In the first of a multi-part series, Paul and Howard talk about metabolic syndrome, from its rise, to its prevalence, to its causes, and its consequences.
- What is metabolic syndrome?
- How is it diagnosed?
- The causes of metabolic syndrome
- The rise to prevalence of metabolic syndrome
- How diet affects our metabolic health
- Metabolic syndrome
- LDL and ApoB Exposure and the evolution of heart disease
- 10 Techniques To Help You Thrive With Knee Arthritis
About The Show
Paul Kedrosky is a frequently injured athlete and a venture capitalist. Howard Luks is a top sports orthopedic surgeon. Smart, candid, and experienced analysis, ideas and tips about health, fitness, and longevity from two athletes and sports orthopedic surgeon—and guests.
Listen & Follow
Paul: [00:00:00] Hey Howard,
Howard: [00:00:00] Paul.
Paul: [00:00:02] we’re going to talk metabolic syndrome this time around, which is a topic we’d enough. I think we’ve actually talked about it. In passing a bunch of times, but never really gotten into it in detail, which is strange because I know it’s a topic we’re both fairly how shall I say acutely aware of sensitized to think is very important.
And yet we haven’t spent a lot of time on it. So it feels like a good time to do that.
Howard: [00:00:28] No, I think this is a great topic to touch on. Cause we always talk about the treatment. But never the root
Paul: [00:00:34] right. Practical minded people that we are which would come as a huge surprise to my parents calling me practical. So so let’s just start off with the, with the easy stuff, which turns out to be not so easy, but we can at least pretend it is. What is metabolic syndrome. It’s one of those catch all types of it feels like it should be something very specific, but as you dive in, it can get a little bit squishy, but at a high level, what would you say is, what would you say is metabolic?
So how would you define it?
Howard: [00:01:02] Metabolic syndrome. It’s average person who has a large belly or abdominal fat. They have high triglycerides. They have a low HDL typically. Hypertension. And they may have been diagnosed with type two diabetes or they’re certainly insulin resistant. And a lot of people simply don’t know they have it.
It’s not a phrase that they’re told very often.
Paul: [00:01:32] No, it’s not. And it’s it’s, it’s operated. I mean, under a bunch of different names over time, I was looking back at, I don’t know whether it was Google data or something else. Cause I was like, why haven’t I, I don’t feel like 20 years ago I heard the words. I maybe, and maybe I should have, and maybe you were talking to patients about it back then.
I have no idea, but I feel like I wasn’t hearing that phrase very much even at 10 years ago or 15 years ago. And I was looking back and you can correct me on this, but it’s in lots of ways has operated under a bunch of different names, whether you talked about it as the discreet. Things that you just described in terms of triglycerides or being insulin resistant or high blood pressure, all these things.
But there’s lots of other things too, right. Insulin resistance syndrome, obesity syndrome this metabolic syndrome, these are all the same thing. Right?
Howard: [00:02:23] Right. What they’re, what they’re hammering on or around is the, the root pot. We know that the root cause of this is a metabolic disorder. Right. Only about 10 or 12% of adults are truly metabolically healthy. And the consequences of not being metabolically healthy leads to metabolic syndrome.
Paul: [00:02:48] So, is it, am I right in saying just those words, is that, is that something that as a, as a field or as a discipline that you found your, your peers using those words more often? Or is it just that it’s I just missed it. Meaning metabolic syndrome.
Howard: [00:03:04] Yeah, no, it’s, it’s interesting. You and I have talked, talked about this a lot. If I was talking to a colleague, they would say I have a 55 year old, 280 pounds, a BMI of 40 hypertension, high cholesterol and a big belly. They could have just said, a 52 of metabolic syndrome and I would have gotten the whole picture.
But on the flip side of that, these patients, physicians are not telling them they have metabolic syndrome. They’re saying you have hypertension, here’s a medication.
Paul: [00:03:46] Yeah. Right. And then you get into this, this, this mode where now you’re just dealing with discreetly with each of the individual indications, each of the individual symptoms with specific medications, rather than saying these all have, can be traced back to something, organically. And it’s something we increasingly call metabolic syndrome.
So. Let’s and you’ve started to answer this question, but the obvious one is how widespread is it? And then more specifically, why should we care? And maybe the first question first, I think, I think you already alluded to this, but it’s, it’s, it’s, it’s a silent killer in lots of ways. It’s everywhere.
Howard: [00:04:20] It’s silent until it’s
Paul: [00:04:21] Yeah, yeah,
Howard: [00:04:22] it, when it shows its head it’s, it’s, it’s not too late, but you’re really far down the road. Mean human existence comes to an end and in very predictable ways, right? Cardiac disease, cancer, et cetera. And all of these have very similar root causes and its metabolic dysfunction. It, your heart attack didn’t come on because you ate a hot dog tonight. As we’ve discussed a lot, it’s an area under the curve issue. It’s because, and the Y axis is time. And because you’ve been eating those since you were 12 and it’s been slowly building up and it’s not just the LDL, it’s not just the reactive oxygen, species and inflammation.
It’s not just the uric acid. It’s not just insulin. It’s it’s, it’s, it boils down to the same root cause of excess calories. And. Poor calories ultra processed foods over a very long time course.
Paul: [00:05:28] And let’s maybe the good time to be clear here about something that I was confused about for a long time. It’s not this, this idea that you’re eating fat makes you fat. We’re not, this is not what we’re saying. It’s this, as you say, this area under curve issue. Respect to the long-term exposure to a poor diet that lacks balance and breeds inflammation and obesity and insulin resistance.
It’s not some one, direct relationship between, as you said, I ate a hot dog and now I, I had a heart attack.
Howard: [00:05:57] Yeah, no. For anyone who’s on Twitter, they know how messy nutritional Twitter is. And it’s really a shame because there’s a lot of good scientists up there who we can learn a lot from. So, no, it’s not. The complex carbs. It’s not just fats, it’s not just seed oils. It’s not that honey that you put out, you drizzle on your Apple.
It’s, it’s really comes down to an excess caloric burden in general. Right. I mentioned that high triglycerides are associated with metabolic syndrome. But. Most people have no clue how that fits into insulin resistance and type two diabetes and where it comes from. You’re not eating too many triglycerides,
Paul: [00:06:50] right. Exactly. Yes.
Howard: [00:06:52] Your liver is manufacturing that. Why? Because it’s has too many calories to process. Why? Because your skeletal muscle can’t take the glucose in why? Because it’s insulin resistant and can’t make glycogen from the glucose that’s out there.
Paul: [00:07:08] Yeah, and there’s a whole bunch to unpack there, but that’s a great condensed summary of exactly the pathway here of what’s going on and at each stage, and not, it’s not always the case in medicine that there’s a the why questions can be answered. But in this case we can actually answer a lot of why questions fairly definitively.
Right. So at
Howard: [00:07:27] Hundred percent.
Paul: [00:07:34] Let’s talk a little bit about prevalence here. I’ve last I saw something like 70 or 80% of Americans are overweight. Maybe not morbidly obese, but at least overweight from a BMI standpoint, I think I saw.
And maybe you shared this stat with, Oh, I, it was a, yes, it was that, something like half of undergraduate students being insulin resistant. So these are crazy numbers.
Howard: [00:07:55] These are crazy numbers and the undergrads who are insulin resistant It was very interesting data because it only affected the skull of a muscle. And when we dive into insulin resistance, we can get into how it then starts to affect the liver. And that’s where things really go downhill. But what was also nice is exercise reversed it in these young kids. But this brings back the AUC area under the curve issue. This is starting really early in our lives.
Paul: [00:08:29] really early. And I, I suppose I’m not particularly surprised that a college student can reverse it with exercise and well, it’s not impossible to reverse later on, you give it enough time. And that process becomes really, really difficult. So it’s, it’s important to identify these things early, which gets to the question of, we talk about why we should care, which is for all the reasons that we’ve just described.
But. And it’s a bit tricky to diagnose because it’s, I’m not going to, if it’s uncharitable to say it’s a garbage can diagnosis, but it is a basket of indications, not one thing where you said, Oh, I had my, I had my metabolic syndrome test today and it came out as a 92. There’s no such test, right?
There’s no specific number. I can point you to on one specific test and say, here’s, here’s the name of the thing you have? It’s more that, here are four or five things. A large waistline, high triglycerides, low LDLs, high blood pressure insulin. These are a basket of things that all in the, in the in combination, if they all start skewing the wrong direction may be a sign that this is the
Howard: [00:09:35] You have a beer belly or a little gut, you probably have metabolic syndrome. And as I mentioned, physicians and other people are not connecting the dots for our friends out there now. So if you’re on lisinopril, a tour of a statin ezetimibe yeah. And Metformin, you have metabolic syndrome. Yeah. You haven’t been told it.
You’ve been told you have. Insulin resistance, hypertension and high cholesterol. But you have to connect these dots.
Paul: [00:10:14] So one of the things we, you, you, you talked about this a little bit, a couple of minutes ago, but maybe get into this a little bit more about the role of the liver here. One of, one of the consequences of this syndrome is that it puts a lot of stress on some specific body organs, pancreas the liver to the point that this is rapidly becoming one of the causes of one of the major causes of liver transplants, because of something like, well, NAFLD Dean non-alcoholic fatty liver disease.
Why don’t you talk a little bit through that connection, which is, I think would be surprising to people that there’s these other backdoor insidious things going on at the same time.
Howard: [00:10:50] As I started to mention in insulin resistance. The defect is that early on, you’re making enough insulin probably making more than you need, but your tissues aren’t responding to it. And your muscles are the largest sink in your body to hold glucose as glycogen. But you need insulin to open up a channel to let.
That glucose into your muscle cell, so it can manufacture and store that glycogen and insulin resistance, the muscle can’t do that. And so those calories travel on through the muscle, into the, the hepatic or liver blood supply and enter the liver. So the liver has to deal with it, right. It tightly regulates your glucose until it can’t And that mainly does so to support the brain.
So it packages this excess caloric burden and triglycerides and there’s a lot of hormone changes that take place in these hormones, favor fat synthesis as energy storage. And you start to store this not only in septic, Candiace fat and visceral fat, that’s the fat around your organs, but you start.
To get the liver building up fat within the liver itself. And that’s the non-alcoholic fatty liver disease. And when you add inflammation to the mix or Nash, non-alcoholic stay-at-home hepatitis now that’s the number one coming or has become, I’m not sure. The number one cause of liver failure.
Paul: [00:12:33] Yeah, which is, which is remarkable. And how do we know that what’s this is imaging studies, right? I guess not just imaging studies. I mean, there’s also obviously some tissue samples being done too, but this is, there’s no way for someone to stand there and say, there’s nothing specific I can do, which is back to my point about these being insidious things that I can’t, there’s nothing specific I can see.
That’s going to tell me that I have, NAFLD D or something like that.
Howard: [00:12:58] No. There, it’s interesting, you bring that up. Your routine labs that you get from your physician every year contain two tests, AST and alt. These are two liver function tasks. And it’s interesting because if you go pull up what the norms were two decades ago, they were lower than the norms are now, and it’s not because scientists have said, Oh, but normals can be hired it’s because it’s it’s the median across the PA you know population.
Paul: [00:13:30] Yeah, that’s
Howard: [00:13:31] norms are actually increasing. So if you’re AST and alt are towards a high sides of normal. That, you may want that to trigger a further investigation for NAF LD or fatty liver disease.
Paul: [00:13:45] so not to turn this into an entire discussion about fatty liver disease, but maybe just use it as an example. Some of the things we’re going to talk about, some things we can do to try and proactively, or even, retroactively address the metabolic syndrome, but what’s the prognosis for someone with NAFA LD for example, who.
In terms of nonmedical interventions, whether it’s exercise, diet, weight, or others, is, is it reversible for most people?
Howard: [00:14:11] So NAFLD is somewhat reversible. It’s not easy, but it certainly can involve the same lifestyle changes and they are coming up with some medications. And of course our audience knows it. I am an orthopedic surgeon and you’d be silly to take life saving advice from me. but
Paul: [00:14:33] on what kind of life-saving advice though. Right? So,
Howard: [00:14:35] That’s true, but with respect to NAFL D But yeah, it is going to come back to lifestyle interventions for the most part, the same interventions that are utilized for insulin resistance. And hopefully they come up with various medications and other interventions because once this starts to progress to Nash the inflammatory side of NAFA, the it’s a, it’s a real problem.
Paul: [00:15:10] we talked a little bit about how it’s some of the things that are indicators as you set up, large waistline beer belly. I mean, I’ve seen stats like that. What fraction of your height that your your waist size should be. These are all . Or seat of the napkin. What does that even mean back of the napkin?
What is the seat of that advocate? A back of the napkin calculations you can do, I just need to stop using words. You sock, puppets. Yeah. These are all things that you can look at to get, give you or give your physician a sense of what’s going on here. But. Others that you can see on your own also like high blood pressure can be a sign.
Obviously there are at least at more advanced stages. There’s more specific things you can see that might be indications. You have insulin resistance verging on type two diabetes. So it’s not as if it’s all completely mysterious, like NAFA D. There are things you can see that say, you know what. If my doctor looked at me, they’d say this guy or this guy, or a man or a woman is likely to be a someone who’s.
If I did run the test, they’re going to have metabolic syndrome. And those things are some of the ones you’ve described, like, like the waistline middle-aged slightly overweight or even dramatically overweight doesn’t exercise much. You go down that path and I don’t even need to do too many tests.
Howard: [00:16:20] Right. I don’t want to do what was it back to the napkin?
Paul: [00:16:24] I was actually back of the pants.
Howard: [00:16:26] Back to the, I don’t want people to stick to the rigid definition. Right. I mean, if you’re hypertensive and on a cholesterol medication and have a big belly I can correct that and say, you don’t have it but you either have it or you’re going to have it.
And there’s a damn good chance that you’re insulin resistant. And now your A1C, which you get checked is gonna, it might be normal still, so you’re not on Metformin, but I can guarantee you you’re insulin resistant. So I send a fair number of patients. Yes, I do. For an OGT, an oral glucose tolerance test, where they give you a swig of awfully sweet drank.
And then they check your blood at different intervals. And if you check insulin levels, you should only require a set amount of insulin to bring that glucose load under control, transport it in into your muscles and liver and package it away. But people with insulin resistance need a lot more insulin.
So the insulin levels are a lot higher. So you’ll see this test bump up. Very early on before the A1C starts to bump.
Paul: [00:17:48] Ah, I see. Okay. Yeah, because most people will be familiar with fasting blood glucose tests done in a more, invasive fashion than, than the, than necessarily having done the oral blood cloth, the oral, it’s not a fasting test anymore. Obviously it’s a, you’re directly exposing them to a glucose load.
Howard: [00:18:04] Right. So you can, people who are insulin resistant can maintain a normal blood glucose and a normal A1C for quite a long time before the pancreas, just gives up And they can’t tolerate it anymore. So these an OGT I imagine will become much more useful and widespread. I mean, every pregnant woman gets
Paul: [00:18:29] Yep. Yep.
Howard: [00:18:31] why shouldn’t it be a normal course of evaluation, especially if people are already hypertensive and have an elevated cholesterol
Paul: [00:18:41] let’s let’s it was step further here and talk about the mechanics and maybe start with one that, well, at least closer to both of us than necessarily speculating about blood glucose, but let’s talk about the pathway from being overweight to metabolic syndrome. What’s the, almost in the same way you were making that chain of connections from tiger triglycerides and asking you a series of why questions, what gets us from being overweight.
To metabolic syndrome if you travel the causal path, because I think sometimes people don’t see that connection, how it works.
Howard: [00:19:13] So first I want to draw a distinction between being overweight and abdominal obesity, right. Or having visceral fat. There is a difference between subcutaneous fat and this visceral belly fat, which is a fat that’s actually inside your abdominal cavity, right? A beer belly is visceral fat. Cause there are people who are.
Overweight eat even obese who could be deemed to be metabolically healthy.
Paul: [00:19:43] that’s a really good point.
Howard: [00:19:45] Right. So I
Paul: [00:19:46] tests on some studies, those people had even been shown to some of them, that a mild amount of of, of, of, of a hold to obesity, but deemed mildly overweight from a BMI stand quite as been shown in some studies to actually be somewhat healthy.
So, you have to be very careful about that.
Howard: [00:20:00] You don’t want to be on either side of the BMI scale, you want to be in this wide swath in the middle, correct?
Paul: [00:20:12] so in those cases where we do see a, where we do see a connection between and what we can March through each of these, the insulin resistance in a bit, but let’s talk about being over. What is the pathway in terms of taking us to metabolic syndrome? I mean, the way I’ve characterized it is simply that the body has to do more work, right?
You’re overweight. There’s vascular resistance. Well, it doesn’t want to flow the hardest to work harder. That leads to high blood pressure. Hypertension is a bad thing for a host of reasons, including heart disease. But that’s my, that’s my pathway that I’ll draw for people. Is that the way you would do it or is there more other things you’d rather.
Howard: [00:20:48] Yeah, it’s a little more, I think it’s a little more complicated. It’s like when you talk about cholesterol or LDL associating with heart disease, right. Is it necessary? Yes. Is it necessary and sufficient? No. Right. You need to have that inflammatory side to it as well. So just being obese is not enough, and the difference between.
Between visceral obesity fat obesity and general obesity is different. Granted, a lot of obese people will have metabolic syndrome, but the, and the difference is when you have a chloric excess, that ends up driving insulin resistance, you’re getting a large increase in inflammatory mediators in reactive oxygen species.
Your blood pressure is increasing often because you’re losing the pliability of flexibility of the blood vessel. So when a heart pumps and the blood comes gushing out of the heart, the vessel will normally a healthy vessel will expand and absorb some of that pressure. And if that tube is stiffer, then it’s going to transmit that higher pressure further down. Does that
Paul: [00:22:08] Yeah, no, exactly. Right. No, that’s, that’s, that’s a really nice way to put it.
Howard: [00:22:12] so that’s certainly, that’s one of the drivers of a hypertensive cascade in metabolic syndrome. And yeah. This is so complex. And as much as I read about this and understand this there’s probably five times as much that I don’t under.
Paul: [00:22:32] That’s all right. We can discover it together, but I, I think, but I think we can still stay. At this level and then what he’s going to become a researcher in the topic.
I think it’s more important for people to be somewhat aware of the drivers. And one of the things that I was, this is now years ago, but I’ve still stayed on top of the research somewhat is that, and you’ve talked a couple of times about the important distinction with respect to this pathway between obesity and metabolic syndrome via.
Subcutaneous versus visceral fat. And I had someone put it to me once that it’s really important to recognize that visceral fat isn’t different just because of its location. It’s different in the sense that it’s it’s it’s best characterized as a metabolically active organ. Right. Which I thought was really interesting that the, the, the, the, the dipocytes in my St man, right in, in visceral fat are, are, are actually different from the ones in subcutaneous fat there’s there’s.
You can characterize them in in starkly different ways. And their activity is very different. One is much more passive on as much more active. So one way to think about. Visceral fat as an unwell and unwanted new Oregon you’ve grown on your own. Right. And it’s up to things that left to your own devices.
You probably would rather it not do. And I think that that’s just such an, for me anyways, was such an important and stark realization. And I was like, yeah, I don’t want those. I’ve got enough organs right now. I don’t need another one. And I. I remember years ago, there was a guy I used to work at a golf course years ago.
And there was this guy that was his nickname was the bear. He was like, I don’t know, six foot six or seven or something. Yeah. And he always wanted people to punch him in the stomach. Right. Cause he was like, not like this big strong guy, but his belly was just gigantic. I mean, it was, I don’t know.
I mean the rest of his body wasn’t that big. I mean, he was tall, but it was wet. And in retrospect, you realize this was entirely, this was all this role. This was all this role, fat. This was, it was rock hard, right? I mean, it was, there was, this was not something that was just hanging around at the level of, of the cutaneous subcutaneous tissue.
This was something else that was going on inside. And if you ever watched him drink beer, you had a pretty good idea where it all came from. But anyways, that was, I was in retrospect, realizing that I was watching someone that’s this, this thing that this, that he was carrying around was actually an extra Oregon.
And it has because of its cellular structure, it’s got actually metabolic consequences for your body. So, yeah. There’s another pathway via which metabolic syndrome can emerge, not just because of, you know vascular restrictions with respect to obesity and high blood pressure, but also just because of the metabolic activity of, of, of visceral fat.
Howard: [00:25:16] Right. And you are. Absolutely correct. It is a metabolically more vicious substance. More inflammatory fat in general is not nearly as passive as a tissue, as we used to assume. There’s leptin and leptin resistance and satiety issues in generalize obesity. That’s very complicated to understand and I don’t want to layer that onto this, but with visceral fat, that has much more of a metabolic cause.
And it is tightly woven into this story of metabolic syndrome.
Paul: [00:26:02] We’ve alluded to this a couple of times, speaking of layer things on let’s layer. One more thing on before we go forward. And that’s one of the pieces that links all of this and links so much of what’s going on and you’ve said it already, but we’ll strike it out. Is inflammation, right?
I mean, this is an in metabolic syndrome and if anything is a, is a, a species of. Of whole body inflammation driven by a bunch of the things we’ve talked about, but inflammation is one of its core components.
Howard: [00:26:29] Yes inflammation is. Necessary to create a lot of the issues that we deal with. You both metabolically in terms of our heart health, our liver health, our gut health, that’s such a, and also from an orthopedic perspective, we’ve covered that a number of times your metabolic health and metabolic syndrome will affect your tendons and joints.
And that’s all I’ll say about that. But, inflammation is a key driver of this pathology.
Paul: [00:27:00] Well, the body and the body doesn’t cope well with this is back to your area under the curve point, right? This is the body. He doesn’t cope well with long-term exposure to inflammation, especially long-term exposure to increasing inflammation. And we see we’ve seen all kinds of things. Studies over the last 20 years, 30 years showing.
The impact of, of longterm ex exposures, wrong term, but area under the curve in terms of bottom body inflammation impacts on the immune system on a dysregulation of cytokines and all kinds of stuff. Right?
Howard: [00:27:34] Right. And this. Chronic inflammation or systemic inflammation is actually a fascinating topic. We don’t know much about it. It’s actually very hard to define what causes or what is systemic inflammation. Right. We can’t put our hands on one mediator, right? It’s not aisle six.
Uh, it’s not. it’s. And it’s not just your C-reactive protein.
What’s driving that there are going to be hundreds of compounds and proteins and hormones that are behind this. But they’re tightly linked to our metabolic health. But the overall definition and steps to their creation is to my knowledge is not extremely well elucidated as yet.
Paul: [00:28:24] No, that’s my sense. But as I say, I’m an idiot about this stuff, so that’s possible. I just don’t know what I’m reading, but I, I do buy that on, on that note of inflammation, let’s, let’s park this right here. And when we come back in our next episode, we’ll talk a little bit about more of some of the drivers and then get into what you can do about it and how, if it’s, if you’re succeeding.
Howard: [00:28:49] Awesome. I think this is a great set of talks.
Paul: [00:28:53] Thanks, Howard.
Howard: [00:28:53] Thanks, Paul.