Thank you. Thank you, Rattan, very much. And thank you for preparing this outstanding meeting. I’m very happy to be here. I’ve been asked to discuss the role of bariatric surgery in patients with and without diabetes. And as you all know, I don’t need to tell this audience, that diabetes is a very frustrating, a very, eventually debilitating disease. And I’ll show you that there’s a large proportion of my patients who do come in this state of frustration. And I’m going to demonstrate to you how bariatric surgery is by far, hands down, it’s part of the most effective and durable treatment for diabetes.

You’ve probably all seen these slides. They’re very popular. They come out of the CDC every couple of years. They do a telephone survey of representatives from the entire population. And they try to determine the prevalence of obesity in the United States. This was started back in 1995—’93 even. And they’ve been doing this on a regular basis.

What they do is, they color the states in the map according to their proportion of obese patients, so that the states that are designated in dark blue are the ones that in 1995 had almost a fifth of their population who were considered obese.

Now, I’d like you to all recognize that these are telephone surveys. And as you all know, we all tend to underestimate our weight, overestimate our height, because they were asking about BMIs. So, you have to even add on some numbers to this.

And this is the most recent survey that was conducted in 2005. And you can see how there are more colors on this map demonstrating how obesity has spread like wildfire, really, across America. And you can see there are three states there that have more than a third of their population. Indiana used to be one of these, and it’s dropped. We’re not sure why, exactly.

Not only is there an increase in the absolute number of obese individuals, but also we’ve noticed there’s a segment of this population that is rising faster than the rest. And that is those patients whose BMI is over 50. And we have theories about that. But there’s not doubt that patients, as they get bigger, their BMI growth accelerates even more. It’s like you’re feeding the fire.

This is a global crisis. And Rattan, I enjoyed your pictures and how you put on weight after coming to the United States.

But believe me, if you had stayed anywhere else in the world, your destiny would probably have been also to gain weight in tremendous proportions.

And as you know, diabetes and obesity are very closely linked. And you can see that these are the number of diabetes cases that are projected in the near future. Although we have a 13 percent projected rise in the incidence of diabetes, you can see what’s happening in the developing countries is even higher than that. And of course, this has very significant consequences, as you know, diabetes requires very close monitoring and good control. And all these cost a lot of money. And complications of diabetes can be devastating to these populations. And this is just amalgamating developing versus developed countries. And you can see what sort of a crisis—a real, health, worldwide, global crisis—is impending.

These are some numbers that I use from time to time just to, again, highlight how lethal obesity can be. In this study, they calculated the average years of life lost from obesity for individuals who were 30 years old. And it shows you. And let me tell you, my average patient’s BMI that I operate on is close to 50. So, it shows you a white man whose BMI is over 45 already presents to us with 11 years of his life cut short. And that is how serious this problem is.

And why is obesity so lethal? Well, it’s because it affects almost every sphere of life. It’s associated with numerous comorbid diseases. It causes disability. It drives up medical costs. You know, to add insult to injury, it deteriorates the quality of life for these poor individuals. And then, at the end, it increases mortality.

And the problem, as I said, is huge. We have millions and millions of obese individuals in this country. And with all our resources, with all our healthcare initiatives, we are only addressing less than 5 percent of these patients.

As a bariatric surgeon, I’m telling you, you’ve heard the hype about bariatric surgery and how common it is. And I’ll show you some numbers. We’re only really, really reaching 1 percent of eligible patients. So, you can imagine what the need is out there.

There was a study performed in the American Society of Bariatric Surgeons. They calculated the number of surgeons versus the number of potential patients. And they said that if every general surgeon in the country did nothing but bariatric surgery for the rest of their careers, it would still not be enough.

So, what are the complications of obesity? This is just a short account here. Like I said, they touch on every sphere of life. We’ve talked a lot about metabolic consequences. There are structural ones, orthopedic ones, joints. These are degenerative complications. We know that obesity predisposes to some cancers. And finally, of course, there’s a toll on a patient’s psyche. And all these can deteriorate the patient’s quality of life.

The other problem about obesity and this is what I meant by the heavier patients get, the faster they become even more and more super morbidly obese, is that all these comorbidities seem to enter the patients into a positive vicious cycle. We’ve all heard how insulin is an anabolic drug and how it promotes weight gain. So, once these patients become type 2 diabetics, you know they’re going to add more weight as you start treating them.

Arthritis limits exercise and energy expenditure. They’re going to put on more weight. Sleep apnea. It’s been shown that disrupted sleep rhythms can cause weight gain. And so on and so on. A lot of antidepressive drugs and antipsychotic drugs also are appetite stimulants.

And this is just a map of the human body to show you where obesity touches people. And you can see, really, it’s quite global. It goes from pseudotumor cerebri and increased intracranial hypertension, strokes, heart disease, cancers, all—especially fatty liver disease. We’re finding that the most rapidly growing indication for liver transplantation is nonalcoholic steatohepatitis that eventually leads to cirrhosis.

And as one of my mentors would say, obesity starts at the head, goes to the toes, and gets every organ in between.

Well, just how big a problem is diabetes in these patients? Bruce Wolf, who’s now in Washington at the University of Washington in Seattle, looked into this, and found that of a large group of patients, nearly 57 percent of patients who presented to bariatric surgery had type 2 diabetes. So, more than half of our patients are diabetics.

Now that we’ve established that there is a huge problem with obesity and this is closely linked to diabetes, how are we going to treat these patients?

You’re all familiar with these options. We’ve heard about calorie restriction, which is a better term, I think, than dieting. There are very-low-calorie diets, which I’m sure you’re familiar with. You can combine both. There are medications out there that I’ll touch on, existing medications and others that are coming down the pipeline. And, of course, there’s surgery.

People also say behavioral modification. Well, all these are considered modification, behavior modification. What we really intend to do with all these patients is modify their behavior, modify their relationship to food, whether it’s dieting, exercise, drugs, and surgery.

Let’s talk a little bit about dieting. This is a very nice study that came out that was in JAMA a couple of years ago, three years ago. And we’re all familiar with these diets, whether it’s Atkins, Ornish, Weight Watchers, and so on. And this group from, I believe, they were in Johns Hopkins, they decided to scientifically evaluate the efficacy of all these diets.

So, they took these patients and they placed them in four groups, and each group was carefully supervised in these respective diets. And they followed them for one year. And you can see the results in weight loss here, which ranged anywhere from four kilograms, seven kilograms, and so on. But these are the important numbers. More than half of the patients dropped off. We all know this. We all know how hard it is to stick to a diet. And we know how hard it is for our patients to stick to a diet. The most important message I got from this is that no matter how good any of these diets may be, they did produce some results; the important number is that half of the patients dropped out. And this is in a clinically supervised, scientific environment.

I mentioned a pharmacology, and you might be familiar, I’m sure you are, with sibutramine, which Meridia, and Xenical. Xenical is now available over the counter. It’s known as Alli. They’re both available. They’re both good. They can produce good results. We have to take into consideration, though, that, like any medication in the world, it’s got to have side effects.

Sibutramine, or Meridia, can have a hemodynamic side effect or adverse effect. Orlistat, as you know, if patients are going to consume fatty foods, it’s got to go somewhere. And we’ve had patients with explosive consequences, as I like to tell them. You have to be careful there. But also, they have to be careful of the fact that they sometimes lose the baby with the water, and you have to be careful about replacing especially fat-soluble vitamins.

The other important fact that we have to keep in mind is that these cost money. They’re effective only as long as patients take them. Once they stop taking them, then we’ll go back to status quo and the patients will regain their weight again.

So, I think we’ve established that diets—it’s hard to hang on to a diet, and I’ll show you why. Medications can be effective, they can produce reasonable weight loss, but at a risk of adverse effects or cost.

This is rimonabant that was mentioned earlier today. It was about to be launched, but then the FDA, well, actually the company withdrew its application because there were some suicidal tendencies and other psychological side effects that they need to study a little more. So, its application was withdrawn. It was supposed to be on the market by now. It’s actually been pretty successful in Europe where I think its brand name is Acomplia.

The interesting thing about rimonabant is that it acts both centrally, as you can see, and peripherally, and it has both central effects in reducing appetite, decreasing food intake, and it works on the adipocyte factory of cytokines and increases adiponectin. The end result is a decrease in the hyperinsulinemia that a lot of our patients have and other good effects. It is a promising drug, but it’s still considered investigational at this point.

If we were to compare, if we’re unhappy with all the options that we have so far in terms of dieting and exercise. Let me tell you, exercise is good for the heart. It’s good for the lungs. It’s good for our body in general. But as a solitary weight-losing mechanism, you have to burn a lot of calories to lose any appreciable amount of weight.

So, if we compared all the nonsurgical methods of weight loss with surgical, you can find and we can see here an astounding difference between the two groups of patients: 17 percent excess body weight lost compared to nearly 70 percent. This hasn’t gone unnoticed.

In fact, the government noticed this way back in 1991 and they came out from a consensus conference and made this statement that “Dietary weight reduction with or without behavioral modification or drug therapy had an unacceptably high incidence of weight regain in the morbidly obese within 2 years” of weight loss.

This is when they laid down the recommendations for bariatric surgery, and they described the qualifications or the requirements of candidacy or eligibility for bariatric surgery. So, we had a growth in bariatric surgery, a phenomenal growth. As you can see here, back in the early nineties, there were probably less than 20,000 in the whole country, and it has just shot up.

The other reason for this sudden or remarkable popularity in bariatric surgery was not only its outcomes, but also the fact that we introduced or we adopted laparoscopic principles to it. By doing that, by performing all these operations through what we call keyhole surgery, we’re able to spare the patients the big midline incisions, keeping in mind that these patients are morbidly obese, a lot of them have diabetes, and a lot of them don’t heal well. There were large numbers of wound infections and ventral hernias. Plus, if they’re in pain, they’re not going to get up and walk. They’re going to have DVTs or pulmonary embolisms, chest infections, and so on.

So, the introduction of laparoscopy in combination with the good, reportable outcomes fed or generated this huge rise. So, that by the year 2005, the last numbers we did: 170,000 cases in the country. Still nothing compared to what’s needed out there.

Just a brief overview of what operations we offer patients. The first category is “Gastric Restriction” and I’ll explain that in a minute. And then there are the malabsorptive operations, and the third category, which is a hybrid of both, a combination, is the gastric bypass.

You might have heard of stomach stapling, and this is what we otherwise know as vertical banded gastroplasty. And this was very common in the eighties. The reason why this was common was that there was no anastomosis involved. It was a fairly straightforward operation. Surgeons would perform this operation by stapling longitudinally here and making a little donut-sized hole in the stomach, which was then—and this channel, ensuing channel was banded. That’s why it’s a vertical banded gastroplasty.

The principal being that patients would eat food that as the food came down would encounter these staples here and be forced to come down through this narrow channel. The patients would feel this restriction. They would be forced to eat less and slower. And that’s how they lost weight.

Well, it worked fine in the early stages. But then two things mainly happened: One was these staples would open up. So, patients lost this feeling of restriction, and suddenly, they were able to eat normal amounts of food. Or the second consequence or complication of this was that the band would stenose too much, would restrict too much, and cause a stricture. Patients would have dysphagia, very poor swallowing, and regurgitation, bad reflux. So, this operation has now been abandoned. It’s very rare when this is performed in the United States, but it’s still performed internationally a lot because it is relatively cheap.

The modern derivative of the vertical banded gastroplasty is the lap-band. The principle between the vertical band and the lap-band is that this is like a belt that goes around the cardia, the top of the stomach, and produces restriction in that way. It just doesn’t allow the stomach to stretch at its mouth. The important thing about it is its adjustability.

This belt, or this band, is actually a hollow chamber that has the potential to occupy or to take in saline. Saline is delivered through this tubing that connects to a little reservoir that sits under the skin. And that is accessed with a Huger needle. Over a period of a year or two, there are regular intervals in which the surgeon or some other healthcare provider interviews the patients and assesses their level of hunger, their ability to eat certain foods, their weight loss, their rate of weight loss, and they make a decision on whether it’s time to tighten the band or release it a little bit. So, once it’s tightened, the patients go back to eating less food, losing more weight, and so on.

So, you can imagine that for this modality to be successful, you need a very good dialogue between the patients and the surgeons or the healthcare providers. It’s gaining in popularity. Interestingly, the band was present in Europe for many years before it came to the United States. Over there, it’s actually dropping in popularity.

The other category of weight loss operations is the malabsorptive ones. The malabsorptive operations rely on allowing the patient to eat a normal, if you will, amount of food, but then affecting the absorption of the food. It’s like the surgical cousin of orlistat, of Xenical. The initial operation that was performed in the seventies was the jejunoileal bypass where we bypassed most of the small intestine. In fact, the absorptive surface of the small intestine was only 50 centimeters.

Clearly, the patients lost a huge amount of weight. But, because of this large, blind loop, you had bacterial overgrowth, you had a lot of toxins that were developed, and the patients eventually did very poorly. Some of them had kidney stones. Others had liver failure. There were many deaths. I know several surgeons who built the first half of their careers performing this operation, and the second half of their careers taking it down. So, again, this operation is canceled.

The modern derivative of it is the BPD or DS, biliopancreatic diversion or duodenal switch. These operations bypass a far less amount of intestine. They still have significant side effects in terms of a large number of bowel movements and a higher tendency to have nutritional deficiencies. We personally don’t offer it here at IU, but other surgeons do. And these patients have to be very carefully monitored.

By far, the most common operation in the United States and considered to be the gold standard is the gastric bypass. In this operation, what we do is we create what we call a pouch out of the stomach. The way I explain it to patients is that normally our stomach is about the size and shape of a football, and I create a pouch about the size and shape of a thumbnail. The capacity is usually between 15 and 30 cc. We separate it even though it’s been stapled across. Again, the staples would open and we had a lot of fistulas here.

So, now, we separate these two, and we bring up a loop of intestine, anastomose it to that, and then the biliopancreatic limb that delivers the gastric juices and enzymes and the pancreatic enzymes mixes with the food lower down. This distance is usually about 100 to 150 centimeters. This is a good combination of restriction and some malabsorption; although, the malabsorption component is much less.

Just to summarize. The gastric bypass, we’ve actually separated the pouch from the stomach. This has what we consider to be excellent weight loss. We talked this morning about a 5 percent weight loss being beneficial for patients who have comorbidities. We are reporting 70 to 80 percent excess weight loss, very good long-term results, and I’ll show you some of those, and patients tolerate the food very well, so long as they start eating in a graduated manner. There’s always the potential for nutritional deficiencies, and that’s why we follow up our patients very carefully and periodically perform labs for nutritional parameters.

I mentioned I was going to give you some data on how durable this operation is. And Walter Pories is one of the pioneers of gastric bypass. And he followed up his patients for 14 years. And he actually was able to locate more than 90 percent of them. He measured their weight loss. And he showed what we have all found to be the case, as well, is that most of the patients have their largest weight loss within the first two years, 70 to 80 percent weight loss. And then there is an inevitable little bit of weight gain. So, that by 14 years, they reach a steady state, if you will, of about almost 50 percent excess weight loss.

All the patients lose a lot of weight then regain it. But certainly less than the dropout rate, if you will, is much less than dieting. And we tell patients that we expect about 10 percent, 10 to 15 percent of patients will have weight regain.

I’m sure you’re thinking, well, why is it that gastric bypass is so effective and durable? And how is it different from all of the modalities that we’ve talked about? Well, here’s the main difference.

This is not a diet. One thing that all our patients enjoy is the elimination of hunger. We talked earlier this morning, and Rattan did a very good job of describing the very powerful stimulus that’s within us all to eat, because it’s survival.

Whenever you place a patient on a diet or you restrict their intake in any way, they immediately go into starvation mode. The problem with getting into starvation is that the body tends to shut down. It tends to become very efficient. So, patients tend to exercise less or expend less energy. Their stress, if you actually measured their cytokines and other chemical modulators, you’ll find that they rise.

Whereas, with gastric bypass, appetite is not an issue. They still get their cravings. They still say, oh, that cheesecake really looks good. They’ll take one bite, and that’s it. They’ll feel full. The satiety business is very effective in these patients. One thing you’ll notice about all our patients is that they are just full of energy. In fact, one patient told me that his greatest problem was that, he was flying to China, long flight, and he just could not sit still. It was very hard to do that. They’re always on the go. They drive their spouses crazy.

This is why this operation is so effective. Because once the patients are released from this overpowering stimulus to eat, they can start planning their meals. They can start making healthy food choices and so on.

I’m sure you are all familiar with this concept of us all having a set point that we live in. Just like we have a set point for body temperature, we have a set point for where our BMI should be. And it all depends, really, on this formula or this equation that you’re all familiar with: energy intake versus energy expenditure. And where these two lines meet is our set point. So, say you have a healthy patient whose set point should be 25. This slide should have come before the other one.

There’s been a lot of research into trying to determine what it is about gastric bypass and how is it that it affects appetite. You’ve all heard of ghrelin and leptin and these other hormones. And I’ll touch on that briefly. But there’s certainly a signaling process that becomes interrupted between the gut and the brain.

So, back to the set point again. We have a patient who is obese, whose BMI is 40. This is where her set point is. What happens is that after surgery, their energy intake drops a lot and at the same time I mentioned that their energy expenditure rises. So, their set point moves down. And now they become more comfortable, their body becomes—it’s called a zone of comfort—at a much lower set point.

The other operation that we perform is the lap-band. And I mentioned this briefly to you. Again, this is a better diagram. It shows you the lap-band in position right at the cardia of the stomach. And it’s a much safer operation because it doesn’t involve any anastomosis.

But the price you pay is that the weight loss associated with it is much less than with a gastric bypass.

And these are some of the outcomes. You’ll remember that the weight loss with the bypass was up to 80 percent. This is 40 to 50 percent if we’re lucky. And it’s a much shorter and much easier operation. Patients usually go home either the same day or the next day. They’re all admitted as a 23-hour observation.

These are some of its complications. Some bands, if they’re not properly placed, they can erode into the stomach, and some of them have been taken out endoscopically. Or they can prolapse, meaning they’ll slip on the stomach and patients present with reflux. So, if you encounter any patients who have had a lap-band and they’re complaining of bad heartburn, you have to get an upper GI and check the position of the band.

A new operation that’s gaining a lot of popularity is the sleeve gastrectomy. And you remember my analogy of describing to patients how their stomachs change from a football to a thumbnail. Well, in this one, I tell patients their stomach changes from a football to a hotdog. And basically, it’s a very long, narrow tube, and it’s a purely restrictive operation that, in terms of efficacy, sits somewhere between the band and the bypass.

If we were to compare the three main operations, the lap-band, the gastric bypass, and the duodenal switch… The duodenal switch was this operation here, where it’s one of the malabsorptive operations that I mentioned.

So, it’s a more complex operation, but certainly more effective, as you can see from this, in terms of weight loss. But the mortality rises. But look at that resolution of diabetes: lap-band, nearly 50 percent; duodenal switch, nearly 100 percent.

Well, I haven’t talked much about diabetes today. You’ve seen the slide earlier today that shows how just at a BMI of 35 there is a very large relative risk of contracting diabetes, or getting diabetes.

As bariatric surgeons, we discovered the efficacy of weight loss surgery back in 1995, when Walter Pories, again, wrote a paper with this very intriguing title.

He showed that out of his relative small group of patients, his prediabetic patients all got a result after operation. His type 2 diabetics, you can see the numbers there, how successful this operation was.

 In Pittsburgh, we actually looked into this, as well, and we decided to research our data from our patients.

And we found, out of 1100 patients, 240 had either prediabetes or type 2 diabetes. And we had 80 percent follow-up. What we concluded was that there was a very large amount of resolution of diabetes.

But it depended—and this is what we found very interesting—depended on the duration and severity of type 2 diabetes. The patients who were diagnosed with diabetes within 5 years almost uniformly improved. Those who had diabetes for more than 10 years, only 50 percent improved.

The message is that the earlier diabetic patients are referred to weight-loss surgery, the better the outcome.

You can see here again, this is another study that shows you how effective all the kinds of bariatric operations are on resolving diabetes.

This Swedish obesity study followed patients for 10 years.

And again, shows the marked improvement in comorbidities.

How does bariatric surgery resolve type 2 diabetes?

Well, you’ve all heard of GLP-1 today. It’s certainly a molecule of great interest these days. This is produced in the L-cells, and—I don’t need to repeat all this—but the important thing is the ileal break phenomenon that reduces, it actually slows down the gastric emptying and gut motility and increases satiety.

There are two hypotheses on how gastric bypass affects GLP-1.

And one is the proximal hypothesis in that by bypassing the foregut, we are probably bypassing, preventing the contact of nutrients with the foregut, and we are preventing some kind of unidentified as yet molecule or mechanism from being stimulated that, in turn, stimulates the L-cells.

The distal hypothesis, which really has much more support, is that because we are bypassing small intestine, the nutrients are being delivered at a much faster rate to the terminal ileum, where all the L-cells are. So, it’s accelerating the stimulation of GLP-1.

There is an interesting study that comes from Greece, actually from one of the Greek islands. They took patients who had sleeve gastrectomy, this operation, and they measured their gastric emptying before and after sleeve gastrectomy.

And they fed them this meal  and they determined that a large proportion of them had significant accelerated emptying of their stomach.

That shows that even restrictive operations actually may have an affect on diabetes because of acceleration rather than restriction.

Most recently, Francesco Rubino, who came from Italy and has actually just recently joined New York University, performed these animal experiments where he takes a portion of the terminal ileum and transposes it very proximally, just in the beginning of the small intestine. He found that all these animals, who were all diabetic, their diabetes markedly improved. Di Paola in Brazil has actually been operating on patients whose BMIs are between 25 and 30, these are diabetic patients with complications, missing feet, and so on, amputated toes. He has been rendering them euglycemic simply by transposing about 50 centimeters of small intestine from the ileum to the foregut. So, I think that the distal hypothesis has merit.

Just a brief review of a meta-analysis on all bariatric surgery, and it shows you here some of the outcomes that we have in terms of weight loss. In terms of comorbidity resolution, you can see from a meta-analysis nearly 77 percent of patients have resolution. This has not escaped the media. You might recall, I don’t know if you saw this back recently in August, there was a front-page article, “To Heal Diabetes, Doctors Push Weight-Loss Surgery.”

And these are some other long-term studies. This was from Utah, where they studied 10,000 patients nearly who had gastric bypass with 10,000 controls that were derived from the Department of Motor Vehicles. You know, they all have their height and weight measured.

They followed them up for 7 years and found that the patients who received gastric bypass, their mortality was reduced by 40 percent and mostly as a result of improvement in these diseases, including diabetes.

This is another study, a similar idea, a concept from Australia, where nearly 6000 patient years, about 1500 patients were compared with 2000 controls. You can see the difference in deaths here.

One final study, this is the SOS study that I mentioned earlier, the Swedish Obesity Subjects study. Two thousand patients versus 2000 controls, follow-up 10 years, mortality rate reduction in surgery group 25 percent. Let me just tell you that the majority of the patients in this study received vertical banded gastroplasty, the VBG, the stomach stapling that I told you about, which is now not performed in large amounts around the world. That is why we feel that their mortality rate reduction is less than the other papers. However, it’s still very good.

So, in summary, the prevalence of obesity continues to rise, as you know. We know that just having a BMI over 35 gives you 100 percent relative risk, higher risk of diabetes. The patients that we receive, more than half of them are diabetic. We’ve shown that it’s the most effective and durable option. We don’t really understand how it works, but we feel very confident that GLP or the terminal ileum has something to do with it.

Thank you very much.