Insights on Insulin Resistance and Health

Good morning. I am delighted to be here. When Sam first reached out and invited me to be a part of it, I was honored because I have long respected what Sam has been attempting to do. And I'm just delighted by the not only extent of the community, but the clear. affection that exists here in what you've created. Again, I'm delighted to be here. I'm particularly thrilled because Sam teed this up so well, and I can see why he might want a guy like me to come speak at an event like this, because I have a view of chronic disease that I think has value, and you'll be the judge of that in the end. So what I want to present to you today is the idea that when you look at not only metabolic health, but others, as I'll touch on, There is a common soil from which all of these noxious weeds are springing that we call diseases. And rather than continuing to trim down each individual weed only to have it grow back, we can go right to the soil and address the one common root from which all the others are springing. So what is metabolic health? If this is the impetus for having a guy like me come give a talk as a metabolic scientist. What is it? There would be multiple ways of defining it. Indeed, as I was putting this together, one version or several versions of this talk had several definitions. But one definition is the metabolic syndrome. We can define metabolic health through what is called the metabolic syndrome. The metabolic syndrome is defined somewhat differently depending on who is explaining it. But one definition is this constellation of complications that you see here. Within the UK specifically, it's often defined as just the top three, and the dyslipidemia sometimes isn't included. But regardless, this is the general consensus that if a patient comes in with dyslipidemia, high blood pressure, high glucose, and a large waist circumference, they would be defined as having the metabolic syndrome. And this is a problem here, where within the UK, 33%, so a third of all the adults, have confirmed metabolic syndrome. That's pretty sobering and it's even more sobering when we look a little farther further abroad. When you look across the globe we can see that the problem in fact the problem in South Asia, in the Middle East, in the Pacific Islands, in Southeast Asia and then across the pond we have issues in Mexico and the United States as much as the world wants to point the finger a chubby finger at the United States it's actually far from far from the worst. And thankfully the UK is doing a little better than the US is. But this helps you get an idea of the prevalence of the problem. It's not just a problem here. And one of my hopes as this message spreads, and I echo Sam's sentiments to share whatever you can, and part of my motivation is to present this material in such a way that the idea will plant a seed in your brain and you're able to take some of what I've said You say it in your own way. If I can give you a sound bite, then as a professor I will consider my job as having been done. Now within the UK, the problem actually might be a little worse than we think. Because within the UK, we know that 58% of adults, almost 6 in 10, have confirmed hypertension. And hypertension is a part of the metabolic syndrome. Indeed, it's a critical part. And it's often the first sign that something's gone awry. Because while we might not measure all the other things too often, we are always measuring blood pressure. So might that mean that 58% of adults within the UK actually have insulin resistance? Now why would I make that connection? It's because the metabolic syndrome used to be referred to as the insulin resistance syndrome. This is a better title. While the word metabolic is certainly a little sexier, if you'll pardon me for being a little crass, it has a little more of an appeal. Whenever we hear the word metabolic or metabolism, we immediately have our interest piqued. But it used to be called the insulin resistance syndrome. When the constellation of complications was first identified by a famous metabolic scientist in the U.S. decades ago, which means no one knows who he is at all, he called it the insulin resistance syndrome. Because all of these problems, which I prefer. Because when you call something the metabolic syndrome, it still sounds a little vague. A patient might not know what you're talking about, even though they may like the sound of it or fear the sound of it. If we call it the insulin resistance syndrome, we are identifying the problem. We're pointing the finger at the cause of the complications. So, to make my point, if 58% of adults within the UK have hypertension, and in my speculation, might that mean 58% have insulin resistance? It's not much of a stretch, because insulin resistance is generally, among its first manifestations, going to be identified as hypertension, or higher blood pressure, for reasons and mechanisms that I won't get into now. This is... appropriate because Sam really teed this up well for me, where he was indicating what are the top most expensive diseases within the UK. This matches well with what I like to call the plagues of prosperity. These disorders that were once unheard of. Our great-grandparents in previous generations, they weren't dying from these problems that we are dying from nowadays. And so insulin resistance is fundamental in contributing to heart disease. It would be very uncommon, not totally impossible, for someone to have heart disease and hypertension plays into that without it being preceded and caused by insulin resistance. And then certain forms of cancer, if not caused by the insulin resistance, and I wouldn't say it is, it's exacerbated. Insulin resistance is accelerating the growth of the cancer. And the most common liver problem worldwide, fatty liver disease, is directly caused by insulin resistance and the insulin promoting the growth or the production of fat. within the liver. And then type 2 diabetes, which is what I mean by diabetes here, is one that we'll spend a little more time talking about. I'll revisit that. And then lastly, body fat. You cannot make fat cells grow unless insulin is elevated, regardless of calories consumed. In addition to these big five killers or problems, we have some that range from similarly lethal and tragic, like dementia and Alzheimer's disease being the most common form. And even stroke, as Sam mentioned, is one of the top expenses. That's contributed to here as well. And then less lethal, but very relevant to a population and very heartbreaking for a couple, we have the most common forms of infertility. The most common infertility in women, polycystic ovary syndrome, is more aptly called a metabolic infertility because insulin directly contributes to disrupted estrogen production from the ovaries. And then in men. There was a manuscript published a number of years ago that left an impression on me because the title was so compelling, where they stated, is erectile dysfunction the first manifestation of insulin resistance in otherwise healthy men? The answer is likely yes, due to what insulin resistance is doing to his blood vessels. So all these, across this wheel of misfortune, these plagues of prosperity, we can see that there is, and I don't have the time to show you all the mechanism, You'd have to take my undergraduate class at my university to get all that. But there are direct mechanisms that explain how insulin resistance is contributing and causing these problems. And one of my great hopes is imagining, in my mind, I imagine here in the UK, a patient, an individual goes home and opens their medicine cabinet every morning. And they take out a pill for their hypertension, a pill for their diabetes, maybe a pill for their migraine, headaches, and so on. Thinking that all of these problems, because I have a pill for each of them, must be unrelated and totally distinct. Little realizing that if we could shift the paradigm somewhat to help impress upon the patient that these are not distinct problems, that by changing a few core ideas, which we'll get to and will be discussed aptly in this meeting, none of them will be surprising to you, then we can start to put the medicine back in the medicine cabinet. That one by one, the pill becomes a little less relevant, not that I'm giving medical advice. Now, I've been talking about insulin resistance. And just to help you understand the scope of the problem, I've already shared with you some of the statistics. But I strongly suspect the problem is even worse than the data suggests they are. First one, do you have high blood pressure? Or someone you know, someone you might be thinking of. Do you have a family member with any evidence or history of metabolic problems, like type 2 diabetes, or the... pregnancy version of type 2 diabetes, which is gestational diabetes? Do you have PCOS of females or erectile dysfunction for males? Fatty liver disease. Have you ever been told that your liver enzymes were elevated? Not that that's proof positive. You'd want some further confirmation. Or are there some skin problems? Now, thankfully, freckles are not evidence of metabolic problems, but there are some that stand out. And that is skin tags, and these have more complicated names, and then these dark patches called acanthosis nigricans. These are often manifested on skin folds, and the neck can be the most obvious example of that. But these are, all of these are strong evidence, and with the skin in particular, it's often a window to the metabolic soul. But if you answered yes to any one of these, or the person you're thinking of, they very, very likely have insulin resistance. Each one of these are signs, independently of the others, of a metabolic problem. And this is why the problem is likely much worse. Because you could have someone, say, with skin tags and or akynthosis nigricans around the neck, but they might still have a normal blood pressure. And they might not have any other issues that would typically be identified as being metabolic. Now what is insulin even? I am a professor and I want to get back to the most basic principles. Insulin is a hormone that is produced from the beta cells of the pancreas. Now insulin is a small hormone. Physically speaking the molecule is very very tiny which makes it somewhat in the past complicated for scientists to measure. Also complicating it is the actual amount of insulin we have in our bodies. Insulin is at fantastically low levels compared to other hormones. And yet, it is fantastically effective. A little bit of insulin goes a long way. It punches well above its weight class. Now, the primary stimulus for insulin to be released is glucose. As blood sugar levels or blood glucose is going up, insulin will be released. This is the most famous interaction with insulin. And insulin's primary action, no surprise, if its primary stimulus is high glucose, no surprise that its primary mechanism or action is to lower glucose. Now I'm even misspeaking a little bit as I'm saying that. I don't like to say that it's it's that the lowering of the glucose is insulin's primary action. It is its most famous action but that is almost part of the problem as I'll change the paradigm in a moment. People can't separate insulin from glucose. Whereas glucose is, yes, a stimulus and an effect, insulin does many, many more things. Insulin, the effect on glucose is simply reflective of insulin's actions in nutrient metabolism. It doesn't matter what the nutrient is, insulin has a powerful effect on what the body is doing with it. Indeed, one of insulin's thematic effects across the entire body is to tell cells what to do with energy. Which is why I made that comment earlier, partly, that you cannot lose fat if insulin isn't low, or that body fat is directly contributed or affected by insulin. It is impossible to make a fat cell grow without elevated insulin, completely. Also, it has effects on cellular growth in a very general way. It has effects on electrolytes in a very important way, and many, many more effects. But again, the theme of it is telling cells what to do with energy. And the fact that it lowers glucose, well that's just one of its many effects. And albeit its most famous. Now what is insulin resistance? We've been, I've been alluding to it, I've been mentioning it. And now we understand what insulin is. We need to understand now what happens when it breaks bad. When it turns into the villain. And so that's what we'll define now. To understand insulin resistance, we want to understand it from the level of the cell. Because when we say insulin resistance, That is a cellular phenomenon. And this could be any cell in the entire body. It doesn't matter. Because every cell of the body has a little door for insulin to come and knock on, called the insulin receptor. Literally every cell. And I don't use the word literally like the kids do these days. I don't use it too liberally. I mean literally every cell of the body has an insulin receptor. From brain cells to bone cells, lung cells to liver cells, and all the cells in between. Insulin will come and tell the cell to do something. So, insulin will come and knock on the door of the cell, and in so doing will elicit a cellular action. And I'm just going to call it action and keep it a little vague, because it's no surprise what insulin does at a neuron is very different from what it does at an endothelial cell within the blood vessel. So we have a cellular action. And its most famous action, again, is to lower blood glucose. And it does so by when insulin comes and knocks on the door, it will open another door for glucose to come in. Now, not all of the body's cells will do that. But some of the biggest ones, like muscle cells, will. They will respond to insulin. Part of that response will be pulling the glucose in, thereby lowering blood glucose. Insulin's most famous, but not its most important, effect. Unfortunately, over time... Due to a variety of noxious stimuli, the cell can become increasingly less responsive to insulin. And so what was once a robust action in response to a polite knocking on the door of the cell becomes a diminished one, if not absent entirely. The consequences of this are myriad and well beyond the time that I have to share with you. But suffice to say, the consequences would be a lot of the plagues of prosperity that I've alluded to and Sam did too. But the most famous consequence would be that blood glucose levels start to steadily climb. Eventually. Emphasis on eventually. It is going to be a delayed response. At the same time, what is actually a less delayed response, insulin levels. are elevated as well. And this is because if one polite molecule of insulin knocking on the door isn't sufficient to get the cell to do what insulin wants it to, well then it will recruit an angry mob. And now there is a mob of insulin pounding on the door of the cell, all in an effort to try to restore whatever action it can, to whatever degree it can. Sometimes it can, as we go across the plagues of prosperity, sometimes it can't. Now There are two important takeaways then in this definition. It sounds like I've only been really talking about one, but to understand what insulin resistance is, and this becomes part of the diagnosis later that we'll talk about at the end, you must appreciate that insulin resistance is a coin with two sides, like every coin. But the coin that I would be holding is a coin that I would say this is insulin resistance. And they're part of it. One side of the coin is the whole phenomenon that I just got done talking to you about. That some of the body's cells aren't responding as well to insulin as they used to. But it's some cells aren't responding well. And this becomes a problem when we look at the whole body level. Because if we look across the whole body, insulin levels are elevated compared to where they were before. Indeed, there is no such thing as insulin resistance without hyperinsulinemia. It cannot happen. It doesn't matter what example an individual may be imagining, whether it's the pathological insulin resistance that I focus on as a scientist and that contributes to the plagues of prosperity, or whether it's the few instances, indeed only two, of physiological insulin resistance, when the body has become insulin resistant in an effort to promote dramatic growth. Just as an aside, that's the two P's of physiological insulin resistance, pregnancy and puberty. Those are times of explosive growth. And the insulin resistance and the hyperinsulinemia facilitates that explosive growth. And it's not harmful. It's necessary. Alright, but in this same context, whereas some of the body's cells aren't responding to the insulin, and so the hyperinsulinemia isn't pathogenic or harmful, we have another bunch of cells that are as responsive to insulin as they ever were. Like the ovaries, for example. They don't become typical ladies. They're so sensitive all the time. The ovaries never lose their sensitivity. I'm joking, of course. Don't tell my wife I said that, please. She's maybe sensitive to my joke. So, for example, the ovaries stay perfectly insulin sensitive. And so the hyperinsulinemia is telling the ovaries to do too much. Whereas her male counterpart, his blood vessels have become insulin resistant. And so the insulin isn't telling the blood vessels to do enough. The blood vessels need a lot more signal. Typical men, right? They need to be told a lot more in order to get the action that it needs. All right. Now, in this paradigm, as I've presented it to you thus far, I have described that the hyperinsulinemia is a consequence of the insulin resistance. In other words, the arrow going as I show you here. That's not wrong. I wouldn't have shown it if it were. That is not a wrong perspective, but it's not the whole story, as we'll get to in a moment. All right, now this is another paradigm. We're leaving the cell behind, and now we're looking at an individual, maybe a patient, coming to their GP every year for an annual wellness visit. And we can see over time, in the process of years, that while we are obsessively measuring glucose, the glucose levels are normal for decades, and eventually they start to climb, and perhaps even dramatically. But that's not the whole story. If we were to superimpose insulin on this, it would look something like this. where we can see that there are two distinct time points. The first one being a state of just what we would call insulin resistance or pre-diabetes. It is so important to appreciate that the insulin is elevated in this state, but not the glucose. These are not the same thing. And the GP, a clinician knows this. A clinician knows that insulin and glucose are not the same thing. But what they fail to appreciate so often, I would say, is a conventionally trained clinician. And I'm not a clinician. I'm a biomedical scientist, but I've talked with enough and done enough versions of this talk to see the confusion. In their minds, so often, the two can't help but go together. That they are linked hand in hand, and that if the glucose is high, then the insulin is high. Or, more often, if the glucose is normal, then insulin must be normal. And it doesn't matter because what good is measuring insulin anyway to the conventionally trained clinician? It is only when the body has become so resistant to its own insulin that even though there is still an abundance of insulin, and if it is type 2 diabetes, it is always an abundance of insulin. It does, insulin never goes down to zero or even close. in type 2 diabetes. If that's happening in a patient, it is not type 2. They have developed type 1 or they have some delayed version of another type called MODY. It is not type 2. So even if the insulin levels go from their peak, which might have been 10 times higher than they used to be, and start to come down, which can happen, it never goes down to where it was when the person was metabolically sound. But even still, the body is swimming in a sea of insulin and it just can't work well enough to control the blood. the blood glucose levels. We cannot look at these as equal numbers all the time. Now, we obsessively focus on glucose. It has become the metric that matters to most conventional clinicians, but it shouldn't be. I understand the reasons for it. It's because historically, the most prominent display or evidence of the disorder was the urine production, which is what diabetes means, producing a lot of urine. And that is a direct consequence of the sugar, the blood sugar levels, the glucose. But we are more advanced than our ancestors were in some ways, maybe not others, but we have the ability to measure insulin. So glucose can be elevated about 10 or more years after the insulin has already been elevated. This is well documented in prospective studies. We can see over the person's time of getting measured and coming into their GPs that the glucose levels are staying in check. But the insulin levels are higher and higher. and higher. So here's glucose staying normal for years. Here's the insulin going up and up and up and up and up. Just as I'm showing you here as you go from left to right, we have to shift from the glucose-centric paradigm to an insulin-centric paradigm if we hope to really identify the problem. Because again, it can take decades before the blood glucose levels ever start to change after the insulin. All right, now we understand what insulin resistance is. I've identified the villain of the story. But now we need to understand its origins. How did it become the villain that it is? With insulin resistance, there are what I consider to be primary causes. There are secondary and there are a myriad of them, but I want to focus on the primary for the sake of time and precision, where I define the primary causes as being causes that can independently of anything else contribute or cause insulin resistance in all three commonly used biomedical models. So whether it is isolated cells growing in a petri dish, like I have in my lab back home now, some fat cells are growing, my students just started growing them up, or whether it is in laboratory rodents, or the pinnacle of all creation, the humans, we humans, ourselves. In all three of these biomedical models, there are three, I've identified three primary causes, and I submit to you, these are the primary causes. So the ones that we should focus on the most. Not that there aren't others, but they are stress, inflammation. and hyperinsulinemia, which I just got done describing to you as a consequence of insulin resistance and a cause. Each of these are independent, and for the sake of time, I'm not going to define the top two. We're going to focus on the elephant in the room, the one that is the greatest contributor and the one that we can do the most about. Now, in this scenario, hyperinsulinemia, too much insulin, as the body is flush with insulin, it becomes increasingly less sensitive to insulin. And this is reflective of a fundamental biological principle. It doesn't matter what we're talking about in life, too much of something will result in a resistance to that something. Now let me give you a funny little analogy. This is me and my wife and our darling little children. And sometimes darling, sometimes demonic. But my darling wife is a full-time homemaker, which means she's full-time PTA at the school, she's full-time involved in our church. Full-time involved in playgroups with the kids. Very, very, when I say full-time, I mean full-time. But it means that she's around the kids quite a bit more than I am. And she is used to hearing the noise of the children. And this really leaves an impression on me when I'm home with all our darling little cherubs and when I'm with the family. And I will hear the kids screaming for something. And I'm amazed that my wife doesn't register it at all. She's become somewhat deaf to this signal. Why? Because she hears it so much. She has learned to just drown it out. And if it's true crisis, then she can respond. Well, I'm not around the children as much, and so I hear everything, and I react. I have an action to the screaming, whereas my wife is quite content to let it go. She's become a little deaf to the children's screams. I'm not. I'm acutely sensitive to them. Because she hears it all the time, I don't hear it all the time. This is this analogy. You can see it. Now, if we shift this a little bit and come back to the body and insulin itself, let me impress upon you the relevance of this issue. why it is such a problem. The average, in fact, less than average person, an uncommon person only eats three times a day. A rare individual only eats three times a day. And this might be what their insulin levels do. They have a starchy, sugary breakfast, maybe a little more protein and fat for lunch, and then they have a nice starchy, sugary dinner. This is what would happen. This is what their insulin levels would look like. Every time they spike it, it takes a couple hours or three hours to come down. Now let's talk actually... about the less than common person, in fact, sorry, the common individual, who has been told that they should not only eat, but they should snack in between their meals. And so any moment where insulin might have come down, it's immediately bumped back up, where the average individual is spending every waking moment in a state of elevated insulin. And as bad as this looks, this is what it looks like in a person with insulin resistance. Sorry, insulin sensitive, which again is probably less common. The more common insulin resistant individual will have an insulin level that looks like this, where their insulin levels not only start higher, they never go as low, and they are elevated the entire time of day. By the time insulin is attempting to come down, they've spiked it right back up with their starchy, sugary mid-morning snack, or their starchy, sugary afternoon snack, or their evening snack. So back to this view, where I described how hyperinsulinemia is a consequence of the insulin resistance, you're now understanding the idea that it's also a cause. This becomes a vicious cycle that just keeps accelerating more and more as long as the person continues their habits. Now, how can you correct insulin resistance? There are multiple ways actually, where it's drugs and diet are the main ones. These are the ones I want to focus on because they're often the most leveraged, and rightly so to varying degrees. Now let's talk a little bit about drugs. And in so doing, I cannot help but describe these, what's called anti-diabetic drugs. These are drugs that are thought to be improving the metabolic health of the individual. And here is a list, pretty comprehensive actually, as short as it is, that encompasses many of the most common or popular drugs. For the sake of time, I'm not going to talk about all of them. For example, I'm not going to talk about the GLP-1 agonists. I don't know what the trade name would be here, but in the US, Wigovian, Ozempic, the world has lost its mind with these drugs. And I'm certainly happy to answer any questions you have. I'm very, very familiar with them. But I won't talk about them now because they're less used here. Every time someone's taking a drug, we must balance the consequences. Everything is a consequence to putting that in the body. It's just a matter of, are the consequences I want worth the consequences I don't want? Here is my own version of it, the gospel according to Ben Bickman. Let's start with metformin, which is the most widely used anti-diabetic drug in the world, for various reasons, very, very affordable, and generally effective. However, as effective as metformin is, it has been shown to only be half as effective as even modest lifestyle changes. So this big winner is still a loser when you compare it to lifestyle change, which makes sense, right? metabolic problems are lifestyle problems. I want to introduce you to one other complication of metformin. Most people don't appreciate that metformin's primary mechanism of action is to act as a mitochondrial poison. That's a dramatic term, but of course I'm a professor and I need to keep students interested, so I don't mind being a little dramatic. But it is a mitochondrial poison. It directly blocks the electron transport system, the ability of the mitochondria to actually produce energetic molecules from the food that we have, from calorie molecules. And especially one of its primary sites of action is the muscle. But that's a problem. The muscle has a high metabolic demand. And if we begin damaging the mitochondria, damaging may be a strong word. If we begin slowing down the function or compromising the function of the mitochondria, there are consequences. In this group, in Colorado, in the U.S., they identified in humans, this is a human study, where they had individuals with insulin resistance undergo an exercise training program. No surprise. that when they analyzed the mitochondria of the muscle, the mitochondria were working better, and the body was more insulin sensitive because of the exercise. When they had the group exercise and take metformin, as you can see here in this direct quote, it undid the benefit. It undid the mitochondrial adaptation to the challenge of the exercise, and it even undid the insulin sensitizing effect of the exercise itself. How can we in good conscience tell someone to use a drug That is literally undoing the benefits of the exercise. It's difficult to fathom. Now, SGLT1 and 2 inhibitors, these are generally operated under the trade name with the suffix glyphosate. There are a lot of weird names to these drugs. But this is an interesting mechanism of action. Where SGLT1 is a glucose transporter that will move glucose from the guts into the bloodstream. SGLT2 is a transporter. that will move the glucose from the kidneys back into the blood. The kidneys will pull the glucose in, and then SGLT2 will put it all back into the bloodstream. These drugs, as the name suggests, block that effect. It closes down those transporters. And that's, if we are only looking at glucose, it works. If you can block the glucose from coming in, or push the glucose out through the kidneys into the urine, you will lower glucose. That will lower insulin. And so if we just stopped there, we would say, well, gosh, this works. Let's just keep writing these prescriptions all day. However, there are consequences. There's something within physics called an osmotic gradient to make it. That sounds more complicated than it is. But where there is a lot of glucose, water wants to follow. This is why in diabetes the person's urinating so much, because the glucose that's getting filtered into the kidneys is overwhelming the kidney's ability to pull it back in. And so we have a lot of glucose that stays in the urine. Well, where there's a lot of glucose, there's a lot of water. And so there ends up being a lot of urine volume produced. But there are consequences. If you block the intestine's ability to pull glucose in, you keep a lot of water in the guts as well. And now anytime the person thinks they're going to politely pass gas, they don't know what's going to come out. And it's, you know, they're socially always on edge or on the edge of their seat because the consequences can be quite catastrophic. gastrointestinally speaking. Also less maybe socially complicated but perhaps even a little more pathogenic is that the fact that you are basically creating a diabetes in the form of the polyuria, the excess urine production. And little bacteria eat one thing, they eat glucose. And the urinary tract is constantly being invaded by bacteria. Bacteria constantly trying to come up the urinary tract. Well if we are flushing the urinary tract with all the glucose that we're eating by dumping it into the kidneys, it's like aid stations on the bacteria's marathon to our bladder and then to our kidneys. We're basically saying, hey bacteria, you look like you're getting tired. Here is some energy drink for you. And keep going. And so it's no surprise that UTIs, the urinary tract infections, are so much more common. We are feeding the little beasties, helping them invade our body. But In this paradigm, if we are willing to block someone's glucose absorption and give them catastrophic diarrhea, socially speaking, or we are willing to block the kidney's ability and we're pushing it out, forcing it out through the urinary tract, I submit that there's like a little shoulder angel sitting on someone's side, whispering, maybe just give them less glucose. Maybe tell them to eat less glucose. If we're willing to block it from coming in or forcing it out, just put less in the system in the first place. And then you've undone the necessity or the benefit of this drug class. Now, lastly, I leave the worst for last. Sulfonylureas and insulin. Of course, various trade names. But the actions collectively of these will be to increase the insulin. Sulfonylureas, you take the pill and it will basically force the beta cells to dump more insulin into the system. Then the insulin injection itself, of course, is going to increase insulin. The justification for this is this paradigm. The conventional clinician. has a glucose-centric paradigm. And so we look at the glucose and we say, we just need to lower the glucose at any cost. But a good way to do that is to just push the insulin up. We might not even know where it is because it's so uncommon to measure insulin. The clinician won't even know where the insulin is. The patient won't even know where their insulin is. And so who cares if we push it up even higher? Because we will have the patient's glucose going down. But does that solve the problem? No. This meta-analysis that was published a number of years ago noted that there is no clinical benefit to lowering the patient's insulin. Sorry, lowering glucose in type 2 diabetes with elevating insulin. And in fact, knowing what you know now, that high insulin levels are a common cause of insulin resistance, what do you think happens to the insulin resistance? As you are taking the hyperinsulinemic patient and making them even more hyperinsulinemic, remember it's the noise that's causing the deafness. And we are simply cranking up the volume. It's no surprise that insulin resistance gets even worse. Here are some quotes, and mind you, throughout my study, throughout my presentation, you might have noticed in the bottom left corner, I have these little PubMed ID numbers. So all of these, those are all the citations, if you're ever wondering. So these are some direct quotes, noting in type 2 diabetics that the longer or the more insulin the patient is taking, the worse the insulin resistance is getting. Again, it's no surprise. If you remember that high insulin is a cause of insulin resistance, you can see how we're making the problem worse. Indeed, giving a type 2 diabetic insulin is like giving an alcoholic another glass of wine, hoping that a little extra alcohol will solve the problem. It's the high insulin that caused the problem. And unfortunately, it gets even more dramatic. Whereas you put a patient on insulin therapy, in fact, you look from the moment of treatment, insulin dose over several months goes up. And the body weight starts to climb, all while, based on the metrics being used, the amount of food being consumed is dropping, where over these few months they appear to be eating less, and yet they're gaining fat. Now that might seem impossible if you strictly adhere to the laws of thermodynamics, which I do actually, but I'm not ignorant enough to think that the human body is a closed system. My body is not the universe, as much as I'd like to think that I am the singular reason for the universe, my body is not the universe. I have, and your bodies as well, we are open to the universe and we cannot ever totally account for all the energy that's being exchanged. Case in point, what few people realize is that the moment a diabetic is put on insulin therapy, whether they are type 1, which I'm not really talking about, or type 2, metabolic rate will slow. In type 1 diabetics, it's dramatic where insulin will slow, the metabolic rate will slow by over 20% in a day once they go on insulin therapy. It's less dramatic in a type 2 diabetic. But even still, by dumping more insulin in the system, metabolic rate will slow, which is one of the mechanisms whereby insulin is able to tell the body to gain fat. Now, more lethal than just having too much body fat is the fact that substantial evidence suggests that when you are pushing the body further into hyperinsulinemia, you are increasing cancer mortality. In fact, you're about doubling it. So when the type 2 diabetic is put on insulin therapy, the likelihood of dying from cancer, which is modest, but getting more common all the time. is twice as high, about 90% in this study, about twice as high as it should be. And then heart disease, where the type 2 diabetics who have to take on the highest insulin doses, even if they have perfect glucose levels, they are three times more likely to die from heart disease. So giving the type 2 diabetic insulin is a wonderful way to make sure their blood glucose levels are perfect, but killing them faster, which is not the solution to the NHS's problems. All right. Now, within this grand scope, to step back out and look at the plagues of prosperity again, these are only modestly affected by elevated glucose. So glucose is a modest contributor to these problems, if it's a contributor at all. In some of them, it isn't, directly. But what is directly contributing is the high insulin. It is no surprise, then, that if our therapy is based on increasing insulin, we're killing them faster. We're killing people. Let's go back to the base cause. If hyperinsulinemia is the primary cause, then lowering insulin needs to be the solution. And we do that through the food we eat. And that's all a matter of managing macronutrients. This is the way people eat around the world. And to my great pleasure, I've been able to give versions of this lecture, not quite as specific as I'm giving now, in countries around the world. Southeast Asia, Asia, Middle East, where the problem is even worse than it is in Europe and in the US or in America. These are the macronutrients. Now let's see how these affect insulin. This is what happens when a person eats pure fat. This is what happens when they eat pure protein. And this is what happens when they eat pure carbohydrate or in the form of glucose. This is a direct reproduction of data, mind you. I just literally made this by superimposing it on the figure. You can't quite see the, oh, you can't, you can see it. I can't, mind you. Yes, you see the PubMed ID number. This is what happens. Anyone who tells you that insulin increases, that fat consumption increases insulin does not know what they're talking about. I've literally never seen a study that has shown that. I don't know where that conclusion would come from. I've done some of these studies myself and will be publishing some. This is what it would look like in a different view. The effect of insulin with the various macronutrients or the effect of the macronutrients on insulin. Now, it may seem like I'm just declaring war on carbohydrates and I'm not. The type of carbohydrate matters enormously, of course. But this is part of what plays into the justification on one side or another, whether the person knows it or not. For an insulin resistance scientist who acknowledges that hyperinsulinemia is the primary contributor, one of these versions of the diet, whether it's low-fat and high-carb, or whether it's low-carb and higher-fat, one of them is going to work better at removing the most offending agent here. And my earlier version of this lecture, I was going to go through multiple studies. That was just a little too burdensome. Indeed, PHC has some wonderful graphics. And link that actually highlights a lot of these studies themselves. So you can I just refer you to the phc.org Alright now this is one study though that took individuals and had them overeat carbohydrates Which let's face it is what most people are doing right in the global diet 70% of the calories are coming from carbohydrates. That's quite a majority This is so this is what happened over seven days in a fasted state I'm already showing you the glucose levels now. However, if we were to add on the insulin This is what happened to the subject's insulin levels over the same length of time. By the end of the week, in a fasted state, mind you, their insulin levels at a fasted state were 2.5 times higher than they were at the beginning of the week, just by overeating carbs for a week. This is insulin resistance, normal glucose, and hyperinsulinemia. Now this is how, when we eat these macronutrients, there is a corresponding blood molecule. With fat, triglycerides would be the blood marker of fat consumption. Perhaps, actually, triglycerides, it's more complicated. Amino acids would be the blood marker of protein. And then lastly, glucose is the blood marker of carbohydrate. In diabetes, type 2 diabetes, which is just a prolonged insulin resistance, which of these nutrients in the blood is the body struggling with? Actually, it's a little more complicated than I'm mentioning, but what's the one that we obsess over? Well, of course, it's the glucose. And no surprise, that's the thing we're eating the most of. So I submit to you there are three pillars. If lifestyle is the culprit, it's also the cure. The food we eat is causing or can cure these metabolic issues. And we could expand this to add a lot more. But first one, control carbohydrates. And by that I mean, my suggestion is... Look at the amount of digestible glucose compared to the amount of fiber that would come with it. If it's relatively low, if the fiber to everything else in there is high, then that will be a carbohydrate that's generally going to be good. Fiber will mitigate some of the glucose absorption and thus the subsequent insulin spike will be about 30% or so less than it would be otherwise. So control carbs. My suggestion, focus on whole fruits and vegetables. as primary sources of carbohydrates. Whatever the carbohydrate desire is to eat, focus on fruits and vegetables. Next, prioritize protein. This must be, if you're prioritizing the best protein for the human body, or any animal whatsoever, it will be, because even ruminant animals will digest the protein very differently, but we humans, we need it in our monogastric system, we need it to come from animal sources. Every metric. an animal source will have superior absorption and without the complications of a plant source protein. There are technologies that are improving plant source proteins but we are built to eat other animal and animal source proteins. Prioritize the protein. It's a modest insulin effect. Now in nature protein never comes alone. In our hubris and in our fear of fat we've pulled it apart. But protein always comes with fat in nature. There is truly no exception to this. If it's a natural protein, fat comes with it. That's how we should eat it. Not only do we absorb the protein better, but because we digest it better. Most people don't appreciate that. That we think we have proteolytic enzymes in the intestines coming from the pancreas that will split up the proteins into small enough units so that we can pull it across our intestines. But those proteolytic enzymes don't work as well. without bile. bile enhances the ability of the intestines to digest protein and we only have bile getting released into the intestines when we eat fat they should always come together do not fear the fat that comes with the protein and I would even say be liberal with adding some fat to your protein if not you know eating the fat alone perhaps okay so then don't fear the fat now as I wrap up and I just got done hopefully sharing with you some of the good news That as much as my talk has seemed a bit like a horror story, it's a happy ending. Which is that if we look through the lens, through an insulin-centric lens rather, we appreciate that we just need to lower the insulin. And we do that by managing our macronutrients. Controlled carbohydrates, prioritized protein, don't fear fat. And I could have added frequently fast to keep my alliteration going. But that would be a really helpful way to lower insulin and literally cure the problem. Removing the medic, keeping the medications. tucked up in the medicine cabinet until they expire. All right, so how can we measure it? There are different ways to measure this, and I've lumped them into two categories. And for the sake of time, I'm not going to talk about all of them, but there are dynamic measurements and then static measurements. And of course, the static measurements are easier. The dynamic measurement is a two-hour oral glucose tolerance test with insulin being measured at the time points. I'm not going to talk about it. because it's so uncommon to get it done, but the easiest way to interpret it, in hindsight now, I should have put this image in here because I have it and it's lovely, but I didn't think I'd talk about it. If the peak of the insulin is at 30 minutes and every subsequent point is lower, that's a good sign. If the peak is anywhere except anywhere outside of 30 minutes, if the peak is an hour or 90 minutes, that's a problem. It's a warning of insulin resistance. All right, now again, it's not easy to get those done. no matter where you live. So let's talk about end with the static measurements. So there is the list and I just want to highlight the ones that I think are the most telling. The first one simply being measuring insulin. I hope I got my unit conversion correctly going from the micro units in the US to the picomoles here but if fasting insulin is lower than around mid-30s picomoles that's a very very good sign that I believe. David? Yes, I need a GP here to kind of confirm. But that would be a good sign that insulin levels are in a healthy, low range, and the body is responding well to it. In other words, the body is insulin sensitive. But at the same time, there is another molecule called C-peptide that comes in the nanogram per mil range, very, very low range, mind you. But this, sometimes, I only mention this because I've seen how it gets confused with insulin levels. C-peptide is not insulin. But they are sister molecules. That when they're born, they're born as twins. They come out of the beta cell into the blood one to one. Now, hearing me say that, every time the beta cell releases an insulin, it releases a C-peptide. That is true. You may be tempted to think, well then let's just measure C-peptide. But you can't. It has a very, very different half-life. C-peptide sticks around in the blood much, much longer. So me mentioning C-peptide isn't intended to be... a diagnostic measurement of insulin resistance, but rather illustrative for the patient or the clinician to know, is this a person who's making insulin on their own? Because if you have a type 2 diabetic patient who is on insulin therapy, then measuring insulin won't work because you're just as much measuring what's coming from the syringe as you are what's coming from their beta cells. But C-peptide is only made from the beta cells. So I cite this. Because if a clinician is wanting, or the patient is wanting, to get off their insulin therapy, you need to know, are the beta cells actually making insulin? C-peptide will be the confirmation. That's the proof positive. This is a person who can graduate out of their insulin treatments onto just a dietary regime. And then next, I have the HOMA, homeostatic model assessment, H-O-M-A, the HOMA index. Generally, we want that number to be around 1.5. And the value of HOMA is that it takes both insulin, it takes fasting insulin, and fasting glucose into its equation. And again, if the answer, if the solution to that little equation, and you can find it online, there are HOMA calculators here in the UK too, for UK units, then you know this is a body that is insulin sensitive. If the HOMA score is getting up to around 3 mid-3s, that's insulin resistance, and then beyond that is typically just going to be full-on type 2 diabetes. So the HOMA score is a very good one, and one I recommend. Now, as I wrap up... And I show you this wheel of misfortune in some kind of bizarre game show version. There are four key things we've discussed in the time we've had together. We've talked about what is insulin resistance, where does it come from, what to do about it, and lastly, how to measure it. With this information, in all humility, I believe that you are, and we are all collectively, well-armed to not only understand this problem, have the emphasis be appropriate, and know how to solve it. And it won't be from popping another pill. Thank you all for listening. And during the panel, I hope you'll submit a load of questions because nothing thrills a professor more than getting a lot of questions. Thank you all for listening. Thank you so much. Thank you. Thank you. Thank you. We've actually got time to take one. That's okay. We'll take one question. Okay, yeah. I've got it right here. Right, well, Ben's done wonderfully on timing. Thank you so much. Can't wind nerves. We've got time to take one question, which I'm going to put to... Hey, Sean. Good morning. And... Yes, that is from Katie Whitehead. Where's Katie? There she is. Excellent. So do you think there is value in the suggestions of Jesse and Chapsy, the glucose goddess, who's written about hacks to flatten glucose spikes? For example, vinegar, vegetables first, when you're eating and timing your exercise and things like that. I do. Yeah, so I actually wrote a little blurb for her first book. Because I really appreciated her sentiments. Yeah, so she and I have communicated quite readily. Yeah, apple cider vinegar is one that I'm fascinated by. The effects of those. And vinegar, we don't commonly think of it as a fat. But it is. It's the shortest of the short-chain fats. And short-chain fatty acids, which we don't eat them normally. It only comes from a process of fermentation. But taking milk. which doesn't taste sour and allowing it to ferment which now tastes a little sour is in nature or taking cabbage and then turning it into kimchi now it's quite tart and sour those are short chain fats those hit the mouth and activate these bitter taste receptors anyway that's a long-winded way of coming back to apple cider vinegar short chain fatty acids are metabolic very metabolically active molecules and aggressively enhance insulin sensitivity in the body so jesse's reasons for mentioning apple cider vinegar are very very well justified so i i really appreciate her um sentiments she's a more glamorous version of a guy like me i make no claims to divinity after all like she does excellent all right well thanks again thank you so much

Good morning. I am delighted to be here. When Sam first reached out and invited me to be a part of it, I was honored because I have long respected what Sam has been attempting to do.

And I'm just delighted by the not only extent of the community, but the clear. affection that exists here in what you've created. Again, I'm delighted to be here.

I'm particularly thrilled because Sam teed this up so well, and I can see why he might want a guy like me to come speak at an event like this, because I have a view of chronic disease that I think has value, and you'll be the judge of that in the end. So what I want to present to you today is the idea that when you look at not only metabolic health, but others, as I'll touch on, There is a common soil from which all of these noxious weeds are springing that we call diseases. And rather than continuing to trim down each individual weed only to have it grow back, we can go right to the soil and address the one common root from which all the others are springing. So what is metabolic health? If this is the impetus for having a guy like me come give a talk as a metabolic scientist.

What is it? There would be multiple ways of defining it. Indeed, as I was putting this together, one version or several versions of this talk had several definitions.

But one definition is the metabolic syndrome. We can define metabolic health through what is called the metabolic syndrome. The metabolic syndrome is defined somewhat differently depending on who is explaining it.

But one definition is this constellation of complications that you see here. Within the UK specifically, it's often defined as just the top three, and the dyslipidemia sometimes isn't included. But regardless, this is the general consensus that if a patient comes in with dyslipidemia, high blood pressure, high glucose, and a large waist circumference, they would be defined as having the metabolic syndrome. And this is a problem here, where within the UK, 33%, so a third of all the adults, have confirmed metabolic syndrome. That's pretty sobering and it's even more sobering when we look a little farther further abroad.

When you look across the globe we can see that the problem in fact the problem in South Asia, in the Middle East, in the Pacific Islands, in Southeast Asia and then across the pond we have issues in Mexico and the United States as much as the world wants to point the finger a chubby finger at the United States it's actually far from far from the worst. And thankfully the UK is doing a little better than the US is. But this helps you get an idea of the prevalence of the problem. It's not just a problem here.

And one of my hopes as this message spreads, and I echo Sam's sentiments to share whatever you can, and part of my motivation is to present this material in such a way that the idea will plant a seed in your brain and you're able to take some of what I've said You say it in your own way. If I can give you a sound bite, then as a professor I will consider my job as having been done. Now within the UK, the problem actually might be a little worse than we think. Because within the UK, we know that 58% of adults, almost 6 in 10, have confirmed hypertension. And hypertension is a part of the metabolic syndrome.

Indeed, it's a critical part. And it's often the first sign that something's gone awry. Because while we might not measure all the other things too often, we are always measuring blood pressure. So might that mean that 58% of adults within the UK actually have insulin resistance? Now why would I make that connection?

It's because the metabolic syndrome used to be referred to as the insulin resistance syndrome. This is a better title. While the word metabolic is certainly a little sexier, if you'll pardon me for being a little crass, it has a little more of an appeal.

Whenever we hear the word metabolic or metabolism, we immediately have our interest piqued. But it used to be called the insulin resistance syndrome. When the constellation of complications was first identified by a famous metabolic scientist in the U.S. decades ago, which means no one knows who he is at all, he called it the insulin resistance syndrome. Because all of these problems, which I prefer. Because when you call something the metabolic syndrome, it still sounds a little vague.

A patient might not know what you're talking about, even though they may like the sound of it or fear the sound of it. If we call it the insulin resistance syndrome, we are identifying the problem. We're pointing the finger at the cause of the complications.

So, to make my point, if 58% of adults within the UK have hypertension, and in my speculation, might that mean 58% have insulin resistance? It's not much of a stretch, because insulin resistance is generally, among its first manifestations, going to be identified as hypertension, or higher blood pressure, for reasons and mechanisms that I won't get into now. This is...

appropriate because Sam really teed this up well for me, where he was indicating what are the top most expensive diseases within the UK. This matches well with what I like to call the plagues of prosperity. These disorders that were once unheard of.

Our great-grandparents in previous generations, they weren't dying from these problems that we are dying from nowadays. And so insulin resistance is fundamental in contributing to heart disease. It would be very uncommon, not totally impossible, for someone to have heart disease and hypertension plays into that without it being preceded and caused by insulin resistance. And then certain forms of cancer, if not caused by the insulin resistance, and I wouldn't say it is, it's exacerbated. Insulin resistance is accelerating the growth of the cancer.

And the most common liver problem worldwide, fatty liver disease, is directly caused by insulin resistance and the insulin promoting the growth or the production of fat. within the liver. And then type 2 diabetes, which is what I mean by diabetes here, is one that we'll spend a little more time talking about.

I'll revisit that. And then lastly, body fat. You cannot make fat cells grow unless insulin is elevated, regardless of calories consumed.

In addition to these big five killers or problems, we have some that range from similarly lethal and tragic, like dementia and Alzheimer's disease being the most common form. And even stroke, as Sam mentioned, is one of the top expenses. That's contributed to here as well.

And then less lethal, but very relevant to a population and very heartbreaking for a couple, we have the most common forms of infertility. The most common infertility in women, polycystic ovary syndrome, is more aptly called a metabolic infertility because insulin directly contributes to disrupted estrogen production from the ovaries. And then in men.

There was a manuscript published a number of years ago that left an impression on me because the title was so compelling, where they stated, is erectile dysfunction the first manifestation of insulin resistance in otherwise healthy men? The answer is likely yes, due to what insulin resistance is doing to his blood vessels. So all these, across this wheel of misfortune, these plagues of prosperity, we can see that there is, and I don't have the time to show you all the mechanism, You'd have to take my undergraduate class at my university to get all that. But there are direct mechanisms that explain how insulin resistance is contributing and causing these problems. And one of my great hopes is imagining, in my mind, I imagine here in the UK, a patient, an individual goes home and opens their medicine cabinet every morning.

And they take out a pill for their hypertension, a pill for their diabetes, maybe a pill for their migraine, headaches, and so on. Thinking that all of these problems, because I have a pill for each of them, must be unrelated and totally distinct. Little realizing that if we could shift the paradigm somewhat to help impress upon the patient that these are not distinct problems, that by changing a few core ideas, which we'll get to and will be discussed aptly in this meeting, none of them will be surprising to you, then we can start to put the medicine back in the medicine cabinet.

That one by one, the pill becomes a little less relevant, not that I'm giving medical advice. Now, I've been talking about insulin resistance. And just to help you understand the scope of the problem, I've already shared with you some of the statistics.

But I strongly suspect the problem is even worse than the data suggests they are. First one, do you have high blood pressure? Or someone you know, someone you might be thinking of.

Do you have a family member with any evidence or history of metabolic problems, like type 2 diabetes, or the... pregnancy version of type 2 diabetes, which is gestational diabetes? Do you have PCOS of females or erectile dysfunction for males?

Fatty liver disease. Have you ever been told that your liver enzymes were elevated? Not that that's proof positive. You'd want some further confirmation.

Or are there some skin problems? Now, thankfully, freckles are not evidence of metabolic problems, but there are some that stand out. And that is skin tags, and these have more complicated names, and then these dark patches called acanthosis nigricans. These are often manifested on skin folds, and the neck can be the most obvious example of that. But these are, all of these are strong evidence, and with the skin in particular, it's often a window to the metabolic soul.

But if you answered yes to any one of these, or the person you're thinking of, they very, very likely have insulin resistance. Each one of these are signs, independently of the others, of a metabolic problem. And this is why the problem is likely much worse. Because you could have someone, say, with skin tags and or akynthosis nigricans around the neck, but they might still have a normal blood pressure.

And they might not have any other issues that would typically be identified as being metabolic. Now what is insulin even? I am a professor and I want to get back to the most basic principles.

Insulin is a hormone that is produced from the beta cells of the pancreas. Now insulin is a small hormone. Physically speaking the molecule is very very tiny which makes it somewhat in the past complicated for scientists to measure.

Also complicating it is the actual amount of insulin we have in our bodies. Insulin is at fantastically low levels compared to other hormones. And yet, it is fantastically effective.

A little bit of insulin goes a long way. It punches well above its weight class. Now, the primary stimulus for insulin to be released is glucose. As blood sugar levels or blood glucose is going up, insulin will be released. This is the most famous interaction with insulin.

And insulin's primary action, no surprise, if its primary stimulus is high glucose, no surprise that its primary mechanism or action is to lower glucose. Now I'm even misspeaking a little bit as I'm saying that. I don't like to say that it's it's that the lowering of the glucose is insulin's primary action.

It is its most famous action but that is almost part of the problem as I'll change the paradigm in a moment. People can't separate insulin from glucose. Whereas glucose is, yes, a stimulus and an effect, insulin does many, many more things. Insulin, the effect on glucose is simply reflective of insulin's actions in nutrient metabolism.

It doesn't matter what the nutrient is, insulin has a powerful effect on what the body is doing with it. Indeed, one of insulin's thematic effects across the entire body is to tell cells what to do with energy. Which is why I made that comment earlier, partly, that you cannot lose fat if insulin isn't low, or that body fat is directly contributed or affected by insulin. It is impossible to make a fat cell grow without elevated insulin, completely.

Also, it has effects on cellular growth in a very general way. It has effects on electrolytes in a very important way, and many, many more effects. But again, the theme of it is telling cells what to do with energy.

And the fact that it lowers glucose, well that's just one of its many effects. And albeit its most famous. Now what is insulin resistance? We've been, I've been alluding to it, I've been mentioning it.

And now we understand what insulin is. We need to understand now what happens when it breaks bad. When it turns into the villain. And so that's what we'll define now.

To understand insulin resistance, we want to understand it from the level of the cell. Because when we say insulin resistance, That is a cellular phenomenon. And this could be any cell in the entire body.

It doesn't matter. Because every cell of the body has a little door for insulin to come and knock on, called the insulin receptor. Literally every cell.

And I don't use the word literally like the kids do these days. I don't use it too liberally. I mean literally every cell of the body has an insulin receptor.

From brain cells to bone cells, lung cells to liver cells, and all the cells in between. Insulin will come and tell the cell to do something. So, insulin will come and knock on the door of the cell, and in so doing will elicit a cellular action. And I'm just going to call it action and keep it a little vague, because it's no surprise what insulin does at a neuron is very different from what it does at an endothelial cell within the blood vessel.

So we have a cellular action. And its most famous action, again, is to lower blood glucose. And it does so by when insulin comes and knocks on the door, it will open another door for glucose to come in.

Now, not all of the body's cells will do that. But some of the biggest ones, like muscle cells, will. They will respond to insulin.

Part of that response will be pulling the glucose in, thereby lowering blood glucose. Insulin's most famous, but not its most important, effect. Unfortunately, over time...

Due to a variety of noxious stimuli, the cell can become increasingly less responsive to insulin. And so what was once a robust action in response to a polite knocking on the door of the cell becomes a diminished one, if not absent entirely. The consequences of this are myriad and well beyond the time that I have to share with you.

But suffice to say, the consequences would be a lot of the plagues of prosperity that I've alluded to and Sam did too. But the most famous consequence would be that blood glucose levels start to steadily climb. Eventually. Emphasis on eventually. It is going to be a delayed response.

At the same time, what is actually a less delayed response, insulin levels. are elevated as well. And this is because if one polite molecule of insulin knocking on the door isn't sufficient to get the cell to do what insulin wants it to, well then it will recruit an angry mob. And now there is a mob of insulin pounding on the door of the cell, all in an effort to try to restore whatever action it can, to whatever degree it can.

Sometimes it can, as we go across the plagues of prosperity, sometimes it can't. Now There are two important takeaways then in this definition. It sounds like I've only been really talking about one, but to understand what insulin resistance is, and this becomes part of the diagnosis later that we'll talk about at the end, you must appreciate that insulin resistance is a coin with two sides, like every coin.

But the coin that I would be holding is a coin that I would say this is insulin resistance. And they're part of it. One side of the coin is the whole phenomenon that I just got done talking to you about.

That some of the body's cells aren't responding as well to insulin as they used to. But it's some cells aren't responding well. And this becomes a problem when we look at the whole body level.

Because if we look across the whole body, insulin levels are elevated compared to where they were before. Indeed, there is no such thing as insulin resistance without hyperinsulinemia. It cannot happen.

It doesn't matter what example an individual may be imagining, whether it's the pathological insulin resistance that I focus on as a scientist and that contributes to the plagues of prosperity, or whether it's the few instances, indeed only two, of physiological insulin resistance, when the body has become insulin resistant in an effort to promote dramatic growth. Just as an aside, that's the two P's of physiological insulin resistance, pregnancy and puberty. Those are times of explosive growth. And the insulin resistance and the hyperinsulinemia facilitates that explosive growth. And it's not harmful.

It's necessary. Alright, but in this same context, whereas some of the body's cells aren't responding to the insulin, and so the hyperinsulinemia isn't pathogenic or harmful, we have another bunch of cells that are as responsive to insulin as they ever were. Like the ovaries, for example. They don't become typical ladies.

They're so sensitive all the time. The ovaries never lose their sensitivity. I'm joking, of course.

Don't tell my wife I said that, please. She's maybe sensitive to my joke. So, for example, the ovaries stay perfectly insulin sensitive.

And so the hyperinsulinemia is telling the ovaries to do too much. Whereas her male counterpart, his blood vessels have become insulin resistant. And so the insulin isn't telling the blood vessels to do enough. The blood vessels need a lot more signal.

Typical men, right? They need to be told a lot more in order to get the action that it needs. All right.

Now, in this paradigm, as I've presented it to you thus far, I have described that the hyperinsulinemia is a consequence of the insulin resistance. In other words, the arrow going as I show you here. That's not wrong.

I wouldn't have shown it if it were. That is not a wrong perspective, but it's not the whole story, as we'll get to in a moment. All right, now this is another paradigm. We're leaving the cell behind, and now we're looking at an individual, maybe a patient, coming to their GP every year for an annual wellness visit.

And we can see over time, in the process of years, that while we are obsessively measuring glucose, the glucose levels are normal for decades, and eventually they start to climb, and perhaps even dramatically. But that's not the whole story. If we were to superimpose insulin on this, it would look something like this. where we can see that there are two distinct time points.

The first one being a state of just what we would call insulin resistance or pre-diabetes. It is so important to appreciate that the insulin is elevated in this state, but not the glucose. These are not the same thing. And the GP, a clinician knows this.

A clinician knows that insulin and glucose are not the same thing. But what they fail to appreciate so often, I would say, is a conventionally trained clinician. And I'm not a clinician. I'm a biomedical scientist, but I've talked with enough and done enough versions of this talk to see the confusion. In their minds, so often, the two can't help but go together.

That they are linked hand in hand, and that if the glucose is high, then the insulin is high. Or, more often, if the glucose is normal, then insulin must be normal. And it doesn't matter because what good is measuring insulin anyway to the conventionally trained clinician?

It is only when the body has become so resistant to its own insulin that even though there is still an abundance of insulin, and if it is type 2 diabetes, it is always an abundance of insulin. It does, insulin never goes down to zero or even close. in type 2 diabetes.

If that's happening in a patient, it is not type 2. They have developed type 1 or they have some delayed version of another type called MODY. It is not type 2. So even if the insulin levels go from their peak, which might have been 10 times higher than they used to be, and start to come down, which can happen, it never goes down to where it was when the person was metabolically sound. But even still, the body is swimming in a sea of insulin and it just can't work well enough to control the blood.

the blood glucose levels. We cannot look at these as equal numbers all the time. Now, we obsessively focus on glucose. It has become the metric that matters to most conventional clinicians, but it shouldn't be. I understand the reasons for it.

It's because historically, the most prominent display or evidence of the disorder was the urine production, which is what diabetes means, producing a lot of urine. And that is a direct consequence of the sugar, the blood sugar levels, the glucose. But we are more advanced than our ancestors were in some ways, maybe not others, but we have the ability to measure insulin. So glucose can be elevated about 10 or more years after the insulin has already been elevated.

This is well documented in prospective studies. We can see over the person's time of getting measured and coming into their GPs that the glucose levels are staying in check. But the insulin levels are higher and higher. and higher. So here's glucose staying normal for years.

Here's the insulin going up and up and up and up and up. Just as I'm showing you here as you go from left to right, we have to shift from the glucose-centric paradigm to an insulin-centric paradigm if we hope to really identify the problem. Because again, it can take decades before the blood glucose levels ever start to change after the insulin.

All right, now we understand what insulin resistance is. I've identified the villain of the story. But now we need to understand its origins.

How did it become the villain that it is? With insulin resistance, there are what I consider to be primary causes. There are secondary and there are a myriad of them, but I want to focus on the primary for the sake of time and precision, where I define the primary causes as being causes that can independently of anything else contribute or cause insulin resistance in all three commonly used biomedical models. So whether it is isolated cells growing in a petri dish, like I have in my lab back home now, some fat cells are growing, my students just started growing them up, or whether it is in laboratory rodents, or the pinnacle of all creation, the humans, we humans, ourselves.

In all three of these biomedical models, there are three, I've identified three primary causes, and I submit to you, these are the primary causes. So the ones that we should focus on the most. Not that there aren't others, but they are stress, inflammation.

and hyperinsulinemia, which I just got done describing to you as a consequence of insulin resistance and a cause. Each of these are independent, and for the sake of time, I'm not going to define the top two. We're going to focus on the elephant in the room, the one that is the greatest contributor and the one that we can do the most about. Now, in this scenario, hyperinsulinemia, too much insulin, as the body is flush with insulin, it becomes increasingly less sensitive to insulin.

And this is reflective of a fundamental biological principle. It doesn't matter what we're talking about in life, too much of something will result in a resistance to that something. Now let me give you a funny little analogy.

This is me and my wife and our darling little children. And sometimes darling, sometimes demonic. But my darling wife is a full-time homemaker, which means she's full-time PTA at the school, she's full-time involved in our church. Full-time involved in playgroups with the kids. Very, very, when I say full-time, I mean full-time.

But it means that she's around the kids quite a bit more than I am. And she is used to hearing the noise of the children. And this really leaves an impression on me when I'm home with all our darling little cherubs and when I'm with the family.

And I will hear the kids screaming for something. And I'm amazed that my wife doesn't register it at all. She's become somewhat deaf to this signal. Why? Because she hears it so much.

She has learned to just drown it out. And if it's true crisis, then she can respond. Well, I'm not around the children as much, and so I hear everything, and I react.

I have an action to the screaming, whereas my wife is quite content to let it go. She's become a little deaf to the children's screams. I'm not.

I'm acutely sensitive to them. Because she hears it all the time, I don't hear it all the time. This is this analogy. You can see it.

Now, if we shift this a little bit and come back to the body and insulin itself, let me impress upon you the relevance of this issue. why it is such a problem. The average, in fact, less than average person, an uncommon person only eats three times a day. A rare individual only eats three times a day. And this might be what their insulin levels do.

They have a starchy, sugary breakfast, maybe a little more protein and fat for lunch, and then they have a nice starchy, sugary dinner. This is what would happen. This is what their insulin levels would look like.

Every time they spike it, it takes a couple hours or three hours to come down. Now let's talk actually... about the less than common person, in fact, sorry, the common individual, who has been told that they should not only eat, but they should snack in between their meals.

And so any moment where insulin might have come down, it's immediately bumped back up, where the average individual is spending every waking moment in a state of elevated insulin. And as bad as this looks, this is what it looks like in a person with insulin resistance. Sorry, insulin sensitive, which again is probably less common. The more common insulin resistant individual will have an insulin level that looks like this, where their insulin levels not only start higher, they never go as low, and they are elevated the entire time of day.

By the time insulin is attempting to come down, they've spiked it right back up with their starchy, sugary mid-morning snack, or their starchy, sugary afternoon snack, or their evening snack. So back to this view, where I described how hyperinsulinemia is a consequence of the insulin resistance, you're now understanding the idea that it's also a cause. This becomes a vicious cycle that just keeps accelerating more and more as long as the person continues their habits. Now, how can you correct insulin resistance?

There are multiple ways actually, where it's drugs and diet are the main ones. These are the ones I want to focus on because they're often the most leveraged, and rightly so to varying degrees. Now let's talk a little bit about drugs.

And in so doing, I cannot help but describe these, what's called anti-diabetic drugs. These are drugs that are thought to be improving the metabolic health of the individual. And here is a list, pretty comprehensive actually, as short as it is, that encompasses many of the most common or popular drugs. For the sake of time, I'm not going to talk about all of them. For example, I'm not going to talk about the GLP-1 agonists.

I don't know what the trade name would be here, but in the US, Wigovian, Ozempic, the world has lost its mind with these drugs. And I'm certainly happy to answer any questions you have. I'm very, very familiar with them. But I won't talk about them now because they're less used here. Every time someone's taking a drug, we must balance the consequences.

Everything is a consequence to putting that in the body. It's just a matter of, are the consequences I want worth the consequences I don't want? Here is my own version of it, the gospel according to Ben Bickman.

Let's start with metformin, which is the most widely used anti-diabetic drug in the world, for various reasons, very, very affordable, and generally effective. However, as effective as metformin is, it has been shown to only be half as effective as even modest lifestyle changes. So this big winner is still a loser when you compare it to lifestyle change, which makes sense, right?

metabolic problems are lifestyle problems. I want to introduce you to one other complication of metformin. Most people don't appreciate that metformin's primary mechanism of action is to act as a mitochondrial poison.

That's a dramatic term, but of course I'm a professor and I need to keep students interested, so I don't mind being a little dramatic. But it is a mitochondrial poison. It directly blocks the electron transport system, the ability of the mitochondria to actually produce energetic molecules from the food that we have, from calorie molecules.

And especially one of its primary sites of action is the muscle. But that's a problem. The muscle has a high metabolic demand. And if we begin damaging the mitochondria, damaging may be a strong word.

If we begin slowing down the function or compromising the function of the mitochondria, there are consequences. In this group, in Colorado, in the U.S., they identified in humans, this is a human study, where they had individuals with insulin resistance undergo an exercise training program. No surprise.

that when they analyzed the mitochondria of the muscle, the mitochondria were working better, and the body was more insulin sensitive because of the exercise. When they had the group exercise and take metformin, as you can see here in this direct quote, it undid the benefit. It undid the mitochondrial adaptation to the challenge of the exercise, and it even undid the insulin sensitizing effect of the exercise itself. How can we in good conscience tell someone to use a drug That is literally undoing the benefits of the exercise.

It's difficult to fathom. Now, SGLT1 and 2 inhibitors, these are generally operated under the trade name with the suffix glyphosate. There are a lot of weird names to these drugs.

But this is an interesting mechanism of action. Where SGLT1 is a glucose transporter that will move glucose from the guts into the bloodstream. SGLT2 is a transporter. that will move the glucose from the kidneys back into the blood. The kidneys will pull the glucose in, and then SGLT2 will put it all back into the bloodstream.

These drugs, as the name suggests, block that effect. It closes down those transporters. And that's, if we are only looking at glucose, it works. If you can block the glucose from coming in, or push the glucose out through the kidneys into the urine, you will lower glucose. That will lower insulin.

And so if we just stopped there, we would say, well, gosh, this works. Let's just keep writing these prescriptions all day. However, there are consequences. There's something within physics called an osmotic gradient to make it.

That sounds more complicated than it is. But where there is a lot of glucose, water wants to follow. This is why in diabetes the person's urinating so much, because the glucose that's getting filtered into the kidneys is overwhelming the kidney's ability to pull it back in. And so we have a lot of glucose that stays in the urine.

Well, where there's a lot of glucose, there's a lot of water. And so there ends up being a lot of urine volume produced. But there are consequences. If you block the intestine's ability to pull glucose in, you keep a lot of water in the guts as well.

And now anytime the person thinks they're going to politely pass gas, they don't know what's going to come out. And it's, you know, they're socially always on edge or on the edge of their seat because the consequences can be quite catastrophic. gastrointestinally speaking. Also less maybe socially complicated but perhaps even a little more pathogenic is that the fact that you are basically creating a diabetes in the form of the polyuria, the excess urine production.

And little bacteria eat one thing, they eat glucose. And the urinary tract is constantly being invaded by bacteria. Bacteria constantly trying to come up the urinary tract.

Well if we are flushing the urinary tract with all the glucose that we're eating by dumping it into the kidneys, it's like aid stations on the bacteria's marathon to our bladder and then to our kidneys. We're basically saying, hey bacteria, you look like you're getting tired. Here is some energy drink for you.

And keep going. And so it's no surprise that UTIs, the urinary tract infections, are so much more common. We are feeding the little beasties, helping them invade our body.

But In this paradigm, if we are willing to block someone's glucose absorption and give them catastrophic diarrhea, socially speaking, or we are willing to block the kidney's ability and we're pushing it out, forcing it out through the urinary tract, I submit that there's like a little shoulder angel sitting on someone's side, whispering, maybe just give them less glucose. Maybe tell them to eat less glucose. If we're willing to block it from coming in or forcing it out, just put less in the system in the first place. And then you've undone the necessity or the benefit of this drug class.

Now, lastly, I leave the worst for last. Sulfonylureas and insulin. Of course, various trade names.

But the actions collectively of these will be to increase the insulin. Sulfonylureas, you take the pill and it will basically force the beta cells to dump more insulin into the system. Then the insulin injection itself, of course, is going to increase insulin. The justification for this is this paradigm.

The conventional clinician. has a glucose-centric paradigm. And so we look at the glucose and we say, we just need to lower the glucose at any cost. But a good way to do that is to just push the insulin up.

We might not even know where it is because it's so uncommon to measure insulin. The clinician won't even know where the insulin is. The patient won't even know where their insulin is.

And so who cares if we push it up even higher? Because we will have the patient's glucose going down. But does that solve the problem? No.

This meta-analysis that was published a number of years ago noted that there is no clinical benefit to lowering the patient's insulin. Sorry, lowering glucose in type 2 diabetes with elevating insulin. And in fact, knowing what you know now, that high insulin levels are a common cause of insulin resistance, what do you think happens to the insulin resistance?

As you are taking the hyperinsulinemic patient and making them even more hyperinsulinemic, remember it's the noise that's causing the deafness. And we are simply cranking up the volume. It's no surprise that insulin resistance gets even worse. Here are some quotes, and mind you, throughout my study, throughout my presentation, you might have noticed in the bottom left corner, I have these little PubMed ID numbers. So all of these, those are all the citations, if you're ever wondering.

So these are some direct quotes, noting in type 2 diabetics that the longer or the more insulin the patient is taking, the worse the insulin resistance is getting. Again, it's no surprise. If you remember that high insulin is a cause of insulin resistance, you can see how we're making the problem worse. Indeed, giving a type 2 diabetic insulin is like giving an alcoholic another glass of wine, hoping that a little extra alcohol will solve the problem. It's the high insulin that caused the problem.

And unfortunately, it gets even more dramatic. Whereas you put a patient on insulin therapy, in fact, you look from the moment of treatment, insulin dose over several months goes up. And the body weight starts to climb, all while, based on the metrics being used, the amount of food being consumed is dropping, where over these few months they appear to be eating less, and yet they're gaining fat. Now that might seem impossible if you strictly adhere to the laws of thermodynamics, which I do actually, but I'm not ignorant enough to think that the human body is a closed system.

My body is not the universe, as much as I'd like to think that I am the singular reason for the universe, my body is not the universe. I have, and your bodies as well, we are open to the universe and we cannot ever totally account for all the energy that's being exchanged. Case in point, what few people realize is that the moment a diabetic is put on insulin therapy, whether they are type 1, which I'm not really talking about, or type 2, metabolic rate will slow. In type 1 diabetics, it's dramatic where insulin will slow, the metabolic rate will slow by over 20% in a day once they go on insulin therapy. It's less dramatic in a type 2 diabetic.

But even still, by dumping more insulin in the system, metabolic rate will slow, which is one of the mechanisms whereby insulin is able to tell the body to gain fat. Now, more lethal than just having too much body fat is the fact that substantial evidence suggests that when you are pushing the body further into hyperinsulinemia, you are increasing cancer mortality. In fact, you're about doubling it. So when the type 2 diabetic is put on insulin therapy, the likelihood of dying from cancer, which is modest, but getting more common all the time. is twice as high, about 90% in this study, about twice as high as it should be.

And then heart disease, where the type 2 diabetics who have to take on the highest insulin doses, even if they have perfect glucose levels, they are three times more likely to die from heart disease. So giving the type 2 diabetic insulin is a wonderful way to make sure their blood glucose levels are perfect, but killing them faster, which is not the solution to the NHS's problems. All right.

Now, within this grand scope, to step back out and look at the plagues of prosperity again, these are only modestly affected by elevated glucose. So glucose is a modest contributor to these problems, if it's a contributor at all. In some of them, it isn't, directly.

But what is directly contributing is the high insulin. It is no surprise, then, that if our therapy is based on increasing insulin, we're killing them faster. We're killing people.

Let's go back to the base cause. If hyperinsulinemia is the primary cause, then lowering insulin needs to be the solution. And we do that through the food we eat.

And that's all a matter of managing macronutrients. This is the way people eat around the world. And to my great pleasure, I've been able to give versions of this lecture, not quite as specific as I'm giving now, in countries around the world.

Southeast Asia, Asia, Middle East, where the problem is even worse than it is in Europe and in the US or in America. These are the macronutrients. Now let's see how these affect insulin.

This is what happens when a person eats pure fat. This is what happens when they eat pure protein. And this is what happens when they eat pure carbohydrate or in the form of glucose. This is a direct reproduction of data, mind you. I just literally made this by superimposing it on the figure.

You can't quite see the, oh, you can't, you can see it. I can't, mind you. Yes, you see the PubMed ID number.

This is what happens. Anyone who tells you that insulin increases, that fat consumption increases insulin does not know what they're talking about. I've literally never seen a study that has shown that.

I don't know where that conclusion would come from. I've done some of these studies myself and will be publishing some. This is what it would look like in a different view. The effect of insulin with the various macronutrients or the effect of the macronutrients on insulin. Now, it may seem like I'm just declaring war on carbohydrates and I'm not.

The type of carbohydrate matters enormously, of course. But this is part of what plays into the justification on one side or another, whether the person knows it or not. For an insulin resistance scientist who acknowledges that hyperinsulinemia is the primary contributor, one of these versions of the diet, whether it's low-fat and high-carb, or whether it's low-carb and higher-fat, one of them is going to work better at removing the most offending agent here.

And my earlier version of this lecture, I was going to go through multiple studies. That was just a little too burdensome. Indeed, PHC has some wonderful graphics. And link that actually highlights a lot of these studies themselves.

So you can I just refer you to the phc.org Alright now this is one study though that took individuals and had them overeat carbohydrates Which let's face it is what most people are doing right in the global diet 70% of the calories are coming from carbohydrates. That's quite a majority This is so this is what happened over seven days in a fasted state I'm already showing you the glucose levels now. However, if we were to add on the insulin This is what happened to the subject's insulin levels over the same length of time. By the end of the week, in a fasted state, mind you, their insulin levels at a fasted state were 2.5 times higher than they were at the beginning of the week, just by overeating carbs for a week.

This is insulin resistance, normal glucose, and hyperinsulinemia. Now this is how, when we eat these macronutrients, there is a corresponding blood molecule. With fat, triglycerides would be the blood marker of fat consumption. Perhaps, actually, triglycerides, it's more complicated. Amino acids would be the blood marker of protein.

And then lastly, glucose is the blood marker of carbohydrate. In diabetes, type 2 diabetes, which is just a prolonged insulin resistance, which of these nutrients in the blood is the body struggling with? Actually, it's a little more complicated than I'm mentioning, but what's the one that we obsess over?

Well, of course, it's the glucose. And no surprise, that's the thing we're eating the most of. So I submit to you there are three pillars. If lifestyle is the culprit, it's also the cure. The food we eat is causing or can cure these metabolic issues.

And we could expand this to add a lot more. But first one, control carbohydrates. And by that I mean, my suggestion is... Look at the amount of digestible glucose compared to the amount of fiber that would come with it. If it's relatively low, if the fiber to everything else in there is high, then that will be a carbohydrate that's generally going to be good.

Fiber will mitigate some of the glucose absorption and thus the subsequent insulin spike will be about 30% or so less than it would be otherwise. So control carbs. My suggestion, focus on whole fruits and vegetables. as primary sources of carbohydrates.

Whatever the carbohydrate desire is to eat, focus on fruits and vegetables. Next, prioritize protein. This must be, if you're prioritizing the best protein for the human body, or any animal whatsoever, it will be, because even ruminant animals will digest the protein very differently, but we humans, we need it in our monogastric system, we need it to come from animal sources.

Every metric. an animal source will have superior absorption and without the complications of a plant source protein. There are technologies that are improving plant source proteins but we are built to eat other animal and animal source proteins. Prioritize the protein. It's a modest insulin effect.

Now in nature protein never comes alone. In our hubris and in our fear of fat we've pulled it apart. But protein always comes with fat in nature. There is truly no exception to this.

If it's a natural protein, fat comes with it. That's how we should eat it. Not only do we absorb the protein better, but because we digest it better. Most people don't appreciate that.

That we think we have proteolytic enzymes in the intestines coming from the pancreas that will split up the proteins into small enough units so that we can pull it across our intestines. But those proteolytic enzymes don't work as well. without bile.

bile enhances the ability of the intestines to digest protein and we only have bile getting released into the intestines when we eat fat they should always come together do not fear the fat that comes with the protein and I would even say be liberal with adding some fat to your protein if not you know eating the fat alone perhaps okay so then don't fear the fat now as I wrap up and I just got done hopefully sharing with you some of the good news That as much as my talk has seemed a bit like a horror story, it's a happy ending. Which is that if we look through the lens, through an insulin-centric lens rather, we appreciate that we just need to lower the insulin. And we do that by managing our macronutrients.

Controlled carbohydrates, prioritized protein, don't fear fat. And I could have added frequently fast to keep my alliteration going. But that would be a really helpful way to lower insulin and literally cure the problem.

Removing the medic, keeping the medications. tucked up in the medicine cabinet until they expire. All right, so how can we measure it? There are different ways to measure this, and I've lumped them into two categories.

And for the sake of time, I'm not going to talk about all of them, but there are dynamic measurements and then static measurements. And of course, the static measurements are easier. The dynamic measurement is a two-hour oral glucose tolerance test with insulin being measured at the time points. I'm not going to talk about it. because it's so uncommon to get it done, but the easiest way to interpret it, in hindsight now, I should have put this image in here because I have it and it's lovely, but I didn't think I'd talk about it.

If the peak of the insulin is at 30 minutes and every subsequent point is lower, that's a good sign. If the peak is anywhere except anywhere outside of 30 minutes, if the peak is an hour or 90 minutes, that's a problem. It's a warning of insulin resistance.

All right, now again, it's not easy to get those done. no matter where you live. So let's talk about end with the static measurements.

So there is the list and I just want to highlight the ones that I think are the most telling. The first one simply being measuring insulin. I hope I got my unit conversion correctly going from the micro units in the US to the picomoles here but if fasting insulin is lower than around mid-30s picomoles that's a very very good sign that I believe.

David? Yes, I need a GP here to kind of confirm. But that would be a good sign that insulin levels are in a healthy, low range, and the body is responding well to it. In other words, the body is insulin sensitive.

But at the same time, there is another molecule called C-peptide that comes in the nanogram per mil range, very, very low range, mind you. But this, sometimes, I only mention this because I've seen how it gets confused with insulin levels. C-peptide is not insulin. But they are sister molecules. That when they're born, they're born as twins.

They come out of the beta cell into the blood one to one. Now, hearing me say that, every time the beta cell releases an insulin, it releases a C-peptide. That is true. You may be tempted to think, well then let's just measure C-peptide.

But you can't. It has a very, very different half-life. C-peptide sticks around in the blood much, much longer.

So me mentioning C-peptide isn't intended to be... a diagnostic measurement of insulin resistance, but rather illustrative for the patient or the clinician to know, is this a person who's making insulin on their own? Because if you have a type 2 diabetic patient who is on insulin therapy, then measuring insulin won't work because you're just as much measuring what's coming from the syringe as you are what's coming from their beta cells. But C-peptide is only made from the beta cells.

So I cite this. Because if a clinician is wanting, or the patient is wanting, to get off their insulin therapy, you need to know, are the beta cells actually making insulin? C-peptide will be the confirmation.

That's the proof positive. This is a person who can graduate out of their insulin treatments onto just a dietary regime. And then next, I have the HOMA, homeostatic model assessment, H-O-M-A, the HOMA index.

Generally, we want that number to be around 1.5. And the value of HOMA is that it takes both insulin, it takes fasting insulin, and fasting glucose into its equation. And again, if the answer, if the solution to that little equation, and you can find it online, there are HOMA calculators here in the UK too, for UK units, then you know this is a body that is insulin sensitive.

If the HOMA score is getting up to around 3 mid-3s, that's insulin resistance, and then beyond that is typically just going to be full-on type 2 diabetes. So the HOMA score is a very good one, and one I recommend. Now, as I wrap up...

And I show you this wheel of misfortune in some kind of bizarre game show version. There are four key things we've discussed in the time we've had together. We've talked about what is insulin resistance, where does it come from, what to do about it, and lastly, how to measure it.

With this information, in all humility, I believe that you are, and we are all collectively, well-armed to not only understand this problem, have the emphasis be appropriate, and know how to solve it. And it won't be from popping another pill. Thank you all for listening.

And during the panel, I hope you'll submit a load of questions because nothing thrills a professor more than getting a lot of questions. Thank you all for listening. Thank you so much.

Thank you. Thank you. Thank you.

We've actually got time to take one. That's okay. We'll take one question. Okay, yeah.

I've got it right here. Right, well, Ben's done wonderfully on timing. Thank you so much. Can't wind nerves. We've got time to take one question, which I'm going to put to...

Hey, Sean. Good morning. And...

Yes, that is from Katie Whitehead. Where's Katie? There she is.

Excellent. So do you think there is value in the suggestions of Jesse and Chapsy, the glucose goddess, who's written about hacks to flatten glucose spikes? For example, vinegar, vegetables first, when you're eating and timing your exercise and things like that.

I do. Yeah, so I actually wrote a little blurb for her first book. Because I really appreciated her sentiments.

Yeah, so she and I have communicated quite readily. Yeah, apple cider vinegar is one that I'm fascinated by. The effects of those. And vinegar, we don't commonly think of it as a fat. But it is.

It's the shortest of the short-chain fats. And short-chain fatty acids, which we don't eat them normally. It only comes from a process of fermentation.

But taking milk. which doesn't taste sour and allowing it to ferment which now tastes a little sour is in nature or taking cabbage and then turning it into kimchi now it's quite tart and sour those are short chain fats those hit the mouth and activate these bitter taste receptors anyway that's a long-winded way of coming back to apple cider vinegar short chain fatty acids are metabolic very metabolically active molecules and aggressively enhance insulin sensitivity in the body so jesse's reasons for mentioning apple cider vinegar are very very well justified so i i really appreciate her um sentiments she's a more glamorous version of a guy like me i make no claims to divinity after all like she does excellent all right well thanks again thank you so much

Transcript for:Insights on Insulin Resistance and Health

Transcript for:
Insights on Insulin Resistance and Health