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It's /. 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 am a focuses on questions. We've gathered around metabolic disease. If you listen to his podcast or read my book you're probably familiar with what I call the four horsemen which are 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
This factors that you can manipulate in which, to improve your metabolic health, and 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. Am a number 51,
Peter. Welcome to another AMA. How you
Good. Thanks for having me.
So today's am a 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 my moloch disease which is really a range of conditions kind of from obesity all the way to type 2 diabetes and we haven't covered it on recent amas that closely. And so what we wanted to
To 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. In this will look at nutrition sleep and exercise. So we
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 will 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, 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 kind of a scary 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.
Or he passed away because I did know him and I 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 will review in a second and he referred to it as Syndrome X. So he said look, when people have truncal obesity elevated,
Ah, glycerides, 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 agent 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 exit? Preferred 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 you know, we're now defining trunk.
Basically is a waist circumference of more than 40 inches in men, more than 35 inches in. Women were defining, elevated, triglycerides is over 150 milligrams per deciliter, were defining low HDL, cholesterol is below, 40 milligrams per deciliter and Men below 50 and 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 to is worse, than having one etcetera. So, in an Ideal World, you wouldn't want to have any of these things
now. And I think that's good to kind of set that Baseline there and so,
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, am a going through the literature on this. It's so voluminous and so one-sided. That I don't think it's particularly interesting while 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,
The cardiovascular mortality cancer, mortality, cancer incidents, dementia incidents. All of these things all point in the same direction. Once you have metabolic syndrome, you're at an increased risk of everything. We risk of cardiovascular disease, goes up by 135 percent. 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 percent. When you look at cancer, it's a
Six percent increase in age, adjusted risk of cancer. Mortality. If you have Mets in in particular, there are a handful of cancers that seem especially impacted by this. So endometrial cancer, seven times as likely esophageal cancer. Almost five times as likely. Gastric cancer twice as likely liver kidney twice as likely. So there are a handful of cancers that even appear to be especially exacerbated by metabolic syndrome, or by obesity and overweight and so
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. And 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
And room 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, sixty six percent increase in Risk when it comes to Alzheimer's disease. It's about a 10 percent increase in Alzheimer's disease for those with Mets in. And 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. But if you look more closely at the data, you'll realize that they're actually appears to be a protective role in the abdominal obesity risk factor. So when you do the analysis by looking at each of the metrics of metzen individually, there's about a 16 percent reduction 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. But 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 disease. Vascular dementia Lewy Body dementia, frontotemporal dementia. So, all comers, vascular dementia is about a 37 percent increase in Risk.
Yes, I think that's a really good and kind of quick overview of how metabolic syndrome.
You 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 know, 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 its from but
It's from, you know, 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, you know, the NIH and these turn out to be kind of conservative numbers. But conservatively speaking, you have, at the time of this analysis, 2020 108 million obese. People in the United States. These are adults and 150 million non-obese. So obese being
Is a BMI over 30. Now, if you look at the people who are obese and have metabolic syndrome, it's 62 percent 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. Will do dexa, scans will 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 will double
Click on each of them. Some of them going into more detail than others depending on past content but I think it just become a helpful for people just to hear that full list
quick. Yeah, I mean, we kind of organize them as functional tests Imaging tests, you know, 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 / traditional blood-based biomarkers, we look at Yorick acid home.
Justine triglycerides HDL, cholesterol fasting, glucose insulin hemoglobin A1c and liver function tests. And 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 2 output. We look at see Pat testing. So effectively the oxygen utilization, CO2 production.
Under stress or will 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 sweets, 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 combined liver, ultrasound with blood test, 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.
If so, you could look at C, 16 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, Schulman 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 traditional biomarker test 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 patience.
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