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Another outcome of bariatric surgery?
New techniques show promise in reversing type 2 diabetes.
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SEATTLE — Although bariatric surgery is beneficial in helping obese patients lose weight, new data suggest it may also play a role in treating type 2 diabetes.
Several experts presented data on bariatric surgery, both for weight loss and the reversal of diabetes, at the American Association of Clinical Endocrinologists 16th Annual Meeting and Clinical Congress.
“There is an undeniable correlation in the relationship between bariatric surgery and endocrinology,” Jeffrey I. Mechanick, MD, director of metabolic support and an associate clinical professor of medicine in the division of endocrinology, diabetes and bone disease at Mount Sinai Hospital, said in a press release. “We’ve seen the stratification of various procedures on the amount loss of excess weight. In some cases, we have seen a significant remission in the rate of diabetes and an unexplained regeneration of the beta cell.”
Bariatric surgery continues to grow in popularity because more surgeons are performing it and more insurance companies are willing to pay for it, according to Brant K. Oelschlager, MD, an associate professor and director of the Swallowing Center, the Center for Videoendoscopic Surgery and the Bariatric Surgery Program at the University of Washington–Seattle.
Approximately 120,000 procedures were performed in 2004, 10 times the number performed in 1994. The number of procedures performed every year increases 40% to 50%, Oelschlager said, and approximately 10 million people meet eligibility criteria for bariatric surgery.
New treatment approach
Bariatric surgery may promote long-term remission of type 2 diabetes in normal-weight and overweight patients, according to researchers. Karen E. Foster-Schubert, MD, acting instructor in the division of metabolism, endocrinology and nutrition at the University of Washington–Seattle, discussed Roux-en-Y gastric bypass, a procedure successful in reversing type 2 diabetes in 84% of patients based on a meta-analysis of 22,094 patients. After Roux-en-Y surgery, many patients were taken off of diabetes medications and insulin before they left the hospital, Foster-Schubert said.
Bariatric surgery may lead to diabetes remission in 40% to 100% of patients. With the surgery, however, patients can experience a number of adverse conditions: malabsorption, nutritional deficiencies, osteoporosis and hyperparathyroidism.
A new investigational surgical procedure for diabetic, non-obese patients has been developed. The duodenal jejunal bypass — the Roux-en-Y gastric bypass without gastric restriction — led to resolution of diabetes in two patients who had been taking insulin and rosiglitazone prior to surgery and had high fasting glucose and insulin values. The surgical model was developed in animals first to explore the effects of duodenal-jejunal bypass on diabetes in the Goto-Kakazaki rat. Surgeons in Brazil then tried this technique in humans (Cohen RV et al).
This technique was successful in normalizing HbA1c levels within four months of the surgery. The two patients also experienced dramatic decreases in fasting glucose and fasting insulin almost immediately. After the duodenal bypass, the patients did not lose weight and their BMI was maintained (Cohen RV et al).
The results suggest a clear improvement in glucose homeostasis, however the precise mechanism bringing about the improvement remains to be elucidated, according to Foster-Schubert.
Another model was developed that is similar to the duodenal jejunal bypass but does not exclude food from the proximal intestine.
Both have been tested in animal models with similar dramatic results. Researchers found that, in rats, when the surgery bypassed the proximal intestine, there was a resolution of type 2 diabetes. The researchers from this study suggested that this type of proximal intestinal bypass could play a role in treating diabetes (Rubino F et al).
Surgical influence on diabetes
Researchers Francesco Rubino, MD, and Jacques Marescaux, MD, FRCS, at the University Louis Pasteur in France, expressed their confidence in the duodenal jejunal exclusion technique and its role in diabetes research in the Annals of Surgery in 2004.
“The demonstration that surgery can directly influence type 2 diabetes, as opposed to being a secondary effect of the treatment of obesity, is not a mere intellectual exercise. It implies the new concept of ‘diabetes surgery’ as an independent new surgical discipline for which surgeons need to develop specific knowledge and competence,” the researchers wrote.
All bariatric procedures are not created equal, however. Some techniques hint at curing diabetes, whereas others, like Roux-en-Y gastric bypass, produce the greatest weight loss.
“Could this just be starvation and then weight loss that’s coming along after the procedures that is promoting this amelioration of diabetes, or is there something special going on here?” Foster-Schubert said. “If this is all due to starvation followed by weight loss, we would expect rates of remission of diabetes and improved glucose homeostasis to occur equally across all of these procedures. They all involve an initial period of no food intake, followed by slow advancement of the diet, and by this time weight loss from the procedure begins.”
Hormonal influence
The data are provocative, according to Foster-Schubert, who pointed out that other factors may also be playing a role. Hormonal mechanisms may have a mediating effect on body weight and glucose homeostasis, she said.
“The fact that these individuals experience such a dramatic decrease in their appetite has led others to postulate that some hormones involved in regulating food intake might be involved,” Foster-Schubert said.
Ghrelin, a peptide hormone produced primarily by the stomach and proximal small intestine, powerfully stimulates appetite and food intake and is an interesting candidate for evaluation. Ghrelin increases with weight loss and decreases with weight gain; in humans, following Roux-en-Y gastric bypass, David Cummings et al first showed ghrelin levels fall despite major weight loss, and others have largely corroborated this decrease, or at least that levels remain stable despite weight loss, according to Foster-Schubert.
Decreased ghrelin secretion after Roux-en-Y gastric bypass could improve glucose homeostasis, she said. Data support the notion of ghrelin as a hormone involved in both glucose, as well as body weight regulation.
Distal intestinal hormones may also play a role, including peptide YY and glucagon-like peptide-1 (GLP-1), which are both secreted from L cells in the distal small intestine and colon. Data have demonstrated that gastric bypass dramatically increases peptide YY and GLP-1 levels.
Another surgical technique, ileal interposition, which was actually developed for different reasons than weight loss, uses a 10-cm distal transsection and proximal re-anastomosis with no malabsorption, led to increased plasma peptide YY, GLP-1 and reductions in food intake and body weight after surgery in animal models (Strader AD et al).
There are quite likely other hormone mediators yet to be discovered, Foster-Schubert said.
Post-procedure tips
“Ultimately, what we’re going to have to do is weigh the relative benefits and the potential risks [from bariatric surgery] with respect to nutrition and metabolites,” Mechanick said.
“With this type of drastic weight loss, it is common to encounter complications like metabolic bone disease, hyperparathyroidism and osteoporosis after the surgery,” Mechanick said. “The endocrinologist plays an important role in the treatment of these problems.” – by Katie Kalvaitis
For more information:
- Foster-Schubert, KE, Mechanick JI, Oelschlager BK. Bariatric surgery 2007. Presented at: The American Association of Clinical Endocrinologists 16th Annual Meeting and Clinical Congress. April 11-15, 2007; Seattle.
- Rubino F, Forgione A, Cummings DE. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg. 2006;244:741-749.
- Strader AD, Vahl TP, Jandacek RJ, et al. Weight loss through ileal transposition is accompanied by increased ileal hormone secretion and synthesis in rats. Am J Physiol Endocrinol Metab. 2005;288:447-453.