 View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter In this “Ask Me Anything” (AMA) episode, Peter dives deep into the critical topic of metabolic disease. He first sheds light on how poor metabolic health drives up the risk of developing other chronic diseases such as cardiovascular disease, cancer, neurodegenerative disease, and overall mortality. He explores the array of metrics and tests used to assess metabolic health, underscoring his preferred methodologies utilized with patients. Finally, Peter provides an overview of the factors one can manipulate in order to improve metabolic health. If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the AMA #51 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: Importance of metabolic health and a primer on metabolic disease [1:30]; How poor metabolic health increases one’s risk for other chronic diseases [6:00]; How useful is body weight and BMI for estimating metabolic health? [9:45]; Overview of various tests and metrics used to understand metabolic health [12:15]; Traditional biomarkers and how Peter’s point of view may differ from the guidelines [15:00]; Lactate: insights into metabolic health through fasting and resting lactate levels [17:00]; Zone 2 output: an important functional test of metabolic health [20:00]; Cardiopulmonary exercise testing (CPET) [25:45]; Visceral adipose tissue (VAT): what is VAT and how does it impact health? [27:00]; Oral glucose tolerance test (OGTT): how it works and why it is such an important metric for assessing metabolic health [32:15]; The utility of a continuous glucose monitor (CGM) [40:45]; Liver function and NAFLD [42:15]; Sleep as an intervention [46:00]; Exercise as an intervention [53:15]; Diet and nutrition [59:00]; How reducing stress can improve metabolic health [1:05:15]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

Hey everyone, welcome to a sneak peek Ask Me Anything, or AMA episode of the DRIVE Podcast. I'm your host Peter Attia. At the end of this short episode, I'll explain how you can access the AMA episodes in full, along with a ton of other membership benefits we've created. Or you can learn more now by going to PeterAttiaMD.com forward slash subscribe. So without further delay, here's today's sneak peek of the Ask Me Anything episode. Welcome to Ask Me Anything, episode number 51. I'm once again joined by Nick Stenson. Today's AMA focuses on questions we've gathered around metabolic disease. If you've listened to this podcast or read my book, you're probably familiar with what I call the four horsemen. They're the major disease processes of aging. These include cardiovascular disease, cancer, neurodegenerative disease, and metabolic disease, which is really a continuum of conditions. In today's episode, we really dive into that fourth horseman, these conditions around metabolic disease. These topics that we explore include questions about how metabolic disease feeds the other three horsemen and why we should be aware of our metabolic health. We talk about the various metrics that I use with my patients to understand their metabolic health. Now, this will include some common ones as well as some less common ones. Then of course, we get into the various factors that you can manipulate in which to improve your metabolic health. They include some of the obvious ones, but also some less obvious ones. So if you're a subscriber and you want to watch the full video of this podcast, you can find it on the show notes page. If you're not a subscriber, you can watch a sneak peek of the video on our YouTube page. So without further delay, I hope you enjoy AMA number 51. Peter, welcome to another AMA. How are you doing? Good. Thanks for having me. So today's AMA, we're really going to focus on metabolic health. I think a lot of people are familiar with this term you call the four horsemen, which are the four major diseases of aging. That includes cardiovascular disease, cancer, neurodegenerative disease, and then metabolic disease, which is really a range of conditions kind of from obesity all the way to type 2 diabetes. We haven't covered it on recent AMAs that closely. So what we wanted to do was gather all the questions that have come in on that and then put them into today's AMA. So we're going to hopefully get to as many as we can, but this will include what is metabolic disease and how do you define it, how it feeds the other three main horsemen, and how it can cause problems for people. And then really look at the metrics that you look at with your patients to understand on an individual level where they're at metabolic wise. And so I think a lot of people will look at metabolic health from simple blood metrics such as HbA1c or things that they can get with a typical annual physical. But I know with you and your patients, you look at a lot of other things. And we're going to get into those details today, which is, you know, what are those things? What do you like to see? And ultimately, what can they tell people about their metabolic health? And then we'll end the AMA looking at kind of what are the lifestyle interventions that people can use to help improve their metabolic health. And this will look at nutrition, sleep, and exercise. So we have a lot to get to. So with all that said, anything you want to add before we get started? No, I mean, I just think we're going to structure this discussion by probably spending a bit of time talking about the nuanced ways in which you could define or identify a person who's not metabolically healthy. We'll come up with a very high bar for that on what, you know, real metabolic health looks like. And then as you said, we'll talk about, okay, what do you do about it if you're in this situation? Because most people listening to this, myself included, frankly, will always have an area in which they could improve. Let's start with a little bit of primer on metabolic disease and how it can feed into the other three horsemen, which is cardiovascular disease, cancer, neurodegenerative disease. So to do this, I think we need to kind of define metabolic disease or metabolic syndrome and look at how that feeds those other diseases. I think a bit of historical context is helpful here. There was a very famous, remarkable endocrinologist by the name of Jerry Reven. Definitely one of the regrets I have is not having interviewed Jerry for the podcast before he passed away because I did know him and I'd met him several times. Jerry was at Stanford for most of his career. In the 1980s, made an observation, which was that where the following five signs went, so too did cardiovascular disease, cancer, neurodegenerative disease. He identified these five signs, which we'll review in a second, and he referred to it as syndrome X. So he said, look, when people have truncal obesity, elevated triglycerides, depressed HDL cholesterol, elevated blood pressure, and elevated glucose levels, this thing we're going to call syndrome X, it seems to be a remarkable predictor of all of these chronic diseases of aging. For the sake of time, I'm not going to go through the entire history of this, but what changed was that that terminology became syndrome X. It became now metabolic syndrome. And now we have some numbers that go with those things. So many people are probably familiar with these, but we're now defining truncal obesity as a waist circumference of more than 40 inches in men, more than 35 inches in women. We're defining elevated triglycerides as over 150 milligrams per deciliter. We're defining low HDL cholesterol as below 40 milligrams per deciliter in men, below 50 in women. We define elevated blood pressure as above 130 over 85, or taking medication for high blood pressure over 120 over 80. And fasting glucose is greater than 100 milligrams per deciliter. And the syndrome is defined as having three or more of these. So I won't suggest that this is the best way to evaluate metabolic health. I think there are many more nuances that we're going to go into, but at a minimum, I think everybody should know where they stand on those things. And by the way, even though metabolic syndrome is defined as having three or more of those, having one of those is still worse than having none. Having two is worse than having one, et cetera. So in an ideal world, you wouldn't want to have any of these things. No, and I think that's good to kind of set that baseline there. And so the next question is then, how does metabolic syndrome kind of feed the other horsemen and those other diseases? We could spend the entirety of this AMA going through the literature on this. It's so voluminous and so one-sided that I don't think it's particularly interesting. I'll probably just touch on a couple of high points and we'll leave all the details in the show notes. But if you look at all the meta-analyses of all-cause mortality, cardiovascular mortality, cancer mortality, cancer incidence, dementia incidence, all of these things all point in the same direction. Once you have metabolic syndrome, you're at an increased risk of everything. Your risk of cardiovascular disease goes up by 135%. Your cardiovascular mortality goes up by 140%. Your all-cause mortality is up by 58%. Your MI risk, 99%. It's basically a doubling. Your stroke, 127%. When you look at cancer, it's a 56% increase in age-adjusted risk of cancer mortality if you have Metsin. In particular, there are a handful of cancers that seem especially impacted by this. Endometrial cancer, seven times as likely. Esophageal cancer, almost five times as likely. Gastric cancer, twice as likely. Liver, kidney, twice as likely. There are a handful of cancers that even appear to be especially exacerbated by metabolic syndrome or by obesity and overweight. I think most people understand that smoking is an enormous driver of risk for cancer. It is. It remains the number one environmental trigger of cancer, but obesity is number two. If you look more closely at the data, it's really metabolic syndrome, which obviously overlaps a lot with obesity. If we turn our attention then to neurodegenerative diseases, and we'll start with Parkinson's disease, the largest meta-analysis on this study suggests about a 24% higher risk of Parkinson's disease in those with metabolic syndrome compared to those without. It also appears to be graded. Again, just as we see in atherosclerosis, we see that having three of the risk factors for metabolic syndrome is a 31% higher risk of Parkinson's disease, while having all five, a 66% increase in risk. When it comes to Alzheimer's disease, it's about a 10% increase in Alzheimer's disease for those with Metsin. What's interesting, at least in the meta-analysis we looked at, was I thought that was actually a surprisingly low number. I thought that having metabolic syndrome only increasing Alzheimer's disease by 10% struck me as low. If you look more closely at the data, you'll realize that there actually appears to be a protective role in the abdominal obesity risk factor. When you do the analysis by looking at each of the metrics of Metsin individually, there's about a 16% reduction in, quote unquote, protective benefits of abdominal obesity. Now, this is likely due to reverse causality, meaning having Alzheimer's disease is more likely to lead to abdominal obesity. Nevertheless, I think that's why those numbers don't look as big. When you look at all forms of dementia, because remember, Alzheimer's disease is the most prevalent form of dementia, but there are many forms of dementia that are not Alzheimer's. There's vascular dementia, Lewy body dementia, frontotemporal dementia. All comers, vascular dementia is about a 37% increase in risk. Yeah. I think that's a really good and quick overview of how metabolic syndrome can feed into the diseases. And like you said, we'll have a lot more detail in the show notes because the reality is we just don't want to spend the entire AMA on that because I think at this point, people kind of understand, okay, this is an important thing to care about and I should understand this for myself. And so the next section then starts to get to how do you identify beyond just the metabolic syndrome, what are some other metrics that someone can look at to know their kind of specific metabolic health? And one question that we get a lot, which is just starting at the basics, is how helpful is body weight and BMI to actually understand someone's metabolic health? It's such a crude tool. It's understandable why body weight and BMI are used as health indicators at the population level. You're stuck with things that are very simple and reliable, but if you hold up the figure from, I don't remember which chapter in Outlive it's from, but it's from an analysis that I did to basically try to disentangle obesity and metabolic syndrome. So if you take a look at that figure, and by the way, these are data that came from the NIH and these turn out to be kind of conservative numbers, but conservatively speaking, you have at the time of this analysis, 2021, 108 million obese people in the United States. These are adults and 150 million non-obese. So obese being defined as a BMI over 30. Now, if you look at the people who are obese and have metabolic syndrome, it's 62% of the obese have metabolic syndrome. So that's 67 million people are obese with metabolic syndrome. Conversely, if you look at the 150 million people who are not obese, 22% of those people have metabolic syndrome for a 33 million. And so what you can see is that you've got 100 million people, and again, I think that's a very conservative estimate. Others have come up with numbers as high as 125 million, but call it a hundred million people with metabolic syndrome in the US. But what I think is most interesting is a third of them are not obese. And so if you think about all the things that we look at in our patients and all of the metrics we have on them, I can just tell you, I don't know the BMI of one of my patients and I don't care because I'm not trying to practice medicine on a population basis. So I don't even know my BMI. I know I'm overweight by BMI, but it's not something that we're going to manage. Ultimately, BMI, it's not that helpful. It doesn't account for body composition. It doesn't account for insulin sensitivity in any way, shape, or form. We just don't rely on it at all. We'll do DEXA scans. We'll get into those details, but we don't care about BMI. That kind of leads us, it's a good intro to this next section, which is what are those metrics that you use with your patients to understand their metabolic health at an individual level? And so I think what might be helpful for people is if you just kind of run through what those are and then what we'll do after is we'll double click on each of them, some of them going into more detail than others, depending on past content, but I think it'd just be kind of helpful for people just to hear that full list quick. Yeah. I mean, we kind of organize them as functional tests, imaging tests, typical or regular biomarkers, maybe some special tests. And we'll even talk about things that are only done in research that we don't do, but you might see these things show up in papers that you're reading. So on the kind of regular slash traditional blood-based biomarkers, we look at uric acid, homocysteine, triglycerides, HDL cholesterol, fasting glucose, insulin, hemoglobin A1C, and liver function tests. I'd say one of the less common things that we do look at is resting and fasting lactate levels, and obviously lactate performance in response to exercise. So that's also kind of a functional test. When it comes to the functional stuff though, we're looking at zone two output. We look at CPET testing. So effectively the oxygen utilization, CO2 production under stress, oral glucose tolerance tests. Again, I don't put that down as a traditional blood-based biomarker because I think of that as really a functional test, although of course it relies on these biomarkers. Continuous glucose monitoring and then whole body respiratory suites. We personally don't do that in our practice. We do all the others, but we don't do the whole body respiratory stuff. But you can do that to obviously get a sense of respiratory quotient. Imaging studies can be really valuable here. So DEXA scans, which are measuring visceral adipose tissue and also measuring muscle mass, body fat, which is certainly more relevant than body weight or BMI. We certainly would never rely on CT scans for looking at visceral fat, although one could do it. And you do get it with MRI if you have the right software. Liver ultrasound, along with algorithms that combine liver ultrasound with blood tests to look at fibrosis scores become very important as you want to understand the prevalence of fatty liver disease. And though we don't do this, you might see this kind of stuff in research studies and it's very interesting stuff. So you could look at C16 saturated fatty acids. This gives you a sense of fat metabolism. And of course, intramuscular biopsies will give you a great sense of how much fat is being stored in a muscle, and that can be obviously relevant for insulin resistance. And it's obviously mechanistically important as well as we discussed in the Jerry Shulman podcast. Again, those aren't things that we're doing in clinical practice. I think it's really helpful for people just to kind of hear that whole list. And now we'll jump into kind of each of those into a little more detail, some more than others, and we'll kind of look at what trends you're looking for, what are the ranges you like to see, and then ultimately it will lead to the second section of this, which is how do you improve those various metrics. So why don't we start with some of the more regular or traditional biomarker tests that most people will probably get at any type of physical screening annual exam they go to. Can you kind of walk through what those are and what metrics you're hoping to see within your patients? 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Sun Sep 17 2023