Epidemics of Obesity and Diabetes

Dr. Beutler's research has focused on how the gut and the brain communicate with each other to maintain body weight, and how this goes awry in diseases such as obesity. This interview focuses on new research, including dual incretin agonist tirzepatide as the first pharmacological agent that rivals the efficacy of bariatric surgery for obesity management.

Epidemics of Obesity and Diabetes
Featured Speaker:
Lisa Beutler, MD, PhD

Lisa Beutler, MD, PhD is a Assistant Professor of Medicine (Endocrinology). 

Learn more about Lisa Beutler, MD, PhD 

Epidemics of Obesity and Diabetes

Melanie Cole, MS (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And today, we're going to dive into the complex issues surrounding the epidemics of obesity and diabetes. Joining me is Dr. Lisa Beutler. She's an Assistant Professor of Medicine in Endocrinology at Northwestern Medicine.

Dr. Beutler, thank you so much for joining us today. You and I were talking a little bit off the air about this complex situation that we have, and there are way too many factors for us to solve in this episode today, but I'd like you to speak about the current state of obesity, how the prevalence of obesity and diabetes and the comorbid conditions that come with both of these has changed over the past few decades. What have you seen are some of the key factors? And again, I say there are so many of them, but what are some of the key factors contributing to this epidemic?

Dr. Lisa Beutler: Thanks so much for having me talk about this complicated problem and touch on just a few aspects of it. I think a couple of things have changed over the past few decades to crystallize the rising rates of obesity. And, you know, I think we have all seen the maps of the United States getting redder and redder as more people develop obesity, and that's true globally as well.

And I think over the past few decades, a couple of things have changed. One, we eat more. And in particular, we eat more highly processed foods with added fats and sugars. And two, we're more sedentary. And I think this has been a bad combination for body weight regulation in our society. That sounds like a really simple and obvious answer. But underneath that, I think there's a lot of room for nuanced debate on what specific aspects of our diets are to blame. Is it the time of day we eat? Is it just how much we eat? Is it specific nutrients? But at the end of the day, I think we're eating too much, we're eating too processed, and we're not as active as we used to be. 

Melanie Cole, MS: Well, and therein lies the other big factor, which is urban deserts and the inability of our children to walk to school because the sidewalks and gym and recess going away, and our children are obese at a young age, the portions are bigger. Like I said, you know, this is a huge problem. So with all of this, this obesity epidemic we're seeing, and even in our little ones coming up, where in the spectrum of diabetes diagnosis is obesity a factor, or where in the spectrum of obesity does diabetes start to come into the picture? 

Dr. Lisa Beutler: Got it. So, obesity is the single biggest risk factor for type 2 diabetes that we're aware of. You can find statistics that slice and dice the numbers in different ways. Basically, people who have obesity are on average three to seven times more likely to develop type 2 diabetes. And that number actually, that's not all people with obesity wrapped up into that number. That number gets higher as BMI increases, particularly past 35. And something like 80% of overall type 2 diabetes risk probably comes from being obese. Being obese is really kind of the single biggest modifiable risk factor that we're aware of that we can treat to try to prevent type 2 diabetes and its complications. 

Melanie Cole, MS: So, let's talk about you as a clinician and the significant challenges that clinicians face in managing patients with both obesity and diabetes. And as you and I have said, this is a sensitive topic and not always easy. And when you've got a child that's obese and then discussing that with the parents, I mean, this is kind of a vicious cycle. Speak about some of the challenges that you face, the potential complications and comorbid conditions that are associated with this, and how that overall impacts outcomes. 

Dr. Lisa Beutler: Yeah, that's a great another complicated question. Every aspect of this is complicated and every aspect of this is challenging. One issue I've thought about a lot as a clinician is access, both patient access to doctors, educators, and dieticians for patients with type 2 diabetes and access to affordable medications across this population. I think a lack of access to any of those things is going to drive up complications and increasing complications from obesity from diabetes is going to worsen outcomes. So, there's access to the things I can control, like education and medications.

 And then, another massive challenge that clinicians face is patient access to the stuff we can't control. And you alluded to this a moment ago, I can tell people to eat more fruits and vegetables. That's very cheap, easy advice for me to give. But can they afford more vegetables? Is there a grocery store near them that has those vegetables? I can tell people to exercise more, but is their neighborhood walkable? Is it safe for them to be out and about walking and using this as a way to improve their metabolic health? So, I think those are the challenges I've been thinking about a lot lately, really focused on access to all of these different things that are going to be important for combating these two epidemics. 

Melanie Cole, MS: Well, as you're thinking about that, and as we said, this is so complex. Tell us about your research goals and how important it is to recognize obesity as a disease because that's key, Dr. Beutler. Additionally, how can we better our understanding of how the gut and brain communicate with each other to help maintain body weight? You and I did a previous podcast on that and how this goes awry in diseases such as obesity. 

Dr. Lisa Beutler: As you know, I'm excited to talk about my research, which focuses on understanding how what we eat is communicated to the brain. How do the nutrients in our gut translate to changes in behavior, like decisions about what and when to eat and decisions about when to stop eating? How does this work in individuals with healthy weight and how does this change in individuals on diets that promote obesity, specifically diets that are high in fats and sugars? 

To study the effects on neural activity of the food that we eat, we use mice where we can record from the neurons of our choosing using sophisticated fluorescence-based techniques. What we found is that obesogenic diets, which are highly palatable, dramatically impact how our brain interprets the food we eat. And specifically, these diets blunt our normal responses to food intake. In other words, the neural signals that tell you, "I'm full and should stop eating" become less responsive as obesity develops on these diets. 

We've shown that this depends on what you eat, too. So mice that we feed a high-fat diet have altered responses to fat intake, and mice that we feed a high sugar diet have altered responses to sugar. And what's even, I think, more important is that these altered neural responses don't seem to go away with weight loss. Once you've become obese, your ability to kind of respond appropriately to nutrient intake is impaired pretty persistently. We think this might partially explain why weight loss and maintaining weight loss is such a challenge for so many people. And there's so much more work to do than what we've already done and so much more to understand. 

So, for now, I'll just wrap up by saying that kind of the meta goal of my work is to mechanistically understand obesity in part to come up with better treatments for it to understand how to prevent and control it. But also, in part to destigmatize it and have it viewed as a disease, like cancer, like diabetes, like the many other diseases that we treat. 

Melanie Cole, MS: I wish you luck in that respect because having been in this field for so long, I've seen the stigma firsthand. And it is tough because people will look at someone with cancer and think one thing, but when they look at someone who's obese, they blame them right away and there are so many factors. So speak about some of the treatments that are out there that are exciting for you right now. Some of the latest advancements in pharmacological, and surgical treatments, anything you'd like to discuss. 

Dr. Lisa Beutler: Yeah, it's such an exciting time to be a physician who treats obesity. The last five years or so have seen the release of the first medications that rival the efficacy of bariatric surgery to treat obesity. And there are many, many more drugs pretty deep in the clinical development pipeline that have insanely promising clinical trial results. 

And the truth is that these medications, there's semaglutide, which is currently approved for both diabetes and obesity management; and tirzepatide, which is currently approved for diabetes, but will, I think, pretty imminently be approved for treating obesity. I've changed the algorithm of how I treat obesity, versus when we were dealing only with prior anti-obesity meds, which had more limited efficacy and some challenging side effect profiles as well.

 That said, I think there's a whole lot left to do. Number one, the current medications for obesity do have their side effect profile. They are intolerable to some people. And there's work to be done to improve the tolerability of these new weight loss medications. Number two, we don't live in an ideal world where I can just prescribe these medications to anyone seeking obesity treatment who walks into my office. As we talked about before, access is a major issue, both because insurance companies won't cover anti-obesity medication and because these drugs have now become so popular that there are global shortages of semaglutide.

 So, some of the earlier medications still have a place in obesity treatment. And then within Northwestern, while I treat a lot of patients with obesity in my endocrinology clinic, we also have this incredible interdisciplinary center for lifestyle medicine where patients have access to comprehensive medical care, education, and psychological support for a holistic approach to treat their obesity. 

Melanie Cole, MS: Well, as you said, it's an exciting time for advancements and I appreciate you sharing your expertise today. As we wrap up, I'd like you to speak about your approach to patients living with obesity, the comorbid conditions, diabetes, and all the things that come with it. It is a sensitive topic to discuss with patients. Tell us your approach, Dr. Beutler. 

Dr. Lisa Beutler: Yeah. So in my experience, I approach this by straightforwardly addressing a patient's obesity, framed as a medical concern or disease with many life-limiting complications. And I have found that to be more successful than beating around the bush and more successful than simply not addressing a patient's obesity, which is easy to do. A patient comes to the office with a whole list of concerns and multiple metabolic diseases and focusing on obesity itself is a hard conversation. And so, there is a tendency I think to avoid it. But I approach it in a straightforward manner framed as a medical concern. And I have found in general that people respond to that. 

I'll also add that the new meds that are coming out, semaglutide, tirzepatide and all these other drugs in the pipeline are helping with this. One, the fact that we now have effective medications, I think, makes this seem like more of a real medical illness. So using these medications to help frame my conversation about what we can do to manage their obesity, I think helps to medicalize and remove stigma. 

The other way these medications have changed my approach is that for the first time in my career, patients are coming to me saying, I want to go on one of these meds for obesity therapy. And of course, if they say that, that opens up multiple conversations we can have, both about treating their disease with medication and all the other lifestyle stuff that we've kind of alluded to earlier in this conversation. 

Melanie Cole, MS: Thank you again, Dr. Beutler. What a fascinating episode this was. Such an interesting conversation. Thank you again. To refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. Please always remember to subscribe, rate, and review this podcast and all the other Northwestern Medicine podcasts. I'm Melanie Cole. Thanks so much for joining us today.