Dr. Ben Bikman
Appearances
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
Yeah, there are a lot of ways we could define metabolic health and even overall health. For me, it is a matter of insulin resistance. The problem with defining a lot of cardiometabolic outcomes is that we have a very glucose-centric paradigm. And this has led conventional clinical care to focus almost exclusively on glucose as the primary metabolic marker.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
And yet, underlying the changes in glucose that could be happening over time is the humble little hormone insulin who's just overlooked, you know, just kind of crying out for some attention sitting in the corner. But to sort of bring these ideas together, we look at glucose all the time.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
And any blood test when someone goes into the clinic, they're going to measure glucose and they're going to measure hemoglobin A1c. And it could be normal and normal and normal for years, but the person has high blood pressure, they're gaining weight, they have migraine headaches.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
And so there's no even suspicion that the glucose could not only be contributing to these problems, but that there is any problem, metabolically speaking. But while the glucose levels have stayed at a normal range during all these years, decades even, the hormone insulin has been the canary in the coal mine. It has been increasing steadily year over year over year.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
And so to answer your question explicitly, if I were to say is there a marker that has been overlooked, it is fasting insulin completely, full stop. Because it is the earliest sign of metabolic disruption that if we could shift
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
from the glucose-centric paradigm away from the glucose and have an insulin-centric paradigm, by measuring insulin, we can not only detect the problems decades before they manifest, in other words, insulin would be elevated potentially 10 or 20 years before the glucose ever starts to change, so we detect it at its earliest stages,
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
But by focusing on the insulin, we also embrace more effective strategies. Because with a glucose-centric paradigm, conventional clinical care will say, we need to lower the glucose at all costs, even at the expense of increasing insulin.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
and that is a way to make people fatter and sicker, which is why people with type 2 diabetes who are given insulin therapy to correct their glucose, because it's only seen as a glucose disease, do in fact get fatter and die faster.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
They're twice as likely to die from cancer, three times as likely to die from heart disease, twice as likely to develop Alzheimer's disease, because those chronic diseases are not problems of hyperglycemia per se, they're problems of hyperinsulinemia. So focus on the insulin.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
We can detect problems sooner and we can treat them better because it's the high insulin that's contributing, not the high glucose. The high glucose is a symptom.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
Yeah, and I wish that there were firm consensus with regards to fasting insulin like we have with so many other markers. There isn't. And the ranges will vary almost from lab to lab. Someone could, if they convince their clinician to get their fasting insulin measured, it's entirely possible that the lab will say anything under 15 microunits per mil is normal. And I blanch at that idea.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
I think that's way too high. So with a little bit of scrutiny in the evidence,
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
Digging through the evidence my conclusion is that if someone has a fasting insulin of six micro units per mil or less It's a very very good sign that the body is insulin sensitive in other words You only need a modest amount of insulin to get the job done You know whatever insulin needs to do and insulin does a lot of things because as a reminder to the audience literally every single cell of the body
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
is responsive to insulin, or to say that another way, every cell has insulin receptors, these little docking sites for insulin to come and dock onto the cell and then tell the cell to do something. And there are all kinds of somethings that insulin will tell the cell to do, depending on the cell. So measure the fasting insulin, hopefully less than six microunits per mil.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
That to me is a very, very good sign. if it's um up if it's above if it's around say 7 to 17 or so that's a warning and i know that's a bit of a big range but it's just hard to know in that range whether you are consistently at say 15 or whether you are consistently at five and you just happen to have a peak in your insulin at that moment when you measured.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
And then anything above the high teens in insulin I would say is almost guaranteed to be a problem. But in that kind of middle range to the mid to low teens, It might be a problem, but again, it might be that you just caught the peak of insulin's natural circadian rhythm.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
And that's why, as much as I am a great advocate of measuring insulin, I also don't ever mean to imply that it's the only marker, that I think there are other scores like, for example, the triglyceride to HDL ratio. Take triglycerides fasted, divide by HDL fasted, and that number It varies a little bit across ethnicities, but the average point appears to be around 1.5.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
So get your fasting insulin measured, absolutely, but also couple that with your triglyceride to HDL ratio. And if that number is less than 1.5, it's a very good sign that you're insulin sensitive. Even if your insulin creeped up into the teens, don't lose hope. Look at that number and that'll help fill in some details.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
And the value of that number is in the event that anyone listening is not able to convince their clinician to measure their insulin, because let's face it, it's not easy to do. It's often a bit of a battle to get it done. You will always get your triglyceride to HDL ratio measured, or not even the ratio, but those two numbers. Every blood test will include triglycerides.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
Every blood test will include HDL cholesterol. So take that ratio, just compute it on your own. And if it's less than 1.5, then you can be really confident that your fasting insulin is also going to be good.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
Yeah, we can start with the one that appears to have the greater mass appeal, which would be calories or what I would like to refer to as just energy or sufficient energy. So you must have sufficient energy in the body coming into the body in order to provide the fuel for the growth of the fat cell. So that is pretty easy.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
That's very palatable because we have such a calorie-centric idea or view of obesity and weight gain, weight loss. However, what is too often overlooked is the absolute requirement of elevated insulin. A fat cell... does not inherently know what to do with the energy that it has surrounding it. And let me just refer to my own lab.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
Here I am at my university, right across the hallway in my building is my laboratory. And we are regularly growing fat cells on little petri dishes. And it is so stark to look at the difference in the way the fat cells behave in the absence or later the presence of insulin. So as we are growing the fat cells out across this little plate, they are surrounded with energy, calories.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
There's fat and there's glucose, which are the two building blocks for triglycerides within the fat cell itself. The triglycerides which are kind of giving the fat cell its big fat blob, or what we call a lipid droplet. And so again, the fat cells are surrounded by calories, an abundance of energy, and yet they're small.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
There's no changes on those fat cells until we start sprinkling in insulin into the culture, into the bath, the medium we call it, the liquid that the cells are bathing in. Once we start putting in insulin, now the fat cells know what to do, which is store the energy. So that's a part that's so often overlooked. And this doesn't apply to all metabolism in all cells, but
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
It is a pretty central theme that cells need to be told what to do with the energy they have available. Whether it's energy available on the outside to come in, or whether it's energy that the cell already has available within itself, it's the
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
Hormones, it's hormones like insulin or glucagon or epinephrine, adrenaline, and others, growth hormone, that signal to the cell what to do with the energy that it has access to. The cell doesn't just know what to do with the energy. The hormones are what's sort of sampling the entire body understanding what's going on in the entire body, and then dictating individual cells.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
It's like the hormones are the conductor to the orchestra. Any individual section, the brass, the woodwinds, the percussion, they don't know what notes to play on their own. They need something to tell them when to come in, the pace, the volume. The hormones are the conductors of the orchestra. And when it comes to fat cell growth,
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
You have on one side the hormone insulin, which is overwhelmingly promoting the growth of the fat cell, and it is so powerful in its own right that it is offset by multiple other hormones that tend to have a catabolic effect to insulin's anabolic effect. like some of the other ones I mentioned, glucagon and epinephrine, most obviously, and growth hormone.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
So there are a handful of hormones that are trying to get the fat cell to shrink and share its energy, all to try to offset the incredible power of insulin, which is telling the fat cell to store energy. But insulin goes even further than that.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
As much as insulin has a very pronounced central effect or directed effect on fat cells to stimulate their growth, insulin also has effects at the brain stimulating to a degree some degree of appetite or satiety in various instances. Not to mention the effect that insulin has on leptin levels from the fat cells. Again, a direct effect at the fat cell.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
But insulin will also elicit a whole body effect to slow metabolic rate. We have known that for decades.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
Indeed, over a hundred years ago, two famous Harvard scientists, Elliot P. Joslin and Francis G. Benedict, Joslin kind of being the father of modern endocrinology, Benedict being the father of modern metabolism, they came together to try to understand the metabolism in what they called severe diabetes, which we would just say kind of uncontrolled type one diabetes.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
that they noted in these individuals who have no insulin, their metabolic rate was 20 to 30% higher than it should be. There was something uncontrolled, this fire just raging through their body. And you see this in people with type 1 diabetes. In fact, it's so obvious that some type 1 diabetics are tempted to capitalize on it and engage in a
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
pattern of disordered eating, which is commonly called diabulimia. In other words, the type 1 diabetic learns that if they can eat whatever they want and enjoy it, eat it, swallow it, and keep it in their stomach and digest it, and they can be as skinny as they want to by simply deliberately underdosing their insulin.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
That is the most powerful evidence of the absolute requirement of insulin in telling fat cells to grow or to shrink, because they learn Again, if they skip their injections, they will be as skinny as they want. Now, there is metabolic mayhem in the body in that instance. Their glucose levels are 10 times higher than they should be. Their ketones are 10 or 20 times higher than it should be.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
And they're dying, but they look as lean as they want to be. And that is because they have learned...
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
that insulin injecting insulin is like injecting fat shots as one type one diabetic referred to it that they learn that it's the insulin that's making them gain weight whether they you know want to or not so insulin tells the fat cells what to do with the energy that it has available namely grow but insulin also helps that growth
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
by enriching the availability of total energy by reducing overall metabolic rate. And we even see this in people with type two diabetes. People with type two diabetes who go on insulin therapy, taking their already kind of high insulin and putting it even higher, their metabolic rate slows at the moment the therapy begins.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
And it's no surprise that diabetics around the world, type 1 or type 2, when they begin their insulin therapy, they gain weight. In a type 1 diabetic, it's often essential because they've been losing so much weight that the insulin hopefully will just get them back to where they should be.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
But in a type two diabetic who's often already overweight, once they start insulin therapy, it's guaranteed they're gonna gain more weight, and so up they go. And so within this long-winded answer, Drew, I've touched on a lot of points. If I were to sort of bring it together,
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
I would present what I hope is a unifying hypothesis, which is that there are two camps, and I don't want to strawman any one of them and speak for either of them, but you would have the kind of pure caloric theorists who would say, no, it's purely a matter of calories in, calories out, hormones be damned.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
Or you have the other camp, which they would say it's purely a matter of insulin and it's pure hormones. I might have misspoke earlier, but then in that case calories don't matter, whereas the other group would say hormones don't matter. But in reality both do.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
You must, to put it in a succinct sort of thesis statement, you must have elevated insulin to signal the growth of fat cell, and you must have sufficient energy to fuel the growth of the fat cell. Either is insufficient. You need both. I simply harp more on the insulin because it's the one that's so much more readily overlooked.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
The caloric-centric view of obesity has so enamored the world that there's almost no room intellectually to consider that there's another facet to this, namely hormones. But let me just revisit the role of the fat cell very briefly. And this is a particular interest with two guys like me and you. You have Ben Bickman, who is kind of European, Northern European descent. And I have Drew.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
Drew, I think you're South Asian. Indian. Yep. So these are two remarkably comparable ethnicities. When I did my postdoctoral work in Singapore, one of the reasons Singapore was so interested in partnering with Duke University, which is where I was,
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
was to understand these ethnic differences on how you can take ethnicities, particularly in Singapore, with both Chinese, South Asian, Malaysian, and European, and you have these four different guys who are best drinking buddies and they're all gaining weight, and yet they start to suffer the consequences of that weight gain at very different rates.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
But a study done in Caucasians compared to South Asians, not only do we know that the average South Asian Indian has a fasted insulin that is more than double what his Caucasian counterpart is, but also, even at the same body weight, his fat cells are about three to four times larger than his Caucasian counterpart. And this could explain why partly India has more people with type 2 diabetes.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
Absolute numbers more than anyone, but of course India's population is so massive. Even per capita, it's approaching the number one spot in the world, being truly the diabetes capital of the world. And a part of it is this combination, yes, environment, diet matters, but also genetics. And so it's very much important for us to understand what we could call the personal fat threshold.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
That based on our genetics and partly our diet, certain bodies have the potential to store fat in their fat cells to varying levels. And just Caucasians in the case of this example appear to have the higher threshold. But basically, as long as you can continue to store fat in fat cells, the body stays metabolically sound.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
And that it's once the fat cells start to reach a point of maximum dimension, and by that I mean every individual fat cell is getting too big, now the body has reached its threshold. And if insulin is attempting to still tell the body to store energy, now you have a war, a metabolic mutiny, where the fat cell starts to rebel. So we gain fat through two different processes.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
You know, you have two buddies, you have Drew and Ben, we're going on vacation, hanging out together, and we both come back from our trip 10 pounds fatter.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
Because of our unique ethnicity and the genetics that come with that, some of my weight gain potentially would have happened through some modest degree of hyperplasia, where when my fat cells started to get a little big, I would simply create some new fat cells. Whereas Drew, with South Asian ethnicity, your fat cells have a very limited potential for hyperplasia.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
In other words, you're not going to multiply your fat cells. The number of fat cells is pretty set. So then what happens is the fat cells each just get bigger and bigger and bigger. So each fat cell is carrying a bigger metabolic load than it would normally.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
Whereas again, in another body that can undergo hyperplasia, the fat cell gets a little big and it recruits a new fat cell, which gets a little big. So more important than the mass of fat we have on our body is the size of each individual fat cell. which of course is impossible to measure outside of a lab. We can do that thing here in my lab by taking biopsies of people's fat tissue.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
But even still, it's not something you're gonna really do. That's why you start to look at these other markers that we mentioned. But to sort of wrap through this idea quickly, when the fat cell gets really, really big, two problems start to happen.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
One, it starts to reach a point of maximum dimension that it can't grow anymore, otherwise the cell membrane starts to lose its integrity and literally start to pop, which would be a very messy inflammatory process. And at the second, the fat cell, as it's swollen up to 10 or 20 times bigger than it used to be, is now suffocating. It's getting pushed too far from capillaries.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
In other words, blood vessels where it can get oxygen and give it CO2 and get nutrients. So the fat cell starts to get too big and it starts to suffocate. This elicits two responses. When the fat cell starts to get so big, it starts to tell insulin, insulin, you are trying to make me big and yet I can't grow anymore. And so while you are trying to block me from breaking down my fat,
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
I'm not listening, and I'm going to start leaking fats. To say that in a more precise term, insulin normally inhibits lipolysis, which is the term for breaking down fat. That's the primary mechanism whereby insulin promotes the growth of a fat cell. Not necessarily force-feeding it, but preventing it from breaking it down.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
So the fat cell says insulin fats are still coming in or glucose is still coming in but now I'm going to start breaking down fat even though you're trying to tell me not to. So one, the fat cell, the hypertrophic or swollen fat cell becomes insulin resistant to prevent further growth.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
Leaking free fatty acids into the blood in the midst of elevated insulin and those two things should not be high at the same time. High insulin and high free fatty acids now means you're going to start storing fat in other places throughout the body, most especially the liver, getting fatty liver and excess fat in the pancreas, creating insulin resistance in those tissues.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
But the second problem, as I mentioned, is that the fat cell becomes hypoxic. It starts to suffocate, if you will, as it's gotten pushed too far from the capillary. The fat cell has a potential solution for that too, and that is by secreting a bunch of pro-inflammatory cytokines into the bloodstream.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
So the hypertrophic fat cell becomes very pro-inflammatory because some of those cytokines that it's secreting have the ability to promote the growth of new capillaries. And so it starts to correct its hypoxia by stimulating the growth of new fat cells, which is a better outcome than suffocating and becoming necrotic. You know, once again, a very messy, inflamed death if that were to happen.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
So the hypertrophic fat cell, in order to ensure its own survival, becomes insulin resistant to prevent further growth, inadvertently thereby flooding the body with free fatty acids to be stored elsewhere, and two, becomes very pro-inflammatory in order to correct its own hypoxia, but in the process flooding the body with pro-inflammatory cytokines, things like C-reactive protein, for example, which is increasingly measured on blood tests.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
But the combination of these two things, high free fatty acids and high inflammation is a wicked combination. Because now you start promoting the accumulation of these other types of fats in the body called ceramides within the cells. And when these two signals come to a cell, promote ceramide development or accumulation, now those cells become insulin resistant as well.
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
Whether it's the brain, whether it's the muscle, whether it's the liver, or the blood vessels promoting hypertension. This is why I have a fat first focus, that fat cells are the first domino to fall. That when the fat cells become insulin resistant, that's that earliest stages where the insulin's going up, but it's all still enough to keep glucose in check
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
you know the muscles are still responding to the insulin pulling in glucose the liver is still responding to the insulin pulling in and storing glucose helping blood glucose levels stay low but once the fat cells have become insulin resistant now pro-inflammatory they start spreading that insulin resistance to like for example muscle and liver now you have the glucose levels start to climb so where where you have other people who may promote or advocate an idea that the muscle becomes insulin resistant first or the liver
Dhru Purohit Show
The Labs You Need Your Doctor to Run to Know if Your Metabolically Healthy
I don't agree with that, because if that were the case, then glucose levels would start to climb immediately. They don't. Glucose levels stay low because insulin resistance starts in the very low metabolic rate fat cells, and then it spreads to the higher metabolic rate, higher glucose-consuming tissues, like the muscle, for example.
The Dr. Hyman Show
Encore: Mastering Your Metabolism: Expert Advice You Need
There are three primary causes of insulin resistance. And by primary, I mean that literally I can cause insulin resistance in isolated cells, in laboratory rodents, and in humans with all three of these. And that is elevated insulin itself, elevated stress hormones, and elevated inflammatory proteins or cytokines.
The Dr. Hyman Show
Encore: Mastering Your Metabolism: Expert Advice You Need
all three of those things are considered primary in my definition because you can just make insulin resistance happen at the cell in the rodents and in humans all three biomedical models but in as you were kind of alluding to if we were to tell someone all right here but there are others like you said like noxious toxins that can accumulate in fat cells and alter fat cell growth absolutely that is relevant um so i'm not suggesting that there aren't others there are
The Dr. Hyman Show
Encore: Mastering Your Metabolism: Expert Advice You Need
But I kind of put these ones as the kind of holy trinity or the unholy trinity of insulin resistance. But we would tell someone, control your stress. And they would say, well, great, doc, how am I going to do that? You know, it's a little difficult. Stress is one of those difficult things to truly wrap your head around. But even still, you'd mentioned like meditation and quiet.
The Dr. Hyman Show
Encore: Mastering Your Metabolism: Expert Advice You Need
I wholly agree with that. But even still, it's a little difficult to fully manage stress. Same with inflammation. We would say lower your inflammation. They'd say, well, how do I do that? You know, we'd have to find out what are the stimuli that are inducing that increase in that immune level. But if we say control your insulin, easy, easy.
The Dr. Hyman Show
Encore: Mastering Your Metabolism: Expert Advice You Need
That is a lever we can grab with both hands and immediately start to pull down just through time-restricted eating and intermittent fasting and by just managing macronutrients. And altering that ratio, you know, focusing more on the foods that have the lower effect on insulin, like in the fat and protein and controlling the starchiest of the carbohydrates or the most sugary.
The Dr. Hyman Show
Encore: Mastering Your Metabolism: Expert Advice You Need
Now, neither you nor I are declaring war on carbohydrates. And I'd hate for someone to leave this talk, leave this discussion thinking we are. We're not, you know, neither of us is advocating a carnivore diet, but we are certainly, my view is don't get your carbohydrates from bags and boxes with barcodes. I love that. Yeah, I love alliteration, so I'm glad you appreciate it.
The Dr. Hyman Show
Encore: Mastering Your Metabolism: Expert Advice You Need
But that's where people get it wrong, right? They're thinking they have a box of crackers or a bag of chips or a box of cereal. No. Eat fruits and vegetables. Eat them. I'm an advocate of fruits and vegetables. Eat them. But don't drink them and don't get them in processed foods. Bags, boxes, and barcodes.
The Dr. Hyman Show
Encore: Mastering Your Metabolism: Expert Advice You Need
Yeah, yeah, great question. So my postdoctoral work really was seminal in that it scrutinized the degree to which fatty acids themselves can contribute to insulin resistance. And this is a conversation that I'm passionate about because so many people –
The Dr. Hyman Show
Encore: Mastering Your Metabolism: Expert Advice You Need
start beating this drum of saturated fats and use it as evidence against animal products because animal products do contain saturated fats invariably. Now, they're never completely saturated fat, and that's important. There's a mix of saturated mono and polyunsaturated fats. And by the way, all saturated fats aren't the same.
The Dr. Hyman Show
Encore: Mastering Your Metabolism: Expert Advice You Need
Oh, my gosh. Yeah. There's dozens of them. Yeah, that's right. I'm a huge advocate of a full spectrum of fats, namely of saturated fats, even long chain, which we get a lot of medium chain and then short chain.
The Dr. Hyman Show
Encore: Mastering Your Metabolism: Expert Advice You Need
Putting that to the side there, when you incubate a cell, if you have a cell culture, whether it is muscle cells, liver cells, neurons, fat cells, and if you incubate those fat cells with palmitic acid, which is the prevalent saturated fat in the human body, certainly in circulation, palmitate or the 16 carbon saturated fat.
The Dr. Hyman Show
Encore: Mastering Your Metabolism: Expert Advice You Need
When you incubate cells with palmitate or stearate acid even, 18 carbons, they will become insulin resistant. And so you treat them with the fats. Then you put on some insulin a little later and then measure. Then you take all the cells and measure what insulin did. And it is compromised. That doesn't happen when you incubate the cells with monounsaturated or polyunsaturated fats.
The Dr. Hyman Show
Encore: Mastering Your Metabolism: Expert Advice You Need
that it will not cause direct cellular insulin resistance. So I've done these studies myself. Maybe the most cited study of mine I've ever done was this exact series of studies. And the same thing happens in rodents.
The Dr. Hyman Show
Encore: Mastering Your Metabolism: Expert Advice You Need
When you infuse the rodent with fat, when you're infusing it directly IV, the saturated fat will cause insulin resistance, but the monounsaturated, like olive oil, for example, doesn't. So there is a direct effect of saturated fats at the cell to cause insulin resistance.
The Dr. Hyman Show
Encore: Mastering Your Metabolism: Expert Advice You Need
And this is all, once you actually get into the cell itself, it's because of how these fats will induce the accumulation of another molecule called ceramides. And if anyone has ever heard ceramides in the audience, they might be thinking of it as like in lotions or shampoos and stuff. But it is a slightly different version of it.
The Dr. Hyman Show
Encore: Mastering Your Metabolism: Expert Advice You Need
But saturated fats will induce the accumulation of these molecules called ceramides within a cell. Then ceramides will directly prevent insulin, the insulin biochemical pathway from doing its job. It directly antagonizes what insulin is trying to do. So that's the actual where the rubber meets the road molecular mediator.
The Dr. Hyman Show
Encore: Mastering Your Metabolism: Expert Advice You Need
So now to zoom back out to the level of the whole body, some people look at those studies, even possibly my own, and will use that as evidence against saturated fat. And they will say, see, saturated fat causes insulin resistance, but... It doesn't work.
The Dr. Hyman Show
Encore: Mastering Your Metabolism: Expert Advice You Need
When you actually go to the whole body and look at the consumption of fat, the paradox is the vast majority, overwhelming majority of saturated fat in our blood is palmitate, but it's not from the diet. It comes from the liver. The liver is the primary source of saturated fats that are circulating in the blood.
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When we eat saturated fats, they're packaged into the chylomicron, and there can be some depositing of that throughout the body, but it goes to the liver, and then the liver will repackage all that fat. Almost always, the saturated fats will have two things happen to them. They get elongated by two carbons, so you'll take that 16-carbon palmitate, which is the most prevalent saturated fat.
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We take that 60 carbon, we make it into an 18 carbon, and then we desaturate it. There are these two steps. And so we end up taking the palmitate in the diet and turning it into oleic acid or the primary fat. Olive oil. Olive oil. And that is the primary fat that is stored in every single person's fat cells.
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No, no, no. So the fat cells turn it into olive oil, but the liver makes palmitate. Yeah, yeah. So when we eat saturated fats, the body will turn it into olive oil, basically. But when the liver is making fat, it makes saturated fats.
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And so this is why you can take someone and put them on a ketogenic diet, low carb, high fat, and they could be eating three times more saturated fat than the other group, than the low fat, high carb group. Three times more saturated fat. And yet the actual composition of fatty acids in their lipoproteins in their blood is much less saturated.
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So the actual amount of saturated fat circulating in their blood is much lower than it is if someone is eating a diet that is spiking their insulin. Because most of the saturated fat in the blood, which is what's coming to the cells throughout the body, you know, the phenomenon that I mentioned a moment ago, most of that saturated fat is coming from the liver.
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And the liver makes saturated fat when insulin is up. This is a process called lipogenesis. Lipogenesis. Yep, lipogenesis. Yep, and insulin is what turns that on. And that's the paradox here, really, to put a kind of fine point.
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Starchy, refined carbs.
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Yeah, and it's a one-two punch. Absolutely. It ends up being a one-two punch where these starchy, sugary carbs will both act as the skeleton. The liver will take those carbons and rearrange them to create a saturated fat. And at the same time, the starchy, sugary carbs are increasing insulin, which is what's driving the signal. That's the signal to tell the liver to do that in the first place.
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Because the liver will not make fat out of carbs unless insulin is elevated. It is antithetical. It is impossible for the liver to do. Because like every cell in the body, insulin tells the liver what to do with the energy that it has available. And when insulin is up, one of the things it wants the liver to do is turn the carbs into – turn the glucose, those carbons, into fat.
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And the only fat the liver is making and packaging and releasing is palmitate, that saturated fat.
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Yeah, yeah, yeah. Well, I will try not to be too redundant to what you said, but I would say anyone who has any potential, get your insulin measured. And you'd mentioned some wonderful metrics. I've always said below six. I think you said below five. I think that's a brilliant way to do it. Now, at the same time, insulin, like every hormone, has a bit of a rhythm to it.
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There's a diurnal or circadian rhythm. So it's possible someone would go get their insulin checked and maybe it's 12 or 13 or so. And you and I both would say, oh, that's a little high. We need to be a little worried. But it's possible the person has measured it at a peak. And that in reality, give it an hour or two later and it would have gone down to five. It's possible.
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So I think it is important to note that there are other things like challenging it in a dynamic glucose test like you'd mentioned. That is absolute gold standard. Alternatively, and another metric you'd mentioned is looking at lipids because insulin controls the production of fats and the regulation of lipoproteins in the body because lipoproteins are energetic molecules.
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And so look at the triglyceride to HDL ratio. And if a person has a triglyceride to HDL ratio and it's above 1.5, that's strong evidence that they're insulin resistant. Now, that ratio doesn't hold across all ethnicities. It starts to get a little loose from Caucasians to Asians to African-Americans or so.
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But nevertheless, that ratio of 1.5 is generally going to be a pretty good indicator that if you're lower than that, If your triglyceride to HDL ratio is lower, that's a good sign that you're insulin sensitive.
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The good old fashioned waist to hip ratio or the waist to height ratio, if you measure your waist, like the biggest part around your belly, and if you multiply that by two, if that number is higher than your height, That's a very, very good indicator that you have metabolic syndrome or insulin resistance to be more precise.
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If your waist circumference times two is less than your height, that's a good sign that you're generally doing okay. And then one other metric among many is what's on the skin. And there are two things people can look for on their skin, which are it's almost proof positive of insulin resistance. The first one is skin tags.
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Those are these little kind of mushroom like or columns, little stalks of skin. They're not like a flat kind of round mold. They just sort of jut right up and they're small. I bet everyone already knows what I'm talking about. People can get them in their armpits or around their neck if they have a fat fold around their neck. So those are skin tags.
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And in the same place, especially around the neck or the armpits, anywhere where skin is rubbing, they can start to develop something called acanthosis nigricans or these patches of skin that are a little darker pigment. And they have a kind of altered texture, kind of this velvety kind of texture to it. But that's another one.
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So the skin, I kind of joke, the skin is the window to the metabolic soul just because like every part of the body, it responds to insulin. And so we start to see these little hints of it.