Gastric Bypass Surgery Explored as Cure for Type 2 Diabetes

Source: Medscape Medical News

April 13, 2007 (Seattle) — A bariatric surgery procedure used for treating severe obesity is now being explored as a cure for type 2 diabetes mellitus in normal-weight and moderately overweight patients with diabetes. Specific recommendations for using surgery in these patients are expected to appear this summer, according to a presentation here at the annual meeting and clinical congress of the American Association of Clinical Endocrinologists.

When used as a last resort for weight management, certain gastric bypass procedures have been known to completely reverse, or at least mitigate, type 2 diabetes. Until recently, researchers had assumed that weight loss alone was somehow responsible for this benefit. However, new research in rodents and very preliminary work in humans suggest that hormonal and metabolic changes caused by the surgery must be responsible, not simple weight loss, said Karen Foster-Schubert, MD, acting instructor at the University of Washington in Seattle.

"We really don't know what is being affected yet," Dr. Foster-Schubert told Medscape about the mechanism of diabetes reversal. Research in the laboratory of her colleague, David E. Cummings, MD, of the University of Washington, shows that ghrelin, a recently discovered peptide that stimulates appetite, is decreased after gastric bypass surgery. Other peptides, including the distal small intestine hormone peptide YY (PYY), and glucagon-like peptide 1 (GLP-1), secreted by intestinal L cells, increase after the operation, she said.

Dr. Foster-Schubert reported on bypass operations performed on 2 mildly overweight patients under the care of Francesco Rubin, MD, of the Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD) in Strasbourg, France, and the Catholic University of Rome, Italy, and discussed at the International Conference on Gastrointestinal Surgery to Treat Type 2 Diabetes (the "Diabetes Surgery Summit") held in Rome, March 29-31, 2007. The data showed that duodenal bypass dramatically lowered fasting glucose, fasting insulin, and hemoglobin A1c levels in these 2 patients within 1 month after surgery. Yet the body mass indexes (BMIs) of these patients have remained stable during 9 months of observation. One patient has had a stable BMI of approximately 27 kg/m2, while the other patient's BMI has ranged from 29 to 30 kg/m2. (A normal-weight BMI is defined as 18.5 to 24.9 kg/m2; overweight is 25 to 29.9 kg/m2; and obesity starts at 30 kg/m2, with "super super obesity" starting at 60 kg/m2.)

The surgical technique discussed by Dr. Foster-Schubert, Roux-en-Y gastric bypass (RYGB), is one of several procedures indicated for weight reduction. A recent meta-analysis of 22,094 patients showed that 84% experienced complete reversal of type 2 diabetes mellitus, with most stopping their oral medications or insulin injections before leaving the hospital, Dr. Foster-Schubert said.

The ethics of using RYGB to treat a disease that can be managed medically might be controversial, Dr. Foster-Schubert allowed. Those who participated in the Diabetes Surgery Summit have announced that they will publish recommendations for treatment by this summer, she added.

Guidelines from the National Institutes of Health have set a BMI of 40 kg/m2 or greater as the threshold for bariatric surgery, according to Jeffrey I. Mechanick, MD, associate clinical professor of medicine at Mount Sinai Medical Center in New York City. The surgery can cause a variety of complications, including electrolyte abnormalities, nutrient deficiencies, kidney stones, and osteoporosis, he said.

"There is an interest among bariatric surgeons in doing [surgery for diabetes]," said Dr. Mechanick during an informal discussion with reporters. "This is going to become an issue between the endocrinologists and the surgeons." He added, "There's an economic incentive. With more and more drugs, there will be less need for bariatric surgery and a greater need for metabolic surgery and diabetes surgery."

Drs. Foster-Schubert and Mechanick both expect many patients with type 2 diabetes to want this surgery, despite its inherent risks, including the risk of death. "It's a lot of heartache and headache" to have diabetes, Dr. Foster-Schubert told Medscape. "I expect a pretty large percentage of individuals would be interested, at least in exploring the risks and benefits."

This research was independently funded. The authors report no relevant financial relationships.

AACE 16th Annual Meeting and Clinical Congress: General Session. Presented April 12, 2007.