Understanding Obesity as a Disease

JOEL BERVELL: Welcome back to The Dose. I’m Joel Bervell, and I’m hosting a special season focused on health equity. On today’s episode, we’re looking at an aspect of equity that often goes overlooked. I’ll be talking about the controversy around classifying obesity as a disease with my guest, Dr. Fatima Cody Stanford. Why is the data in evidence demonstrating that obesity is a disease so controversial?

Dr. Stanford is an obesity medicine physician scientist at Mass Gen, an associate professor of medicine and pediatrics at Harvard Medical School. She served as the chair of the Minority Affairs Section for the American Medical Association, chair of the American College of Physicians Obesity Advisory Committee, and is the director of Diversity and Inclusion for the Nutrition Obesity Research Center at Harvard. Dr. Stanford’s research focuses of the utilization of antiobesity pharmacotherapy after bariatric surgery, outcomes and utility of adolescent bariatric surgery, and pharmacotherapy for the treatment for obesity.

Thank you so much for joining me, Dr. Stanford.

FATIMA STANFORD: Thanks for having me. It’s a delight to be here.

JOEL BERVELL: So, Dr. Stanford, you’ve been working in the field of obesity medicine for many years, and it seems like there’s been increasing awareness about it. The FDA approval of medications like semaglutide, which is being used to treat obesity, makes it seem like we’ve come a long way, but not without controversy. Can you give us a snapshot of the history of obesity and how we got to where we are today?

FATIMA STANFORD: Absolutely. So let’s look at how we define obesity, which is based on body mass index, or BMI. So if we go back to the 1800s, there was a Belgian statistician who sought to determine what was considered to be normal for Belgian soldiers, white male soldiers at the time, with regards to body habits, et cetera. This was then taken by a guy by the name of Sir Francis Galton to determine normality in terms of body size, race, ethnicity, immigrant status, socioeconomic status, and became the basis for eugenics, determining what was considered to be desirable for reproducibility.

This also became the framing of Nazi Germany by Adolf Hitler. And then subsequently in the 1930s and 1940s, the Metropolitan Life Insurance Company sought to determine what was considered to be normal weight status for white men and women that were insured by the company at that time. Hence, the term morbid obesity — which I don’t agree with — but it was based at that time on actuarial table data: What was your risk of dying based upon your weight status?

This became the basis for the BMI that we utilize today to determine whether or not someone has this disease of obesity. Now, you’ll notice in what I just explained that none of that was derived from medicine or science, or necessarily determined one’s health risk. BMI is defined based upon this epidemiologic measure, which isn’t always going to be germane to every population, every group, as I just mentioned. Looking at this number as a rigid point, as if all of us are the same, has some major flaws.

JOEL BERVELL: I think there’s so much in there that’s so important to what you said of understanding the history of how we got to where we are today, these things that are built into systems that people don’t often see, but impact how care or just science is thought about in the general population. I wanted to pick up on the academic piece as well. So in 2013, the American Medical Association resolved at the House of Delegates meeting to recognize obesity as a disease state. I know you had a huge impact on that, so thank you so much, because I think as medical students, that’s what we need, right, to understand this.

But just the year before the AMA’s own Council on Science and Public Health had said that there wasn’t sufficient data to support calling obesity a disease. So I’m curious: How would you characterize this conversation that’s going on amongst people doing the research on obesity medicine when there’s these kind of conflicting things that happen or are said?

FATIMA STANFORD: A lot of the research that was utilized in that public health perspective was looking at obesity just as a public health issue. What’s the epidemiology show us, not looking at the science or pathophysiology of the disease of obesity. I think the reason why that wasn’t really included was because a lot of the people that were involved in writing the report, but also the lack of education for physicians at large surrounding obesity. The disease did not explain or teach the pathophysiology.

It wasn’t really for me until I did a three-year obesity medicine fellowship here at Mass General and at Harvard that I understood the pathophysiology of this complex disease that is obesity. And so when we look at the science side of it, what we can recognize is that the brain is really important in terms of regulating weight and that there’s two primary pathways that help us to determine what one’s weight status would be in the brain, particularly in the hypothalamus of the brain.

There’s one pathway that tells us to eat less and store less. Those people that tend to signal very well down that pathway have a lean expression of adiposity. Adipose meaning fat. So you don’t express much adiposity. Whereas those that have obesity often don’t signal as well down that pathway and they signal down an alternate pathway. Interestingly enough, particularly, Joel, because I know your interest in looking at health equity and disparities, if you look at large what we call GWAs, or what we call genome-wide association studies, we actually see that there’s certain groups that have a higher likelihood of signaling down that alternate pathway.

We have seen in studies with 30,000-plus individuals that individuals of African descent, those that are Hispanic in descent, tend to actually signal more likely down that alternate pathway. So when we start looking at disparities in obesity on a genome level — this is not using race as a biologic marker, actually looking at the genes themselves — we do see a higher predilection to signaling down that pathway in groups that are of African origin, like I said, and those that are of Hispanic origin, in both pediatric and adult populations.

So this is not the conversation we hear. We do hear about social determinants of health, and we can get into that, but when we actually look at it from a genetic perspective and look at the actual genes themselves, we do see these differences that may account for some of the disparities we see and the prevalence of obesity in racial ethnic minority communities, for example, here in the U.S.

JOEL BERVELL: Definitely, and thank you so much for that lesson on just better understanding the pathophysiology that goes on behind obesity because, as you noted, we often don’t hear about it talked about in that way. I’m curious: When we talk about obesity being classified as a disease, are there losers in this conversation when we discuss it like this instead of the result of a set of habits? Is there a lot of investment in the status quo to keep the incumbent treatments that we do currently? Why is that and how can we shift this narrative and mindset institutionally and nationally?

FATIMA STANFORD: I think that if we look at the “weight-loss industry,” there are a lot of people that have gotten very, very rich on selling very simple measures, right? Maybe I do restricted eating, very-low-calorie diets, things that just focus on maybe exercise. People have made a lot of money off of these things and people try them. They of course eventually stop them and then of course eventually gain back weight.

So I think that people that have simplified and said, “Oh, if you just do X and you lose all of this weight” or the late-night infomercial group, that they potentially are losers as people begin to understand this as a really complex, multifactorial, relapsing, remitting chronic disease.

It’s interesting. I haven’t really thought them as losers, but I think that there is probably some pushback because they have been able to be very profitable with these kind of very simplified notions. And then they show before and after pictures or January 1st through the 20th where certain magazines may put “This person lost half their body size,” and then we never hear about these people ever again. We don’t know what happened five, 10, 20 years down the road.

Because for me, it’s not just about weight loss, it’s about maintaining it: to have these people that are successful with diet and lifestyle, which is great. I always tell my patients, “If that’s what works for you, phenomenal.” But it fails 90 percent of the time. So what about all of those people? Do we just say, “Sorry, you’re in a bad group. Something is wrong with your body.” Just “I’m sorry, you’re a lost cause,” or do we actually help them? Obviously, I’m in the camp of like, “Let me help you, let me help you. You’re trying to do this alone, but I can offer some assistance to help your disease process.”

JOEL BERVELL: So you’ve kind of hit on my next question a little bit about the winners of this. You’ve talked about patients and how they’re able to better keep it off. But there’s also some business opportunities too for big pharma. I’m curious what you see on the long-term horizon.

FATIMA STANFORD: Yeah. I mean, it’s interesting. I guess we could call big pharma a winner because if they’re making money off of medications that are effective for the population, I think pharma has to step up and recognize that if this disease is affecting almost half the population, right? The numbers from NHANES, or the National Health and Nutrition Examination Survey, was 42.4 percent of U.S. adults; that was 2018 data. We have not seen the recent NHANES. I think that is due out either this year or next year, that we’ll see close to half the population that has this disease here in the U.S.

And so yes, if you can just get 5 percent, 10 percent of that population that is on a therapy, then potentially obviously that’s a financial gain. But I think the onus lies back on pharma to recognize that, for example, for medications, particularly the newer classes, that these medicines are exorbitantly priced. Why would we make it inaccessible, where if we brought down the price and supplied it to a much larger demographic, there’s more money to be made, right? There’s more winning. If we’re talking about winning in terms of who wins. Those are probably the key winners outside of patients, who I think really have the most to gain from this recognition.

JOEL BERVELL: What about research funding? Are you seeing more of a flow of cash towards research for curing obesity for patients, et cetera?

FATIMA STANFORD: I haven’t seen a major shift, at least if you’re looking at it from federal funding perspective. So the NIH [National Institutes of Health] for example, there hasn’t been per se a significant shift in funding to obesity. If you look at even the way the institutes are named, you have NIDDK and NHLBI, the National Heart, Blood, and Lung Institute, the National Institute for Diabetes and Digestive Kidney Disorders. That’s where most of the obesity funding is.

But notice obesity is not in either of those titles. So even while the NIH is definitely putting — that’s where most of the money for obesity research is, under those two — we haven’t seen, per se, a huge, huge shift. I do think that that’s going to gradually change over time as people that are outside of just the key obesity, I guess, research domain start to explore obesity in their respective areas.

It’s going to impact every field of medicine because there are obesity-related diseases in every system. And so I think that because of that, we’ll see more and more people that are researchers and investigators begin to open up their portfolio to consider obesity, like maybe obstetrics and gynecology decide, “Hey, well let’s look at reproductive health in obesity.” These types of things that are less frequently entertained.

JOEL BERVELL: Yeah. I mean that intersectionality is so key to understand how obesity is dealt with in different disciplines or not dealt with at all. And I think as you are doing, you’re opening everyone’s minds to thinking about this differently, which I think will open up new research questions too that’ll hopefully be able to better understand how do we tackle this from all fronts.

I want to shift a little bit now, talk a little bit about your work in equity and public health. So your work really does intersect around those two areas of your expertise and concern, both as an obesity medicine doctor, but also as an active past chair of the Minority Affairs Section of the AMA. I’m really curious: Where does equity show up in the obesity work that you’re doing right now?

FATIMA STANFORD: It shows up in all facets. But I’ll talk about some of my current research and areas of interest, particularly some of my newer funding from the NIH, which really looks at increasing the workforce surrounding those that are conducting nutrition and obesity research. There are very few people in this space that you see that look like me. And what do I mean by that? As a Black woman, physician scientist, born and raised in the South — this is just not the person that’s typical to be out and amongst the key experts in any field, let alone this field of obesity.

So one of my current larger grants from the NIH, it’s specifically seeking to improve the workforce and nutrition and obesity research, with a particular focus on underrepresented individuals. So we, here at Harvard, we are one of the sites, and there are three other sites around the country: UCLA, UNC Chapel Hill, and Pennington Biomedical Research Center.

But our entire focus of our work is increasing the pipeline for individuals that are from underrepresented groups to do this work. What we find is that persons that are from racial and ethnic minority communities tend to want to study what’s going on in their communities much more than others, but they’re not typically funded or they don’t have the training or expertise or guidance to really get to the large grants that then allow them to answer the big questions that need to be answered.

So a lot of my focus right now is how do I help bring those people behind me that want to do this work and helping them to prepare for their big grant to do key research questions. And so that’s where a lot of my focus and attention is currently, is really how do I prepare those that are coming behind me to be the 200-plus publication people like myself and actually change the narrative in their own right.

JOEL BERVELL: Yeah. That’s really interesting. I’m curious if we can talk a little about stigma when it comes to obesity and how can stigma against people who are living with obesity make people more sick?

FATIMA STANFORD: Absolutely. I’m so glad you brought this up. This is an area that emotionally touches me because I see my patients struggle with what they experience in health care and in just their daily lives. So when a person experiences weight stigma, this actually sets us up for significant change, physiologic changes. We see higher levels of C-reactive protein, hemoglobin A1C, higher blood pressure — all of these things they actually experience as a result of experiencing stigma.

Unfortunately, the bias or weight bias is the second-most-common form of bias, behind race bias, here in the U.S. So imagine if you are a black woman with obesity. You’re facing the race bias, then you’re facing the weight bias, and then you’re facing the gender bias. And so you’re dealing with all of these forms of bias about who you are, your value, your worth, in a system that is set up already not to treat you very, very well, but it can start from the moment the patient walks through the door in a health care setting.

Let me take you through the journey of a person. They walk through the door of their physician, whatever type of physician they are, and they check in with the front desk staff, and then they want to take a seat in the waiting room. But let’s say the seats in the waiting room have arms that are confining, which means they can’t sit down. And so they choose to stand in the waiting room and the office staff says to them, “Oh, well, why don’t you have a seat?” And they’re like, “Oh, no, no, I’m fine standing.” They’re really not fine standing, but there is no seat that’s appropriate for them. So they’ve received already a nonverbal cue that they don’t belong.

So then they get back to get their vitals taken. This would include blood pressure, things of that sort. The blood pressure cuff, you know what? It’s not the appropriate size. They only have the regular size blood pressure cuff, so it’s popping. They’re recognizing, “Oh gosh, I don’t belong here either.” They go back to now the physician’s office and they go to give them a gown to put on and, “Oh, you know what? We don’t have the right size gown.” I mean, this person has gotten several cues that I don’t belong here. Oh, let’s give them another cue. Maybe the exam table doesn’t quite accommodate me, so I choose to sit in the chair that’s on the right side instead of the exam table.

Then I finally walk in. Let’s just say I’m the doctor, and I’m like, “Well, why are they sitting in my seat?” But then I realize, “You know what, the table doesn’t accommodate them.” So they’ve received all of these nonverbal cues that I don’t belong before I say the first word.

So imagine what that’s like to be on the receiving end of this? And this is not an uncommon phenomenon for people in health care here in the U.S. or around the world in many circumstances. So then they get in and I ask them, I see they maybe struggle with disease because unlike other diseases, Joel, obesity is a disease you wear. People see it, right?

JOEL BERVELL: Yeah.

FATIMA STANFORD: You can have diabetes, you don’t see it, right? You can have cancer, you don’t see it unless maybe they’re undergoing chemo and maybe have lost hair or something. You don’t see other diseases. You don’t see depression. You don’t see anxiety. But you see obesity. So the patient comes in and you start asking them questions. And we’re taught to assume that everything is related to weight, and we make assumptions or judgments about that person if they happen to carry excess weight: “Oh, they don’t exercise. They must eat horribly.”

Whereas if a person is lean and they come through the door, we assume they’re doing all the right things. They must be eating healthy. They must be exercising. So maybe we don’t even ask that person about what their diet looks like or what their exercise schedule is because they just are naturally lean. So stigma is so entrenched in everything that we do in medicine.

For my fellow orthopedist, since that’s one of the things you’re interested in, it’s frustrating to me and to patients when a person needs a new knee to be more active, and then they’re like, “Okay, well go lose a hundred pounds.” And the patient is, “Okay, so how am I supposed to do that? I hear you.” And they assume that the person hasn’t tried once, twice, 60, 70 times. But now they’re supposed to be able to leave and just magically, they’re supposed to figure out how a hundred pounds are going to be gone so they can get that new knee that they need to be more active. So you see how it’s a vicious cycle?

I just call out ortho specifically there, but in every field, I mean as internists, pediatricians, everything, it’s like, “Oh, well, it’s because of their obesity.” And yes, it could be because of their obesity, but are you helping them solve the issue? Are you just making them feel more and more insecure about what a failure they are because of their excess weight? And that’s typically what we do.

JOEL BERVELL: Yeah. I absolutely love the way that you painted that picture of a patient coming in and exactly what’s going to happen to them as they walk through from all these things that we might think is minor, but it’s death by a thousand paper cuts. Right? It’s these little things that make people feel like they don’t belong and can lead to treatment avoidance, to not even going to the doctor anymore, to feeling that everything, like you’re saying, is ascribed to their weight, that you might miss something that could be going on underneath.

FATIMA STANFORD: Actually, I want to give one other key example.

JOEL BERVELL: Yeah, please.

FATIMA STANFORD: I think it’s particularly related to what you said, people missing things. There was a patient that came into our office that was having significant hip pain. Orthopedics told them they needed to lose weight to get a hip replacement. So they came in. They were never imaged by ortho, but had some high degree of excess weight. Came in. They ended up getting bariatric surgery. They did lose a pretty significant amount of weight, got re-imaged, and they had an osteosarcoma that had been growing in their hip.

JOEL BERVELL: Oh, wow.

FATIMA STANFORD: Because the pain never subsided, right? So you were like, “Oh, well, this patient’s lost 100, 110 pounds. This delightful.” The patient is like, “My pain is more intense.” And so had to have a large part of their leg resected, et cetera. I think that we don’t listen to patients with obesity. They’re telling you what’s going on, and yes, it could be related to their weight, but if they’re explaining something, I think the onus lies on us to still get them imaged. This patient, I think, could have salvaged, first of all, time to diagnosis would’ve been much sooner.

By the time they had finished surgery, and were going back to the orthopedics we were talking about two and a half years later, but they were never imaged before. So we presume that cancer was growing, but nobody ever checked. And how many situations? I mean, this is one key situation I can point out that I know directly about, but this is just one of tens of millions of, I think, diagnostic errors associated with just the assumption that this person with excess weight, all they need to do is lose weight and their hip will feel better. Or, oh, they need to lose weight and their knee will feel better. Yes, will they likely feel better? Definitely. Can we just assume that it’s just due to their weight? Absolutely not.

JOEL BERVELL: Yep. So we’ve talked a lot about the positives of thinking about obesity as an illness. Just to play devil’s advocate, I’m curious, would you say, are there any dangers in thinking of obesity as an illness?

FATIMA STANFORD: I don’t really see any dangers, but I will talk about one such movement that I think has led into some potential dangers. So there’s the fat acceptance health at every size movement, which believes that just accept me for who I am, accept me for my size, which I agree that I’m not going to treat someone differently because one person weighs 150 pounds and the next person weighs 300 pounds. I agree that we should not treat people differently.

However, what I think that particular movement is set us up for is not doing a deep dive, not looking to see if that cancer is in the hip. If you go to the doctor and every time you left you feel worse, “Why should I go to the doctor and they’re not going to tell me anything except that I’m just not doing something well enough?” And so I think that we, we as the medical community, have actually given birth to a movement that we didn’t and tend to because we have been so vilifying towards individuals that have excess weight.

So I would say that this is a negative, and maybe I twisted your question a bit, but I see this happen quite a bit. Well, even for a lot of the people in the Hayes community or the fat acceptance community that I see as allies to me, but say, “I really like that you think everyone should be treated with dignity, but I don’t think obesity is a disease.” That pushback is because most of us haven’t taught them in a way that helps them understand that this hate is not your fault. I’m not judging you for where you are. And so that sets up a really negative dynamic often with the fat acceptance community where I think there can be synergies and we can over for overlie.

I can accept you for who you are because of your size, but I could also seek to make sure I’m not missing key things that could significantly affect your life expectancy and your disease process. Not only obesity itself, but the 230-plus diseases related to obesity.

JOEL BERVELL: It’s really getting people to understand that nuance that’s there that’s often lost in these conversations. So I want to start wrapping up with a look ahead. So as we discuss at the start of this episode, change in this field is happening so tremendously fast right now, especially in just the past year, like I mentioned, with what’s happening at the FDA stage. I’m curious: How has that impacted your work, and what do you think are the next significant areas that we’re going to be moving into?

FATIMA STANFORD: I see the change in obesity as I would say that it’s finally moving at a pace that I think reflects the disease state. I think that we’re going to hopefully see this, and I think that I’ve already seen this, so on an international level, see a really increased focus on understanding obesity as a disease beyond BMI as the key metric. I’m currently working on the Lancet Commission of Obesity with experts from over 60 countries to help define obesity as a disease.

You can imagine getting experts from 60 countries together is interesting. I do think that we’ll see changes, and I’m hopeful for changes in access because what I see now is there’s this differential between those that have appropriate access and then those that do not. Medicare, like I said, sets the stage for everything we do. And the bill that we’ve been trying to get across, that Treat and Reduce Obesity Act that we’ve been introducing in Congress for over a decade now, still has not moved in a way that allows for access to the Medicare population, which then sets up problems for those that are privately insured or those that have Medicaid.

So the Medicare we know sets the standard for everything. And I’m hoping that these things begin to shift. Now, federal employees, for example, get antiobesity medication coverage. That was a major shift recently, but we haven’t seen that translate to Medicare, which is also a federally run program. So why do we give one group under the federal government access and then another group not access? I think we need to figure this out. So are we going to give access? Are we not going to give access? I’m hoping that we see that shift.

And I’m hoping that, much like depression was stigmatized for so long and people say, “I’m taking X, Y, or Z drug now,” and people would hide it in the past. I’m hoping that the bias towards with individuals with obesity starts to change. I think it’s going to be a slower process than other previously stigmatized disease processes because it is so visible, right? It’s such a visible disease, and people still have such emotionally charged responses when we deviate from what they see as the status quo, which is this is all just about your moral failing as an individual, why you have this disease. So that’s what I’m hopeful for in the future.

JOEL BERVELL: When we think about the future of therapies, can these therapies be targeted towards specific people? What is therapy going to look like in the future?

FATIMA STANFORD: So what I would like for it to look like, Joel, is I would like for us to actually begin to explore pharmacogenomics in obesity research. One of the key things I’ve noticed in caring for patients with obesity for many years now is that you have those high responders and you have those really low responders. But wouldn’t it be great, much like when we’re using cancer therapy, to know which receptor we’re targeting so we give the patient the right drug for them?

So for those patients that I put on phentermine and topiramate and they lose 55 percent of their total body weight loss, I’d like to know that before I start them on that. Would I ever start them on a GLP1 agonist if they already are responding with that from two generic, very inexpensive, long-term used medications? No. I would just go ahead and put them on that. So I think if we begin to personalize and tailor therapy based on that pharmacogenomic data or have better outcomes just like we see in cancer therapy where we’re finally starting to see a decline in cancer rates because we do target therapy. So that’s what I would like to see the future look like in obesity care.

JOEL BERVELL: Well, on that note, I want to say thank you so much, Dr. Stanford, for taking the time to enlighten myself and all the listeners about obesity as a disease. I think it’s really going to hopefully change the way that future medical students practice, that current physicians look at their patients, and just give us an opportunity to step back and really better understand these biases, the stigmas that we carry around in our own lives, and how that can actually impact our patients, how we can root it out in our own lives as well. So once again, thank you, thank you, thank you so much for being here.

FATIMA STANFORD: Thanks for having me.

JOEL BERVELL: This episode of The Dose was produced by Jody Becker, Mickey Capper, Naomi Leibowitz, and Joshua Tallman. Special thanks to Barry Scholl for editing, Jen Wilson and Rose Wong for art and design, and Paul Frame for web support. Our theme music is “Arizona Moon” by Blue Dot Sessions. If you want to check us out online, visit thedose.show. There you’ll be able to learn more about today’s episode and explore other resources. That’s it for The Dose. I’m Joel Bervell, and thank you for listening.