Insulin resistance masterclass: The full body impact of metabolic dysfunction and prevention, diagnosis, and treatment | Ralph DeFronzo, M.D.

**Peter Attia, MD** (0:11)
Hey everyone, welcome to the Drive podcast. I'm your host, Peter Attia. This podcast, my website, and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness, and we've established a great team of analysts to make this happen. It is extremely important to me to provide all of this content without relying on paid ads. To do this, our work is made entirely possible by our members, and in return, we offer exclusive member-only content and benefits above and beyond what is available for free. If you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of a subscription. If you want to learn more about the benefits of our premium membership, head over to peterattiamd.com/subscribe. My guest this week is Dr. Ralph DeFronzo. Ralph is a distinguished diabetes researcher and clinician known for his pivotal work in advancing the understanding and treatment of type 2 diabetes. He's widely recognized for his groundbreaking contribution to the concept of insulin resistance, which has reshaped the understanding of type 2 diabetes and its progression. He played a very important role in bringing metformin to the United States as a standard treatment for the disease nearly 40 years ago, along with the discovery and development of SGLT2 inhibitor, a class of drugs you have no doubt heard me discuss many times before. With over five decades of research in the field, Dr. DeFronzo has received numerous prestigious accolades, including the Banting and Claude Bernard Awards, the highest honors that can be given to a diabetologist. This episode with Ralph is really a masterclass in the organ specific aspects, the pharmacology, the diagnosis of type 2 diabetes, and it draws from his vast experience. Now, if you listen to my conversation with Jerry Schulman a few years ago on insulin resistance, what amazed me was how little overlap there was, not because the information is not congruent, but because of how much we were able to go into different topics. So the discussion with Jerry Schulman, which I would encourage everyone to listen to if they have not, really focused on one of the areas that insulin resistance manifests itself, which is in the muscle. What we talk about here is about all of the other organs. Spoiler alert, there are seven that are impacted by this condition, and therefore we go into much greater detail there, in addition to the pharmacologic interventions. And I just have to say, I learned more in this podcast than I do in most podcasts. It's one of the few that I had to immediately go back and listen to. And my notes from this podcast are so voluminous that they even provided substrate for internal meetings with our team in the practice. In short, there are many things that I've taken away from this that will directly impact my patients. Just as far as some of the other things we discuss, we get into details about how insulin resistance impacts liver. We do talk about muscle, but we talk more about fat cells. We talk about his development of the U-glycemic clamp, something that some of you have probably heard of as the gold standard for measuring insulin resistance. Again, we talk about the pharmacology, not just the SEL2 inhibitors, but the GLP-1, agonists, metformin, and another class of drug that we don't talk about that often that frankly for me was a real eye-opener. There's a lot more I can say, but I think at the end of the day, you just got to listen to this one maybe twice. So without further delay, please enjoy my conversation with Dr. Ralph DeFronzo.
Ralph, thank you so much for coming down to, I guess up to Austin from San Antonio. Very excited to sit down with you and talk about potentially one of the most important subject matters in all of health. People who listen to me all the time here and are familiar with me talking about these four horsemen, cardiovascular disease and cerebrovascular disease, cancer, neurodegenerative and dementing diseases. And then there's this fourth horseman that I talk about. And it's in many ways the squishiest because it's not the one that shows up on the most death certificates. But in many ways, it's the foundational one that is amplifying the risk of all of those other causes of death. And I refer to it as metabolic disease spanning the spectrum from hyperinsulinemia to insulin resistance to fatty liver disease, all the way out to type 2 diabetes. So given how much I speak about that, it seems very important that we should have a really thorough discussion of that foundational metabolic disease and no one better than you to have that discussion. So let's start a little bit with just telling folks briefly about what you're doing at UT San Antonio and why you've spent the last 40 plus, almost 50 years now working on this problem.