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Bariatric surgery — a cure for diabetes?
People who could benefit from surgical control of diabetes may not be getting that opportunity.
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Surgical control of type 2 diabetes, although not the current standard of care for the disease, may be coming closer to the mainstream. The surgical treatment of obesity is associated with the subsequent resolution of type 2 diabetes, according to a meta-analysis published in the Journal of the American Medical Association. This widely reported result has prompted researchers to consider surgery a treatment modality for diabetes. Others have gone a controversial step further and suggested that type 2 diabetes, independent of obesity, is an operable disease.
In a 1995 report published in the Annals of Surgery, Pories and colleagues determined gastric bypass to be effective and safe for obesity and its associated morbidities. “No other therapy has produced such durable and complete control of diabetes,” they concluded in the article. Since then, various research groups have sought to determine the mechanisms responsible for surgery-induced diabetes resolution, while clinicians in multiple disciplines continue to ponder whether surgery, despite its chronicled efficacy, is truly the optimal treatment modality for type 2 diabetes.
“Early clinical studies show that surgical control of diabetes can be achieved in patients with BMI below 35,” said Francesco Rubino, MD, chief of Metabolic Surgery at New York Presbyterian Hospital-Weill Medical College of Cornell University. “This does not necessarily mean that surgery should be offered to every patient and regardless of BMI. However, it suggests that the current NIH criteria do not adequately identify all ideal candidates for surgical treatment of diabetes and that many patients who may potentially benefit from surgery are actually being denied an opportunity. More research needs to be done to determine better criteria and not only rely on BMI,” he said.
“Patients undergo bariatric surgery, they intake fewer calories, they lose weight, and subsequently, their diabetes goes away,” Andrew Gumbs, MD, assistant attending surgeon at New York Presbyterian Hospital, told Endocrine Today.
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However, Rubino contested that the improvement in diabetes following surgery is not due to weight loss.
“The assumption has been that these patients develop diabetes because they are obese; therefore, if you treat the obesity, as a result you are treating the diabetes. Unfortunately, that equation has delayed the understanding of what is actually going on,” he said.
In a study reported in the Annals of Surgery in 2004, Rubino and colleagues found that the surgical bypassing of the proximal intestine is what leads to resolution of diabetes, independent of weight loss or decreased food intake.
 Caroline Apovian |
“The evidence that surgery exerts a direct impact on glucose tolerance in diabetic subjects suggests that type 2 diabetes might be remedied specifically by surgical operations that bypass the proximal small bowel,” he wrote.
These operations result in two types of consequences, both of which have potential antidiabetic effects: firstly, elimination of duodenal passage of nutrients, which might offset signals negatively involved in the regulation of insulin secretion and/or action (“proximal hypothesis”); and, secondly, nutrients meet the distal intestine early on, which thereby enhances incretin glucagon-like peptide 1 secretion from the L-cells of the distal intestine (“distal hypothesis”).
Caroline Apovian, MD, director of the Nutrition and Weight Management Center at Boston University Medical Center, is another advocate of the distal hypothesis. She believes that the surgery is “changing the hormonal milieu, so that even before you observe weight loss, the patient is experiencing improvements in insulin sensitivity.”
A more recent study published by Rubino in the Annals of Surgery in 2006, pointed toward the exclusion of the upper intestine (proximal hypothesis) as a primary mechanism of diabetes control.
Is surgery the answer?
“Diabetes is a chronic condition with severe morbidity and mortality, which is fast becoming a worrisome epidemic with potentially dire consequences for the U.S. health care system. If we can reduce the burden of disease, specifically type 2 diabetes which is the focus of this conversation, which is manifesting itself in increasingly younger populations, we can significantly impact society and reduce the health and economic burden associated with all the complications of diabetes down the road,” said Luigi Meneghini, MD, of the Diabetes Research Institute, University of Miami Miller School of Medicine.
 Luigi Meneghini |
Rubino commented that surgery is a “single-shot treatment” modality with important implications, beyond the potential clinical advantages.
“You never achieve durable control of diabetes without continuous treatments,” he said. “The fact that by using a one-time treatment you can induce long-term remission of diabetes suggests that surgery is probably affecting a very important factor in the genesis of the disease.”
“We are mainly interested in improving the health, longevity and quality of life of individuals with type 2 diabetes,” added Meneghini. “There are data that have shown that a bariatric intervention compared with no intervention not only improves quality of life but improves longevity,” he said, referring to a retrospective cohort study published in The New England Journal of Medicine. Adams and colleagues determined the long-term mortality (from 1984 to 2002) among 7,925 patients who had undergone gastric bypass surgery and 7,925 severely obese control patients matched for age, sex and BMI. During a mean follow-up of 7.1 years, adjusted long-term mortality from any cause in the surgery group decreased by 40%, compared with that in the control group (P<.001). Cause-specific mortality in the surgery group decreased by 92% for diabetes (P=.005), according to the study.
“These results represent perhaps the most profound effect on diabetes that we have ever observed,” Rubino said.
Does this mean that type 2 diabetes alone will be an indication for surgery, regardless of the current NIH criteria, which is a BMI >40 or BMI >35 plus a comorbidity related to obesity? “We are heading in that direction; however, we are not there yet,” Rubino said.
According to Alfons Pomp, MD, Leon C. Hirsch Professor of Surgery, chief of the section of laparoscopic and bariatric surgery at Weill Medical College of Cornell University and New York Presbyterian Hospital, researchers are trying to obtain funding to assess patients who do not meet these criteria.
“We are trying to start trials in the United States for patients with a BMI of 30 and above to compare medical control of their diabetes with surgical control,” he told Endocrine Today.
Rubino said that, “while appropriate in patients with obesity alone, the current criteria are not supported by a medical rationale when it comes to diabetes. Indications to surgical treatment of type 2 diabetes should be defined based on a careful and reasonable assessment of risks and benefits, as it happens for any other disease. Diabetes should be no exception.
“I personally do not think that all patients with diabetes, and not even the majority of them, should be operated on,” Rubino said. “There are patients with diabetes who do well with diet and exercise; I would not recommend surgery for those patients.”
All individuals need to modify their behavior and develop healthier lifestyles. There is no “easy way,” according to Donna Rice, MBA, BSN, RN, CDE, who is the Wellness Program Manager at Botsford Center for Lifestyle Management in Novi, Mich. and an Endocrine Today editorial board member. Today, people look for the magic pill or surgery as an easy way to achieve goals; however, in reality, education and lifestyle management are critical for successful diabetes management regardless of the treatment chosen, according to Rice.
“There is a growing debate as to how long should you try lifestyle interventions and nonsurgical therapies before you say that, in the long term, a patient would benefit from a bariatric intervention,” Meneghini added.
Surgery stimulates research
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Photo by Weill Cornell Medical College and Amelia Panico |
“Unfortunately, guidelines for metabolic surgery [as opposed to bariatric surgery] have not been released because it is such a new concept. But that would clearly apply to patients who do not meet the BMI criteria,” Gumbs said, highlighting that metabolic surgery would only be performed in a controlled, clinical trial setting.
Rubino disclosed that new international guidelines for metabolic surgery will be published soon.
“The Diabetes Surgery Summit held in Rome last year has established new guidelines specifically for surgery of diabetes,” he said. “This is an effort to promote a safe and reasonable development of this new approach, based on available evidence. There is no doubt that more clinical trials are necessary to better define the risk/benefit profile in all patients.”
He added: “This is not an easy task. In fact, type 2 diabetes is a heterogeneous disorder and moving toward lower BMI levels increases the chances to find forms of diabetes with different pathophysiologic mechanisms that might be less likely to respond to surgery. We clearly have a lot of work to do.”
Although surgery may not become a mainstream treatment modality for type 2 diabetes, “it might be an ally for pharmaceutical research,” Rubino continued. “Surgery could be used as a tool to identify targets for new medications.”
Apovian added that understanding the mechanisms by which gastric bypass is improving diabetes control is necessary, and then studies are needed to completely understand the mechanism. This would be followed by attempts to mimic that mechanism with a medicine, she said. According to Rubino, the gastrointestinal tract may harbor some potential mechanisms that lead to diabetes. Most of the research he has conducted to date points toward the exclusion of the upper intestine as the primary mediator of diabetes resolution after gastric bypass surgery.
Gumbs said one of the newer operations that surgeons are talking about is the laparoscopic sleeve gastrectomy. He and Pomp have recently published a report in Surgery Today comparing this procedure with the laparoscopic adjustable gastric band in patients with a BMI greater than 60.
“The gastrointestinal tract produces a large number of hormones that can influence glucose metabolism. We should not be surprised that surgical alterations of gastrointestinal anatomy can have an impact on diabetes,” Rubino said. “On the other hand, it is also likely that different operations may elicit different mechanisms of diabetes control.”
New operations in the future may focus on one or another of these mechanisms, according to Rubino. So far, however, operations that are based on the concept of duodenal bypass have proven to be more effective for diabetes.
The documented success of these techniques for obesity and diabetes will undoubtedly lead to further surgical experimentation for patients with diabetes, with or without obesity. As a result, controversy surrounding such interventions may intensify.
“Some endocrinologists say that thinking of surgery for treating diabetes is ‘insane’ because diabetes is a medical condition that is best treated by diet and exercise,” said Rubino. “I am not quite sure that a patient with inadequately controlled diabetes and at risk for amputations, renal failure, blindness, stroke and death would agree that a surgical option is insane as a concept. Surgery is actually the best promise we have ever had to make a significant impact on diabetes, whether it is used to treat an individual patient or to open new avenues for research.” – by Rebekah Cintolo
For weight loss and/or diabetes control, which type of bariatric surgery do you prefer?
Bariatric surgery’s effect on diabetes: Perspective from Endocrine Today’s Chief Medical Editor
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The unproven issue with bariatric surgery is the durability of the antidiabetic effect. Since we know that there is a progressive loss of beta cell function after the diagnosis of diabetes, could the disease re-emerge after time when further loss of beta cell function led to the re-appearance of hyperglycemia? This happens with almost all current medications for diabetes and there is no reason to suppose that surgery is any different.
A long-term durability trial similar to ADOPT is required to differentiate surgery from medications in this regard. The surgeons omit an additional possibility to explain the almost immediate effect of surgery on glucose control. Almost all hyperglycemic, recently diagnosed diabetic patients have reversible glucose toxicity at the level of the beta cell. Thus, acutely lowering food intake reduces prandial glucose excursions and improves endogenous insulin secretion by overcoming this glucose toxicity. This effect of surgery is no different than starvation, which will effectively treat most forms of diabetes, at least in the near term.
Alan J. Garber, MD, PhD, is a Professor in the Departments of Medicine, Biochemistry and Molecular Biology, and Cellular & Molecular Biology at Baylor College of Medicine, Houston, and is the Chief Medical Editor of Endocrine Today.
For more information:
- Adams TD, Gress RE, Smith SC, et al. Long-term mortality after gastric bypass surgery. N Engl J Med. 2007;357:753-761.
- Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292:1724-1737.
- Gagner M, Gumbs AA, Milone L, et al. Laparoscopic sleeve gastrectomy for the super-super-obese (body mass index .60 kg/m2). Surg Today. 2008;38:399-403.
- Gumbs AA, Modlin IM, Ballantyne GH. Changes in insulin resistance following bariatric surgery: role or caloric restriction and weight loss. Obes Surg. 2005;15:462-473.
- Moo TA, Rubino F. Gastrointestinal surgery as treatment for type 2 diabetes. Curr Opin Endocrinol Diabetes Obes. 2008;15:153-157.
- Pories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg. 1995;222:339-350.
- Rubino F, Forgione A, Cummings DE, et al. 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.