Ben Bikman - Why We Get Sick: The Role of Metabolism in Health

[Music] this lecture is being brought to you in part by the generous Gifts of these sponsors hello and good evening I am so delighted to be here with you this is my first time in Pensacola and I have just been delighted walking around the town and seeing these old buildings many of which are older than the entire state of Utah so it is quite wonderful where which is where I call home I'm delighted to be here and I while I miss the mountains a little bit I can trade them for some warm Ocean Breeze thank

you for coming I'm going to pretend that you're here for me and not just the wine and cheese um assuming you are prepared to be somewhat educated nothing thrills an old professor's heart more than having a new group of students so thank you there will not be a quiz so you're just here to learn and I appreciate that Ken and Michelle uh thank you for the invitation and for arranging this I really am grateful to be here as noted I'm a professor at at BYU in the cell biology Department I'm an adviser for RX sugar

who's sponsoring this as Ken mentioned um my main focus as a scientist is to better understand the relevance of the metabolic health of an individual in their chronic diseases that they may suffer from and it is a problem uh within the United States uh we have determined that up to 88% of adults are considered metabolically unhealthy or as this study quoted they found that there was an alarmingly low level of metabolic Health even in people who were normal weight as much as we want to rely on body weight to try to give us an indication

of where we're at where where we are at metabolically now just by way of orientation you'll notice on my slides from time to time I'll have little numbers in the corner those are the citations of the scientific report that I'm citing or sharing data from so if you ever are inclined to think I'm making it up that will be my defense in the in in the in the court of science all right now it's a very American thing to think America is terrible and I say that as a foreigner um who's come to the most

wonderful country on the planet thank you for letting me be here um but it is a very American attribute to think that America is awful uh people around the world actually don't feel that way as I've traveled and lived in multiple different countries and visited dozens and dozens more even metabolically we're not the worst in fact we're far from the worst as bad as the problem is here it is substantially worse in Asia substantially worse in the Middle East in fact the most diabetic countries type two diabetic countries on the planet are all in the

Middle East and through the Pacific Islands southeast Asia where I did my post-doctoral fellowship why is a country like Singapore trying to recruit metabolically minded scientists because it's even worse they have higher levels of type two diabetes per capita than we do and then even in our own backyard we're not the worst so take some pride that as sobering as the St the statistics are it could be worse and indeed it is now been talking about metabolic health and in the last few moments I was hinting at what I'm referring to but what is metabolic

Health there are Myriad ways we could Define this I submit that one of the simplest and indeed there's a consensus around this ways to Define it is based on the metabolic syndrome you've likely heard of the term metabolic syndrome it has such a lovely ring to it um right there's something so sexy about the term metabolic or metabolism and I appreciate the irony when you're a freckled bald man saying the word sexy you don't expect to hear those words out of a mouth like mine but it is a sexy term and so that term has

been adopted and embraced and it is simply the reflection of this this cluster of complications that tend to come together to some degree or another someone has too much central obesity so their waist circumference is a little too big or their blood pressure is too high or their blood gluc glucose levels are too high or their blood triglycerides are too high or their HDL cholesterol is too low um this to varying degrees you know three of the five depending on who you're asking would constitute someone being diagnosed with the metabolic syndrome however as sexy as

that term is there is a better term better not only because it preceded it but because it is more accurate another Once Upon a Time another name for the metabolic syndome was the insulin resistance syndrome that was one of its first terms but that's not quite as lovely sounding doesn't attract as much attention so the name was changed now insulin resistance has a far greater relevance than just these disorders that tend to come together in fact virtually every chronic disease is in some way either directly caused by insulin resistance or exacerbated by insulin resistance including

the big Killers like heart disease diabetes certain forms of cancer or the most common liver problem fatty liver disease less lethal but perhaps somewhat more heartbreaking include things like infertility where the most common forms of infertility in men and women erectile dysfunction and polycystic ovary syndrome respectively share this common metabolic core where insulin resistance is likely either directly causing it or making the problem worse and then even some that are perhaps among the scariest like Alzheimer's disease or painful like migraines once again have in common with every other problem here insulin resistance as a root

issue now I'm not suggesting that insulin resistance is the only cause of these problems please don't misunderstand me um each of these undoubtedly have distinct unrelated noxious stimuli in other words an individual cause for that problem that is UN that is not shared with any of the others but the fact that they all do have one thing in common does suggest that as much as we're trying to shoot multiple targets to address all of these diseases we should at least be spending some of our ammo on the common Target that should be the biggest if

we're looking at it correctly all right now up until this point I have instilled in you a great fear of insulin resistance and I'm cognizant of the fact that you may not really know what it is let's define it in in order to understand insulin resistance let's start at the level of a cell within the body now this could be literally any cell in the body because literally every cell in the body has insulin receptors now I'm a college professor so I know how kids use the word literal these days and when I say literally

I'm not using it too liberally I mean indeed every single cell of the body has an insulin receptor from brain cells to bone cells lung cells to liver cells and everyone in between so insulin will be flowing through our bloodstream and it will come and knock on the door of a receptor on the one of the receptors on that cell and a receptor is like a door that is specifically designed for whatever the hormone may be in this case insulin so there's an insulin receptor insulin will come and knock on the door now because every

cell has an insulin receptor what insulin does can vary tremendously so just to accommodate every cell I will just say that insulin elicits an action whatever it may be and it will differ based on the cell insulin's most famous action is to control blood glucose or blood sugar levels now I'm being very deliberate with my language not its most important because insulin does a number of fantastically important things that are more important than controlling blood sugar levels that is the most famous effect so the most famous effect is that at some cells of the body

like muscle cells or fat cells not every cell some cells insulin will knock on the door and then other doors will open allowing the glucose to come rushing from the blood into some of the cells of the body again that's the most famous effect and that can matter clinically now over time some cells of the body start to resist the signal they're not responding as well to insulin as they used to that is the insulin resistance part of this definition although it's not complete yet but as a result of this it's no surprise that the

most famous effect isn't working very well anymore and whereas a little bit of insulin was sufficient to keep blood sugar levels at a normal level now that the cells some cells aren't responding as well to the insulin the blood sugar levels start to go up eventually and this becomes of course a very obvious clinical sign of the problem albeit late as I'll come back to in a moment now at the same time if this given amount of insulin is insufficient to elicit the action that the cell is wanting that the body is wanting to maintain

normal function or homeostasis as we would say in the realm of physiology if that amount of insulin is insufficient well then the body can make more insulin and what was once one polite molecule of insulin knocking on the door becomes an angry mob pounding on the cell all in an effort to try to take what is now a diminished action and restore it to the robust action that the body is looking for all right now in the midst of this definition I have actually discussed two aspects so insulin resistance is a coin with two sides

one side of the coin is the obvious phenomenon where some cells aren't responding to the hormone insulin as well as they used to that's that's the obvious part of what we call insulin resistance but there's a less obvious but equally relevant part of this as we flip the coin over and that is if we move out of the level of the cell and en Encompass the entire organism the body now we determine that blood insulin levels are significantly higher so this is essential there is no such thing as insulin resistance without hyperinsulinemia or in other

words elevated blood insulin these two things will always come together in every instance of insulin resistance now the Paradigm that I've presented actually has planted this directionality in your minds which is that insulin resistance is leading to the hyperinsulinemia that is not wrong but it's not complete we're going to come right back to this Paradigm in just a few minutes all right now let's shift the Paradigm even more oddly and look at an individual over time who is slowly experiencing an increase in his or her blood glucose levels and they're becoming ever more and more

Diabetic Type 2 diabetes is a disease defined by the glucose that is the clinical diagnostic it is purely based on blood glucose levels interestingly it is purely a problem of insulin resistance as I'll show you now this is what the glucose looks like however if we were to superimpose insulin it would look like this if we had a clinician who was aware enough of the problem or a patient who was aware and insisted sufficiently that we should also measure insulin we would get a curve that would look like that and you can see they do

not run together and this is on the time frame of years so we're following the person through Decades of life now there are two perhaps among more time points here that I believe are relevant this first time point is insulin resistance when blood glucose levels are normal thus flying under the clinical radar which is based purely on looking at glucose but blood insulin levels are significantly elevated this is a state that can last for decades and then eventually the body starts to become so resistant to insulin and or the insulin production starts to come down

a bit but never going to zero if this is type 2 diabetes they start to move into type two diabetes so type two diabetes is when the insulin is still elevated but so two is the glucose now the problem with the conventional clinical Paradigm is that we have a glucose Centric view of metabolic health and that's not wrong it's okay for our perspective to Encompass glucose but if we are doing so at the expense of overlooking insulin then we are missing the early metabolic signal the canary and the coal mine that could have warned this

clinician and patient that there's going to be a future problem would have come from encompassing or having our clinical view be more insulin Centric on the problem that makes sense if we appreciate that type 2 diabetes is in fact the disease of insulin resistance and all those other chronic diseases are also derivative of insulin resistance well then let's look at the insulin all right now you have a pretty good understanding of what ins insin resistance is and even this somewhat unique view of how insulin resistance progresses into one of the most common metabolic and lethal

diseases type two diabetes let's discuss for a few minutes where insulin resistance comes from what are the origins so this is now the the horror story as we talk about insulin resistance and this is how it becomes how it breaks bad how the how the villain kind of come where it comes from the origin story all right so where does it come from I have I i' like to use the word that there are primary and secondary causes of insulin resistance so for the sake of time we'll only discuss the primary causes and by primary

I have a very strict set of circumstances that must be met in other words these whatever is qualified as a primary cause of insulin resistance must be capable of causing insulin resistance independently of any other signal but also having been validated or shown in all three commonly used biomedical models from cell cultures so growing little cells in a Petri dish from rodent models mice or rats which are very helpful for scientists to be able to use and humans The Pinacle of all creation if we can DET we can detect this working in all three levels

then we've met the criteria and it is a primary cause so what are the primary causes I submit that there are three stress it'll be interesting for you guys to come next week to hear that talk about stress inflammation and hyperinsulinemia so you can already see how're we are revisiting that one and indeed it is worth revisiting because it is the big one it is the one that matters most now let's nevertheless just review the top two briefly and we'll spend a little more time justifiably on the last one so by stress understand please that

you are hearing that word coming from a professor who teaches a graduate class in endocrinology I can't help but look at human health through the lands of hormones it is my favorite subject and so I Define stress I look at stress as an endocrine phenomenon or a hormone-based phenomenon and these are two hormones that you're probably very familiar with you're all very familiar with cortisol um it is a widely accepted villain not entirely fair but that's how it's viewed and then epinephrine sometimes known as adrenaline which you perhaps are more familiar with these horon hormones

actually have practically nothing in common they come from different cell types they're created on in very different ways they're transported through the blood in completely different ways they act on target cells in completely different ways almost the only thing they have in common is that they both seek to increase blood glucose and do so very very quickly so if cortisol goes up blood glucose will follow very quickly if epinephrine goes up glucose will go up as well even more quickly than with c that is the one thing they have in common but you can see

that begins to put them at odds with insulin who is now struggling and working harder and harder to push glucose down and so the more these stress hormones are eliciting an upward pressure on the blood sugar the harder insulin has to work to push it back down thus we have a state of insulin resistance now what about inflammation if some of you are going to be diligent students and look into some of these papers you'll find some of mine in there this was largely the focus of my entire postdoctural fellowship with Duke and we followed

it up in some ways that I'll mention here but anytime cyto kindes are elevated the body will become less insulin sensitive or more insulin resistant now cyto kindes are basically hormones that signal inflammation the activation of the immune system which we of course need none of these things are bad stress is not bad we need stress or we would be dead as a species and an animal as is a life form we need inflammation otherwise we'd be dead we could never defend ourselves or heal and recover the these are all essential it's just too much

of a of a good thing if you will in the case of cyto kindes these Pro these these inflammatory kind of signaling hormones this doesn't just happen when the body is sick although it matters if someone has a cold or a fever or a flu if they're wearing a continuous glucose monitor or they're diabetic they will find that they have to treat themselves with much more insulin they become insulin resistant but less obvious instances also apply here like when fat cells get too big they become very pro-inflammatory and it was tremendously difficult for me not

to include that in this lecture because most of the cells I study is fat cells I'm a fat scientist but I figured I just that would be a tangent too big and so I would lose you forever and and I would and we would gleefully be skipping down that rabbit hole for the entire night because it's such a cool topic but diesel exhaust particles as they are inhaled we just published another paper on that topic cigarette smoke induces inflammation that causes insulin resistance and autoimmune disorders it's what's interesting one of these studies I'm citing shows

this autoimmune diseases will EB and flow and they'll they'll be really aggressive and active and then they subside and they're quiet for a time as the autoimmune disease is turned on or off so too is the insulin resistance it tracks very very closely all right now now third and final is the hyperinsulinemia anytime the body has too much insulin for too long it becomes insulin resistant at first glance this it looks a little odd or it sounds a little strange but at Second Glance there is generally a nodding of the head and an acceptance of

it because this is reflective of a fundamental biological principle an incessant stimulus will result in a resistance to that stimulus this is actually something that I believe is far more relevant than just the I believe this applies to every aspect of our life if we are are exposing ourselves to something too much we will become resistant to that thing for better or worse um and often For Worse unfortunately but even to the point of like addictions and habits uh it's it's the constant stimulation and then the the the sensitivity to the stimulation goes down and

so now you need more of it the cell is no exception when it comes to insulin too much insulin or the body too much insulin will make insulin resistance now why do I focus on this and why do I believe that it is the most relevant let me just present to you at first what is an uncommon Paradigm let's imagine we have an uncommon individual who is in fact ignoring the conventional dietary advice and only eating three times a day because we've been told to eat five or six times a day um so so let's

say we have an uncommon individual who's only eating at the three standard meals during the day and this is what their insulin levels would look like somewhat you can see it spiking up and it takes even in a very insulin sensitive person a 20-year-old college aged male the most insulin sensitive person on the planet is going to have an insulin that would still take about three hours to come back down and so and if a person in fact I'll get I don't want to get ahead of myself so this is an uncommon person let's look

at a slightly more common person still very insulin sensitive so the body gets a glucose load by eating something starchy or sugary insulin will Rush up to try to clear the glucose out and then insulin having done its job will go back into the background or get cleared out so this is what it might look like in the person only eating three times a day now again most people don't do this unfortunately in the wake of such an significant insulin Spike often comes hunger and so what most people do after having a very starchy sugary

breakfast well they need a starchy sugary midm morning snack and then they need a mid-afternoon snack and then they need an evening snack because you just have to have a few bowls of cereal or popcorn or ice cream at the end of the day but even still this is an uncommon response because this is an insulin sensitive person and most adults are not very insulin sensitive if we were to take the same eating strategy and look at what the insulin levels are like in a person who's insulin resistant then all of a sudden they never

come down the average person is in a constant state of hyperinsulinemia every waking moment of the day and several hours into their non- waking moments into sleep and one of the worst things you can do as a brief aside and for the sake of time I cannot do too many of these um is go to bed with hypoglycemia if you go to bed with the blood sugar levels elevated while insulin's trying to bring it down you activate your sympathetic nervous system you make yourself hotter you're sweaty you make your your heartbeat harder and faster and

you're lying there wondering why you're so an why why am I so anxious everything's fine everything is fine you just induced a an acute kind of diabetic State and now your sympathetic nervous system is active so good luck trying to calm down it's not going to work until you clear that blood sugar out which will be about 1:00 am. so anyway let's come back to this the way I presented this earlier I presented to you the idea that as the cell stops responding to insulin the body compensates by making more but now I've shown you

that if there is more insulin it can contribute to the diminished response so this very much becomes a vicious cycle that we have to break now as much as this has sounded like a horror story you can break it um and in fact you can break it exceptionally quickly insulin resistance can become totally reversed not only in many people within weeks but there are full-on type 2 diabetics in insulin whose insulin resistance is so severe they can't control their blood sugar anymore who can get off every medication in just months literally reversing their disease all

right now how can you do it the two primary ways of doing it is through drugs that's the conventional way you already can tell that I'm not an overly conventional fellow um but also diet which is less popular to talk about now for the sake of drugs um I'm going to I have to unfortunately present this somewhat through the in the context of typee two diabetes um just because if it's an anti-diabetic drug which is the how that class of drug would be called generally it is only really helping if it's solving the insulin resistance

so let's just take a little time to talk about these anti-diabetic drugs this these are the most common metformin glp1 agonists sglt Inhibitors thadine diones sulon uras and insulin for the sake of time we won't talk about all of them but just to look at any drug when you were putting this foreign substance in your body what you have to appreciate is that you are picking up the stick and you're going to pick up both sides of this stick even though you might only have wanted to pick up one or to say that all another

way you must balance everything that happens when you put this thing in your body is going to be a consequence so it is are the consequences I want worth the consequences I don't want and unfortunately in many of these instances it is very much on the right side of that maybe I should have swapped it um all right so this is my own kind of classification of these drugs and and very very briefly metformin is the most widely prescribed anti-diabetic drug on the planet and for good reason it actually works pretty well at improving insulin

sensitivity so it actually is improving insulin sensitivity and thus improving blood glucose levels and generally improving the metabolic health of the person even still as effective as this drug is there can be substantial GI problems which is why people generally stop it if they do even still even modest lifestyle changes are capable of two times the Improvement of Metformin at improving metabolic health and then a final thought on Metformin that gives us some pause and why I can't give it an a grade is that it actually partly works by being a mitochondrial poison now that's

Dr IC thank you for giving me that somewhat of gasp response um I am a professor who has to keep 20-y olds entertained so you can tell my lecturing style has been somewhat informed by the Temptation of students to look to social media if I get too boring but nevertheless metformin does affect the ability of the mitochondria the PowerHouse of the cell to work well it inhibits its function and this becomes a problem in muscle and this is then no surprise that in human studies they find that if a human exercises the mitochondria get a

little better and bigger and stronger if they exercise and take Metformin it wipes it out completely so if you have been told thank you than if you have been told if you've been told to take Metformin to improve your diabetes and and you're being told also to exercise more one of those is directly negating the other yeah pretty sobering all right now what about glp1 agonists you guys have probably heard of wovi and O this is a drug that people are even bragging about I've never seen anything like it now what about gp1 agonists glp1

agonists are taking advantage of this incretin hormone incretin being a hormone that comes from the guts and helps regulate blood sugar the most famous being glucagon like peptide 1 gp1 again this is the most famous class of drug on the planet at the moment um it is ridiculous how much um how popular these have become now the at the lower dose of of the gp1 agonists which was the is the drug OIC at the lower dose although even that dose has moved up a bit over time the main mechanism of action is that it it

lowered the level of a hormone called glucagon and glucagon is insulin's opposite whereas insulin wants to lower blood glucose glucagon wants to to increase blood glucose and because glp1 agonists when they inject that in it's inhibiting glucagon so it's bringing down this hormone that's trying to increase blood glucose levels does that make sense so by inhibiting glucagon it's lowering the glucose that is in the blood thereby improving the diabetes and when this drug first came out at that lower dose I actually said I can I can get behind that which is why I kind of

give it a slightly green color unfort fortunately at the same time the scientists learned well if a little bit of this is working that well let's just dial it up to an 11 and boost it up and that's the difference between um OIC and wovi it is simply about five times the dose of the exact same molecule what happens at that dose is that not only do you still get the inhibition of glucagon which can lower the blood glucose but now you begin to really slow the movement of food through the stomach and intestines that's

a process called peristalsis it's the natural contraction we we're not doing it on purpose it's what's called smooth muscle the intestines are just slowly moving stuff through themselves all to be eventually evacuated from the body what happens then at this level is that they basically stop moving so if you eat something in your we've all been eating a little bit um the food is going to stay there in our stomach turning around and digesting for about 3 to 4 hours normally when people are on these high levels of gp1 an Agonist it can stay up

for 24 or 30 hours and so people will find that they actually have this putrid burping in breath because the food is literally festering in their stomach isn't that delightful all right and so hunger goes down and they lose weight but I need to speed up a little bit um so let's skip this I'm just taking too long let's go to this one um so here this last class of drug I want to talk about before we get into diet is very relevant sulon uras are a class of drug that will stimulate the pancreas to

just start making more insulin and so it's saying hey pancreas I already know you're making a lot of insulin but I just want more because we just need more insulin in order to push down that glucose and then of course in some instances of insulin resistance when it gets to the point of type 2 diabetes they are also just prescribed exogenous insulin a type 2 diabetic will be given insulin injections in order to control their blood sugar levels I hope that you're already beginning to see the problem with this view now that you have embraced

an insulin Centric view you can start to see how catastrophic that really is now remember the conventional clinical Paradigm is glucose Centric and so the conventional clinician is looking at this and thinking well the only thing here that matters is the glucose they may not even know what the insulin levels are because it's just it's such an afterthought it's not even an afterthought it is not a thought it doesn't enter into the conversation so if your view is only we need to do whatever we can to lower the glucose even if it means increasing the

insulin well then who cares until you actually start looking at the clinical outcomes as published where you end up coming to statements like this a direct quote there is no significant evidence of long-term efficacy of insulin on any clinical outcome in type 2 diabetes in fact it gets even worse but what do you think if you take this person and you start pushing up their insulin what will happen to their insulin resistance it will indeed go up it increases insulin resistance these are some more direct quotes from these studies long-term insulin therapy increases insulin resistance

or intensive insulin therapy increases insulin resistance again direct quotes from these studies now I've also suggested to you that insulin resistance is fundamental to most chronic diseases so if we're making the body more insulin resistant you shouldn't be very surprised to find that once insulin therapy starts patients will get fatter they will have an increased risk of cancer death and an increased risk of cardiovascular death so just as a funny sort of example I can say funny because this one's just the body fat there's nothing funny about the next ones um but here this is

a study in type two diabetics and from the PO from the moment they start insulin therapy up till six months the insulin dose increases over these six months no surprise right insulin increas too much insulin increases insulin resistance body weight for reasons I don't have time to get into all also goes up any person who has made you believe that body fat or obesity is purely a result of calories in versus calories out is silly and deserves to be laughed at this is an alternative view of human obesity is that it is just as much

an endocrine or hormone phenomenon as it is a caloric phenomenon the in the body the cells of the body need to be told what to do with the energy they have just as a very brief tangent and I told myself I wouldn't do any and now I think I'm on my third I I grow fat cells in my in my laboratory in my in my little Petri dishes what one of the ironies of of cell culture work is that it is super easy to grow muscle cells and it is super hard to grow fat cells

isn't that ironic we wish we only wish it were like that in the body so we have fat cells growing on the bottom of a little petri dish and they are swimming in a little bath of of calories lots of fats lots of glucose they are loving life and they are skinny little teeny cells even though there's tons of calories there why aren't you taking those calories in you silly fat cells because they don't know what to do with the energy yet a cell isn't some rational little being it needs to be told what to

do like a naughty little kid and I I'm up to my eyeballs in that that home so what tells the fat cell what to do with that energy insulin the moment we Spike insulin into that culture and we come back 24 hours later now they're big and juicy put a little more in 24 hours later they're bigger still one of the reasons why a type 1 diabetic kid gets scrawnier and scrawnier even though they appetite keeps going up and up is that it is literally impossible for the body of any animal to store fat unless

insulin's elevated in contrast if insulin is down it is impossible to keep that fat so as we bump the insulin up and body weight is going up they're getting fatter and 20 pounds or sorry 10 pounds fatter all while they start to eat a little less well thermodynamics have just been broken well of course they haven't it's just we can't really account for every unit of energy in the body it gets too complicated but insulin starts to literally slow down the metabolic rate all in an effort to promote greater fat storage and that's what this

study found here now what about cancer about 90% increase in cancer death when the type 2 diabetic goes on insulin therapy and with heart disease it actually goes up by about three times times so when we give the diabetic the type 2 diabetic more insulin in this disease that is already a disease of excess insulin we are making them fatter and we are killing them faster all right now as we come back to this wheel of Misfortune and I am some demented version of your game show host who's focusing on this what's interesting is that

it makes this view all the more puzzling because most of these diseases have either nothing to do with blood glucose or very very little in other words glucose is providing very little if any influence on any of these variables but insulin is affecting all of them these are all somewhat related to the insulin not the glucose but the glucose influences the insulin so it's not irrelevant and then let's move into diet now within the diet there are three macronutrients the main parts of the human diet they are fats proteins and carbohydrates now if you look

globally and I've given various versions of this talk literally around the world um uh even this year and more to go because it's such a problem around the world if you look at diet uh macronutrient consumption around the world um the a the global diet is about 70% carbohydrate um and again this is the global population and then the remainder split somewhat between protein and fat as a total percent of calories consumed so we as a global population overwhelmingly consume carbohydrate now unfortunately more and more of that is highly refined carbohydrate that comes from a

bag or a box with a barcode now what do these macronutrients do to insulin this is a reproduction that I'm going to show you literally overlaid on a on this particular study so nothing I'm showing is making up and indeed I have my own data from my own lab um where we have confirmed these when someone eats pure fat which we don't do very often you have no insulin response whatsoever if someone eats pure protein you have no insulin response if someone eats pure carbohydrate now insulin will go up by about 10 to 20 times

and it'll take about 3 hours to come back down remember that's in an insulin sensitive person if this is an insulin resistant person it would have come up and still been going until about five or so hours and depending on the amount of glucose consumed of carbohydrate um it can be elevated for up to 14 hours if you eat like three bowls of cereal which is easy to do for me that is my one true Vice um my wife may list many many more but that's the only one I'm aware of um it is it

is cereal which so we never have it in the bikman home for dad's sake not only for my little cherub's sake I just can't control myself but if I were to eat three big bowls it will take my insulin 10 hours plus or or more to come back down um now let's just look at this in a slightly different way um but same overall thing so no effect protein maybe depending on the person um there can be a very small effect but pure carbohydrate large effect but of course the type of carbohydrate matters I don't

want you to think I'm declaring war on carbohydrates as a class I'm not um unfortunately the type of carbohydrate matters um unfortunately being that we don't eat the right ones if it's typically vegetables or the Lesser tropical fruits um there's very little effect um if the vegetable grows above the ground or things like berries or some citrus fruit the the insulin response is very very modest if at all unfortunately those are not the carbohydrates most people eat most people eat refined starches and sugars eating or drinking them um but just to help you appreciate the

effect of the carbohydrate this study was done in young healthy college aged students and they had them eat a higher amount of carbohydrates for one week and over the week their blood they're fasting glucose levels were normal so the fasting glucose levels weren't changing over this week I'm emphasizing fasted so even in their fasted State like they fast all night and they come in for a blood draw if you look at the insulin levels over just seven days at a fasted State they went up by two and a half times higher insulin normal glucose this

is insulin resistance at its earliest stage if this experiment kept going the insulin would continue to climb and then eventually it wouldn't be able to control the glucose and then that would start to climb as well and what I want to impress upon you is the importance of not ignoring the glucose but saying glucose you matter but you actually matter a little less than the insulin does and so I'm going to get my insulin measured at my next blood test all right and just as a final point to show you how silly some things are

when it comes to typical dietary advice in things like in a problem like type two diabetes which of these kind of manifestations of the macronutrient is the one we focus on on the most well it's glucose and then why should we then encourage the person to eat so much that is the American Diabetes Association recommends a diet that is still primarily carbohydrate that is the one nutrient the person is struggling to control why are you telling them to eat more I don't know why I truly don't but I would say it's a hell of a

way to sell a lot of a drugs it is very effective way to make a lot of money all right now my parting or concluding moments come under time here so I should have focused on that other slide a little more but what do I recommend then in order to put these macronutrients into their place because macronutrients matter most when it comes to controlling insulin levels I believe there are three simple principles that can be adopted the first one control carbohydrates so be careful with carbohydrates that come from bags and boxes with barcodes if it

is whole fruits and veget it can be enjoyed liberally in fact next prioritize protein protein has little to no effect on insulin and that is really at the heart of all of this we want to try to give insulin time to come down give it a break give our body a Break um prioritize protein and that should be animal sourced proteins which is superior by every single metric I know it's not popular to admit that these days but the nice thing about being a scientist who's not at a state school I don't have to worry

about saying popular things um then last third and final don't fear fat in nature yes in nature all protein comes with fat there is literally no exception remember I don't use that word too readily in in nature there is no protein that doesn't come coupled with fat I believe that however that protein and fat came to be however humans came to be through design or Evolution or a mix of both we are designed to eat that protein the way it was created it should come with fat when humans eat protein with fat we digest it

better when humans eat protein with fat it actually elicits a stronger stimulus at growing muscle than just protein alone it's almost as if Mother Nature or God knew what they were doing when they put them together because our bodies are built to get them together it works better we digest it better it has a stronger anabolic or muscle building effect so don't fear the fat that comes with that protein all right in the time we've had together we have discussed you are now experts at answering these questions what is insulin resistance where does it come

from with those three primary stimuli stress inflammation and hyperinsulinemia and what to do about it with those three Cardinal rules control carbs prioritize protein and don't fear fat thanks for listening thank you thank you thank you we've got 15 minutes for questions and I will wait to answer the question until right behind you Michelle until you have the mic I'll get i'll get thank you I wish the whole world could have heard what you had to say tonight thank you awesome and that God the human body is God's highest and best creation and it really

wants to live and it's wonderful at adapting could it be that cancer is the body's way of controlling our minimizing diabetes or insulin resistance okay um that's an interesting question um so I'm not a I'm not a cancer biologist of course although I'm very familiar with the disease um I don't think cancer would be intended to be a solution to insulin resistance if only because insulin resistance can make a cancer more aggressive so you wouldn't have a um if if that were the case then it would be a feedback where the cancer would turn off

the insulin resistance and slow the growth of the tumor so no I don't believe so if only because we know insulin resistance accelerates tumor growth in certain instances like breast and prostate tumors okay who else right here Michelle sorry didn't oh no sorry I meant right here you I'll do you next in the back sorry go ahead you didn't talk talk about exercise in relation to insulin resistance I suspect it's a completely new lecture um well I could have put it in um but I I had to really be selective with my time so is

that the question what's the role of exercise yes okay great yeah so um muscle is the main consumer of glucose in the body mostly because of the mass uh most of what makes us our our mass is because of muscle tissue um and in addition to just the sheer amount of muscle the body has is how hungry the muscle is muscle can be a very hungry tissue so when we have uh when I showed you that glucose curve earlier um right here 80% of what explains this drop is what's going into muscle so muscle is

very very important and it is an insulin dependent glucose door so as you guys are sitting here your muscles aren't really taking in any glucose unless insulin is opening those doors until we start exercising so once we start dynamically moving the muscle cells they become so hungry that they tell insulin I don't need you anymore I'm opening these doors on my own so they have a back alley way of opening the door so this is my long- winded and somewhat silly way of saying exercise is tremendously effective but even then it pales in comparison to

diet as much as exercise can have an acute benefit you can out eat that benefit immediately uh in indeed even in real time so if you are doing a mild exercise and you're taking in a sugary drink you're not getting any insulin sensitizing benefit there was a study done in in human women in in women finding that if they exercised they were more insulin sensitive the next day if they exercised and consumed a sugary drink they were just the same as they ever were so anyone who's slowly going on the elliptical and they got a

smoothie or a Gatorade you're it's net negative metabolically you might be getting bigger muscles but the entire metabolic millu will be more negative or harmful than it was before you ever started now now one final comment I am actually minute for minute a much greater advocate of resistance exercise than I am aerobic exercise I'm an enormous Advocate not only for the sake of controlling insulin sensitivity but aging the more you age one of the greatest predictors of living long life and squaring off the curve of mortality uh you know most people unfortunately we have this

slow expensive miserable decline into older age and death we want to be functioning functioning functioning and die yeah and the best way the best way to square that curve is by having muscle mass so I strongly strongly encourage minute for minute do some type of activity to failure um whatever it is fatigue those muscles um but the best exercise is the one you will do so don't let me discourage you from doing whatever you're going to do over the last 50 60 years we've significantly increased our intake of vegetable oils that contain high levels of

Omega 6 yeah Omega 6 promotes all of those cyto kindes um that uh cause the stress uh what's uh your thought on that yeah yeah great thank you so you'll notice that earlier I said that there are primary causes of insulin resistance then there are secondary causes and linolic acid which is the omega-6 polyunsaturated fatty acid enriched in these refined seed oils is I consider a secondary cause only because it can cause insulin resistance in cells but if you have an animal or a human just eating it you don't see that cause insulin resistance in

real time even though I believe it contributes to it so I will speak to what I know with regards to linolic acid although others know a lot more about it in different contexts like fatty liver disease or mitochondrial damage I'm aware of it in the context of the fat cell when linolic now so linolic acid is important this is very important question as much as we've been all told to be afraid of saturated fat um that is uh wickedly stupid um phenomenon this is a fat we've been eating since time immemorial saturated fats they've existed

in our in our diet literally since the beginning even among the leading theories of evolution it is that humans departed from other primates because we started eating other animals and all of their fat allowed our intestines to shrink a lot because we ate such nutrient-dense Foods and because we atee such nutrient-dense Foods while our intestines were shrinking becoming much more like that of a wolf than any other primate from mouth to anus were much more like a wolf than than monkeys and chimpanzees or whatever well that was shrinking and this was growing rapidly so that's

one of the leading theories and of course that would have been saturated fat now back to my point we eat most of the calories we get in our diet of fat come from soybean oil soybean oil is now the most widely consumed source of fat in the global diet and soyan oil is a refined seed oil highly enriched with linolic acid when the linolic acid is consumed it actually has multiple metabolic Fates it can be burned it can be peroxidized which is what you're talking about with inflammation or it can be stored and fat cells

will very readily pull in the linolic acid and often get converted through peroxidation into a molecule called 4hn an abbreviation of a much longer word but when that happens the fat cell is forced to undergo what's called hypertrophy and that's somewhat what I was alluding to before um but just to keep the answer somewhat brief when a fat cell gets swollen or hypertrophied it becomes very pro-inflammatory and very insulin resistant so that's what I'll speak to and and leave it there yeah right there oh no hold on behind you you didn't get the microphone you

have to get the microphone um you mentioned endocrinology and hormones earlier does thyroid or lack thereof play a role in this picture very very much yeah thyroid hormone is you could almost argue that it's even more important than insulin as much as it pains me to say it um um but yeah I mean thyroid hormone is essential for every cell functioning I mean so critical that if a woman doesn't have enough she she can only hope she aborts her baby if she's pregnant um yeah I mean and the results on the developing fetus are just

catastrophic um if the fetus is developing in a low thyroid state so yes thyroid influences it very very much and almost in a predictable way if a person is hypothyroid and Hashimoto thyroiditis is one of the most common forms actually it's largely dietary caused um gluten by the way if anyone has Hashimoto it's very very likely you have a gluten sensitivity and I don't believe gluten is the of all the Earth to quote Isaiah in the Old Testament um like many people do but it is it is a problem for many people um anyway hypothyroidism

will contribute to insulin resistance you put the MU thyroid get their thyroid back the insulin resistance is gone if they're hyper thyroid they're also very insulin sensitive to insulin sensitive in fact where they start to waste away um everything's happening too quick they're revving the metabolic engine too quickly that's not as common a problem hypothyroidism is going to cause insulin resistance and contribute to weight gain in diabetes um yeah let's try to stay yeah right there in the middle you can't speak until you have the microphone told how's my timing now okay in your opinion

when you paray whole fruit does that have any impact on reducing the fa fiber or increasing theic index of it yeah yeah that's a great question so that is the difference between like eating the fruit versus drinking the fruit very often when we've Juiced it which is not what you're saying we've removed all fiber when we puree it we've kept the fiber in there and I'm unaware of evidence in humans that's looked at the shearing effect it's likely very better than juice I would submit it's probably not as good as eating the fruit because you've

kept the fiber there although at the with these highspeed blenders you've likely sheared them into pieces or sheared it but even the act of just not chewing you know chewing slows down how much we end up eating so I have to speculate it's got to be right in the middle somewhere better than juice but not as good as eating it the way God intended if you will yeah right here that's great so Dr bentman yes uh and with the goal of uh increasing age or anti-aging uh with uh three different exercises number one or three

different goals or three different directions exercise uh diet and intermittent fasting so so if if one Incorporated those three to the best of one's ability not being a PhD like you uh what is your opinion on that uh operational yeah goal yeah so another version of this talk actually had me include a fourth step and because of my love of alliteration I called it frequently fasting so in indeed I have invoked that principle so control carbs don't uh prioritize protein don't fear fat and then frequently fast I'm a very big advocate of fasting I'm a

very religious man I fast for religious purposes and metabolic purposes although they're not the same might do it differently um but yes I'm a big advocate of fasting because minute for minute is the fastest most effective way of bringing insulin down now it's a double-edged sword because you have to eat at some point right and so as much as people have embraced fasting which I am here for and I'm an advocate of I think it's very important even for the sake of just mental discipline of telling the fleshy Tabernacle of our bodies no I'm in

charge there's a part of me that is separate from the wants and desires of this body I'm in charge and I'm telling you I'm not eating right now I know I have enough energy I'm fine so I'm an enormous advocate of fasting however I have seen it maybe because I'm a college professor and these young women are crazy these days and even boys now I've seen it getting used as a bit of binge and Purge where someone will fast fast fast fast fast they'll say I I'm going to do a 30 hour 36- hour fast

they get hungry hungry hungry and then they break and they binge and eat garbage then they stuff themselves they feel ashamed which is not effective shame is not good guilt is okay really I mean as a parent I'm okay with my kid feeling guilt I don't want them to feel shame shame is not healthy guilt is okay if it can prick your behavior into being better so you feel shame you feel disgusted with yourself you go to bed thinking why the hell that I do this I'm going to even do better tomorrow and you do

the exact same thing so my paring comment on this is how you break your fast matters much more than how long you fast so come back to those same three principles of managing your Macros my love of alliteration knows no bounds um manage those macros and then when you can structure in your fasting and have it a deliberate this is exactly what I'm eating when I'm done and then an hour later if I'm still hungry this is exactly what I'm eating when I'm done the worst thing you can do is have a per iveness to

your dieting to your fasting and say well because I didn't eat I'm going to go Hog Wild on everything let that whatever that meal is when you break your fast imagine it's the same size of meal that you would eat if you had been eating all day that's the way to do it so how you break your fast matters more than how long you fast at the back this be the last last question snuck it in ben the the question is about fat metabolism and Ketone bodies oh yeah so the point to make is somebody

treating hyperinsulinemia with nutritional ketosis a keton body of two is it better than one to burn more fat or decrease the hyperemia faster yeah yeah that's a great question in fact you're saying that if ketones are 2 millimolar versus one does that help you resolve the insulin faster yeah yeah so in fact we can almost flip the directionality of that and say if your ketones are up to one that means your insulin has come down to this level so let me actually back up very very briefly um the the the human body is a metabolic

hybrid and there are two primary fuels within the they're actually more than that but there are two main fuels that can fuel the metabolic engine of the body blood sugar so glucose or fat those are the main fuels there are other fuels including ketones including lactate it's some amino acids very rarely but largely it's I'm burning sugar or I'm burning fat insulin is the switch if insulin is elevated the body is sugar burning if insulin is down the body is fat burning now let's say that insulin has been down for up to 16 hours maybe

through a fast or a very low carbohydrate diet at that point the the cells of the liver like most of the cells of the body are relying on almost fat totally for fuel interestingly what begins to happen happen in the liver and this is kind of a primer on ketogenesis or the synthesis of ketones the liver cell the liver mitochondria has been burning so much fat that it actually gets overloaded or kind of backed up that's a better word it's so filled with fat burning but it can't stop burning fat so the liver cell is

basically saying all right I this is how much energy I need to survive as a cell um and we're burning fat uh and and I've met all my energetic needs I'm I'm done I'm good we have everything the battery is full but because insulin is low it literally cannot stop burning fat so it keeps going and that keeps going is what if you will gets kind of diverted into ketogenesis into the Ketone pathway now what is so important about that and I've mentioned it I'm revisiting it and emphasizing it it can only happen if insulin

is at a very low level a fasting like a nice low level a few micro units per Mill if you're ever able to get it measured you want it to be ideally below six micro units per Mill the lower that insulin's getting the more the ketogenesis is happening so if someone fasts overnight measures their ketones with a finger prick or a ketone monitor which is coming out soon and they're in ketosis then their insulin is low and that is a good sign that they're insulin sensitive so ketones end up being a pretty good surrogate um

albeit inverse marker of what insulin levels are it's not easy to get your insulin measured it's very easy to measure your ketones and so if you did say a 24-hour fast you would want to ideally be at least 0.5 or so Millar that's not really codified so I'm kind of speculating a little bit but after 24 hours if your ketones were about 0.5 Millar I would say that means your insulin is down and you're generally probably doing pretty well and your insulin sensitive anyway hopefully that helps okay guys thank you so much for coming I

hope it was helpful thank you thank you very much