Insulin Toxicity (How to Reverse Type 2 Diabetes)

 

Intro to Insulin Toxicity

so anyway thank you Jason thank you all looking forward to here President Kennedy has to say so thanks

for coming so what we're talking about today is something I don't think has really been discussed which is insulin

toxicity and I think we never really think about it for the reasons doctor in

this slide basically I think that we've been kind of thinking about diabetes in

a certain way and because of that we kind of missed the truth so the greatest

enemy of truth is very often not the lie deliberate contrived and dishonest but

the myth persistent persuasive and unrealistic too often we hold fast to

the cliches of our forebears we subject all facts to a prefabricated set of

interpretations and we enjoy the comfort of opinion without the discomfort of thought so with that let's think about

so with that let's think about type two diabetes this is the way we think about

type two diabetes so we always say it's a chronic disease it's a progressive disease so while you can actually treat

it for a short period of time after after a while after a period of two to three years it progresses and that's

just the way we think about diabetes and we say that because type 2 diabetes they

say has multiple pathophysiologic abnormalities that is there is all these different mechanisms and they all

contribute to the hyperglycemia and that's the reason it tends to progress over time

but what if we got it wrong what if it's not actually a progressive disease and

what if it's actually a curable disease that would really change our whole practice because if we can think about

the pathophysiology and we can really understand it then maybe we can think about rationale treatments for diabetes

and maybe we can cure it so let's get started you have to go back a little bit

firm and think about type 2 diabetes because really the core of type 2 diabetes is

insulin resistance so I've depicted here what insulin resistance is and basically it is the cell is resistant to the

effect of the insulin and because of that you can see that you get very very high levels of insulin and the question

always is what causes insulin resistance and some people say it's obesity but

then it's hard to show any kind of mechanism so let's back up a little bit

further and say how do you develop resistance in a biological system well if you think about antibiotic resistance

it's very clear that the causative agent does the antibiotic itself if you think

about viruses for instance such as a vaccine a vaccine is basically a killed

virus viruses caused viral resistance if you think about drugs you can take any

kind of drug but particularly the addictive drugs you can see that at first they produce a very high effect

but over time the effect tends to diminish in essence the body has developed a resistance to this drug and

many many drugs show this very same phenomenon nicotine nitroglycerin

alcohol benzodiazepines so many many drugs show this type of pattern so in

fact the drugs themselves can cause drug resistance and we know the mechanism in

the case of drugs I mean in case of hormones for instance if you expose a

body to a constant high level what you develop is down regulation of the

receptors and you actually take advantage of this in the case of edd so

you have these hyperactive kids and what you give them is ritalin which is not a sedative it's a stimulant so you'd think

at first wow that's really crazy why would you give any stimulant to a two stimulated kid well the reason is

because of this phenomenon of down-regulation receptors so as you develop the resistance the body develops

a resistance to the stimulants therefore you get not increased activity with

with the ritalin you actually get decreased activity so this is a very well-known phenomenon so it's these high

persistent levels which are really key to causing the down regulation of the receptors and the resistance and you can

see that these all show a reinforcing cycles of resistance that is as you have

an exposure a persistent exposure it gives you resistance and the resistance

leads to higher exposure what does that mean if you're to take the example of

antibiotics if you use antibiotics you develop resistance the resistance causes

you to use more antibiotics and that causes more resistance so you can see

these are vicious cycles so they keep going round and around so if we think about it that way let's think about the

question now what causes insulin resistance so the first thing to ask is does insulin itself cause insulin

resistance yeah church you know antibody

use diseases would be different from other drop mechanism right I mean check

the ritalin is the receptor but you know the antibiotic

resistance is quite different plasmids the transmitting with so I don't know

where that one can you know put this everything into the same cycle no I'm

just trying to use it again as an example I'm not saying that it's the same as antibiotic resistance I'm saying

that the first place we should really be looking for resistance is the agent itself I'm not saying that that proves

the antibiotics is quite different for hormonal systems it has more similarity but let's move on and look at insulin

because that's really what we're interested in not antibiotics right so if you look at insulin resistance you

can take the example of insulin Ouma's for instance these are rare tumors that produce too much insulin and if you look

at the insulin resistance you can see that the higher your level of insulin the more insulin you develop and that

really makes a lot of sense because if you have an insulinoma and you don't develop resistance your sugars are going

to be less than one and you'll die so the body produces resistance to protect

itself that's a normal thing and you can actually show that if you reset these adenoma 's you actually restore the

insulin resistance so in this case you can see that the insulin has actually caused the insulin resistance and you

can actually do this experimentally in in men what they did here was that they

took a group of men and they just infused them with insulin and these are not diabetics these are just normal

healthy men in a metabolic lab and what they did is they used a you glycemic plant which means that they kept the

glucose the same but they infused higher and higher doses of insulin and then they measured what happened so what

happens is that when you measure them after a certain period of time they can't use the glucose as well so those

ones that got a lot of insulin couldn't use the glucose as well in essence you've produced insulin resistance and

you can do the same thing in with physiological levels of insulin that is

this is the same sort of experiment but they use much lower levels of insulin so

they use physiologic levels as opposed to the previous study where they use very high levels these are levels that you would normally see in

your body and when you infuse them you can see that the insulin sensitivity

significantly decreases in other words if you give chronic physiologic

hyperinsulinemia you actually get insulin resistance so you can produce

this in anybody I could do this in you if you give high persistent levels of

insulin you will get insulin resistance so this is a causal relationship because you've actually caused it by giving the

agent and this is what we do in type 2 diabetics so this is a study from 1993

and what they did was they took diabetics and at the time the focus was

on glucose and controlling the glucose so what they did at time zero was that

they took these diabetics and said we're going to control your Sugar's really really without really well we're going

to give you lots of insulin so by six months they're on a hundred units a day of insulin the sugars were really good

the problem was that you can see that there's a very clear relationship between the total insulin dose and the

resistance so this is the glucose disposal rate so how well your body is using the insulin and what you see is

that the higher the dose of insulin the more the insulin resistance since insulin resistance is really the heart

of diabetes what you've got is the insulin making the sugars better but

making the diabetes worse even worse of course there was a huge weight gain because they're getting all this insulin

so 8.7 kilos which is roughly 20 pounds now what the other really really interesting part about the study was

that they looked at the caloric intake and what you can see is at time zero they had 2,000 calories and by six

months they're only taking 1,700 calories a day so even as they were getting fatter they were eating less and

less and why is that that's because the influence of insulin but as you can see

the main point is that you're developing increasing resistance in other words the

insulin is making the diabetes worse and if you look at this from David Ludwig he's a

pediatric endocrinologist from Harvard you can see that the insulin resistance certainly causes the hyperinsulinemia

but the other thing you have to recognize is that the hyperinsulinemia drives the resistance as well but which

one came first that's the real question right it's kind of like the chicken and the egg well you could luckily we've studied this in juvenile obesity and

what you can see is that really the first thing that you see is high insulin levels so if you take people with

obesity and these are children and you split them into three groups you can split them into a group that has that is

not obese you take a group that has obesity but of short duration so less than four point five years and you take

one that is more than four point five years and you study their insulin mechanics now what you see is that all

the obese patients actually show a spike in their glucose and a spike in their

insulin so it doesn't matter how long you've had the obesity and that contrast with the non obese where they don't

actually have this high spike of insulin the insulin of course is the one of the major players in the obesity if you look

at insulin resistance though you see a different picture that is as you have an increasing duration of the obesity you

have higher levels of plasma insulin fasting plasma insulin and higher levels

of resistance so the resistance is not there to begin with the resistance is

normal to begin with but under the influence of this hyperinsulinemia you

Hyperinsulinemia

develop insulin resistance the insulin resistance translates into a fasting

plasma insulin that goes high so the time sequence of juvenile obesity which

goes along with diabetes is that the insulin seems to be the primary insult and from the high insulin levels then

you get the insulin resistance and you might think well if that's the case why

don't we get resistance all the time because insulin is you know there all the time but the truth of the matter is

that if you release the hormones in a pulsatile manner you prevent the development of

resistance so if you look at almost any hormone in the body it's not a steady state so insulin is released in a

pulsatile circadian rhythm and it's the same with cortisol certainly the case with PTH and virtually every hormone in

the body and by releasing an impulse at I'll Manor you actually can prevent the development

of this resistance this is the way we give insulin certainly not pulsatile but

very very steady state which is going to lead to more resistance and you actually

know this because you can take advantage of this in therapeutics again so if you look at your nitroglycerin patch you put

it on for 12 hours and you take it off for 12 hours right why don't you leave it on 24 hours a day

well it stops working why because you're developing resistance when you take it

off that's when you can prevent the development of this resistance so this

is what we know so far so insulin causes insulin resistance it's not the only

cause but it can cause insulin resistance insulin resistance is going to lead back to high insulin levels and

what you need is really high persistent levels that's what really drives the

resistance in other words insulin causes diabetes so let's let's with that

background let's think about the complications of diabetes and this is the way we think about the complications of diabetes now there's a lot of

complications of diabetes affects virtually every organ system in the body and we think of type 1 and type 2

diabetes as the same ok so type 1 and type 2 diabetes leads to high blood

sugars and through various mechanisms such as advanced glycation end-products

oxidative stress and other things it leads to the complication so our current

treatment paradigms as well if we can get rid of those high blood sugars then

we can get rid of the complication and that's the way that we treat diabetes as it stands today the problem with this

treatment paradigm is that it's not true it's not true in any way if you look at

the Accord study so this was published in 2008 what you see is that you can

randomized two groups in one group the intensive therapy is going to get much less Sugar's much better controlled

Sugar's so according to that that that paradigm you should do much better the

problem is you don't you actually do worse so there's an increased risk of death and you can do this with almost

every study because it wasn't that simply that one study all the studies showed the same thing so the advance study if you have intensive control

there was simply no benefit the VA DT which was published shortly thereafter showed the same thing and most recently

the origin trial which took patients with impaired glucose tolerance gave him insulin or not there was no benefit so

it turns out that there this treatment paradigm is completely not true and what we always forget is this there's a

difference between type 1 and type 2 diabetes type 1 diabetes is the lack of

insulin so most of your toxicity is mediated through the high glucose but in

type 2 diabetes you have high insulin levels so is it possible that in type 2

diabetes as opposed to type 1 diabetes the toxicity is actually mediated through both the high blood sugars as

well as the increased insulin now if you think about insulin and atherosclerosis there's a lot of reasons why you might

think that might be true and I've listed some of them here and we'll go through those but can we look back and see if

they see if insulin actually is a toxic treatment well it turns out you can easily find that so if you look at this

study from 2010 they took all the patients in Saskatchewan so 12,000 odd

new diabetics and they looked at what they were on and they said well if you're on insulin

you have a much higher risk of death that is compared to no exposure a high

high exposure to insulin more than doubles your risk of death and this is

the same thing that was found this was 2013 published by Curie and he looked at

not just insulin but he looked at insulins metformin so far no ureas as

well as insulin so so far no ureas as a class raise insulin levels not as bad as

insulin but they still do and you can see clearly that when you compare to metformin the Savano ureas have about a

43% increased risk of cardiovascular events and the worst one is the

metformin which has about an 80% so it's certainly consistent with the hypothesis

that the insulin itself is a toxic agent and if you look at populations you can

see for instance in native populations so this was the Kitab ins off of New Guinea here and what you can see is that

their insulin levels are very very low and this is a Swedish reference range so

it's when 10% now you can see that the average native dis Katahdin has the

average has lower than the the 10% of the Swedish so if they have very very

low insulin levels and they really have non-existent cardiovascular disease if

you look at regular European populations so this was published in 2004 Daiya

bellator logica you can see there's a relationship between serum insulin as an

mortality but the problem is these studies don't actually answer the question because is it really the

insulin or is insulin simply the marker of insulin resistance so for that we

actually have to look step back a little bit so if we step back to the basic science we can think about Acuras

chlorosis because that really is what mediates most of the toxicity so

hyperinsulinemia actually makes worse at every stage all the steps of atherosclerosis so

atherosclerosis of course is not sin the cholesterol plugging up the artery but it's actually considered to be a

response to injury so there's many different steps and every single step along the way is helped by insulin so

you have increased adhesion molecules on the endothelial cell you have increased

trend and the figlio migration of these leukocytes so the white blood cells can get into the vessel wall

it stimulates the smooth muscle proliferation and it has inflammatory

effects which is really at the pathophysiology of atherosclerosis and insulin makes all of these works these

are the references if you want to look them up if you actually biopsy these

human atherosclerosis and what you find

is that there's insulin receptors at all the small vessels not the big vessels either LV is the large vessel but at all

the small vessels in this human plaque there's insulin receptors so what you

can do is you can bathe these human plaques in insulin and you can see what

happens and what happens is that they grow blood vessels because they have insulin receptors there so they grow

blood vessels so what you can find is that you get much more atherosclerosis in the presence of insulin the other

thing you know about insulin is that it causes salt and water retention that is dr. parven showed all the way back in

1989 that if you give insulin you will retain salt and water mostly at the

level of the proximal tubules which is not a good thing because you're going to get hypertension and edema and

all sorts of things so on that level you also might think that insulin might be actually a very very bad agent for

people so really if we're thinking about insulin toxicity there actually is a lot

of good reasons that you might think that insulin treatment is very toxic and

this is where it's really really starts to get interesting is that after the failure of the VAD tea

the advance and the Accord trials people started to look at different agents and see if there's a difference between them

and what they found was very interesting so if you take 28,000 patients from the UK general practice database so all

these patients were on one agent and you intensify them to two agents as your

hemoglobin a1c goes up your mortality goes up so that's okay that we can understand that's gluco

Increased mortality with insulin

toxicity toxicity from high glucose but what you don't expect is that there is

actually a very an increase in the mortality as your hemoglobin a1c goes

down and it's especially mark when you look at insulin that is to say if you're

on insulin and your a1c is 6% it's as bad for you as if you're a 1c is ten and

a half percent that's crazy that should

not happen because we think of all the toxicity as gluco toxicity and this was

confirmed in another study from diabetes care what they said is that if you look

at the six to eight percent range as you go up your mortality goes up so that's

fine you get about a 20 percent increase in mortality but as you go down below 6% your mortality also goes up and can we

if you look at insulin there's a huge increase and the problem is that this shouldn't happen because if you look at

non diabetics as you go down four on your a1c your mortality goes down

because your glucose is better so therefore you have less mortality and you can't actually understand why this

actually occurs until you realize that the treatment itself is talk is toxic

that is at the top end here you're looking at gluco toxicity but at the low

end here you're looking at insulin toxicity and the reason the so faunal

urea is not as bad is that it doesn't insolent so much so starting about mid

2012 that's when it's really really starts to get interesting because what's what you can do is compare metformin

versus a sulfonylurea so the metformin of course does not raise the serum insulin levels because it's an instant

insulin sensitizer the sofa no urea does but they're both they're both oral

agents and they both we both had the same targets in terms of hemoglobin a1c so if you take this VA database and you

look at patients who are started either on metformin or library and look at the

difference in cardiovascular disease or death what you see is that the sulfonylureas do much worse if you look

at this retrospective database of 90,000 plus patients from the UK you see the

same thing so a first-generation sulfonylurea second-generation sulfonylurea they both

show about a 30 to 50 percent increase in cardiovascular events compared to

metformin and again what you're seeing here is the effect of the treatment toxicity so a lot of people talk about

hypoglycemia and the second generations have less hypoglycemia but there's no difference there's no difference in the

risk of myocardial infarction or mortality it carries the same risk it's

not the risk of hypoglycemia it's the treatment toxicity this is another study

just from last year which showed exactly the same thing if you compare metformin to three different types of

sulfonylureas what you see is that there's a substantial difference in

terms of cardiovascular events so there's a 40 to 60 percent risk of myocardial function or death and it's

the same whether you compare them against the first or second generation to farm finally we also have a randomized

multicenter randomized the placebo controlled trial so in this study which was very interesting it was metformin

versus glipizide which is another so faunal urea and what you see is that in

every case you have less deaths Les Mis

less strokes less revascularization when you put it all together you have almost a 10% reduction in your risk of these

bad events when you use metformin compared to the sofa Andrea's and it

doesn't matter which so far no urea they all are about the same and again you can't understand it until you realize

you're looking at treatment toxicity you see the same thing in insulin infusions

actually for a while that it was popular to give insulin plus glucose after an mi and what they found was that if you look

four to eight years after that trial when you give insulin post them on your risk of reinforcing was almost double

that if you didn't which is actually very scary because this is only like you know a several week infusion or protocol

study this is the de gommi study there was no benefit but turns out it actually might be very very harmful to infuse

insulin at the time of your Marc card infarction for all those basic science reasons we talked about you can also

look at cancer because nobody ever thinks about diabetes and cancer so diabetes is actually associated with an

increased risk of cancer and it almost doesn't matter which site you look at there's about a twenty to thirty percent

increase in the risk of cancer but again what is the mechanism here is it

hyperinsulinemia or is it hyperglycemia it's hard to tell it starts to get

interesting when you compare metformin versus others because at the time of course there was no DPP for so metformin

was the only one which lowered the insulin levels the rest of it we treated by raising insulin levels and what you

can see is that when you compare people using that foreman to the others not

using that foreman their risk of cancer was substantially lower about 14% lower

they showed exactly the same thing in this study where they compared metformin

to other users and basically almost a 40% reduction in cancer I don't actually

believe it's a reduction in cancer I believe it's an increase in cancer on the other side particularly the

sulfonylurea side and the insulin side when you break it down again this is dr.

Currie again who's done a lot of this work you can see that if you compare to metformin what is your risk of cancer so

the so follow URIs have almost a 36 percent increase in your risk of cancer and the insulin of course is the worst

you have 42% increase in risk of cancer insulin of course is a growth factor so

you might well be worried that the insulin is going to make your cats or worse and sure enough it does there's a

also a very small study which showed an increase in the risk of colorectal cancer if you compare insulin users to

non-insulin users but this was a much smaller study late last year they

actually identified a pathway whereby cancer and insulin sensitivity actually

were mediated through the same gene so they actually were looking at these tumor suppressor genes one called p10

and what was very interesting was that they knew that this had something to do

with cancer but at the same time these people were extremely sensitive to insulin and there were also obese and

they developed cancer in other words it goes through the same pathway at least

in this mutation there's a common pathway for insulin cancer and weight

gain that is this mutation the p10 mutation leads to a very high insulin

effect so even though your insulin level is not high the effect is all there what

do you get you get weight gain decreased a1c soar lower risk of diabetes your

sugars are better but increased cancer and this is probably why the t's IDs

didn't really have didn't really catch on because they really work too well because they increase the effect of the

insulin which in the case of the sugars was very good but it wasn't so good and

everything else in fact if you look at the people who responded the best to the

t's IDs they actually had the highest increase in fat mass because they are

having the highest effect of the insulin so it decreased a1c and we thought that

was good but then later on what we found they all gained weight they had increased risk of MI and they

had an increased risk of cancer so clearly there's a link between the insulin the cancer and the

cardiovascular disease as well as the obesity but that is much more well known so if you think about our current

treatment paradigm it really is an epic fail because we only concern ourselves

with the gluco toxicity but we don't think about the insulin toxicity at all

we actually consider it irrelevant so we give higher and higher doses to get the

sugars lower and lower so insulin for sure cures type 1 diabetes but it causes type

2 diabetes that is it is making the resistance worse and the resistance is

insulin insulin causes type 2 diabetes and yet that's how we treat them so if

insulin is the problem it's probably not the solution this is our current

treatment paradigm we keep increasing the insulin and we keep getting more and

more resistance and you all know this from your patients over the years they

take 10 units than 20 units than 40 units and 80 units and you think you're doing a good job but you're actually

making them worse not better because as you increase the insulin you are getting decreased a1c which you

think is so good but you're getting more weight gain more heart attacks and more

cancer so really this is what we're doing right we're giving more and more

insulin and we're getting more and more resistance so we're getting more and more diabetes so you can't treat a

Increased insulin resistance with insulin

hyperinsulinemic state with insulin it's really like giving alcohol to an alcoholic so it's fine in that you can

actually get rid of the delirium tremens right it takes care of the symptoms but

it doesn't do anything for your alcoholism so let's look at studies for

instance where you can lower the glucose without the hyperinsulinemia if our

hypothesis is true we should see a beneficial effect so remember I talked

about the origin trial so this was impaired glucose tolerance so not full-blown diabetes but impaired glucose

tolerance and you see that there's no benefit okay but if you compare this to

using a carbo's which prevents the absorption of carbohydrates so it lowers

the sugars but doesn't raise the insulin levels what you see is that's as a randomized control trial in 2003 almost

1400 patients and followed for three and a three point three years what was their

results well a 49% relative risk reduction in

cardiovascular disease in a very large two-and-a-half AB percent absolute risk

reduction if you think about the cure trials for instance like plavix that's

about the same magnitude of benefit yet everybody and their mother is on plavix and nobody's on akribos yet the truth is

that if you lower glucose with insulin you don't see any effect but if you

lower without raising the insulin you do have a benefit and that takes us oh the

other thing on this study which is very interesting because remember I talked about the pathway of insulin and

hypertension what you can see is that you actually get less hypertension if

you treat these patients with a carbo's so compared to placebo which I had a 17%

probability of developing new hypertension you only had an 11% which was highly statistically significant and

it actually makes a lot of sense because if you're giving a lot of insulin you're going to get a lot of salt and water retention you're going to get

hypertension so the that the other class of drug which is relatively new is the

DPP fours and we don't have the trials yet but they are coming but it makes a

lot of sense the signals are all there because if you look at the onset to

first mace major adverse cardiovascular event you can see that this was a

randomized but this is not a real trial they kind of put all these patients in a

mishmash and kind of lump them all together but you can see that if you look at them there seems to be a very

significant protective effect against cardiovascular disease with the use of

saxagliptin you can see that that effect actually exists for all the DPP for so

sittig lipton saxagliptin and linagliptin and it seems that the DPP 4 is much better than the comparator which

makes sense because the DPP 4 is not going to raise your serum insulin levels on a chronic basis so this is the same

sort of data and you can see that even though as only one year you start to see a lot of significant benefits this is

not a real trial this is just kind of clumping everybody together what's very

interesting is that in the case of linen Lipton they look at the comparison so if

you compare linagliptin to sofa SIBO it actually didn't look any better what was

what what it was was versus the sofa no urea it seemed to be that it's not so much

that the linagliptin is so good for you it's this so fond of urea is bad for you

and that's the real treatment toxicity this is where all the toxicity lies and

these are the trials that are coming up and we have actually a number of trials the earliest of which I believe is

coming out later the here looking at saxagliptin in

comparison to Sasebo and later on next year it looks like there will be a siddig lipton trial as well so those

should be very interesting and all the signals point to the fact that there likely is a significant protective

effect against cardiovascular disease but we all have to wait for those so if

we think about the treatment of diabetes now let's go over things so insulin causes diabetes insulin also increases

cancer and cardiovascular events so the real key to the rationale treatment of

diabetes is to decrease the insulin if you can decrease the insulin you can

reduce diabetes cardiovascular events and cancer so insulin is really the

problem not the solution this is where the problem lies if you decrease the amount of insulin you take your sugars

are going to go high so there definitely is an effect of the gluco toxicity so how are you going to get around that

well so there's good medications to use for diabetes so definitely metformin definitely

januvia and akribos the problem is that they may not be enough there's bad ones

too so insulin we know is a bad agent sulfonylureas and teas ADIZ because they

increase the insulin effect those treatments actually increase your diabetes but take care of your Sugar's

for you and the other thing we don't think about a lot is surgical treatments so you can do surgical treatments for

the treatment of obesity that is you can do a roux on why bypass this is a sleeve gastrectomy where they cut you know most

of your stomach out and there's this banding where they put a band around your stomach so you can't eat what's

really interesting about these is that the cure rate for diabetes in these surgical treatments is more than 90%

if you take patience and you give them a 500 kilo calorie per day diet for eight

weeks you say so you see actually the same thing their plasma in the glucose

goes down their hepatic glucose production goes down and the fat comes

out of the liver as well as the pancreas but what's interesting is that they reverse the type 2 diabetes in these 10

patients which is actually very important because it means that the changes in the insulin sensitivity and

beta cell function are reversible that's very important because the way we think

about diabetes right now is that it's a chronic progressive disease and the truth of the matter is that it's not

it's a reversible disease we just couldn't reverse it because we were making it worse yeah

Yeah right but they should actually be worse in terms of their diabetes they

should actually be worse so if it is a chronic progressive disease and you actually get beta cell failure which is

what they all say the extremely obese should never get back off of there they should never cure their diabetes because

their beta cells should have all failed by now right so this both this one as well as the the

this one I'll show you which is the surgical patients they're all the worst diabetics you could ever have

right and they all got better that's

true this is this is obese yes there's a stream in obesity but they go hand-in-hand so there's a lot of

diabetics as well but the point is that it's actually not progressive it's actually reversible we know it's

reversible because who can cure it right that's the only point exactly

Reversing type 2 diabetes

exactly so the point is that it's not a progressive disease which is the way we think about diabetes so if you look at

surgical treatment so both Rouen Y as well as the sleeve gastrectomy there's a

90 plus percent cure rate so if you look at number of diabetic medications they come really close to zero by the end so

that means it's actually reversible but if you think about it basically the surgery they're just

basically enforced fast they're just fasting whether you use a low calorie diet or whether you use

fasting that's the same thing but why do I need to do surgery for these people

then if all of the benefits is mediated through fasting why can't I fast them so

the thing about fasting is that it's really a time-tested treatment so this is asterisks I loved it as a kid but

it's a bit it's a cartoon about the ancient Greeks and the ancient Romans so

what they did was this guy was the chief and he was fat he had fatty liver and

all that so they sent him to the hot springs where he fasted and you know took hot baths and stuff just to show

you that it's actually not some crazy idea that I just came up with they've been using fasting for like 2,000 3,000

years so Hippocrates was actually a major believer in fasting so he said our

food should be our medicine or medicine should be our food but to eat when you are sick is to feed your sickness so

there's a lot of myths about fasting and we'll go through them one by one but a lot of people say oh it puts your body

into starvation mode it deprives the body of nutrients a lot of this weight

loss is from water it causes hypoglycemia it causes yo-yo dieting

you're overwhelmed with hunger and what most people say to me it's crazy like

most people who haven't thought about it for more than two minutes it's crazy so when they did actually use fasting this

was back in the 60s they studied this and one of the things that was very very interesting about fasting was that

people were not overwhelmed hunger so in fact the most astonishing aspect when they actually fasted these

people for anywhere from 12 to 117 days that's like more than three months of

fast was the ease with which it was tolerated that is the hunger actually

disappears and in fact it disappears after the first couple of days the other

thing people say is that while you're going to eat more afterwards so it's going to be nothing right well when they

studied that it turns out it's not true so when you fast for a day the next day you do eat more so in this study they

increase from 24 to 29 hundred calories so they add in an extra few hundred calories on the day they were eating but

since they ate nothing on the other day you can have a total net caloric deficit

of 1958 calories so yes you do eat more the next day but not nearly enough to

make up for what you didn't eat on the day that you're fasting so the world record was actually 382 days of fasting

and what was interesting this was in 1973 when they still did this kind of stuff they measured his blood work all

the time and there was no problem the blood glucose comes down but doesn't you

don't become hypoglycemic the plasma calcium plasma phosphorus uric acid all

those were measured and there is no problem there was he was four hot he is

456 pounds to start haha so it's not a total fasting it was a

total fast this was published in 1973 fluid yeah yeah oh no no no you can't do

that burgers all Tigers but they drink no and this one is just

water this is like with Sam so this was

the system world record this is not typical

what's interesting what's interesting when you look at fasting is what actually happens to the hormone levels

so in 1974 this is the New England Journal of Medicine they looked at it and what they saw was that the glucose

just like the previous patient it goes down but it remains stable but plasma insulin significantly decreases and you

not only do you get that but you get a significant spike of growth hormone well that's very interesting if you look at

more recent studies of fasting what you see is the same thing stable blood

sugars but the insulin level just drops like a stone if you look at the free

fatty acids it actually significantly increases because you're actually feeding your body through your own fat

that's great if you look at the weight it comes down

but if you look at the resting metabolic rate it actually maintains itself very

well even after 22 days of alternate day fasting so this is of course the major

problem with most diets and this has been shown over and over again as you diet your metabolic rate drops and that

makes your caloric intake equal again and you're not going to lose weight so your plateau if you think about those

diabetics who decrease their calories from 2,000 to 1,700 they gain 20 pounds

why because the resting metabolic rate goes down but it doesn't happen in the

case of fasting if you look at fat oxidation it's significantly increased

so the fat is being burned off and the carbohydrate and goes down because you're not taking carbohydrates you

don't have any stored carbohydrates save a little bit of glycogen it's all fat stores and that's what's happening

Fasting and type 2 diabetes

that's excellent if you look at insulin sensitivity you can show a significant

improvement so if you put them on a you glycemic lamp again and then infuse insulin you can tell how well the body

is using the glucose how well it goes into the cell and that's a measure of the insulin resistance so what you do is

you've put people healthy people on intermittent fasting and you see that there is a significant difference in

their insulin sensitivity the other interesting thing is that the norepinephrine levels significantly

increase so this is resting energy expenditure again you can see that it is maintained over four days of fasting so

people think oh you're going to be tired you're not you're Mazal basal metabolic rate and you're resting energy

expenditure is the same but look at norepinephrine your norepinephrine levels your adrenaline levels go through

the roof you have more energy while you're fasting not less so here's your

insulin levels your insulin levels go down which is what we expect your glucose levels go down it is what we

expect and your fatty acid levels go up that's exactly what we want

now think about ICU care for for a minute this is what happens when you fast think about when you go into septic

shock or if you get a pneumonia or cold the first thing your body does is put you into severe anorexia

you don't eat why your basal metabolic rate stays the same

your epinephrine your adrenaline levels go up and your glucose goes down which

is what you want you want to put the glucose and lock down because if you got bacteria circulating all over your body

the last thing you want to do is have a lot of sugar running around all over the place that's exactly what you want so

you lock down the glucose it's like a prison break right everything goes into lockdown so you lock down the glucose you lock

down the iron because that's what the bacteria want you pump up the norepinephrine because you want to

support your blood pressure and then you wonder in the ICU why when you shove a nasal gastric tube the first

day and start feeding them you don't have any benefit the body is already

telling you don't eat severe anorexia they're not going to want to eat the

eyes you talk I know they all say that

they all say that I don't think they're correct this is they didn't tonight yeah

yeah yeah that's a different that's

through the stress hormones and so on that's a little bit different but if you look at the nice sugar study from this

was the New England Journal in 2009 this was tight glucose control in the ICU what happens when you give people

insulin to control their sugars then contrary to what was expected you didn't

show a benefit to tight glucose control with insulin you actually showed

increase mortality in the ICU so the

other interesting thing hormonal wise is that you get a spike in their growth hormone so you can see that as you fast

your growth hormone actually spikes up and the growth hormone we know increases the availability and utilization of the

fat and also preserves your muscle mass which is very important the if you look

and this is I think the best study because what they did was they took caloric energy restriction but they did

it two ways so these are equal calories one is a continual everyday lower your

calories a little bit the other one was a fasting protocol but the calories are

the same between the two arms and what you see is that the weight there's no difference but you can see that the

intermittent ier which is intermittent energy restriction actually loses a bit

more weight their body fat goes down a bit more their waist size goes down quite a bit more

look at the insulin sensitivity if you take the same amount of calories every

day your body just gets used to it so your insulin sensitivity doesn't change

but as you do intermittent energy restriction your insulin sensitivity

significantly increases and this gets back to the nitro patch because the way

that you have to increase your sensitivity is to have periods of extremely low levels so that's what

you're doing you're just taking off the nitro patch as you have a fasting day

your insulin levels are going to go down and that low levels of insulin are going

to increase your sensitivity so is that a holding fast and you just not in

carbohydrate you can't because protein actually raises your insulin levels

that's not very well known but if you look at studies of whey protein or other

types of protein your insulin levels your glucose does not go up but your

insulin does so beef for instance actually is fairly insulin genic and so

is way which is very protein so you can't it's not going to work you can eat all fat for the day but that's what

you're doing actually when you're faster yeah the all-butter diet you can

actually do that but you're doing that when you fast because all you're doing is you're burning fat you're not burning

protein because your lean mass stays is saying but you're basically oxidizing your fat and this is the insulin levels

as well as the Homa which is a measure of insulin sensitivity so this is intermittent energy restriction and this

is continuous energy restriction so you can see there's a significant difference and a much better outcome when you use

intermittent energy restriction and this is independent of the calorie restriction so both arms have the same

amount of calories so if you think about the clinical effects you might say well is there any clinical benefits to

fasting and the evidence is still accumulating one of the things that's very interesting about the Mediterranean

diet is that people actually thought studies were done in Crete where they

say oh the cretians had very very low cardiovascular disease and they said

well it's because of the Mediterranean diet but they what they forgot is that the Greek Orthodox Church fast like all

the time right some people say between 180 and 200

fasting days a year I know I know but nevertheless it's still it's still an

essential I know I've asked a few people who are because it's actually I'll get

the bat in a second so you can see that actually that fasting reduces your diabetes so if you take obese type 2

diabetics and you put them on a standard calorie restriction they do okay as in

their weight does put down on a standard color car but you can see both fasting

protocols whether it's one day a week or episodic five days they come down much better

what's again interesting is if you look at the percentage of subjects with the hemoglobin a1c less than 6% you can see

compared to the standard diet the fasting patients did much much better so

they had much better glucose control the other thing that's important is that the

five-day they add do episodic 5 days 5 days of fasting right then a break yeah and as episodic

you'd have to go back to the haha fast things not nearly as difficult as you

think it is the other thing that you see in fasting which is always which is

actually compared to standard diet what happens and people always forget this is

that weight comes down but in most diets you lose both fat mass as well as lean

mass and that's in almost every single diet study you see this but when you look at the fasting study the fat mass

comes down so day one is 43 down to 38 but you're look at your fat free mass it

goes from 52 to 51.9 in other words there's no difference there's no muscle

loss in a fasting diet and that makes sense because if you think back to the

caveman days and you couldn't hunt anything you couldn't get anything for three days if you were weak as a kitten

you'd never eat again because you couldn't get out there and hunt so what the body does is it preserves the lean

mass with the growth hormone pumps up the adrenaline and gives you enough energy to get out there the waist

circumference of course comes down much more but it's all fat it's all fat mass that's being burned if you look at

cardiovascular risk factors you can see that the total cholesterol on this alternate daily fasting is down about 20

something percent the LDL cholesterol comes down the HDL does come down somewhat but you can see it's much less

than the others and the triglycerides significantly decreases almost about 30%

in these fasting protocols another doctor dr. Horne recently has published

a couple of studies these are association studies but he looked at Mormons because they typically fast one

day per month and he took these mormons and he compared them to the ones who

fasted and the ones who didn't fast and he tried to see who did better well he actually didn't do it for fasting but he

looked at all different you know religious observance social supports and he couldn't find any relationship except

for fasting the only thing that came out was the fasting fasting seemed to have a significantly protective effect

so then he went on to do a prospective study of patients undergoing angiography and he looked at the people who fasted

and the people who didn't fast and again what he showed was that for a similar age in a similar BMI they had far less

diabetes and slightly less coronary artery disease now this one is they're all going for angiography so you might

expect that there's a very high prevalence but there seems to be an association this is not randomized but

it there seems to be an association between less diabetes and less coronary disease so let's think about treatment

of diabetes again so we know that insulin causes diabetes

garbled especially relatively

yeah with the South Asians I there's really you know the data is just not

there I couldn't really comment either way it could be true it could not be true I couldn't really tell you for that

population so if we think about type 2 ba diabetes and how we treat it so what

we've gone over is that insulin causes diabetes it increases your cardiovascular events and cancer and the

other thing is that it's a curable disease but we have to lower the insulin levels so what we need to do is

basically bariatric surgery without the surgery then that would be a fasting protocol because all these beneficial

effects of fasting are going to help our diabetic patients so this is the real

question we have now can you actually

can we actually cure type 2 diabetes because we know is a curable disease

well think about it for a second that's incredible because if there's no

diabetes there's no more diabetic nephropathy no more diabetic retinopathy no more

neuropathy all right ha ha ha

the whole problem with diabetic nephropathy and we treat this all the time is that we don't do anything for

these patients you're just marking time until dialysis because you can't cure

the diabetic nephropathy without curing the diabetes it's the same with the

nephropathy the retinopathy you're just marking time and the treatment would be

no drugs no surgery in fact you'd be reducing your drugs there's no cost to

the patient in fact you'd be saving them money and there's no long-term side effects the treatment has been used for

5,000 years and in fact we know what happens when you fast somebody by stapling their stomach for six months or

eight months or ten months at a time nothing they get better the Swedish obesity study which is on

bariatric surgery they're living longer without diabetes but why do I have to do

the surgery in fact I think that we could use a six to 12-month course of

intensive fasting to cure diabetes and in fact I've already done it so this is

my patient I just saw yesterday so he's 45 years old he's had diabetes for 20

years he was on a hundred units of insulin a day I said to him about two

months ago this is crazy I think we're killing me he said you know you you're right so I

said okay come to my clinic I'm gonna put you on a fasting regimen so I saw

him yesterday he's off all his insulin his sugars are like 5 to 7

I said you're basically cured of your diabetes tell us more helos I just want to know

what you told it okay I'll get to that insect let me just finish up and then I'll get to that in sexy do it okay this

is actually not my only patient I actually have three patients now to which were much less severe who are only

on metformin I put them on two months they are very much less severe no

medications their a1c was six point three percent in other words they are

cured of their type two diabetes the other one had diabetes for twenty five years told I was seeing them

because they had nephropathy now they're cured so what do we do now it's time to

get started I think we need to change the way we think about diabetes and

change the treatment that's the only way we're going to treat it what we've been doing is just making it worse and

because we've been making it worse we say it's a chronic disease that's the wrong idea we've misunderstood diabetes

and we have to change that I think that's the

English (auto-generated)