 2 diabetes. When you eat too many calories, the theory goes, the extra fat may spill over from your fat cells and get stored in other cells, which causes problems, like insulin resistance. And when diabetic patients lose enough weight, their diabetes goes into remission. The diabetes-obesity connection has led some people to theorize that gastric bypass surgery works because it allows patients to lose dramatic amounts of weight.

“Anything that reverses the caloric surplus will reverse the type 2 diabetes,” says Dr. Roger Unger, a professor of internal medicine at the University of Texas Southwestern in Dallas, who studies the role of fatty acids in type 2 diabetes. Losing just 10 pounds, he says, can cause diabetes to disappear.

However, while many people think that weight loss is likely to be part of the surgical “cure,” they also think there are other factors in play.

“Weight loss is definitely a huge asset because it’s rapid, it’s large magnitude, and it’s sustained,” says Dr. Blandine Laferrère, an endocrinologist at St. Luke’s-Roosevelt Hospital Center in New York City. “But most people think there is something else happening,” she adds.

Many researchers believe that “something else” lies in the organ that receives the most re-working during bariatric surgery — the gut, specifically, the upper intestine. This highway for food, which plays an important role in normal regulation of glucose, could also be involved in fixing diabetes after the surgery.

The gut has not always received this much attention from diabetes researchers. “Everybody totally ignored the gut” until about 15 years ago, says Dr. Eric Epstein, an endocrinologist at Albert Einstein College of Medicine in New York City. Instead, he says, much of the attention was focused on the pancreas and the two organs that receive the insulin signal — the liver and the skeletal muscle. But since gastric bypass surgery has such a dramatic effect on people with type 2 diabetes, the gut has become a major area of diabetes research.

The gut is responsible for releasing many hormones when you eat, and some of these hormones, called incretins, regulate insulin levels. Studies have shown that gastric bypass surgery alters incretin levels, which may account for the rapid diabetes remission.

There are two competing hypotheses for how changes in gut hormones after the surgery may cause diabetes to disappear. One idea has to do with the fact that the surgery connects two parts of the gut that are normally separated by a large portion of gastrointestinal tract. The new connection allows nutrients to come into contact with the lower half of the small intestine much more rapidly than they normally would. This fast delivery of nutrients to a particular part of the bowel may stimulate the intestine to secrete more incretins. Higher incretin levels would promote the release of insulin from the pancreas, and more insulin would help lower blood glucose levels.

The other hypothesis, proposed by Rubino, is centered on the part of the gut that is bypassed in surgery, the upper small intestine. It is possible, he says, that this portion of gut secretes hormones that actually cause insulin resistance. He calls these hypothetical hormones “anti-incretins,” and if they existed, they would balance out the effects of incretins. By bypassing part of the small intestine, the surgery would prevent the release of “anti-incretins.” Without the anti-incretins, insulin resistance would diminish, and diabetes symptoms would disappear.