Mary Stanford knew the deal. Diagnosed with type 2 diabetes 13 years ago at age 33, she was painfully aware that her weight, which hovered around 250 pounds, was a major factor. She knew all too well about the hazardous complications of diabetes, since her father-in-law had struggled with and eventually died of them. And she recognized that losing just 10 percent of her body weight would improve her symptoms—but simply couldn't keep the pounds off. "You know what you're doing to yourself," says the biotech company senior manager from Port Washington, N.Y. "You get to a point where it takes a toll on you." Desperate, she chose gastric bypass surgery in late 2004, when she'd peaked at a smidgen over 300 pounds. Today, at 46, Stanford weighs 160 and shows no sign of her disease. Last year, she ran the New York City Marathon.
Stanford's story is a potent reminder of how intricately weight is entwined with type 2 diabetes—and an illustration of what many researchers now are calling the most effective treatment. The American Diabetes Association says that almost 90 percent of people newly diagnosed with the disease are overweight; obesity, a body mass index of higher than 30 (197 pounds at 5 feet, 8 inches tall, for example), considerably elevates risk. Because research suggests that one form of weight-loss or "bariatric" surgery—gastric bypass—offers health benefits beyond simply cutting the pounds, medical practitioners and patients are increasingly seeing surgery not as a last resort but as a really good option, as well as an avenue to learn more about the mechanisms behind the disease.
"The insights already beginning to be gained by studying surgical interventions for diabetes may be the most profound since the discovery of insulin," wrote David Cummings, an associate medical professor in the division of metabolism, endocrinology, and nutrition at the University of Washington, in an editorial that appeared in the Journal of the American Medical Association last month.
Cummings's comments accompanied a report by Australian researchers that underscores the promise—and unresolved questions—surrounding surgery to treat diabetes. In a small group of 60 patients with BMIs between 30 and 40, one form of surgery combined with conventional therapy sent the disease into remission in 73 percent of the cases, meaning normal blood sugar levels and no need for diabetes medication. In the therapy-only group, just 13 percent went into remission.
It comes as no surprise to obesity experts that something as drastic as surgery is now being used to make people lose weight. One of the key findings of the JAMA study was that the nonsurgical patients, even with medical and behavioral help following a diet and exercise program, lost only 1.7 percent of their body weight, compared with almost 21 percent in the surgical group. When it comes to preventing diabetes through lifestyle changes, the failure rate runs about 95 percent outside of a research study or similarly intensive program. "There isn't anything that really works for obese people—the heavier you are, the harder it is," says Edward Livingston, chairman of GI/endocrine surgery at the University of Texas Southwestern Medical Center.
But several questions about surgery to treat type 2 diabetes remain. The biggie: Which patients stand to get the biggest benefit? Right now, National Institutes of Health guidelines recommend this sort of surgery only for patients with a body mass index over 40—about 262 pounds at 5 feet, 8 inches tall—and for people with diabetes or other life-threatening disease whose BMI is over 35. "It's a good parameter to use when operating on those who are only obese," says Francesco Rubino, director of the newly created gastrointestinal metabolic surgery program at New York-Presbyterian Hospital/Weill Cornell Medical Center. But that might not be the case, he says, "if we are treating a patient with diabetes. There's a strong need for doing carefully conducted trials."
His program plans to do just that. Meantime, the Cleveland Clinic is recruiting patients for a five-year study that will compare medical therapy by itself with bariatric surgery combined with medical therapy for type 2 diabetics who have a BMI as low as 30. "I can envision a day when mildly obese and even overweight [those with a BMI between 25 and 30] diabetics make even better candidates," says Rubino. "In the end, what affects the choice is the risk of dying from the disease and the risks of the surgery." Patients need to be studied over the long haul, too, not just for a few years. "We haven't felt that the longer-term studies are really sufficient to really know what the risks and benefits are" over 10 or 20 years," says John Buse, president of medicine and science at the American Diabetes Association.
The ideal type of surgery to use for treating diabetes is also not yet known—and there are different variations being developed all the time. The JAMA study looked at laparoscopic adjustable gastric banding, a procedure that uses minimally invasive surgery to put in place a band to cordon off part of the stomach, effectively making it smaller. The more complex gastric bypass procedure Stanford had, which surgically shrinks the stomach and reroutes the digestive tract so that food reaches the lower regions more quickly and less is absorbed, carries greater risk but also potentially higher rewards. While the banding surgery treats diabetes through the gradual beneficial effect of weight loss alone, there's evidence that doing an end run around parts of the digestive tract can send diabetes into remission within days of surgery and promote greater weight loss over the long run.
No one knows exactly why. Theories include the idea that shunting food directly to lower in the intestine stimulates a substance called glucagon-like peptide 1, which can increase insulin production, and that hormones that prompt hunger are damped by rearranging the anatomy. "You may be dramatically changing the release patterns of hormones that are important to controlling appetite and weight," says Garth Ballantyne, director of minimally invasive and telerobotic surgery at Hackensack University Medical Center in New Jersey. Other surgeries are also being studied, including one pioneered by Rubino that keeps the stomach intact but bypasses the uppermost part of the small intestine, thus bringing the hormonal benefits without producing such drastic weight loss. "We can find new operations that might be similar to the most effective operations but maybe cut back on the complexity, particularly for patients who are not morbidly obese," says Rubino.
The ideal time window for treatment is also up for debate. The JAMA study focused on people who had been diagnosed within the past two years and had no major complications. It's not so clear how long it takes for the disease to set in and destroy the pancreas' beta cells, which make insulin. "The later you intervene, the lesser the likelihood of having complete remission," says Rubino. He says there are exceptions—he's seen longtime diabetics achieve remission—but it's ideal to operate early rather than after pancreatic function has severely deteriorated. And no surgery will consistently reverse the secondary effects of diabetes, like diabetic retinopathy, says Sasha Stiles, medical director of the bariatric surgery program at Kaiser Permanente. "For the superobese, who need to lose 50 percent of their body weight, maybe we say, 'Let's go right to bypass,'" says Cummings.
Until more extensive trials are done, researchers and clinicians say that surgery should at least be more fully included as part of the regular menu of care for diabetics who meet the current guidelines. Cummings noted that more than 90 percent of the type 2 diabetics eligible for surgery don't have the procedure, and most probably aren't even informed of the option. Vickie Klubek from Murphysboro, Ill., is a 56-year-old type 2 diabetic whose height and weight put her BMI at more than 37. She's tried everything to lose weight and says she eats well and exercises. No one has told her about gastric bypass, though her doctor has told her to skip doughnuts for breakfast (a food she says she doesn't even like). "Probably, in routine clinical practice, we aren't offering this as a therapeutic option for patients as often as we should," says Martin Abrahamson, medical director at the Harvard-affiliated Joslin Diabetes Center in Boston. Part of that may be due to cost; private insurers won't always cover the surgery and the necessary follow-up, which can run tens of thousands of dollars.
And the timeliness factor should be emphasized. "If you aren't winning with an intensive program [of medical treatment and lifestyle] within six or 12 months, think about the clock ticking on those pancreatic beta cells," says John Dixon, first author of the JAMA study and a researcher at the Centre for Obesity Research and Education at Monash University Medical School in Melbourne, Australia. "We're seeing the tragedy of people who are adolescents and in their 20s having their lives ruined and shortened by diabetes."
It's important to realize, though, that surgery isn't the quick fix it once was thought to be. There are risks; though an editorial in the Archives of Surgery in October put the one-year risk of death for the average patient at about 1 percent, that figure varies from institution to institution. Patients really have to do their homework to find a good surgeon. And the rewards aren't automatic; people can "eat around" these operations and regain the lost weight—bringing the disease back with it. "Surgery is a tool," says Stiles. "Unless you learn your triggers and address your lifestyle issues, diabetes won't stay in remission.""
Mary Stanford says her surgery—at New York-Presbyterian/Weill Cornell—provided an instant silencing of the "demon of wanting to eat all the time." But she was extremely careful to set up new habits to keep herself on the right path. "I made a decision that I'd had my share of cakes and candies in my life and I didn't need to have any more," she says. "The surgery was like a reset button that gave me a second chance." But she had to totally revamp her behavior, from eating to exercise. "You have to understand that it's a chance to make a lifestyle change," she says. In her case, that might even mean a new marathon habit. "I told everyone I wasn't sure if I'd do another one," Stanford says. "But when I crossed the line, I immediately said, 'I'm doing it next year.'"