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Robert F. Kushner, MD: Hi. I am Dr Robert Kushner. Welcome to Medscape's InDiscussion series on obesity. This is episode two. Today we'll be discussing the changing paradigm about obesity as a disease. First, let me introduce my guest, Dr Donna Ryan. Dr Ryan is a professor emerita at Pennington Biomedical in Baton Rouge, Louisiana, USA, where she oversaw clinical research for 25 years. Her research interests include lifestyle intervention and diet for weight loss. And she was the investigator for multiple National Institutes of Health studies, including POUNDS Lost, Look AHEAD, the DPP [Diabetes Prevention Program], and DASH [Dietary Approaches to Stop Hypertension]. She has also served as president of the Obesity Society and the World Obesity Federation. Donna and I go back multiple decades. Donna, welcome to InDiscussion.
Donna Ryan, MD: Delighted to be here, Bob. Thanks for having me.
Kushner: Donna, today we're going to be focusing on obesity as a disease. Let me set you up for this first question. It seems to me that how we think about obesity is in the eye of the beholder, meaning that everyone has a different way of looking at the problem. Is obesity a result of sloth and gluttony, which happen to be two of the seven deadly sins? Or is it really a disease that individuals are predisposed to develop due to genetics, biology, and the environment that we live in?
Ryan: Bob, Bob, Bob. It is not a sin. It is a disease. You know, it's really amazing to me how ingrained in our culture this idea is that people could easily change their body weight if only they wanted to. Individuals develop obesity because they have genetic susceptibility and are exposed to a modern environment that really promotes food intake. Not a lot of energy is required in our work and in our play. There are also other factors that drive weight gain in susceptible people, such as pregnancy. The average weight gain with each baby is 2 lb and is cumulative. Medications that we are taking for depression, diabetes, and other chronic diseases can drive weight gain. There are many, many drivers. I don't want to make it sound like it's simple. It's complicated. Obesity is a complicated disease, but it's a disease. It is not a lack of character or being morally upstanding. Individuals with obesity would love not to have obesity; they would love to be lean. But it's a disease. The real problem is that once we develop excess body fat, our bodies defend that excess abnormal body fat. Weight gain usually occurs gradually. But to try to lose weight, our bodies resist that weight loss.
Kushner: I agree completely. It is a disease. I think there are still confusing messages out there. And of course, with podcasts like this, you and I and others are trying to get the message across. Hopefully we will convey that obesity truly is a disease. Given the mixed messages, what do you think the roles are of insurance companies, regulators, healthcare professionals, and, most important, people living with obesity? What's the common message we're trying to get across in the role of all the stakeholders?
Ryan: I think the most important thing we have to do is to make sure everybody understands what obesity actually is. Our healthcare providers are not all up to speed on obesity. Obviously, there's a lot of bias within the healthcare professions. Individuals with obesity have had bad experiences in their healthcare. They've been blamed for their body weight. I think that bias and stigma that individuals with obesity face on a daily basis is something we must counter. And the way to counter it, I think, is understanding what obesity really is. I can't imagine another disease where individuals are required to try a diet before they can be eligible for medications. We don't require that with people who have cholesterol problems. Why are we doing this with people who have weight problems? Before they have a surgery, they're required to try a diet and physical activity. People with obesity have tried multiple times to lose weight. It's the body's biology that they need help with. And in terms of payments for obesity treatments, I can't imagine another disease where adequate provision of care, which can be lifesaving, is not allowed or sanctioned by our insurers, employers, and regulators.
Kushner: I can't agree with you more. We're seeing this particularly among the newer generation of medications that are not really covered adequately, not at all by Medicare, but really as part of treatment. I want to go back to the biology of disease. You brought that up in the first question. I mentioned to you that it's not just willful misconduct and so on, but it really is biology. I wonder if you could unpack that a little more, particularly about appetite dysregulation and what we call lipotoxicity.
Ryan: When we accrue excess body fat and we try to lose weight, our bodies react almost immediately with these physiologic mechanisms that defend our settling point of body fat. Our body doesn't want our fat mass to decrease; it loves it where it is. That's our settling point. And so when we start to lose weight, we get changes in the appetite signals, and we can actually measure the effect of these signals. In regard to the appetite hormones, ghrelin, the hunger hormone, the satiety hormones, CCK, GLP-1, PYY, amylin, when we start to lose weight, we get an increase in the hunger hormone and a decrease in the satiety and fullness hormones. And so we can measure the hormones and we can also measure hunger and fullness. As long as we are trying to reduce, as long as we're in this reduced state, we have greater hunger and less satisfaction and fullness. But there's something else that occurs that makes it even more difficult. When we're trying to lose weight, something kicks in, called metabolic adaptation or adaptive thermogenesis. When we start to lose weight, our metabolic rate decreases more than you would expect just by being a smaller size, and that metabolic adaptation, that lower metabolic rate, works together with increased hunger to drive weight regain. That is why it is so difficult to lose weight.
Lipotoxicity, Bob, is something else. When we exceed our ability to store excess calories in healthy fat, that's usually fat around the hips and thighs. We start storing those extra calories in abnormal body fat stores — fat stores within the abdomen, we call that visceral adipose tissue; fat around the heart, that's pericardial adipose tissue; around blood vessels, that's perivascular; around kidneys, in the liver, in the muscle, and in the pancreas. And this adipose tissue is bad. It looks different under the microscope. The fat cells are big. There's evidence that they're not healthy. We see evidence of their cell death and dying helmet cells. There are a lot more white blood cells in there, indicating inflammation, and that fat tissue is producing lots of bad actors. It is producing hormones — adipokines and cytokines — that promote thrombosis, inflammation, and insulin resistance. We get into trouble not just where that fat is. The coronary arteries are running straight through the epicardial adipose tissue, and those products of that abnormal adipose tissue drive atherosclerosis. They also affect the heart muscle itself. So, it's a direct effect of where the adipose tissue is located. There also are systemic effects all around the body. There is a prothrombotic and proinflammatory milieu that people with obesity are living in. Lipotoxicity means that fat is an active endocrine organ. And when we store fat in these ectopic spots, it's something that really produces all of the complications of obesity.
Kushner: That's a good description of the biology and pathophysiology of obesity. It sounds like we know a lot more than we did two decades ago, for example. We have a lot of folks who are living with obesity in this country. Can we identify those individuals who have this underlying biology that you just described and who are predisposed to developing obesity and its complications?
Ryan: I know you'd like me to tell you, "Oh, yeah, we've got a blood test. We've got a genetic risk score that can identify." Bob, 70% of the US population has a BMI over 30. We've got lots of individuals who have a lot of excess abnormal body fat. And the way we start off identifying people at risk is with BMI. It's a good screener. It's the body mass index. You calculate it from your height and your weight, and it tells you a lot about what your body size is. It doesn't tell you anything about where body fat is or how unhealthy body fat is. And so that's why BMI is just a screener. The next thing we do is look at waist circumference, a very important measurement, especially in people with a BMI of 25 up to about 35. That waist circumference really gives us an idea of ectopic fat storage. We also want to know what the metabolic risk factors look like. What is the C-reactive protein, what is the blood pressure, what is the blood glucose, the A1c? What's happening to the lipids? We get signals from those risk factors that help identify a metabolic syndrome — that is, individuals who are at increased risk for diabetes and heart disease by virtue of having lipotoxicity.
Kushner: You mentioned about how many Americans, adults particularly, have obesity. It's over 42% by BMI; if you had overweight, probably 3 out of 4. So let me ask you kind of a provocative question: Are we saying that 42% of Americans have a disease of obesity? Let's say you have an actor who puts on 30 lb for a role. Does that person have obesity, and when they lose weight, they no longer have obesity as a disease? Do we understand enough about that?
Ryan: First of all, many of those individuals do have obesity, the disease. And there are some people who do have a BMI of 30 or higher who don't have evidence of abnormal risk factors. These are metabolically healthy individuals with that high BMI. What we usually find with these individuals is that over time, over the lifespan, they tend to develop metabolic complications. We worry about those individuals and we follow them closely. The way we really diagnose obesity as a disease is a clinical diagnosis. It's the demonstration that an individual has excess abnormal body fat by virtue of dysmetabolic syndrome.
Kushner: By the WHO definition, as you're alluding to, it's excess body fat that impairs health and quality of life. But, Donna, as an individual goes to see their primary care professional, it's pretty uncommon that they have a body fat measure, yet it's a disease of excess body fat. Do we just assume that the excess weight is body fat, or should we be measuring body fat, since you delineated so well that the target pathology is a sick fat?
Ryan: I wish we had an easy, safe, inexpensive, and quick measure of body fat; we would use that for the diagnosis of obesity. Right now, our best and most accurate measure of body fat is DEXA, dual-energy x-ray absorptiometry. But Bob, that exposes people to a tiny bit of x-ray, and we don't want to use that as a screening tool. I think we're going to get a little closer in the next few years with digital anthropometry — that is, measuring circumferences around the waist, hips, arms, and neck with just a digital photograph. And then, if we know the weight and we have those measurements, we can calculate a pretty good body fat. It's been compared to DEXA measurements and it's good, very good. I think we're likely to move in that direction in the future. We're not quite there yet in the clinic.
Kushner: Okay. Stay tuned on that one. Donna, I want to have you quickly return to the challenges that individuals living with obesity have in maintaining weight loss. Earlier you described metabolic adaptation and change in the gut hormones. Should that be treated biologically being that why the weight is being regained seems to be a biological problem? Should we be focusing individuals to turn to biologic treatments, which I guess is pharmacotherapy?
Ryan: Yes, it is pharmacotherapy. But you know, Bob, a lot of the things that we do in our lives, all our interventions, are intended to work through biology. For example, when we're teaching people how to develop skills to help them lose and maintain weight, we do things like having them self-monitor. Being aware of your body weight, your food intake, being mindful about food, recognizing the body's signals of fullness and not just eating automatically — those are all things that we're doing that work through biology. Think about it: Some of the things we teach in our lifestyle intervention, like eating slowly to give those appetite signals time to come into play, help reinforce so that we can stop eating sooner. We don't have to eat everything on the plate, gulping it down. If we eat more slowly, we're more likely to eat less. We're already doing those things. What we think goes on with those medications that work through appetite is that they help reset that settling point so that when we take our medications, we will lose weight and will reach a new level that, as long as we keep on the medications, will be maintained. With our older medications, that's usually on average about 5%-10% weight loss. Our newer medications are coming out with more weight loss — 10%, 15%, even up to 20% weight loss. And so what's happening there is that the impact on those appetite signals is making it easier for patients to follow their dietary intentions.
Kushner: Good advice and good insight on how to deal with weight regain. Donna, I mentioned when I introduced you that you're the past president of the World Obesity Federation. You had a global approach, unique among many of us. What have you learned about the global problem of obesity — either similarities or differences between the US and other countries?
Ryan: Obesity is really a global pandemic. It is increasing everywhere. The G20 countries are those that have higher socioeconomic status. And those countries are the ones that are having the highest rates of obesity. We seem to have done a really good job of exporting this Western lifestyle around the world and, along with it, our obesity rates. It was really interesting to identify that the highest rates of obesity in the world are in the Pacific Islands. But we also have enormous problems with obesity in the Middle East and in Mexico. Everywhere in the world, especially as countries begin to emerge economically, we're really identifying increased rates of obesity. One of the most interesting things is that although the cultures of these countries are different across the world, we do observe that same obesity stigma across all of those countries. We seem to have exported our value of slimness around the world too.
Kushner: What should we as a society, we as providers, and all the other stakeholders be thinking about regarding obesity as a disease?
Ryan: I think it's so important that we help our patients understand what they're dealing with. All patients seem to own their disease. They feel responsible for their body weight. They think it's their problem. It's important that healthcare providers get into the swing of things; it's our job to help patients understand the biology that makes it hard for patients to lose weight and keep it off. Some patients think taking medications is cheating. They think, Oh, I just need to try harder. No. Medications work through biology to help you follow your intentions. Our goal really is to move patients toward healthier lifestyles, right? Well, medications can help patients do that. And, Bob, for some people with severe obesity, we need to be more proactive about helping get those patients to surgical evaluation, because that is currently our best and most long-acting weight loss approach.
Kushner: Today we've had Dr Donna Ryan discussing the changing paradigm about obesity as a disease. Donna, thank you. This has been wonderful. Thanks for sharing all your insights about obesity.
Ryan: I love being here. Thank you.
Kushner: I want to thank all of you for joining us for episode two. I look forward to another great discussion in episode three. This is Dr Robert Kushner for InDiscussion.
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Cite this: Obesity as a Disease: Changing the Paradigm - Medscape - Apr 05, 2023.