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Gastrointestinal Surgery as Treatment for Type 2 Diabetes

Jun 3, 2008

Francesco Rubino M.D.Chief, Section of Gastrointestinal Metabolic Surgery, Weill Cornell Medical College of Cornell University-New York is part of the 1st World Congress on Interventional Therapies for Type 2 Diabetes. He has done considerable work in researching surgery for diabetes control and has agreed to share his insights with you, our readers. He begins a 2 part series Gastrointestinal Surgery as Treatment for Type 2 Diabetes.

Gastrointestinal Surgery as Treatment for Type 2 Diabetes
Francesco Rubino M.D.Chief, Section of Gastrointestinal Metabolic Surgery
Weill Cornell Medical College of Cornell University-New York
Presbyterian Hospital

Part 1 of 2
There is now a substantial body of evidence showing that gastrointestinal surgery can induce long-term remission of type 2 diabetes. This is well documented in several studies of obese diabetic patients undergoing bariatric surgery as well by smaller studies and case reports in less obese diabetic patients. The pathophysiologic basis of the improvement in diabetes after surgery is still unclear; however the dominant hypotheses involve changes in hormone signaling from the small bowel. Surgery therefore provides not only a promising therapeutic option but also a unique opportunity to better understand the pathophysiology of this disease. Not surprisingly, the interest for this emerging field is rapidly growing in the scientific community and among the public at large.

The growing attention to the topic over the last few months follows an event held last year in Rome, when about 60 international diabetes experts, endocrinologists, surgeons and scientists gathered in the Eternal City for the first International Consensus Conference on Gastrointestinal Surgery for the Treatment of Type 2 Diabetes. Known as the “Diabetes Surgery Summit” the Rome’s Consensus Conference has established recommendations for clinical practice and to guide research in this field (a position statement is being prepared for publication). Ever since, an entirely new concept has gained acceptance and is at the center of much debate in the medical community:  the notion of “diabetes surgery”, that is, surgery to intentionally treat diabetes.

While interest about diabetes surgery grows the issue, however, remains controversial. In fact, the concept that a surgical procedure may be used to treat diabetes is a very radical departure from how diabetes has been treated for thousands of years.

Some traditional diabetologists feel “bothered” by the idea; others are skeptic; many are concerned for the risk of surgery. A few say that thinking about surgery as just a way to treat diabetes “doesn’t make sense because there are lots of (more reasonable) ways to treat the disease”.  

Yet, the number of patients with vanishing diabetes after surgery is mounting. Hundreds, thousands of patients who once where taking shots and pills, often with poorly controlled blood sugar levels, are now normoglycemic, have normal or dramatically improved lipid levels and struggle much less to control their blood pressure. Furthermore, these effects are not a transient phenomenon. Many of these patients remain normoglycemic for over a decade (Pories, Ann Surgery 1995), possibly for life, and their diabetes-specific risk of death is reduced by 90% according to a study published in the New England Journal of Medicine last summer. All this, after a single, one-shot type of treatment: surgery.

Surgery for Diabetes: A Revolutionary Concept
The possibility to achieve long-term remission of diabetes is revolutionary, per se. When I was at medical school, not long ago indeed, I was taught that diabetes is an incurable disease. Still now, medical students can hear the same concept every day. Textbooks describe diabetes as a chronic, irreversible illness. Doctors carefully instruct their patients that suspending drugs, forget insulin, invariably results in disease progression raising the risk of complications.

All this is at odds with the fact that up to 80% or more of patients who undergo certain bariatric operations experience long-term, medication-free remission of diabetes. Considering just the magnitude of the effect, it is unprecedented and inexplicable with conventional thinking of the disease. Maybe just because of this surgery should be regarded not just as an opportunity to broaden the therapeutic options but (maybe even more so), as one of the most promising lead to the origin of the disease.
Skeptics would argue that a surgical operation is too drastic a measure to treat diabetes, when one could just use pills and shots. Yet, it is not true that pills and shots can cause remission of diabetes or achieve adequate control in everyone. Medical treatment of diabetes is less than adequate in way too many patients. Furthermore, as complications associated with diabetes progress, the need for more intensive management is necessary adding cost of pharmacologic therapy to the cost directly related to treating the complications of diabetes.

Many of those who see surgery as extreme therapy for diabetes are concerned about the death rate of operations like gastric bypass and the alike. They suggest that the potential benefits of surgery may not stand the upfront risk of dieing from the procedure.

One could argue that surgery is today an accepted treatment modality for a variety of illnesses for whom taking the risk of an operation does not generate the same concern. Yet, these illness are not necessarily more severe than diabetes.
For instance, if a patient has recurrent abdominal pain or develops cholecystitis due to the presence of stones in his gallbladder, no one would argue that removing his or her gallbladder is a wise idea.  However, mortality rates of elective cholecystectomy range between 0.26% and 0.6%, (Khuri et al; Ann Surg 2001), not much different than the 0.22%-0.34% rates reported after bariatric surgery (Buchwald et al. Surgery 2007).

Furthermore, in patients with significant coronary or carotid artery stenosis consideration is given to surgical operations associated to an operative mortality that can be 5-10 folds higher than that from bariatric surgery. Considering that the risk of disability or death from a poorly controlled diabetes is not trivial and diabetes is undeniably a much less “benign” condition than having stones in a gallbladder, surgery to treat diabetes may be seen as a much less drastic a measure than one might initially think.

There is no doubt however, that the dangers of surgery are not just the operative mortality.

Many of the operations aren’t harmless and can cause serious problems such as infections, gallstones formation, hernias, anemia, severe hypoglycemia, and some of these complications can require additional surgery to fix. Like for any other situation, the decision to undergo an operation should be based on the risk-benefit ratio.

Diabetes Surgery: When is it Indicated?
While a robust body of evidence and several decades of experience with bariatric surgery suggest that in patients with both diabetes and severe obesity (Body mass index > 35kg/m2) surgery should be indicated, it remains unclear whether the benefits outweigh the risks of short- and long-term complications also in moderately obese or non obese patients.

Although many colleagues surgeons have recently began to operate on less obese patients with diabetes, the experience in this patients population is limited. Adequate clinical studies, ideally comparing surgery to conventional therapies are necessary to define who is an ideal candidate to surgical treatment of diabetes.

Some enthusiast proponents envision a day when surgery will become an acceptable solution for every patient with diabetes. Skeptics think surgery will never become a diabetes treatment.

Chances are they may both get it wrong.

In medicine, things are rarely, or ever, “all or nothing”.

Taking again the same examples made above, not all patients who have gallstones are candidate for laparoscopic cholecystectomy, and most of those with carotid or coronary stenosis can live without ever seeing a surgeon. The decision to operate for a carotid stenosis likewise in other surgical conditions, depends on a careful evaluation that weighs the risks and benefits of surgery against the risk of experiencing complications and death from the disease. Diabetes should make no exception to that rule.

Patients with diabetes who do well with diet and exercise, or using a reasonable medical regimen may not need to take the risk of an operation. On the other hand, why not considering surgery when diabetes is inadequately controlled by any available conventional treatment?

Currently, the U.S. National Institutes of Health Guidelines recommend that gastric bypass and other bariatric operations be considered only for people who have a BMI of at least 35. Many are now suggesting that the limit should be lowered to a BMI of 30 for those with diabetes.

This approach may seem reasonable, but is, in my opinion, quite misleading. The concept that a certain BMI threshold should be used to define indication to surgery when the primary goal is to treat obesity is understandable. But things are different when the primary goal is to treat diabetes.

Although we admittedly need more data to know if a lower BMI cut-off for surgery is acceptable in patients with diabetes, I am concerned that a meaningful question is not whether a lower BMI level should be used but whether BMI should be used at all when defining indication to diabetes surgery.

Future studies should be done to understand what are the parameters that can be used to predict the effectiveness of surgery on diabetes while correctly assessing the risk associated to diabetes itself.

BMI does not predict any of those.

In 1999, I started my personal research in rats to examine whether the effects of surgery on diabetes were due to just caloric restriction and weight loss alone or if there was an anti-diabetic mechanism directly resulting from the change in intestinal anatomy. Using a modified-RYGB, which reproduces the characteristic bypass of duodenum and jejunum but maintains the stomach intact, we found that lean animals with type 2 diabetes had the same positive effects as obese ones and that the improvement of diabetes was not due to weight loss.

These animal findings were confirmed in humans first by Dr Ricardo Cohen who used the same operation, called “duodeno-jejunal bypass” (DJB) in non obese patients with diabetes. After about a year of follow-up most of Cohen’s patients enjoy normal HbA1c levels without significant weight loss. Other surgeons have been using the procedure, reporting encouraging early results.

The early experience with DJB in animals and humans is still too limited to endorse a broader clinical use of the operation in clinical treatment of diabetes. DJB should still be considered as an investigational procedure, to be performed only within clinical trials in centers with specific expertise.

Nevertheless, the results of DJB in animals and humans supports the idea that similar operations, such as the conventional RYGB, may be a valuable option to treat diabetes not only in the morbidly obese, but also in moderately obese or just overweight patients.

A reasonable concern about using conventional bariatric operations in patients with lower BMI levels is that this type of surgery may cause excessive weight loss. Although apparently counterintuitive, several observations show that bariatric operations may even cause no weight loss if performed in normal-weight individuals. In fact, Mingrone et al reported in Diabetologia in 1992, the case of two patients with chylomicrhonemia, a genetical hyperlipidemia syndrome, that were successfully cured of their disease using a malabsorptive bariatric operation called biliopancreatic diversion, or BPD (the equivalent of “Duodenal Switch” in US). Intriguingly, with a preoperative BMI of 22-24 the patients never actually lost weight after surgery and their body weight even increased as they started to eat normally. Blood lipids and diabetes were still under control and BMI was now at 24-26 at the last follow-up a decade after surgery (personal communication of Drs Mingrone and Castagneto).

It is clear then that diabetes-specific parameters, rather than specific BMI levels should be evaluated as potential criteria to define indication and contraindication to diabetes surgery.

Next time Part 2: Diabetes Surgery: The Choice of the right Surgical Procedure

The 1st World Congress on Interventional Therapies for Type 2 Diabetes will be held in New York City, on September 15-16, 2008. It is a comprehensive and multidisciplinary forum where world leaders in the health community will conduct an organized review and discussion of the latest scientific data, trying to craft an agenda of health policy initiatives and seize the opportunity offered by novel interventional therapies. 

The World Congress will hopefully be a historical opportunity to promote the necessary research efforts and try to take a critical step toward a cure for diabetes.

The 1st World Congress on Interventional Therapies for Type 2 Diabetes will be held in New York City, on September 15-16, 2008.   The Congress is focused on the growing body of evidence showing that bariatric and gastrointestinal surgery can induce long-term remission of type 2 diabetes, providing a promising therapeutic option and a unique opportunity to better understand the pathophysiology of this disease. This meeting is a comprehensive and multidisciplinary forum where world leaders in the health community will conduct an organized review and discussion of the latest scientific data, trying to craft an agenda of health policy initiatives and seize the opportunity offered by novel interventional therapies.  Register Now, or for more information visit www.interventionaldiabetology.org.