Bariatric surgery for morbidly obese patients who have type 2 diabetes has been gaining greater acceptance as a treatment modality in the larger medical community, and has a growing number of postoperative patients who are showing a remission in diabetes symptoms, including normalized glucose levels for sustained periods. Well-known and respected bariatric surgeon Francesco Rubino, MD (pictured, lower left) provides some insights as to why this is happening and his thoughts about whether it is a cure or not.
 
By: John Parkinson, Clinical Content Coordinator, DiabetesCare.net

One of the more exciting medical happenings in the type 2 diabetes treatment sphere is the formal introduction of bariatric surgery for people with type 2 diabetes who are classified as obese.

This treatment option was showcased earlier this year when the International Diabetes Federation (IDF) held a press conference in New York to present its position of using bariatric surgery for this patient population.

Specifically, the IDF task force created a criteria for consideration of  surgery, including: a measurement of 35 or more body mass index (BMI) for what they called the “European populations”; a 30 to 35 BMI if diabetes is poorly controlled and there are other metabolic alterations that increase cardiovascular risk (i.e. hypertension, dyslipidemia, etc.); for selected populations like patients from parts of Asia, the BMI limits can be lower by 2.5 points; and patients should be at least 15 years old for consideration of a surgical procedure.

For patients with BMI above 35, the IDF recognizes all current bariatric procedures, including the Roux-en Y Gastric Bypass (RYGB), the Laparoscopic Adjustable gastric Banding (LAGB), the Sleeve Gastrectomy and the Biliopancreatic Diversion-Duodenal Switch (DS). For patients with BMI 30-35 the IDF recommended 2 bariatric procedures: the Roux-en Y Gastric Bypass (RYGB) and Laparoscopic Adjustable Gastric Banding (LAGB).

The IDF expert panel was represented by leading endocrinologists, diabetes experts and surgeons from Great Britain, Europe, Asia, Australia, and the U.S. The conveners of the IDF panel included endocrinologists Paul Zimmet and George Alberti, obesity specialist John Dixon and Francesco Rubino, MD, director of gastrointestinal metabolic surgery at New York-Presbyterian/Weill Cornell Medical Center, who was in attendance at the press conference, and helped draft the IDF position. Dr. Rubino has performed hundreds of the various bariatric procedures and is a leading proponent for considering bariatric surgery in qualified patients.

While he makes the distinction that scientifically we cannot yet say bariatric surgery is a cure for type 2 diabetes, he does acknowledge that clinically speaking, he and other surgeons who follow patients post-operatively have seen normal blood sugars and the absence of diabetes symptoms for several years in some patients.

It is understandable that Dr. Rubino and the larger medical community are not yet calling bariatric surgery a type 2 diabetes cure, but as more studies are conducted on its efficacy and a longer successful surgical track record becomes established, the obvious question becomes how do we characterize it?

Still, what makes this so fascinating is that treatment for type 2 diabetes have been treated with just lifestyle modifications and medication, and, there has not been any surgical modalities being advanced--until now.

DiabetesCare.net spoke with Dr. Rubino about the IDF’s position statement, how some of the various bariatric procedures work, and his own theory on the possible cause for type 2 diabetes.

Diabetescare.net: Earlier this year you were part of the IDF committee that announced the surgical indication of bariatric surgery for 2 diabetes. Can you provide an overview of that statement in terms of who the surgery is indicated for?

Rubino: Surgery can be an ideal treatment for obese patients who have type 2 diabetes. Usually when physicians are seeing patients they consider lifestyle modifications and medications only. Very often, physicians view bariatric surgery as being either a last resort, dangerous, or a cosmetic procedure. That was the background of the IDF statement. The most revolutionary concept here is the fact that surgery is being recognized by a major diabetes organization as a type 2 diabetes treatment.

There is a lack of awareness both in the population at large, and unfortunately, in the medical community about the role of surgery in certain patients with type 2 diabetes. When patients have diabetes and are massively obese, there isn`t any medications out there that could address both problems simultaneously. We recognize that surgery is not for everybody, but for those who have severe obesity and diabetes, it should be considered a treatment option. 

DiabetesCare.net: Both the lap-band (gastric banding) and Roux-en-Y (gastric bypass) were IDF’s recommended procedures for patients with moderate obesity (BMI 30-35) and type 2 diabetes, but the duodenal switch was not one of the bariatric procedures included. However, there has been a lot of excitement of the promise of this procedure. Why is there excitement for the potential of this procedure and where do we stand with this in comparison to the other procedures?

Rubino: All the procedures that are conventionally used for bariatric surgery including the duodenal switch have been shown to be safe and effective for treating diabetes in morbidly obese patients and as such they were all deemed an acceptable procedure by the IDF in this patient population.The reason why, for the moment, the IDF recommended the gastric banding or the gastric bypass procedures for less obese patients (BMI 30-35) is because as effective as the duodenal switch is, especially in diabetes, one must consider its potential side effects.  

The duodenal switch may be a better fit in patients who have a significant amount of weight to lose and poorly-controlled diabetes. In patients who have a BMI of 30-35, and weight loss does not present as the biggest issue, then there are less compelling reasons to take the risks associated with the duodenal switch including vitamin malabsorption and frequent daily bowel movements.

DiabetesCare.net: What are the considerations for the three procedures?

Rubino: It is not appropriate to say that there is one type of procedure that is best in any case. The judgment is very complex and should be based on the individual characteristics of the patients, the aim of the treatment, and whether you are addressing primarily the patient’s diabetes or a weight problem. The choice of the procedure depends also on the severity and characteristics of the disease and whether the patient has other conditions.

We consider the patient’s characteristics first. To make a few examples, if the patient presents with massive obesity (BMI of over 60),  then one could considered the duodenal switch providing the patient understands and accepts a very rigorous postoperative nutritional supplementation and monitoring. This surgery is effective but also risky for that aspect.

If a patient comes with a hiatal hernia and severe gastroesophageal reflux, it might not be the case to consider gastric banding or sleeve gastrectomy, because there is the potential to make it worse. In those cases, the patient might be better served by having a gastric bypass.

In the past, one of the problems of bariatric surgery was the belief that one operation can be good for everybody or that all operations are equivalent--this simply not the case.

DiabetesCare.net: There are some that are saying bariatric surgery is a cure for type 2 diabetes. How would you characterize this group of procedures in relation to treating type 2 diabetes?

Rubino: I don’t like to use the word cure, simply because from a scientific point of view we really don’t know what causes diabetes. We don’t have the ability to say this is a final cure. From a scientific perspective using the word “cure” is probably inappropriate.

However, I do believe the gut may be involved in the pathophysiology of diabetes and that some of these operations may reduce or eliminate factors that can cause diabetes, but this is a speculation.

It is true, however, from a clinical standpoint, that there are some patients who come in post-op and we cannot find diabetes anymore. From a purely clinical perspective, there are some patients who have long-lasting remission of diabetes, where you could consider using the term “cure” because the patient’s sugars are normal and have been normal for a number of years. The American Diabetes Association recently convened an expert panel to try and define the concept of cure in diabetes. The conclusion was that if after an operation, a patient shows no symptoms of diabetes for 5 years or more without the need for continuous medical therapy then one could consider this a cure, but there is legitimate caution about the definition of cure in diabetes.

DiabetesCare.net: How long have you followed patients postoperatively who have clinically speaking had normalized blood sugars and have had remission of diabetes symptoms?

Rubino: There are patients who can experience relapse of hyperglycemia, but there are also patients operated on 14 or 15 years ago who still have normal glycemia. We have patients tell us, ‘I had surgery 20 years ago and had diabetes before it and I don’t have it now.’ Yes, there are cases where you could say, after so many years postop with normalized blood sugars, that the disease is cured.

In a way it is similar to how we talk about cancer and a cure. We were using the word remission in cases where we weren’t sure if the cancer would come back, so in most patients I think we should use the term “remission of hyperglycemia” but in some of our bariatric surgery patients who had type 2 diabetes and they have been disease-free for so many years, you could say, from a clinical standpoint, that it’s a cure.

There are also other reasons for caution. In fact, although it is the way we diagnose the disease, I don’t know for sure that diabetes is simply hyperglycemia. Diabetes is more complex than that, and hyperglycemia might just be a symptom of the disease. Until we know the cause of the disease, we can’t say much. I do believe, however, that if there is any cure today, or a chance of a cure, it is surgery. With surgery, you do the procedure once and patients have been shown to continue to have normal glycemia without further intervention.This is the closest thing we have seen to a cure in diabetes in the history of this disease.      

DiabetesCare.net: In terms of helping people with type 2 diabetes and a remission of their symptoms, including lap-band, Roux-en-Y, and duodenal switch, which has the great potential to help the greatest number of patients and why?

Rubino: It is difficult to say, because you need to think about a number of considerations. Overall, the gastric bypass is probably the ideal approach for most patients with diabetes. It is in fact the most common operation in people who have diabetes.

Sleeve gastrectomy or Gastric banding may be better suited for those with concerns of vitamin malabsorption or who have had intestinal surgeries already. Duodenal switch might be valuable in those who have more severe obesity (BMI over 50-60). In these patients this procedure may provide extraordinary control of their diabetes and greater weight loss compared to other operations. Of course a majority of patients do not fall into that category.

DiabetesCare.net: New York-Presbyterian/Weill Cornell Medical Center has a GI Metabolic Surgery section, and it is also doing clinical investigations on using metabolic surgery to treat diabetes in patients who are not obese enough to qualify for bariatric surgery. What specific surgical procedures are you doing on these patients, and is this an out-of-pocket expense or is this reimbursable by Medicare or insurers?

Rubino: We are doing several studies in this area. In one particular study we are comparing gastric bypass versus optimal medical treatment in patients with a BMI of 26 to 34. The aim of the study is to take a population where the problem is primarily diabetes and not the weight. We already have some data that gastric bypass might be effective in less obese or overweight patients with diabetes.

But we also know that diabetes medications can be very valuable in patients that are not morbidly obese. We know morbidly obese patients are not going to lose a sufficient amount of weight just using medications and that their diabetes is not likely to be appropriately controlled without surgery. But in a patient who is not obese, medications and lifestyle modifications can help so we need studies such as this to understand when one can rely on conventional treatments and when instead surgery is a better option.

We have a research grant from Covidien that allows us to cover all costs of the study including the surgeries. As this is expensive, we are only able to do a small clinical trial. We hope the study will provide data that will change insurance coverage—if we can prove it is effective and preferable to conventional treatment.

DiabetesCare.net: You have developed a theory, which suggests that a malfunctioning of the upper part of the small bowel could be one of the possible root causes of type 2 diabetes. Can you explain your theory?

Rubino: Looking at the physiology of the gut, we know it is an organ capable of producing hormones in response to the passage of nutrients. These hormones affect insulin secretion and sensitivity, appetite and satiety. We also know there are nutrient sensing mechanisms in the bowel that affect insulin sensitivity.  Incretins are intestinal hormones that increase after a meal and induce an elevation of insulin, so every time you eat, you increase your insulin.

My speculation is there must be some physiologic mechanism that compensates or antagonizes the action of incretins, otherwise one would risk developing hypoglycemia at every meal. This anti-incretin mechanism if you will, would balance the action of incretins, and would be modulated by the same passage of nutrients through the gastrointestinal tract ultimately contributing to maintain glucose excursions within normal limits and prevent hypoglycemia, which is very poorly tolerated by the brain and other tissues.

Also, If you think of the gut as an endocrine organ, then you must consider that it may become dysfunctional like any other endocrine organ. This is very plausible, being the gut is exposed and hence particularly vulnerable to environmental pressure, such as chronic stimulation with certain nutrients or food preservatives of our modern diet. Hence, it is possible that the mechanism that fine-tunes incretins and putative anti-incretins may become dysfunctional. An inbalance that favors the production of such anti-incretins might promote resistance to insulin, reduced secretion of insulin or even beta cell death.

If you consider that a potential cause of diabetes may be a dysfunctional gut mechanism, possibly triggered by over nutrition or by the intake of certain types of nutrients in modern diets, then you might explain the epidemic growth of diabetes on one hand, and you would predict, on the other one hand, that every manipulation of food passage through the gut could affect diabetes.

Now, diet is the simplest manipulation of food passage through the gut, and it does improve diabetes, albeit not as dramatically as barbaric surgery. Gastrointestinal surgery, decreases food passage in the gut more radically than diet, and this may explain its extraordinary effects. I speculate that when you remove a portion of the intestine from the flow of nutrients, you might decrease the anti-incretin factors that cause insulin resistance and create a better hormonal balance that ultimately improves insulin secretion, insulin sensitivity and glucose homeostasis.

DiabetesCare.net: Is there any way to test this theory post-op to see if you can measure incretins?

Rubino: We do have good evidence that some gut hormones change after bariatric surgery. After RYGB in particular, incretin hormones increase. However, we cannot say if, in addition to increasing incretins the operation is also decreasing anti-incretins because we don’t have the knowledge that they exist yet. This is pure speculative for the moment.

The reason why I suggest that gastric bypass might be reducing anti-diabetic factors is also because if you do this procedure in subjects that have no alteration in glucose homeostasis, the glucose tolerance actually slightly worsens. In other words, the operation does not appear to strengthen glucose homeostasis per se, but it does this only in patients who have diabetes or impaired glucose tolerance. It seems like it can fix what is broken. This is consistent with the idea that RYGB might tackle one or more factors that contribute to the disease.

DiabetesCare.net: What are the remaining challenges to see a greater proliferation of bariatric surgery for people with type 2 diabetes?

Rubino: There are many challenges, including the need for more widespread insurance coverage. However, the most difficult challenge is the cultural issue, the bias about obesity and its related conditions and the stigma of obesity in our society.

Everyone thinks to know all one needs to know about the disease, but in fact, we really don’t know much about obesity. Most people think it is as simple as "energy in vs. energy out". But in fact, energy homeostasis and weight regulation are controlled by a powerful biological mechanism that leaves little room to manipulations through the will power. We know when obesity is established it is very difficult to lose weight.

Also, given the epidemiological evidence that the more obese you are, the more likely you are to get diabetes; therefore, most people believe that excess weight is the cause of diabetes. I would argue that we do have a link there, but we don’t have proof of a cause/effect relationship. What causes such a link remains an elusive question, and considering diabetes just the result of plain excess of weight and fat may mislead our research of its root causes. If one believes that obesity causes diabetes and that fighting obesity is just as simple as "deciding" to eat less and exercise more, then it will be hard to accept that a surgical operation may be a rationale therapy for diabetes.

Another frequent misconception is that most people think of obesity not as a disease but as a risk factor. That is a mistake. For example, everybody knows smoking can cause lung cancer. If a patient who smokes develops lung cancer, a good doctor should emphasize the importance of smoking cessation. But neither the good doctor, nor anyone else, would suggest that quitting smoking alone would cure the cancer.

When it comes to obesity we tend to make an obvious mistake. Clearly, overeating and a sedentary lifestyle may be risk factors for becoming obese and developing diabetes. However, thinking you can cure obesity and diabetes by just deciding to exercise and eating properly is like thinking you can quit smoking and cure cancer.

For patients with cancer, our society has accepted medical interventions like surgery and chemotherapy, no matter what the risks are, because we know you cannot reverse the disease otherwise. If we don’t understand that obesity and diabetes can be prevented by lifestyle modifications but require appropriately aggressive treatments when fully developed, we will never win the fight against metabolic diseases.