Two decades passed before Pories became the first to recognize the potential of bypass surgery to dispel diabetes. Trained as a general surgeon, Pories was asked to focus on the profitable area of obesity shortly after arriving at the Brody School of Medicine in 1977; the Roux-en-Y ultimately became his favored technique. When a colleague asked him to try the surgery on an obese diabetic patient, he agreed reluctantly, noting that the surgery would be riskier because diabetic patients are usually more prone to infections and require greater insulin regulation.
“After the surgery we were prepared for all sorts of troubles, but there was no evidence of diabetes,” Pories recalls. The patient recovered well, and his diabetes seemed to have vanished. The same thing happened with the next three obese diabetic patients. Pories was so surprised by the change that he initially suspected his colleagues might have been misdiagnosing the patients. At the time diabetes was considered an incurable, chronic disease—it couldn’t just disappear. Even when he rechecked the medical tests, Pories remained unconvinced.
For their fifth patient, Pories and the other doctors sought out the most severe diabetic case they could find. She had sky-high blood sugar of 495 (normal is around 100) and was taking a high dose of 90 units of insulin daily. After the operation, the woman’s blood sugar levels plummeted. “The day after surgery, she needed eight units of insulin, and on the sixth day only four. That was the last day she ever required any insulin at all,” Pories says. “First we were astonished and then just delighted that, good heavens, this means that diabetes can be reversed.” He recalls that it was “such a wild idea” that his group conducted several more surgeries over the next few years before publishing their results in 1982.
Even then there was not much reaction in the medical community. Thirty years ago bypass surgery was risky, involving a large, bloody incision and mechanical metal arms to pry apart the heavy, fatty abdominal walls and hold them in place while surgeons operated elbow-deep in the gut. Patients had long recovery times, and complications could be severe. Pories hunkered down, continuing to collect data and build his case. In 1995 he published a 14-year follow-up showing that bypass surgery proved to be a long-term solution for four out of five diabetic patients.
This time Pories’s extraordinary findings began to attract notice. Researchers had come to recognize obesity as a disease rather than a behavioral problem. And by the first decade of the 21st century, the rapid growth of obesity—rates doubled for adults and tripled for children in the United States between 1980 and 2008—made it an epidemic that could not be ignored. In response, the medical device industry developed new surgical tools with extra-long handles to facilitate minimally invasive, blood-free operations on the obese. The increasingly common bypass surgeries were effective, but researchers were still struggling to figure out why they worked.
One of the key scientists in that effort was Blandine Laferrère, a French-born and -trained endocrinologist who was studying the hormones that regulate appetite at the New York Obesity Nutrition Research Center at St. Luke’s. When the body needs food, rising levels of the hormone ghrelin, produced in the upper stomach and pancreas, signal the brain and trigger a desire to eat. At the end of a meal, specialized endocrine cells in the wall of the small intestine release other hormones (like cholecystokinin, glucagon-like peptide-1, and oxyntomodulin) that signal satiation. In obese individuals these signaling networks malfunctioned, Laferrère knew, leaving them perpetually hungry. When she saw how bypass surgery patients at St. Luke’s lost weight—and their diabetes—after a single operation, she became intrigued.
“Endocrinologists didn’t announce, ‘Let’s find out the role of the gut in type 2 diabetes,’ ” Laferrère says. “It just happened that the surgeons did this type of surgery for weight loss, and that turned out to have a spectacular effect on the remission of type 2 diabetes.”
In studying the mechanism behind diabetes remission, Laferrère focused on incretins, a group of hormones that spur about half of the insulin produced during meals. “I read these fantastic papers from Europe from the mid-1970s and early 1980s,” she says. Werner Creutzfeldt, a German doctor who studied gut hormones that regulated insulin, described an “incretin effect” in which partially digested food exits the stomach of healthy people and enters the small intestine, triggering incretin production. Incretin, in turn, causes the pancreas to crank out insulin, keeping blood sugar down to its proper level. But in diabetics the incretin effect is blunted, and insulin production is thus reduced.
Inspired by Creutzfeldt’s research, Laferrère decided to measure incretin levels and insulin secretion after meals, and also before and after gastric bypass surgery. After studying just three diabetic bypass patients, she could see that the surgery was triggering dramatic shifts in hormone levels. Shrinking the stomach and rerouting the small intestine rebooted the incretin effect, boosting the body’s insulin production within a month. At the same time, the symptoms of diabetes waned. “I was stunned,” Laferrère says. “I had never seen such a magnitude of effect.” Her finding made the cover of Diabetes Care in 2007.
Then, to determine if this change was caused just by weight loss, Laferrère paired a control group of patients with gastric bypass patients, matching for age, duration of diabetes, and ethnicity. The control group was placed on a diet aimed at having them lose as much weight as the bypass patients, enabling her to compare body chemistry meaningfully between the groups. After two months, all patients had dropped at least 22 pounds, and Laferrère began measuring the amount of incretin and insulin in their blood. To her surprise, neither incretin levels nor their influence rose in the dieters. The comparison showed that the bypass operation itself seemed to start the hormone networks: The surgery patients were receiving a metabolic bonus that diet-induced weight loss alone could not provide.
The bonus power of bypass surgery was something Julio Teixeira had long suspected. Some 15 years ago, during a fellowship at New York Medical College, he observed morbidly obese patients undergo open bariatric surgery—an old-school Roux-en-Y, done with giant incisions and often yielding horrendous complications. When he finished his training in 1998, he developed a simplified, minimally invasive version of the Roux-en-Y. In 2001 he moved to Albert Einstein College of Medicine in New York and began teaching his methods to other surgeons, using the longer-handled tools that had been developed for performing surgeries on obese patients. For four years Teixeira fine-tuned his techniques and ran six-week boot camps where surgeons could learn his procedures.
“By 2005 we realized we were doing more than just obesity surgery; we were really manipulating the metabolism of these patients,” Teixeira says. He noticed dramatic improvements in blood chemistry and in clinical conditions like diabetes, high cholesterol, and hypertension. “These patients, in a month, were off all their meds.” Puzzled because the changes were much too rapid to result from weight loss, he decided to join Laferrère at St. Luke’s seven years ago.
“There are over 200 hormones in the GI tract,” Teixeira explains as we chat in his office at St. Luke’s. All of those hormones are vying to control your eating behavior. Ghrelin drives the urge to eat. Stretch receptors in the stomach signal when to stop. This hardwired system worked well for our hunter-gatherer ancestors constantly struggling to find enough food for survival. In the modern world—where cheap, high-calorie food is available all around—taste, smell, emotion, learning, memory, and food addiction tend to override our biological cues and entice us to eat even when there is no need. “We are living in a time of overabundance, and we are engineered to hold on to these calories. It’s like a trap,” Teixeira says.
Surgeon-scientists like Teixeira are seeking biological manipulations that will help set us free. His work focuses on changing the architecture of the stomach and rerouting the small intestine, which is an exceedingly complex organ—hardly a homogeneous, 23-foot pipe carrying food from the stomach to the large intestine, as was once believed. There are three sections of the small intestine, each lined with unique cells that secrete their own hormones and play distinct roles. If you chop out or bypass certain sections, then, particular hormones can be reduced or eliminated.
The first and shortest section of the small intestine, just under one foot long, is the duodenum, which connects directly to the stomach. The duodenum blends partially digested food with bile, a bitter yellow-green liquid made in the liver that helps digest fats. From there the food passes through the eight-foot midsection of the small intestine, the jejunum, where fingerlike projections absorb vital sugars, amino acids, vitamins, and small proteins. The final stretch of small intestine, the ileum, secretes incretins and absorbs more nutrients before emptying into the large intestine for elimination. By cutting and pasting these intestinal links into new configurations, Teixeira can profoundly reconfigure the body’s chemistry.