Gerald Shulman, M.D., Ph.D.: A masterclass on insulin resistance—molecular mechanisms and clinical implications

**Peter Attia** (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, full stop, and we've assembled a great team of analysts to make this happen. If you enjoy this podcast, we've created a membership program that brings you far more in-depth content if you want to take your knowledge of the space to the next level. At the end of this episode, I'll explain what those benefits are, or if you want to learn more now, head over to peterattiamd.com forward slash subscribe.
Now, without further delay, here's today's episode. My guest this week is Dr. Gerald Shulman. Chair, he's a professor of medicine and cellular and molecular physiology at Yale. He's also the co-director of the Yale Diabetes Research Center. In 2018, he received the Banting Medal for scientific achievement, arguably the most prestigious award one can win in this field. He's pioneered the use of magnetic resonance spectroscopy combined with mass spec to noninvasively examine cellular glucose and fat metabolism. Now you may ask, why does that matter? And we get to that right at the outset of this interview.
If you want to understand insulin resistance, if you want to understand hyperinsulinemia, type two diabetes, non-alcoholic fatty liver disease, you have to understand the movement of glucose and fat. A way to think about this is to think about it this way. If you go and get a blood test, even the most fancy blood test imaginable, you're basically looking at a picture, a snapshot, a moment in time.
What these techniques that Jerry and his collaborators have developed over many years are basically allowing you to watch videos. You can see the flux, you can see the movement of glucose.
Furthermore, they've been able to see those things as they happen inside even human cells.
So I'm going to, I guess, maybe make an apology at the outset of this and say that this is about as technical an interview as I probably have done in a while. There are probably only a few interviews that I've done on this podcast that get into more technical weeds than this one. But unfortunately, that is the price one has to pay if they want to understand arguably the most important pathologic condition in our species. And I get into what I mean by that in the interview, so I won't elaborate on that further.
We talk a lot about what it is to be insulin resistant. This term gets thrown around with such ubiquity that you'd think everybody knows what it means, and yet to define it is very complicated. But I think by the end of this interview, you will undoubtedly understand how to define insulin resistance. And I think you will have a very good sense of where it begins and what it means in a subclinical versus a clinical state and what the sequence of events are that lead to a condition in the muscle, ultimately affecting the liver, ultimately affecting the whole body.
I'm not going to promise you that you'll get that on the first listen. I think that might require more than one listen and it probably requires going through the show notes, which will be littered with fantastic figures. In fact, as Jerry and I did this interview over Zoom, for, I don't know, I would say maybe half to two thirds of the interview, he was sharing slides as we were doing it. And keep in mind, I'm quite familiar with these concepts. So for someone who's less familiar with these concepts, I think it will be only that much more valuable. One really nice little bonus thing that came out of this is a beautiful discussion at the end of Metformin, where I actually learned something really profound that was incredibly relevant to my understanding of Metformin in my ongoing interest around the question of Metformin's suitability as a longevity agent. I could say more about this, but I think it's just one of those things where I ask you to sort of take a leap of faith with me that this is important, even if it feels a little bit like drinking your cough syrup at times. But if you really want to understand longevity, you're going to have to sort of figure out what insulin resistance means. So without further delay, please enjoy my very in-depth conversation with Dr. Gerald Shulman.
Jerry, thank you so much for making time to sit down virtually with me today. As I said before we hopped on, this is a topic that is near and dear to my heart. And frankly, all roads seem to point to you. And that goes back to, I don't know, at least for me, probably 2011, when I became really fascinated by this topic. And there aren't a lot of topics where I've personally experienced the following problem, which is the more I think I understand it, the less I do. So now when someone says to me, Peter, what's insulin resistance? You know, I can sort of give glib answers to that question, but the reality of it is, I don't think I fully understand what it is. And I don't know that I can represent to the listener that by the end of this, they will fully understand what insulin resistance is. But what I think they'll understand is how maybe we can think about it through the lens of different tissues and what may or may not be going on. And in large part, I think that's due to the incredible work you've done over your entire career. I guess I'd like to kind of just start with a little bit of background. You did an MD and a PhD and you're trained as an endocrinologist, correct?