Transcription
Good afternoon, Mountain Time, to anyone tuning in for this week's Metabolic Classroom here at InsulinIQ.com. I am, as always, delighted to be able to share with you guys some of the scientific musings that have been bouncing around in my brain. And of course, as always, I'm just your friendly neighborhood scientist, um, not giving medical advice.
But today, it is definitely a very medically minded topic, um, as have the last two topics. Just generally, as we've been discussing the most common health problem worldwide, namely insulin resistance, what it is, and where it comes from. In today's topic, I want to discuss more in the time we have together during this classroom session on, um, the consequences of insulin resistance. So, why it matters, really. Um, because if insulin resistance were its own isolated problem, we wouldn't care. I certainly wouldn't have devoted my career to understanding it. Um, but in this case, uh, now, when we really appreciate how insulin resistance contributes to so many chronic diseases, or what I like to refer to as the plagues of prosperity, we really begin to understand, um, why insulin resistance is so important, why we need to be talking about it as often as we are, or more often, depending on who's speaking.
And if they're not talking about it often enough, you guys, as I get started, let me just share one very personal, uh, announcement. Um, I have a follow-up book coming out called "How Not to Get Sick." And right now, being June, uh, July, rather, uh, sorry, January, January 24th to 26th, um, today being January 24th as I record this live, and for the next, uh, two days, you can actually pre-order it for 25% off at Barnes & Noble.com. Now, you have to have one of their free memberships if to take advantage of this, but you just use the discount code PREORDER25 at checkout. And in doing so, gives you again that 25% off the new book, "How Not to Get Sick." And "How Not to Get Sick" is really just a follow-up, a companion to "Why We Get Sick," just with a much deeper dive into the, uh, approach, into the solution, which is in the Metabolic Classroom. Something we're going to be talking about next week. So you'll get a little bit of a primer version of that book, if you will, but all just like style changes, um, de-diving deep into the science of it, um, to support it and justify it in the evidence, and then get really direct and clear with some of the advice and the strategies that you can do, um, that you could take advantage of to prevent or reverse insulin resistance. So again, that's at Barnes & Noble. Um, the team will put a link, um, to that, um, for for me in the chat here, and then you can find it there. And again, the discount code is PREORDER25 for "How Not to Get Sick" only for the next two days.
All right, so as I mentioned a moment ago, the topics that we discussed in the previous two episodes are defining insulin resistance, to really create, uh, a cohesive and clear definition of the problem. And just to recap that, it's that insulin resistance, and this is important for today's discussion, insulin resistance is a problem with two parts. There's two aspects to this condition that we call insulin resistance. The first being the fact that the hormone insulin isn't working very well. The, uh, some emphasis on some, some cells of the body are resistant to insulin's effect. Now, at the same time that's happening at certain cells of the body, within the entire body, at the whole body level, blood insulin levels are higher than they were before. So insulin isn't signaling entirely properly throughout the body, and insulin levels are elevated in the blood. The precise term there being hyperinsulinemia.
Now, again, those two definitions do matter when we start going through some of the consequences of insulin resistance. You'll begin to see that in some instances, the disease that is, uh, contributed or affected by insulin resistance is a compromise, is an effect of the compromised signaling. Or in other instances, it's an effect of the hyperinsulinemia, and there's just too much insulin. Um, in another instances, it's both. So, we'll, uh, it's very helpful to remember that definition. And then in the second, um, lesson that we did last week, uh, we really discussed the origins, and I highlighted the secondary, um, causes and the primary causes, and I explained how I'm defining those two, or classifying them.
All right, now let's move into the topic for today, which is why does insulin resistance matter? Um, there are just, for the sake of the discussion, um, this is of course something I discuss heavily in my book, "Why We Get Sick." Um, all of this month's Metabolic Classrooms are essentially just various, um, kind of rehashed and simplified versions of what I dive into in the book. But each of these brief, um, disorders that we cover is worthy of not only its own chapter in a book, but also its own book. There's so much material. So you'll have to, um, forgive me for really being a little simplistic in how I'm describing some of this, but it will be more than adequate for you to appreciate the impact, why insulin resistance matters, and hopefully, my hope for all of these lessons, it enables you to go teach someone else. That's not something I've discussed very often, but one of the reasons I take such pains to create my lectures, my presentations, the way I do, and to even articulate certain ideas the way I do, is my hope that it, it is memorable, and that you can share that information yourselves.
All right, so let's just start with diabetes, type two diabetes, because that's the most obvious one. And in, in the end, ultimately, that's the one that, that's the original relationship that brought me to study, uh, insulin resistance. I looked at insulin resistance as the great mediator between obesity and type two diabetes. It is, in fact, and that's not wrong. It is the connection, it is the bridge that brings together these two, um, problems, these two metabolic problems. One very obvious in the form of weight gain, one less obvious, but, but very, um, impactful when it comes to just longevity and health. So the bridge being insulin resistance.
Now, I've, you've heard me say this before, including, uh, last week, where, um, there is a debate within the realm of type two diabetes of which tissue becomes insulin resistant first. Remember, at its earliest stages, insulin resistance is a metabolic state where glucose levels are normal. Remember, we're not talking about type 2 diabetes, which by conventional clinical perspective is defined by elevated glucose. It is defined by its glucose, which is, as I've alluded to before, one of the reasons why we catch it so late. We wait until the glucose starts to climb, when in reality, for years or even decades before that, the insulin has been elevated, and it needs to be elevated. It's working harder as the body becomes resistant to it, in order to keep the glucose in a normal range. So this is insulin resistance, namely high insulin, normal glucose. And this is type two diabetes, which is high glucose now, and very often still elevated insulin. In some instances, the insulin can start to come down, um, but that's not a universal phenomenon with type two diabetes. Just as often, in fact, more often than not, it stays higher than normal. Even if it comes down from when it was at its peak, it's still multiples higher than it was before the disease progression ever started.
All right, now I had mentioned the debate within the scientific realm of which tissue becomes insulin resistant first. Some say the fat cells, like I do. Some say it's the muscle. Some say it's the liver. The problem with invoking the muscle or the liver as the first tissues that become insulin resistant is that if they become insulin resistant, glucose levels essentially cannot stay normal. They must begin to climb. This is why I put them after the fat cells. Fat falls first. And so we have this fat-first focus when it comes to understanding insulin resistance. And then as the fat becomes insulin resistant, or falls, if you will, using this kind of metaphor of, of it's like, uh, insulin resistance is dominoes tumbling into each other. The first one falls, we push it, that's the fat cell, and then the other ones begin to become insulin resistant.
So there are three specific tissues I'll just highlight as briefly as I can for the sake of time to get to the other problems I want to discuss, um, and that is muscle, liver, two I already mentioned, and the alpha cells of the pancreas, one that is totally overlooked as a contributor to type two diabetes. So when the muscle becomes insulin resistant, the body will have a substantially harder time controlling glucose. And that is because, for obvious reasons, by mass, most of what we're made of is muscle. By tissue mass, I mean, most of us is, we're made up of is water, but if we just look at tissue type, mo, most of us, most of our body is made up of of muscle tissue. And as we get fatter and fatter, of course, then adipose tissue can sort of pass that. But muscle is, in most instances, the most dominant tissue on the body. And it's no surprise, um, that it then is the biggest consumer of glucose. When we eat something that is starchy or sugary, and we see our glucose levels going up as we're wearing a CGM, and then as it starts to come down, 80% of what's bringing it down is what, what's being pulled into the muscle. And so if we start to have muscle that becomes insulin resistant, now insulin can't open those glucose doors as well as they did before. Now we have a harder time bringing down the glucose. So at any given moment, the glucose may be a little higher than it was. It certainly will take a lot longer to clear the glucose. And then potentially, even after we've cleared the glucose, we still just struggle to keep the glucose in a normal range, even in a near-fasted state. So that's muscle. If muscle becomes insulin resistant, it can't clear glucose as well from the blood.
Now, second, the liver. The liver is more relevant in that non-eating phase where normally, when insulin is elevated, it will tell the liver to take in glucose and store it as glycogen to be shared later. But that process is dependent on insulin working well. This process of activating what's called glycogenesis, is the formation of glycogen, which requires this moving in of glucose, thereby lowering glucose levels in the blood. Now, unfortunately, as the liver becomes insulin resistant, even though insulin may be trying to keep its handle on maintaining glucose in the, in the liver, by, by keeping it stored as glycogen, insulin can no longer, um, well, there's two parts I should say this. Insulin is not only activating glycogenesis, it's inhibiting glycogenolysis, the breakdown of the glycogen, thereby keeping the glycogen all stored up. So this kind of net intake, net influx of glucose into the liver. However, as the liver becomes insulin resistant, both of these processes is, is broken or disrupted, if you will. Not only does the liver not know what to do with glucose, so it can't bring as much in because it's compromised in its ability to make glycogen, but also it begins releasing glycogen in as glucose into the blood, even if insulin is elevated and it shouldn't be doing it. Normally, insulin would be telling the liver to keep the glucose stored as glycogen, keeping blood glucose levels low. But this signal gets broken or disrupted, and now the liver begins breaking down glycogen because it can't hear insulin's efforts to stop that from happening.
All right, now those are two big tissues, and it's pretty simple in how they work. The alpha cell process is a little more complicated. Now, within the pancreas, in these micro environments, these little kind of islands or these little pockets of cells that are always clumped together, we have the beta cells, which produce insulin, and right next to them, we have the alpha cells, which produce glucagon. And you've heard me discuss glucagon before, but for those who are a little new to all of this, glucagon is insulin's opposite. Whereas insulin wants to lower blood glucose, glucagon wants to increase blood glucose, primarily by acting on the liver by stimulating glycogenolysis, um, the process I just mentioned that gets, starts to fail in insulin resistance.
So the, in this instance, in this micro environment, you know, these are two opposite hormones. The body isn't going to want both of them to be elevated at the same time, or both of them to be down, because they're doing opposite effects. So if one is active, the other one needs to retreat in order for the other one to do its job. Then as the other one retreats, then this other hormone knows it's its turn, it's that hormone's turn to come into the spotlight and have its effect be heard, if you will, throughout the body. The way that happens where you don't get both elevated at the same time is that insulin elicits an inhibitory effect on the alpha cell. So when insulin is coming out of the beta cell, it tells the alpha cell to inhibit the production of glucagon. That allows the body to have the elevated insulin. Now, of course, if blood glucose levels climb after a meal, that's just what we want. Insulin gets stimulated because of the high glucose, and it turns glucagon off by inhibiting the alpha cell's production of glucagon. But then as blood glucose levels go down, insulin's primary stimulus is gone. So insulin comes down, and now glucagon can finally wake up, if you will, and do what it wants to do, namely, make sure blood glucose levels stay at a normal rate, even if glucose isn't coming in, or at a normal level.
So with all of this in mind, what happens is the alpha cell becomes insulin resistant. So even though blood glucose levels may be elevated, even though insulin may be elevated, its ability to squash the release of glucagon gets compromised. And now glucagon starts to climb, telling the liver to release more glucose, thereby simply amplifying the blood glucose levels even more, pushing the patient into full-blown type 2 diabetes, which again, is defined classically clinically as an elevated glucose. So that's how insulin resistance connects to type two diabetes, when the muscle becomes insulin resistant, when the liver becomes insulin resistant, and the alpha cells of the pancreas becomes insulin resistant.
Now let's move on, um, to fatty liver disease. The most common liver problem. There's going to be five total problems we talk about. Diabetes was the first one, then fatty liver disease, then Alzheimer's disease, then hypertension, the most common contributor to heart disease, and then infertility to wrap it up at the end. The least lethal of all of them, but one of the more heartbreaking for those who struggle with it, again, infertility being that one.
So with fatty liver disease, um, a lot of people have a bit of a misunderstanding, um, of what the primary contributor is to fatty liver disease, thinking that it's a consequence of the liver making fat within itself. But that is actually a secondary contributor. But let's start with, with it anyway, because that's the one most people think of, and it's not wrong. It is a very relevant contributor to how much fat is in the liver, or the liver becoming too fat. In the case of non-alcoholic fatty liver disease, sometimes nowadays referred to as metabolic associated fatty liver disease, which is a slightly better, more accurate term. We could just call it metabolic fatty liver disease because it is a metabolic problem, or we call it insulin resistance of the liver, or of the body, which may be the best term of all, but a little more cumbersome.
So in this case, when insulin is elevated, it is able to, even if the liver is insulin resistant, I just got done telling you that when the liver is insulin resistant, insulin's ability to control glucose gets broken. That does not happen with insulin's ability to influence fat metabolism in the liver. That continues unabated. It is not broken. Now we have the hyperinsulinemia of the insulin resistant body, and what insulin tells the liver to do is make fat. It activates de novo lipogenesis, which is this really beautiful term for just saying it tells the liver to make fat from scratch from any carbons. It takes glucose molecules very gladly and will turn it into fat. Glucose being the most likely substrate. So it starts making fats and then packaging them as triglycerides and then dumping those into the body as VLDL, which becomes LDL. So insulin will stimulate the synthesis of fat production, or the synthesis of fat, thereby contributing to how much fat is in the liver, fatty liver disease.
Now, again, that is a secondary, that is the lesser of two causes. The primary contributor to insulin, uh, to fatty liver disease is when the fat tissue, the fat cells, become insulin resistant. You may recall when we discussed insulin resistance earlier, one of the reasons the fat becomes insulin resistant is as the fat cells hypertrophy, feel too much, they start to get so big that they begin to reach a limit that the cell membrane can keep together. And so in order to stop growing, lest it pop like an overfilled water balloon, the hypertrophic fat cell becomes resistant to insulin's efforts to block fat breakdown. Lipolysis is that, is the term for that. So insulin, one of the mechanisms, indeed a primary one, whereby insulin stimulates the growth of the fat cell is not allowing the fat cell to break down and release its fat through the process called lipolysis. So insulin normally inhibits lipolysis. But as the fat cell reaches this maximum dimension, that becomes resistant. And so now you have a fat cell that is leaking free fatty acids into the fat, into the bloodstream. Now, those free fatty acids could have multiple fates, but there are two things that are relevant here. One is the blood flow. One is insulin. With blood flow, as you start looking at the circulation of fat, particularly from visceral adipose tissue, it will go to the liver. And so the liver is right at the front end of who's seeing all this fat. Now, the liver has options with what it can do with fat, but if insulin is elevated, it cannot burn it. It must store it. And so therein is the primary source of the fat that is constituting the fatty liver. It is fat that is dripping out of insulin resistant adipocytes, or fat cells, in the presence of elevated insulin. And if insulin is elevated, then the liver has only one thing, again, that it can do with that fat, which is store it. So it takes in those free fatty acids and packages them as triglycerides, the stored form of fat. And then we have fatty liver disease.
All right, let's move on to the third of the five. Hopefully, you're, you're sticking with me and maybe even taking notes. I wish I had a little quiz for you at the end. Third one, Alzheimer's disease. One of the scariest diseases, um, that is plaguing the world these days. Just as an interesting little history lesson. Now, you're going to say, Ben, you're not a history professor. I'm not, um, as much as I appreciate the discipline, um, but when it comes to this biomedical area and Alzheimer's disease in particular, there's something very interesting. You likely have heard of insulin res, uh, heard of Alzheimer's disease as a problem of plaques within the brain. And if so, it would have nothing to do with metabolism. Unfortunately, the evidence has never really supported that. There are two lines, or two, two relevant things here, two phenomena that occur. One is that there can be plaques in a brain. But two, every intervention that's ever been used, every drug that reduces plaques, does not appear to improve the pathology. It doesn't improve cognition. It doesn't fix the Alzheimer's disease. Moreover, studies that have looked at brains and cadavers, people who died with confirmed Alzheimer's, with, with dementia or without, find that there, each brain in each of these populations is just as likely or not to have plaques. That the plaques appear not to really be a contributing, uh, process in the, in the progression and the onset of Alzheimer's disease. So it's not a plaque problem.
Now, to the history lesson. Come to find out about a year or so ago, that even the very first evidence that supported the plaque-based theory of Alzheimer's disease was fabricated. So it was literally all built on a lie, which could be why all of these anti-plaque therapies have always just failed so miserably, because there was never any relevance to them in the first place. Now, an interesting study was published out of Finland a number of years ago. This was what's called a prospective study, so it's following people through time. They found that there were eight variables, if memory serves, I didn't document this ahead of time, but I'm pretty sure there were eight variables that they identified were statistically significant in, in predicting, if you will, albeit by looking back in time, at who would, who would get Alzheimer's disease. Three of them were somewhat expected, um, namely their age. No surprise, the older you get, the more likely you are to get insulin resistance. That's an obvious one. The next one was level of education, which is, uh, somewhat of a comfort, uh, to, to me, uh, may it help me. But more than that, more than what was your terminal, it's, are you continually challenging your brain? Um, that might be another way of interpreting that. And then third, having what's called an ApoE4 genotype. So you have the ApoE4 gene, um, which you've heard of, which results in this ApoE protein, or these plaque-like molecules, as many people refer to them. And there are different versions of the ApoE gene, two and three, which are considered to have a normal Alzheimer's risk. But ApoE4 does have an elevated risk independent of every other variable. Now, that was the third. And I'm going to come back to ApoE4 in a moment. But the other five of the eight statistically significant variables were all metabolic. Every one of them was a measurement of fasting glucose, or fasting insulin, or two-hour glucose with an oral glucose tolerance test, or two-hour insulin with an oral glucose tolerance test, and then just a general insulin resistance score. So of the eight total statistically significant variables, more than half of them were functions of metabolism, specifically insulin resistance markers.
Now, how does that connect to the brain? Within the hippocampus, which is the memory learning center of the brain, and the brain has a lot of distinct regions, the brain has a couple of different ways that tissue, those cell types within the hippocampus have a couple of different ways of pulling in the glucose from the blood. One of those ways is dependent on insulin. And if, if that's, if those cells become insulin resistant, now the brain's ability to pull in the glucose is compromised. And this is detectable at the whole tissue, whole body level. Dr. Stephen Kahn's work has shown that when you measure the amount of glucose being taken in and metabolized by the brain of someone with cognitive decline or Alzheimer's disease, it is significantly less than other than in a healthy, non-dementia brain. And this is referred to as brain glucose hypometabolism. So the brain's ability to use glucose as a fuel is compromised. That's a problem because the brain is hungry. It has a high metabolic rate. It needs a lot of energy, and it needs to be getting it from the blood all the time. So if the amount of energy that the brain can pull in from the blood is compromised because of insulin resistance, it can't just, it simply can't move enough in. Then the brain has starts to reduce its function, and that can manifest as cognitive decline, memory loss. Now, at, in a less severe instance, it can just manifest as headaches, like a migraine headache. Um, migraines are influenced by this too.
Now, let's just come back to ApoE4 before we finish Alzheimer's disease, because there is such a clear genetic risk, um, an Alzheimer's risk associated with having an ApoE4 genotype. What appears to happen is that the ApoE4 lipoprotein actually disrupts the insulin receptor. And so, even as we look at this molecule and we're wondering about the relevance of plaques, what appears to happen is that this molecule itself is disrupting the insulin receptor, thereby making the cells of the hippocampus more likely to be insulin resistant. Insulin simply can't work as well. Pretty fascinating, in my opinion.
Okay, so that's diabetes, fatty liver disease, and Alzheimer's disease. Now let's move into hypertension. Hypertension is important. Heart disease is still the leading killer until it gets displaced, which it may in the next few years. But until then, or even after that, we should still focus on it and appreciate that hypertension appears to be one of the leading contributing factors to heart disease risk. There are four problems that happen here. Um, first one, in no particular order, it's that during insulin resistance, insulin is elevated, as we've discussed. And elevated insulin drives up the levels of another hormone in the body called aldosterone. One of aldosterone's primary actions is to tell the kidneys to hold on to sodium in the blood, to hold on to salt, not let it go. And as salt stays in the body, as the salt is retained, the body will also keep water in order to prevent the body from becoming too salty or too concentrated with these electrolytes. It wants to try to keep them in a certain range of dilution. And so if insulin, via aldosterone, is forcing the kidneys to hold on to salt, water will come with it. And then as body water stays elevated, uh, blood water, or blood volume is elevated. And as volume goes up, so too does pressure. And so elevated blood pressure. Now, that is not to say that eating salt is a problem. It isn't, by and large. It's that your body can't get rid of it, which it wants to do when blood salt levels are up.
All right, let's go to the next one. Once again, this is a problem of too much insulin. And in this case, one of the unexpected actions of insulin is to increase the sympathetic nervous system activity. So insulin increases the sympathetic nervous system, and the sympathetic nervous system, one of its many effects, is to constrict the blood vessels. It wants the blood vessels to get narrower. This is a problem called, or, or, or a process called vasoconstriction. And as you can imagine, if we start to compress all of the blood, there's going to be more pressure. The blood's trying to push back against the blood vessel wall, which is manifested as an elevated blood pressure. This can also make the heart beat a little harder and a little faster. So insulin stimulates the sympathetic nervous system independently. In fact, so too does glucose. Just if glucose itself is elevated, that also stimulates the sympathetic nervous system. So you can see how these two things would start to work together, regardless of the stimulus. If sympathetic nervous system is turned on, even if a little bit, blood pressure will be up.
Now let's talk about a third one, which is also a consequence of too much insulin, namely growth. Insulin acts primarily as a growth signal throughout the body, including at the endothelium. And the endothelium is the lining of the blood vessels. And when insulin is elevated, it's stimulating the hypertrophy of the blood vessel wall. And so as the blood vessel wall begins to hypertrophy, unfortunately, it does not hypertrophy out. It hypertrophies in, narrowing the lumen. It starts to bring the, the lumen, or the vessel caliber, into an ever smaller diameter or circumference total. And of course, just like when the blood vessels are constricting with sympathetic nervous system stimulation, we begin to compress the vessel, which makes the blood push out harder, and thus blood pressure goes up.
Now, the fourth and final connection between insulin resistance and hypertension is not a pro, not an effect of too much insulin, but rather the other part of it, insulin resistance, namely the compromised insulin action. You see, one of insulin's, of overlooked effects, is to stimulate blood vessels, the endothelium, to create a molecule called nitric oxide. Nitric oxide, as it is created in the endothelium, or the lining of the blood vessel, will seep through and tell the muscles around the vessels to relax. And when the muscles around the blood vessels relax because of nitric oxide, then they dilate, and blood pressure goes down. We're expanding the blood vessel. Now, blood has an easier time moving through, pressures lower. And again, all of that happened because, well, in this case, that's the normal effect. Insulin will normally come and induce vasodilation via the synthesis of nitric oxide. However, the endothelium becomes resistant to that particular process. In other words, it becomes resistant to insulin's ability to stimulate the synthesis of nitric oxide. Thus, even if there is sufficient insulin, the blood vessel is not making sufficient nitric oxide, and the blood vessel that should have been dilated, thereby reducing blood pressure, stays constricted, ultimately leading to an elevation in blood pressure. In fact, I'll be very bold here. Most instances of blood, of elevated blood pressure, or hypertension, are a consequence of insulin resistance. And this is why so many people who are taking, um, blood pressure controlling medications, commonly referred to as antihypertensives, that they, this is a medication that, when working with their clinicians, they have to start changing the dose almost immediately when they adopt a low carbohydrate diet or an insulin sensitizing diet. And we'll talk more about that next time, as I'll come back to in a moment.
All right, the fifth and final disorder I wanted to cover is infertility. Most people don't appreciate the fact that the two most common forms of infertility in men and women are at their core metabolic problems. Now, those two most common forms of infertility are erectile dysfunction in men and polycystic ovary syndrome, PCOS, in women. And again, both of them are metabolic. Let's start, but each is a function of one of the two aspects of insulin resistance. So it's a perfect example. On one hand, we have erectile dysfunction. I just got done explaining to you, deliberately placing it this way, that insulin induces the production of nitric oxide, allowing blood vessels to dilate. And as blood vessels dilate, blood flow increases. That is an essential process to normal erectile function in a man. But unfortunately, in some instances, those blood vessels become insulin resistant, and now insulin cannot produce enough nitric oxide, and the blood vessel stays constricted, and erectile function is compromised. Or, in other words, ED, erectile dysfunction, has settled in, all because of the insulin resistance, specifically at the blood vessel.
Now, in contrast, polycystic ovary syndrome is a problem of hyperinsulinemia. One of the more unexpected, and I've already mentioned a couple effects of insulin, is to regulate the production of the conventionally known, referred to as the female sex hormones, or the estrogens. Now, the fact is, both male and female have estrogens. Um, but a little known fact is that all estrogens in men and women were once testosterone, and they have been flipped. They've been converted, um, within the gonads, whether it's testes in men or ovaries in women. It's been converted through the actions of an enzyme called aromatase. Now, I'm really getting deep here, but aromatase is the name of the enzyme that will take a test, a testosterone molecule in the ovaries or the testes, and it will convert it into estrogens, which is a little small family of hormones. So if aromatase isn't working very well, then the reduction, or the conversion of testosterone to estrogens, is is disrupted. Now, naturally, in the female, in the ovaries, that's happening a lot. The ovaries have very active aromatase, converting a lot of testosterone into estrogens, giving the female these typically higher levels of estrogens than what you'd see in a male. And this goes beyond just inherent differences in male and female. A female needs to have a big estrogen spike as a part of her normal ovulatory cycle. Now, I won't, it's a very complicated cycle, unfortunately, so I don't want to really dive into it. I need to have some figures to kind of show you the curves, but suffice it to say, the elevated estrogens, a big spike, is necessary for normal ovulation. The actual act of a follicle, a kind of budding egg, actually coming out of the ovary into the fallopian tubes, where it would meet the sperm and fertilization would occur. So again, for that to happen, for ovulation to happen, she must have a big estrogen spike. But for the big estrogen spike to happen, she must have very active aromatase to create the estrogens for that spike. Unfortunately, insulin inhibits aromatase. Now, insulin will do that to some subtle degree at any point, but when she has insulin levels that are multiple times higher than they should be because of her insulin resistance, now that's happening too much. There's too much inhibition of the aromatase, and so she's unable to convert enough testosterone to get that big spike. And it ends up being too small of a bump, not enough of an estrogen spike to facilitate or enable the actual ovulation of the ovum, or the ovum, or the egg. And so all that egg, and any other few potential follicles, stay in the ovary, creating cysts. And now the ovaries get big, which is very painful for the woman, and she has polycystic ovary syndrome. And again, all because of this disrupted metabolic function in the name of insulin resistance. Pardon my cough.
All right, so that's it. Now you are familiar with the metabolic origins, specifically how insulin resistance contributes to diabetes, fatty liver disease, Alzheimer's disease, heart disease, and even the two most common forms of infertility. And we could keep going because there are more, but that's all we'll cover for today's Metabolic Classroom.
Now, next week, before I get into any questions you might have, let me just remind you, we're going to be talking about ways to measure insulin resistance clinically, what you can do to sort of identify markers of insulin resistance, and then what you can actually do about it. So this is the good news. That these previous three lessons, including today, have been a bit grim, um, really just highlighting how bad the metabolic problem is globally and where it comes from and why it matters. And now it really is the happy ending, which is that this is a problem that you can start to change, and you can start to change it immediately. And same things preventing it, if this is, these are problems you never want to get into, and you're fortunate enough to have avoided them so far. Okay, so that will be next week.