Dr. Jason Fung – ‘A New Paradigm of Insulin Resistance’

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so today we’re going to talk about his insulin resistance because that’s really the heart of type 2 diabetes and this is my disclosure so I don’t really have any commercial interest so type 2 diabetes is a really important disease because it causes most or is associated with most of the diseases that we care about today which is heart disease cancer Alzheimer’s disease and so on but we really have to think about this insulin resistance and a new paradigm because the one that we’ve been taught the one that we understand actually isn’t the one that’s really true and so type 2 diabetes is a disease with two phases right so there’s if you look at the time course of the blood glucose before the diagnosis of type 2 diabetes there’s actually two phases so there’s a long slow phase where the blood glucose Rises very very slowly and that’s where the insulin resistance is rising okay but the body produces enough insulin to overcome this resistance so the blood glucose stays relatively normal it’s compensated right so it’s called a compensatory hyperinsulinemia at some point the the pancreas doesn’t produce sufficient insulin either the insulin resistance is too high or the the amount of insulin drops so because you lose this compensation the blood glucose goes up in type 2 diabetes is diagnosed but that’s relatively late in the game the slide shows you that even up to 14 years prior to the diagnosis of type 2 diabetes you get this rising insulin resistance so you can see this when you look across the spectrum of lean people and hope these people then as they develop more and more pre-diabetes and diabetes insulin resistance goes up and up and this is a slide of the beta cell so the beta cell in the pancreas produces insulin and this is the black circles you can see as you go across a spectrum from normal to obese to pre-diabetes to diabetes insulin production initially goes up so as you go to the middle the black circles you can see that it goes up but at some point it drops and the white circles is the blood glucose and you see as the insulin production drops the blood glucose goes up and you make the diagnosis of type 2 diabetes but the key problem there’s two key problems right is the resistance and the beta cell dysfunction and for this reason people tell you that the beta cells are burning out right and that’s why type 2 diabetes is chronic and progressive and eventually you know you take medication and you take insulin they take more insulin and Martinson more insulin and that’s the way we tell people to think about type-2 diabetes unfortunately it’s not really true so the key is to understand what insulin resistance actually is okay where does it come from how does it develop so in order to understand insulin resistance you got to think about what insulin normally does so when you eat food insulin goes up right insulin basically tells the body that food is coming in and you should store some of it so you store sugar in the liver which is like a gin and you store fat also so if you produce if you eat too much carbohydrate then that is going to be produced by a process called de novo lipogenesis into fat and when you don’t eat which is simply called fasting right that’s just a flipside of eating when you don’t eat instant falls and as it falls it tells your body to pull some of that sugar and pull some of that fat back out of the system so as long as you balance your feeding and fasting you got a well-balanced system you don’t actually gain any weight right because you eat you store sugar you don’t eat you fast you burn sugar right that’s that’s basically all it is so insulin does a couple of things so it lets all this glucose into the cell but it also produces this new fat right that’s the de novo lipogenesis so there’s two functions not simply one and this is the way we think about type-2 they’ve about insulin resistance it’s this lock and key paradigm that insulin acts like a key on the cell so this is for example a liver cell so you have receptors which is like a lock when insulin is produced it opens the gate and it lets all the glucose in so what we tell people is that insulin resistance is actually a state where this mechanism this lock and key paradigm is completely gummed up okay so it’s not that the lock is defective or the key is defective cuz you can easily sequence the insulin or the insulin receptor they’re normal but something is gumming up the system so all the glucose stays outside and the cell faces this state of quote/unquote internal starvation right so they can’t go in what that means of course is that the liver cell cannot produce fat right you got no glucose and there you’re not going to produce fat so what internal starvation looks like is this because we know in type 1 diabetes untreated type 1 diabetes that the cell faces internal starvation and you look like the the patient on the left so she’s starving away you can feed her whatever you want you can’t use it and she basically waste away until she died if you give her insulin herself now don’t have the internal starvation and she regains the weight so great we know that’s what happens when the glucose can’t go in but this is what type 2 diabetes looks like right this is what we’re calling internal starvation there’s something a little bit wrong with that paradigm of a gummed up lock and key system because there’s a paradox here that is not explained by the gummed up lock and key because if you look at this liver cell ok so insulin it pushes the glucose into the cell and if your insulin resistance it doesn’t do that so okay that’s great but the other thing this liver cell is supposed to do is turn on production of new fat so if your insulin resistant you can’t produce any new fat so like that untreated type 1 diabetes you waste away but that’s not the case in type 2 diabetes if the glucose is not going into the cell how is this cell producing tons and tons and tons of fat because we know that the type 2 diabetes the insulin resistant patient has a lot of insulin resistance has a lot of fatty liver in fact you always see the fatty liver right so how can this cell the very same cell the very same insulin the very same insulin receptor be resistant on the one hand to one of the functions and super-sensitive to the other function it’s not correct and we based our entire treatment of type 2 diabetes on an incorrect paradigm so what happens in this liver cell of course is that you have insulin as you have insulin it puts the sugar and the fat into the liver so I’ve depicted the liver as a balloon right so it blows up when you eat as insulin falls it comes back out right that’s all it is it’s a storage problem but the problem excit liver is that if it fills up with persistent influence if you eat a lot of glucose if you use a lot of fructose you’re going to fill up this liver cell right because insulin you’re acting all the time you’re going to keep pushing it into storage what happens is that you get fatty liver right that’s not so hard to understand but a society liver that’s the key to understanding insulin resistance because if you have a huge fatty liver that’s seeing dose of insulin is not going to be able to shove any more fat into this fatty liver and if you don’t have insulin then it all of this fat and sugar just comes rushing back out right so the reason that you have the central paradox is because this is an overflow paradigm right if the glucose can’t go into the cell but the fat keeps coming out if the glucose can go in you couldn’t make the fat but it’s not a under-filled cell it’s an overflowing cell right and this fatty liver precedes the diagnosis of type 2 diabetes because it’s on that long slow ride where you get the slow rise in the blood glucose slow rise in the insulin resistance so this is the Whitehall study which shows you the time course of the liver enzymes before the diagnosis of type 2 diabetes and what you can see is that they broke the group into two groups one that eventually develop diabetes and one might eventually did it and what was the big difference well if you look at the markers of liver tasks you can see that the liver is slowly getting distended and slowly getting inflamed those alt which is the marker of liver damage is slowly going up and what they called it is the long silent scream from the liver you can’t hear it you can only see it on the blood test you might be able to see it on CT or MRI but it’s this big fatty liver that’s the key to understanding the insulin resistance so it’s really an overflow paradigm right so the cell is like this luggage right as you fill it up it’s harder and harder to put in more stuff so at first you can put in your clothes fine but that’s those last two t-shirts you just can’t shove them in right so you use more force you use more instance you keep shoving stuff in but that’s not the problem the problem is not the insulin the problem is that your cell is overfilled it’s an overflow paradigm just like this your cell is like a train right and it’s got passengers and normally they go in insulin opens the door that goes in well what happens if that cell is already filled right if it’s already filled with glucose and fat that liver cell you keep shoving it in with insulin that’s not the solution right if you have the wrong paradigm you think that the Train is not opening the door so you hire these these guys to keep shoving people in they do this in Japan because because it’s cool but the problem is the glucose stays outside right the passengers can’t get in so you keep trying to shove it in which is fine at first then you go to the next stop you hire more guys right hire more insulin guys keep shoving it in right and it happens it works for the next stop then you hire more guys to keep shoving it in until you can’t anymore then everybody stays outside you make the diagnosis of type 2 diabetes so the key to understanding type 2 diabetes is it’s all about the fatty liver as Mark just talked about right the cell the liver cell is just packed with fat so you can’t shove anymore and that’s the whole point in the meantime the liver is busy trying to decompress itself with all this fat right so what it does so it’s making all this new fat through de novo lipogenesis and it packages it through triglycerides in the blood right and it’s pouring out this triglyceride and that’s why the novo lipogenesis is so high it’s not resistant remember this is the effect of insulin it’s super sensitive it keeps trying to push it all out so how do you get fatty liver well it’s not so hard in geese right this is how you make foie gras right so you take a booze you shove it to down its neck and what do you feed it well you feed it starch right because you want the liver to make new fat you don’t make me fat by eating fat humans don’t do that the dietary fat does not go to the liver it goes directly into the bloodstream through chylomicrons into the thoracic dots into the lymphatic system but what happens is when you feed it starches and fructose particularly you get fatty liver and that’s what happens in humans as well when you over feed carbohydrates glucose and fructose you get fatty liver and that’s how you get insulin resistance so the key again to understanding this is that it’s hyperinsulinemia high insulin but also this insulin resistance that’s the key to obesity that’s the key to insulin resistance that’s the key to everything so if you eat a lot of fattening carbohydrates on left you can stimulate insulin right and that will lead to obesity but high insulin levels over a long period of time are also going to stimulate fatty liver right as you produce this new fat through de novo lipogenesis which is going to lead to insulin resistance which is then going to lead to high insulin levels again the fructose doesn’t do this right so this is why everybody used to say the bad not that bad for you sugars not that bad for you right because fructose does not raise your blood glucose it’s a different sugar altogether and it doesn’t raise your insulin levels so people say that great fruit sugar right it’s great it’s not great the problem with fructose is the way it’s metabolized in the body it’s metabolized slowly in the liver okay so if you take sucrose or sugar is sucrose which is equal parts Lugo’s and fructose when you eat glucose and fructose you have equal amounts if you take an average-sized man 170 pounds you eat a pound of sugar so you get half a pound of glucose and half a pound of fructose 170 pounds of the glucose is metabolized by the body okay so every tissue in your body every part of your body is going to use that glucose but none of it uses the fructose right so that half a pound of sugar sort of half a pound of fructose isn’t it a bolide by five pounds of liver okay so what does the liver do with it well the liver could turn it into glucose but you got lots of glucose so it turns it into fat right so instead of 170 pounds of tissue using glucose right so your cells are kind of helping themselves yeah that’s all you can eat Lucas buffet nobody touches the fructose right so the Fresco’s goes into the liver and gets turned directly into fat so what it means is that if you only have five pounds of liver you’re using it the glucose and the fructose are not equally bad for you the fructose is like twenty times as bad as the glucose so the starch is the rice and the passive stuff that’s all glucose so the fructose is really where the money is so glucose plus fructose is what gives you fatty liver which gives you the insulin resistance and what’s glucose and fructose right it’s sugar and everybody knows this right every diet says to cut the sugar even those diets that say oh you should eat starch oh but by the way you shouldn’t eat sugar as well right because the fructose is really the big problem and a society liver so that’s insulin resistance it’s all about predominantly frog those also glucose and a lot of fatty liver what causes this beta cell burnout doesn’t it burn out doesn’t it die out right and that’s why once you get type 2 diabetes it’s irreversible right well again we know that’s not true because we can prove it if you look at studies on bariatric surgery well this is a study comparing medical intervention to bariatric surgery so this is weight loss surgery they cut your stomach to the size of a walnut right and then they rewire your intestines you can’t absorb what you put in your stomach and what happens of course is that the people on the Left started out with almost three diabetic medications and very quickly within three months many of them were off all their medications with normal blood glucose their diabetes completely reversed and this happens even far before much weight is lost right so if you’re telling me that the pancreas has burned out this tells you that you can take a man or woman with 20 30 years of type 2 diabetes with 3 4 5 medications and completely reverse it completely not just in one person and everybody and you can do the same thing with gastric banding so again if you look at their weight it goes down but if you look at their blood glucose classic banding is where you put a little it’s essentially a belt that cinches around your stomach so you can’t eat but again you look at the blood glucose when you start it’s 8 which is type 2 diabetes within a week it goes down into the normal range right again before a lot of weight is lost so this pancreatic beta-cell that produces the insulin is completely functioning again it wasn’t burned out at all and if you compare fasting versus bariatric surgery you can actually get the exact same effect right so here’s a comparison where they fasted people using very very low calorie diets before and after surgery the point of the the fast thing was not because they were very advanced stinkers is because they wanted to shrink that liver because when they do the surgery if you have a big fatty liver it’s very hard to get in hard to work things right so they know that if people don’t eat that liver shrinks right down right when that fatty liver shrimps right down of course the insulin resistance goes away because insulin resistance is from fatty liver so you can see from the left hand side the weight loss comparing the fast thing to the dot to the surgery and the fast thing actually causes more weight loss and if you look at the blood glucose it gives you lower blood glucose which is actually better and if you look at the counter point study what you see is that the pancreatic fat slowly goes down so your body when it has nothing to eat is pulling that sugar pulling that fat preferentially out of the liver and then out of the pancreas because it’s the fatty infiltration of these organs that is causing the type 2 diabetes so as the pancreatic fact goes down the beta cells recover so they weren’t burnt out at all right this is the restoration of the insulin response they were merely clogged with fat and that’s tremendous news because it means that this whole notion this whole paradigm the type 2 diabetes is chronic and irreversible is completely untrue it’s a completely reversible disease so the idea the way you need to think about type 2 diabetes is basically like a sugar bowl your body is like a sugar bowl right it can hold a certain amount of sugar but once it’s completely full as you eat the sugar it just spills out into the blood remember sugar we’re talking Lucas and fructose it spills out into the blood right and so if you have type 2 diabetes somebody says well you have type 2 diabetes now let me give you insulin because we think that you’re the sugar can’t get into the cell right so we need to give you insulin so what is that insulin do well it doesn’t get rid of the sugar in the blood what it does is it takes our sugar in your blood and crams it back into your body right and then the next time you eat that sugar bowl is still full so you take more insulin and then you cram it back into your body again your body takes it for a while sends that sugar out into the eyes into the kidneys it turns a lot of that into fat right and you haven’t fixed the problem you keep doing this year after year you take more insulin or drugs that stimulate insulin you cram it back into your body and so what happens after 10 15 20 years well your whole body just starts to rot and that’s what happens your eyes go you go blind your kidneys go you go on dialysis you have gangrene and died foot ulcers every part of your body has too much sugar that’s it that’s it that’s the whole pathophysiology and what we’ve done is we’ve completely misunderstood the disease because normal is this right normal is on the left you have glucose you have a cell you have some glucose inside the cell right so if you think type-2 diabetes about is about internal starvation then the correct response is to give as much insulin as you need to shove back glucose from the outside inside but if insulin resistance is really an overflow paradigm then that treatment is completely utterly wrong because you’re taking that glucose from the outside and cramming it into the cell which is now overfilled has way too much glucose inside and it’s desperately trying to pump out this fat right it’s the wrong treatment and if you give the wrong treatment guess what everybody died right you get a huge worldwide epidemic of obesity of type 2 diabetes all because you didn’t understand it right so if you think about the internal starvation model we already know it’s wrong we’ve known it for close to 10 years because in under this paradigm you can take the insulin shove it into the cell and you will get better but the Accord study showed that yes you can give people insulin and medications what you see is that you give you more medication your blood glucose goes down right but remember it doesn’t get rid of the sugar in the body it just crammed it into the cell and what happens well you saw more often there’s a 22% increased risk of death and everybody says well there’s this problem that problem but it wasn’t one side it was like 7 rate study the advance study was the same you can give medications to lower the blood glucose but you can’t make people healthier right and the VA DT showed the same thing that Tico’s studied the elixir study there’s study after study after study and if you look at all of them what you see is that when you take all them together they show you what you knew which is that taking in insulin doesn’t make you any healthier so the good news is that you can actually reverse type 2 diabetes completely naturally as long as you understand this overflow paradigm because there’s only two things you need to do if your body has too much sugar that’s all type 2 diabetes is your body has too much sugar step one is don’t put any more in right it’s a low carbohydrate diet that’s why it works so well that’s why I study after study after study show the low carbohydrate diet works to reverse type 2 diabetes is not that hard to understand so what’s the drug equivalent of a low carbohydrate diet well we have a drug that can block the absorption of carbohydrates it’s a drug called akribos right so you take the drug it blocks the absorption of carbohydrates and the blood sugar doesn’t the sugar doesn’t go into the body which is great right because it’s that sugar bowl you’re blocking you’re not putting it in but it doesn’t lower the blood glucose very much and the other thing is that you get all the indigestion and so on so people don’t use this much but there’s a study in 2003 randomized study three point three years of follow-up and what you see is that you can reduce the risk of heart attacks and strokes right cardiovascular events on the left by almost 50% right you’re not lowering the blood glucose much but you’re lowering your heart attack rate by 50% because you’re not putting sugar in to a situation where you have too much sugar that’s it what’s step two step two is you’d burn it off if you have too much sugar in the blood don’t put any more in and get rid of what you have inside that’s it and that’s intermittent fasting so again do we know it works well of course we know it worked if you don’t eat your blood sugar drops right we know that so what’s wrong what’s wrong with us don’t eat blood sugar drops don’t take your insulin that’s it but your body is getting rid of the sugar so that you’re actually getting better from your diabetes and we have a drug equivalent of this as well so a new class of medications called the sglt2 makes you pee out the sugar okay it’s POS the glucose in the blood and it doesn’t lower the blood glucose a lot but this is the recent study and per regulus published I think last year and what you can see is that this is the risk of cardiovascular events and what you see with the emperor with the emperor flows in is that you can reduce the rate of heart attacks by 15 to 20 percent even though you don’t lower the blood glucose you’re getting rid of the sugar in the body and that’s what makes you healthier because that’s the whole problem right so this is a very powerful paradigm right we have to understand that this is not some kind of chronic irreversible disease and we tell people this all the time right you have obesity or insulin resistance well it’s your fault right you ate too much fat right you’ve been exercised enough you should eat less and move more it’s your fault that’s what we tell people all the time but it wasn’t it was really the failure of the doctors of the researchers to understand that type 2 diabetes is not about too much sugar in the blood it’s about too much sugar in our whole body right that’s what you need to get rid of you can’t simply take the sugar in your blood and shove it in your body and pretend that you’re better it’s like if you have garbage in your kitchen and instead of throwing it out you throw it under the sink so great my kitchens nice and clean right and then when there’s there’s more garbage you throw it into your bathroom right hey great my kitchen is clean right your doctor packed himself on the back oh you know your blood glucose is so good your a1c so good right but what’s the problem you haven’t thrown out the garbage and your whole house just starts to smell right and then the doctors as well that’s what happens you know it’s chronic it’s irreversible but it wasn’t we’ve proved it already why can’t you accept that fact you just have to know how to treat it but again the opportunity before us is enormous because we have now the possibility that you can I should just completely cure the whole damn disease right and if you think about it it’s an incredible notion because if you don’t have diabetes then you don’t have diabetic nephropathy that’s kidney disease you don’t have to do dialysis right if you don’t have you don’t have diabetic foot ulcers you don’t have any blindness from type 2 diabetes right you don’t have heart attacks you don’t have two strokes you don’t have the cancer none of that right and it’s all available to us without any drugs without any surgery and without any cost right if you don’t eat you don’t have to pay for food right you’re saving money right what could be simpler and you’re treating your type-2 diabetes right so this is the whole idea of this conference is that these diseases which cause so much pain so much suffering and we’ve treated them for so long with the wrong paradigm right just take your medications right no that’s not the case this is a dietary disease it demands a dietary solution right and that’s all that’s all we need and we can do it we can do it any time we want to because as long as have knowledge you don’t need the infrastructure you don’t need the hospital you don’t need anything you don’t need any infrastructure you can do it in that world that world that we can see it now that world that is free of type 2 diabetes and free of all of these heart attacks and strokes and all of that it’s there right but it’s not up to me for Mary Ann or Gary your staff or rod it’s up to you it’s up to all of you to tell your friends your family yet your doctors like van says tell your doctors and if your doctors tell your patients it’s all here for us it’s all here for the taking right and we can see it through that open door right David season it already he does it already you can see it through that open door and we just have to walk through that threshold we’re inviting you to come walk with us through that threshold to that world without diabetes without pain without medication without insulin and guess what that world that world starts today thank you [Applause]

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