Scientists spot key players in surgery’s surprising ability to reverse diabetes
Just in time to combat the obesity epidemic sweeping the United States, a surgery called gastric bypass is riding a host of molecular and clinical findings to emerge as the preferred operation for severely overweight people. There is no shortage of patients; fully one-third of U.S. adults are now obese.
Gastric bypass has gained popularity in part because it takes the pounds off. The operation leaves the stomach smaller, meaning a patient gets full faster, eats less and loses weight at a steady pace. Other common obesity surgeries have those effects too, but gastric bypass also reverses type 2 diabetes in most people, an outcome that bordered on alchemy when first noticed years ago.
New research clarifies the molecular players that make this medical sleight of hand possible, as well as revealing other potential payoffs of the digestive changes — less heart disease, fewer breathing problems and lower blood pressure.
Electing to have major surgery is a tough call; gastric bypass doesn’t always succeed. Patients can backslide, regaining lost weight. And about 10 percent of the surgeries have complications that can result in infections, blood clots or the need for repeat surgery.
But many who witness the effects of gastric bypass firsthand suggest that the hard evidence has now tipped the scales in favor of the operation.
“Everything we do in medicine is a risk-and-benefit assessment,” says Guilherme Campos, a surgeon at the University of Wisconsin–Madison. For very obese patients, he says, “the gauge is whether the risk of the present condition may be higher than the risk from the surgery itself. We think the risk of the condition is higher.”
Going all in
Like poker players pushing their chips into the center of the table, up to 70 percent of people in the United States who elect to have weight-loss surgery now go with gastric bypass. It’s a permanent change that diverts food around much of the stomach and the upper portion of the small intestine. Bypass surgery far outpaces gastric banding, a reversible operation that is the second most popular choice at about 20 percent. Other options exist but are much less common.
“I think gastric bypass will continue to be the mainstay of procedures because we understand how it works now,” says Robin Blackstone, a surgeon and president of the American Society for Metabolic and Bariatric Surgery who practices at the Scottsdale Healthcare Bariatric Center in Arizona. “It’s hitting obesity on so many fronts.”
The foremost front is food intake. Patients benefit not only from a smaller stomach, but also from chemical changes that occur as a result of the gastric switcheroo. Bypass surgery quells appetite by knocking back a hunger hormone called ghrelin, which is normally secreted by the stomach lining in response to food. And levels of an appetite stopper called peptide YY have been shown to increase five times as much in response to food among gastric bypass patients compared with levels in people who didn’t get the surgery. A Columbia University team reported last year in the Journal of Clinical Endocrinology & Metabolism that levels of a digestive hormone and appetite inhibitor called oxyntomodulin are doubled in diabetic gastric bypass patients only one month after surgery, whereas similarly obese people who lost weight by dieting saw no increase.
Hormonal switch flipping also appears to give bypass its power against type 2 diabetes, the adult onset kind.
When a person eats, the pancreas cranks out insulin — the hormone that regulates how cells burn sugars for energy. Patients with type 2 diabetes typically make insulin, but their cells resist its effects and leave too much sugar circulating in the blood.
Within weeks of gastric bypass, insulin resistance disappears in most patients, says John D. Scott, a surgeon at the Greenville Hospital System University Medical Center in South Carolina. “Gastric bypass surgery kind of jump-starts that whole process,” he says.
In 2006, a research team at the Hospital Clínic Universitari in Barcelona established that only six weeks after gastric bypass surgery, patients (while still obese) make substantially more of the hormone glucagon-like peptide 1 in response to a meal than they did before having the operation. Shuttling food directly to the middle portion of the small intestine boosts GLP-1, which keeps insulin-making cells alive, delays carbohydrate absorption and boosts insulin supplies as needed — roles that many scientists believe are instrumental in knocking back insulin resistance.
While GLP-1 may do much of the diabetes-reversing job, more recent studies suggest that it has helpers. A 2008 study from researchers at East Carolina University in Greenville, N.C., found that gastric bypass patients have a decrease during the first year after surgery in a compound called IKK-beta, which is known to sabotage insulin signaling. Increases in growth hormone seen within six months of gastric bypass surgery coincided with improved insulin sensitivity. And changes in a gut hormone called glucose-dependent insulinotropic polypeptide also seem to contribute to diabetes reversal.
By skirting the lower stomach and upper small intestine, the surgery reduces the amount of sugars being absorbed from meals, lessening the blood sugar levels that the body must handle. The drop in calories throws the body into what scientists call “negative energy balance.” That may help to regulate glucose metabolism and stop diabetes in its tracks, scientists at Catholic University in Rome reported in a 2009 analysis in Diabetes & Metabolism.
Such changes may extend to some of the body’s most basic biology. In April, members of the Columbia team and their colleagues reported in Science Translational Medicine that gastric bypass patients who had lost 20 pounds showed a dramatic decrease in blood levels of certain amino acids, the building blocks of proteins. This effect didn’t occur in a group of obese people who had lost 20 pounds by dieting. In studies of animals on high-fat diets, high amino acid levels in the blood have been linked to insulin resistance.
Taken together, these biological effects seem to give gastric bypass an edge over stomach banding — in which doctors insert an adjustable band around the stomach, constricting it and limiting how much it can hold at any time. Banding makes a person feel full faster, and the operation succeeds in many people because they eat less. But because the food still takes its normal path through the digestive system, banding doesn’t trip hormonal switches the way gastric bypass does, says Edward Mason of the University of Iowa in Iowa City, who pioneered gastric bypass surgery for obesity in the 1960s.
Other studies have proved bypass’s mettle by pitting it directly against banding. A Swedish study of more than 2,000 obese people who underwent surgery found that after 10 years, gastric bypass patients had lost 25 percent of their body weight, on average, compared with 14 percent among banding patients. The researchers reported the findings in the New England Journal of Medicine in 2007.
Bypass’s diabetes-busting ability has also proved superior. Campos, while at the University of California, San Francisco, found that type 2 diabetes disappeared in three-fourths of gastric bypass patients but in only half of those getting banding. That report appeared in the February Archives of Surgery.
And the benefits of bypass aren’t limited to diabetes. The procedure decreases a person’s risk of heart attack by about half, Scott reported in June in Orlando at a meeting of the American Society for Metabolic and Bariatric Surgery. Isaac Samuel of the University of Iowa reported at the same meeting that of 81 migraine sufferers who underwent gastric bypass, 57 had complete resolution of their migraines after at least a year. Fifteen others had partial improvement. These findings complement previous studies showing that high blood pressure falls among bypass patients and that bypass eliminates or improves sleep apnea — a breathing disorder linked to long-term health problems — in about 90 percent of patients.
To confer such benefits, though, gastric bypass must be done well. It’s a tricky surgery that is difficult to master. Scott says that success rates have risen in recent decades with the development of a more experienced cadre of surgeons, hospital support teams devoted to the patients and the advent of laparoscopy — in which the operation is performed using a series of fingernail-sized incisions.
But the surgery still carries risks, with most severe problems occurring soon after the operation. The risk of dying within a month of gastric bypass surgery, primarily from complications, is around 2 per 1,000 patients in centers that do a lot of obesity surgery, data from the American Society for Metabolic and Bariatric Surgery show.
“That’s about the same risk as a hip replacement,” says John Morton, a surgeon at Stanford University School of Medicine.
Gastric bypass patients risk bloating and nausea if they eat too much or wash a meal down with too much fluid. Bypass also ushers alcohol into the bloodstream rapidly. In May in Chicago, researchers from the Karolinska Institute in Stockholm reported at Digestive Disease Week that blood alcohol levels spike faster and take longer to come down in gastric bypass patients than in others, suggesting an increased risk of alcohol abuse. And studies by Morton have shown that a 5-ounce glass of red wine runs up blood-alcohol levels in these patients to nearly 0.09 percent, over the legal limit.
Stomach banding carries less surgical risk and no added alcohol danger. But it can exacerbate heartburn, and more banding patients need repeat surgery than bypass patients.
Campos thinks gastric bypass outweighs other surgical options in most cases, but he also says that for severely obese patients any weight-loss surgery “is a better option than no surgery.” Though 200,000 to 250,000 people get some form of obesity surgery each year in the United States, some estimates suggest that about 15 million would benefit from it.
Many insurance companies cover obesity surgery. Afterward, a patient requires less medication for diabetes and high blood pressure, says surgeon Henry Buchwald of the University of Minnesota. He and colleagues reported in 2008 in the American Journal of Managed Care that laparoscopic weight-loss surgery had a payback time of just two years.
But many employers don’t include the surgeries in plans covering workers. Buchwald says some people still don’t view obesity as a life-threatening condition. “Employers might say, ‘It’s cheaper if we don’t cover obesity surgery,’” he says. “But they wouldn’t say, ‘We can get a better deal by not covering cancer of the colon.’ ”
Others think obesity is something that can be fixed without surgery, that all a person needs is willpower. But the truth is, most dieting attempts fail.
“The story of our patients is a lifetime of trying,” Buchwald says. Although success stories on TV dieting shows may be heartening to watch, there are millions of severely obese people in the United States for whom dieting hasn’t worked. Ultimately, they are the biggest losers in the obesity epidemic.
H. Buchwald et al. Bariatric surgery: A systematic review and meta-analysis. Journal of the American Medical Association, Vol. 292, October 13, 2004, p. 1724. [Go to]
G.M. Campos et al. Better weight loss, resolution of diabetes, and quality of life for laparoscopic gastric bypass vs banding results of a 2-cohort pair-matched study. Archives of Surgery, Vol. 146, February, 2011, p. 149.
J.L. Chan et al. Peptide YY levels are elevated after gastric bypass surgery. Obesity, Vol. 14, 2006, p. 194.
C.W. Chia et al. Exogenous glucose-dependent insulinotropic polypeptide worsens post-prandial hyperglycemia in type 2 diabetes. Diabetes, Vol. 58, 2009, p. 1342.
P.Y Crémieux et al. A study on the economic effects of bariatric surgery. American Journal of Managed Care, Vol. 14, 2008, p. 589.
Y. Gunay et al. Roux-en-Y gastric bypass (RYGB) achieves substantial resolution of migraine headaches in the severely obese. Abstract # PL-111, American Society for Metabolic and Bariatric Surgery, June 2011, Orlando.
A. Keidar. Bariatric surgery for type 2 diabetes reversal: The risks. Diabetes Care, Vol. 34, May 2011. Supplement 2 S361-S266. doi: 10.2337/dc11-s254
J. Korner et al. Exaggerated GLP-1 and blunted GIP secretion are associated with roux-en-y gastric bypass but not adjustable gastric banding. Surgery for Obesity Related Diseases, Vol. 3, 2007, p. 597.
B. Laferrère et al. Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss. Science Translational Medicine, Vol. 3, April 27, 2011, p. 80re2. DOI: 10.1126/scitranslmed.3002043
B. Laferrère et al. Rise of oxyntomodulin in response to oral glucose after gastric bypass surgery in patients with type 2 diabetes. Journal of Clinical Endocrinology and Metabolism Vol. 95, August 1, 2010, p. 4072.
G. Mingrone and L.G. Castagneto-Gissey. Mechanisms of early improvement/resolution of type 2 diabetes after bariatric surgery. Diabetes and Metabolism, Vol. 35, December, 2009, p. 518.
R. Morinigo et al. Glucagon-like peptide-1, peptide YY, hunger, and satiety after gastric bypass surgery in morbidly obese subjects. Journal of Clinical Endocrinology and Metabolism, Vol. 91, May 2006, p. 1735.
M.P. Ostlund et al. The risk of alcohol dependence is increased after gastric bypass surgery. Abstract # 266. Digestive Disease Week, May, 2011, Chicago.
J.D. Scott et al. Bariatric surgery reduces risk of major adverse cardiovascular events in morbidly obese adults. Abstract # PL-105, American Society for Metabolic and Bariatric Surgery, June 2011, Orlando.
L. Sjöström et al. Effects of bariatric surgery on mortality in Swedish obese subjects. New England Journal of Medicine, Vol. 357, August 23, 2007, p. 741.
T.D. Adams et al. Long-Term Mortality after Gastric Bypass Surgery. New England Journal of Medicine, Vol. 357, Aug. 23, 2007, p. 753.
N. V. Christou et al. Surgery Decreases Long-term Mortality, Morbidity, and Health Care Use in Morbidly Obese Patients. Annals of Surgery, Vol. 240, September 2004, p. 416.
J. Himpins et al. Long-term Outcomes of Laparoscopic Adjustable Gastric Banding. Archives of Surgery, Vol. 146, online March 26, 2011, p. 802. doi:10.1001/archsurg.2011.45
E. Karra et al. The role of peptide YY in appetite regulation and obesity. Journal of Physiology, Vol. 587.1, 2009, p. 19. doi: 10.1113/jphysiol.2008.164269
C.W. Le Roux et al. 2007 Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass. Annals of Surgery, Vol. 246, 2007, p. 780.
R. Morinigo et al. GLP-1 and changes in glucose tolerance following gastric bypass surgery in morbidly obese subjects. Obesity Surgery, Vol. 16, December 2006, p. 1594.
G.A. Woodard et al. Impaired Alcohol Metabolism after Gastric Bypass Surgery: A Case-Crossover Trial. Journal of the American College of Surgeons, Vol. 212, February 2011, p. 209.
Mayo Clinic’s gastric bypass page: [Go to]
American Society for Metabolic & Bariatric Surgery: [Go to]
Note: To comment, Science News subscribing members must now establish a separate login relationship with Disqus. Click the Disqus icon below, enter your e-mail and click “forgot password” to reset your password. You may also log into Disqus using Facebook, Twitter or Google.