AACE: Surgery Proposed for Intractable Type 2 Diabetes

SEATTLE, April 12 -- For long-term remission of refractory type 2 diabetes, a surgical procedure akin to gastric bypass has just entered clinical trials in Europe, investigators said here today.

In the two patients treated with an ileal interposition technique, there was a normalization of hemoglobin A1c levels within four months of surgery, commented Karen E. Foster-Schubert, M.D., of the University of Washington in Seattle, during a general session on bariatric surgery at the American Association of Clinical Endocrinologists meeting.

The HbA1c levels reverted to normal (below 7%) despite a modest BMI gain in one patient, and no change in BMI in the other, she said.

The European trials are predicated on the reduction in glucose intolerance and improvement in beta cell function, a so-called diabetes cure, seen frequently after bariatric surgery.

They are attributable to altered metabolic factors that could, in turn be the target of this new type of "diabetes surgery," commented Jeffrey I. Mechanick, M.D., of Mount Sinai School of Medicine in New York.

The improvement, or even disappearance, of diabetes is incidental to the bariatric procedure, said Dr. Mechanick in an interview. "For a long time we thought it was attributable to the weight loss or due to the decreased fat."

Instead, investigators have found, bariatric surgery, independent of weight loss, alters metabolic factors such as the hunger-regulating peptide hormone ghrelin (as a result of decreased gastric mass). In addition, bariatric surgery results in increases in peptide YY which has an effect on satiety, and GLP-1, which affects gastric motility and beta-cell mass.

And while bariatric procedures can send type 2 diabetes into remission indefinitely in anywhere from 40% to nearly 100% of cases (depending upon the type of procedure), they often do so at the cost of malabsorption and nutritional deficiencies that can lead to new metabolic complications such as anemias, osteoporosis, acidosis, and secondary hyperparathyroidism.

But in animal models and in two European patients, diabetes was resolved by the investigational ileal interposition technique. The procedure involves transposition into the duodenum of a 10 cm to 20 cm segment of the distal ileum, complete with its blood supply and reservoir of glucagon-like peptide 1 (GLP-1)-secreting cells.

With this ileal interposition procedure "you have no net loss of intestinal absorption, there's going to be no nutrient deficiency, and there's no malabsorption, said Dr. Mechanick.

"But now what you've done is when food enters into the intestine it hits those GLP-1 producing cells almost immediately, and it's almost like taking exenatide [Byetta]: you have high levels of GLP-1, you get increased beta-cell mass, so you correct that beta-cell defect associated with type 2 diabetes."

The end result appears to be a healthier response by the pancreatic beta cells, without hyperglycemia, and theoretically, little or no malabsorption, Dr. Mechanick noted.

"Obviously you're disrupting, subverting a natural sequence, so naturally it wouldn't be surprising if we later find out that there were some problems," he said.

For the present, bariatric surgery is limited in the United States only to treatment of the morbidly obese -- people with body mass indices (BMI) greater than 40 with no co-morbidities, or BMIs from 35 to 40 with co-morbidities, but there appears to be interest in bariatric surgery for patients below those thresholds who have significant metabolic problems from type 2 diabetes, Dr. Mechanick said.

Issues that need to be resolved with strong levels of evidence include who should have bariatric surgery, which procedure is better for which patient or subsets of patients such as adolescents, the elderly, or the super-obese patient (BMI > 50).

"If you look at short-term benefit, biliopancreatic diversion with a duodenal switch has the best short-term percent of excess weight loss, and in fact has the best long-term excess weight," Dr. Mechanick said. "Between the band and the bypass, the bypass has more short-term loss of excess weight, but possibly in the long-term, five to 10 years, those two curves approximate each other and they may be comparable."