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George Bray 2018 Transcript




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Pape: I’m Joy Pape with Diabetes in Control. We’re here in Boston for AACE 2018 Meeting. And I am honored to have the privilege to interview Dr. George Bray today. Dr. Bray, you’ve done so much. You’re one of the great pioneers of the field of obesity medicine. I want to thank you for all of your work in the field. And we don’t have the time (laugh) to be here a week to go over things. But you were the lead author on two recent high profile papers. One was a position statement from World Obesity saying “Obesity: a chronic relapsing progressive disease process,” a position paper of World Obesity. The other is a statement from the Endocrine Society on “The Science of Obesity Management: An Endocrine Society Scientific Statement.” Can you tell us some of the main messages from these papers?

 

Bray: I think the “obesity is a chronic disease process” one is trying to counter the long standing idea that obesity is something for which you are responsible. It is because you don’t push yourself away from the table. It is because you’re a weak-willed slob; it’s that kind of attitude that the public has. It’s a stigmatized state, if you want. And that, it makes it difficult to treat in any way except changing your moral character, which is something it clearly is not. About in 1996, leptin was discovered and since then a large number of genes have been identified that indicate that there clearly is a genetic basis for what’s going on. And because of that, the idea that obesity is a disease which was suggested 200 years ago has become more and more prominent. And the idea is to replace the moral naughtiness of being obese with the underlying disease processes which go on. So, the World Obesity statement was intended to do that. It was reviewed by the countries that are members of that group, which is most of the countries that have obesity societies. And they signed onto a statement which was drafted by a group of us for the World Obesity, stating, I think the truth of the matter, “Obesity is a chronic relapsing stigmatized disease process.” And the disease process part really reflects the fact that when you are obese a number of things are going on because of the enlarged fat cells, extra fat, that produce disease in and of itself. And so, if you reversed obesity, you will reverse many other processes, and this is particularly important with diabetes. If we are going to get a handle on the diabetes epidemic which has been going on along with the obesity one, we’re going to have to get a handle on the obesity epidemic because they’re going hand-in-hand. And the more people who become obese, the more people who will become diabetic. The diabetes prevention program clearly showed that a small weight loss of 5% or more will reduce the likelihood of getting obesity — diabetes, sorry, over a three and half year period by almost 58%, nearly 60%. And same thing with was shown in a Finnish diabetes study, similar figures from China and Japan. So, it’s clear that worldwide that we can reduce the risk of diabetes by modest weight losses and that’s a very important message to take home. We can do something with modest weight loss for people who are at risk for diabetes. So, shifting the emphasis from a moral weakness to a disease process makes it possible to think about it in a different framework.

The statement from the Endocrine Society attempted to take that message and broadened it out into what can we do about it, where are some of the gaps in what we can do, how are we going to move forward. And a couple of messages from that — and again, I’ll reemphasize what I said from the World Obesity Society, the obesity is a time bomb. It’s waiting to explode and one of the products will be more diabetes. So, dealing with that is important and we haven’t made much progress. When I started in the field many years ago, the prevalence of obesity was 14% in the United States. The latest figures show it to be 39.7%, nearly 40% of the adult population have a body mass index greater than 30. That’s I’d say almost 40%, that’s two in five people which is an enormous number. And the health implications of that are truly staggering. One of the best things we could do is to reduce that because it reduces the problem with diabetes. It will also do something good for cardiovascular disease but you need more weight loss for that than you do to reduce the risk of diabetes. So, that’s one message out of the Endocrine Society paper, that obesity is getting more prevalent. Not plateaued as some people thought, at least not the most recent data. It’s going up in children. It’s going up in adults. It’s going up in almost — in every country in the world, some more rapidly than others. The other interesting message in it is that not everybody gets obese. And one of the questions is what is it about the people who are thin that keeps them from becoming obese? And that’s one of the real mysteries we have. We don’t fully understand. We know that people like me, who will get fat acutely, will lose weight. I experimented some years ago. I gained 30 pounds just to see what happened and we did some studies on me once I had gotten fat. But when they were finished, my weight came down to what it’s been before and for 40 years since then. And there are lots of these studies now of conscious overfeeding to look at the consequences of that. And essentially every patient who does that comes down to their baseline weight from which they started. So, there’s something different between acute weight gain in people who are not basically overweight to start with, and people who are — who become overweight over time, because when you do that something gets changed.

Pape: Yes.

Bray: And it isn’t easy to reverse it if you do it slowly. Like a pound, a pound and a half a year and you do that for 10 years, you’re 10 to 15 pounds heavier. Losing that 10 to 15 pounds or 20 to 30 pounds, you go 20 years, and 30 — or 40 to 50 pounds, you go five years is very difficult thing to do. So, that’s one of the things we do not understand at all. One of the other messages that came out of this study was that we don’t have very good ways of knowing who will and who won’t respond to treatments. In the large trial Look AHEAD, which is a study of intense behavioral management for a large group of diabetic patients, 5,000 in number, we got a substantial weight loss at the end of one year, 8.5%, but the variability was enormous. A big group lost more than 10% and most of them kept that off. But there were 25% or so who loss essentially no weight, who were less than 3% below in spite of as intense a weight loss program as you can afford to put together. So, we have a great range of responses. And we don’t have any really good information about how to predict it ahead of time and only a few indicators about things that will work at the other end. So, we need a lot more information about those parts of the problem.

Pape: That reminds me of when we’re talking about treatment, what “diet” works best for someone and what medications will they respond to best. It kind of goes with what you’re saying. We don’t know.

Bray: That’s correct. We don’t know. We can’t tell how people will do on diets or medications. Some do very well on the medication or on diet, some do not, and only after the fact can you tell.

Pape: Right.

Bray: It’s an area that we need to understand better, if we’re going to make progress in deciding how to help people overcome this serious problem for their health in general and general well-being.

Pape: So, obesity is increasing in prevalence as anyone visiting a public place can tell. Can you expand a bit on how bad a problem it is and whether you’re optimistic about the future?

Bray: Oh, I’m always an optimist.

Pape: (Laugh)

Bray: If I weren’t being an optimist, I suppose I would have gone to do something else years ago. Unfortunately, I have not been as successful as my optimism would like to have led me to hope I would be. As I said, it’s a worldwide problem but it doesn’t occur equally in the population. One of the fascinating observations is that you could watch people move from one area to another. And we know that the prevalence of excess weight is higher in some ZIP codes than in other ZIP codes. And where we have information tracking people who move from one to another. If you move from a lower income ZIP code to a higher income ZIP code, you’ll become thinner, so you’ll move to the ZIP code mean, if you like. If you move the other direction, you’re at greater risk for gaining weight. So, there’s clearly a demographic component to weight gain that’s got an income element to it. And we know that the income inequality in this country is directly related to the prevalence of obesity. The people at the lower-ends of the income distribution are at considerably greater risk than people at the upper-ends of this income distribution. So, we need to do something about those sociodemographic features which set the environment in which this disease process can occur, which is not an easy thing to do but it’s clearly important.  

Pape: So, where do you think we have limitations that prevent us from moving forward?

Bray: One of them is that we can’t predict very well who’s going to succeed, that’s a clear limitation. One of the other fascinating things to me is, I mentioned leptin a few minutes ago which was discovered in 1996. It’s a rare defect when you don’t have it. When you don’t have it, you become very fat. We had the opportunity to study a Turkish family who had three individuals with leptin deficiency, who came down to the Pennington Center in Baton Rouge and spent some time living in our unit and they are all very, very overweight individuals. And after completing the studies, we were able to obtain leptin for them on a at-needed basis. And when you treat leptin deficient people with leptin, their weight comes down to normal. They will return to the weight you and I are. And if you take leptin and give it to someone who’s overweight, it doesn’t do that. So, one of the really fascinating questions is what is different about people who never had leptin and get it back, and like the person who gains weight and then loses it acutely? The person who had no leptin and gets leptin will slim down perfectly normally. But if you have leptin from birth onward and you picked up those one to two pounds a year over a decade, you don’t respond to leptin. And understanding the mystery of why that leptin resistance or leptin ineffectiveness is there is clearly a very important question. The other very important question is what is it about some people that keeps them from getting fat? We live in a society where food is equally abundant to everybody. I’ve got the same food supply as you do and anybody else watching this show. So, what is it about those who don’t get overweight versus those that do? Well, we know that a good bit of it is genetic. We also know that among the genetically susceptible people there are some kinds of genes that play a particularly important role. And we’ve been interested clinically in pairs of animal groups, one of which gets fat eating a high fat diet and the other animals don’t at all. I mean, you’d feed them on it and they’ll eat a little bit, and then their weight drops right back to normal. While the others will go right on up just like that. Forty percent of our population has been doing this sort of creeping up all of the time. So, what’s the difference in this? And we’ve explored that over a good many years, like 40 years of my career and finally working with a group in New York, we’ve identified a gene protein complex in the brain areas that are involved with feeding and food regulation that is present in one but not in the other. And when you modify it, you change the responsiveness to the high fat diet to which we seem to be sensitive. So, it looks like we’ve began to get some molecular basis for some of the biology that we’ve been seeing about the susceptibility some people have to a high fat diet which others do not have. So, this is I think an important message that will be of use in trying to develop new medications.

Pape: So, I was going to ask you if there are any important breakthroughs that you see now or on the horizons. So, it’s sounds like that’s one.

Bray: Well, that’s certainly one.

Pape: Anything else? Yes.

Bray: That’s certainly one. We know a great deal about some of the things that you can change and which have — it’s probably been changed to ask do they impact the food intake, the beverage intake in the population. There are trials and there’s actually a court case at the moment trying to overthrow the tax that Philadelphia has put on soft drinks. But it’s very clear that where soft drinks are taxed, the consumption goes down and where the follow-up’s long enough, body mass index begins to go down. So, it’s clear that that strategy does work. Is this population prepared to make choices of that kind? Well, we haven’t had the political will to do anything about it yet. And is that what’s going to be required? Well, it may be.  

Pape: It may be.

Bray: And the question is if the problems with the sugar containing beverages isn’t just weight gain, but it’s their association with liver disease, so-called non-alcoholic fatty liver disease which is clearly related to beverage consumption. And the major cause at the moment for a liver transplants are people who have non-alcoholic fatty liver disease. Not cirrhosis, not other poisons that do it, but basically a function of our dietary consumption of sugar-sweetened beverages. So, I am optimistic that we can somehow bite the bullet and that the taxes that Berkeley has put in place and Philadelphia put in place, and some others have put in place. Mexico has done it to all their beverages. It’s nationwide in Mexico. They have a very serious problem with–

Pape: Yes.

Bray: –obesity and diabetes. And they’ve decided they need to do something, because the long-term outcome for diabetics is not good. It’s very unhappy, with blindness, amputations, heart disease, kidney failure, kidney dialysis. None of those are really happy outcomes. And you can’t predict that they’re going to occur to you but they occur to all too many people who get diabetes. So, it’s something we need to tap down before it gets too far out of control. The other interesting — there are some challenges on the horizon, some new interesting strategies. We know that the brain has a number of mechanisms for modulating food intake. We also know that food intake has a pleasure component to it. It activates the same systems that sex, drugs, tobacco and the like activate. They activate the so-called mid-brain dopamine neurogenic pathway. And so, it’s got a regulatory sense and a hedonic pleasure sense. And if we’re going to have all — it’s probably the people who sense the pleasure from their food in excess that get the problems with obesity. And there are numbers of very interesting studies coming out using techniques to look at brain imaging that suggest that this is a serious issue. So, the pleasure part combined with this overwriting these feedback parts are areas we need to understand better. The other component of the feeding system of the messages that come from outside the brain to the brain, telling the body that it either needs or doesn’t need food. And the messages from the GI tract are the earliest ones. You get your taste — the sight, smell, and taste of food is either a positive or a negative feature. Some foods smell very good, you like to eat them, and you do. So, we’d like to prevent the problem or if we can’t prevent it we’d like to have some effective therapies and these seem to be potentially good ones for the future.

Pape: Well, I can’t thank you enough. And tell you that all you’ve told me today and I’m sure others feel the same way, only wants me to ask you more questions. But for lack of time, I guess I’ll ask you just one question.

Bray: Uh-hmm.

Pape: What’s your ZIP code?

Bray: My ZIP code is 94107.

Pape: Okay.

Bray: It’s a San Francisco ZIP code.

Pape: Okay. Well — and so, what’s the rate of obesity there?

Bray: I don’t know.

Pape: Okay.

Bray: The West Coast doesn’t have much. The coasts tend to be less problematic than the center. San Francisco is a high rent area. And the number of people who have weight problems doesn’t appear as high as it does when I go to Disneyland for example, which is a little different.

Pape: A lot different.

Bray: A lot different.

Pape: Well, from all over.

Bray: All over.

Pape: Again, thank you very much!

Bray: Pleasure.