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Dr. Paul Mason - 'Treating Metabolic Syndrome'

this talk that I'm about to give was

going to be about good health and what

good health is and the more observant of

you looking at this picture here will

have figured out the problem already

for this chat with metabolic syndrome so

that we soft drink bottle sitting there

would possibly be a problem

so we're not talking about good health I

thought well what is good health it's

the absence of bad stuff it means you're

not overweight you don't have high blood

pressure you don't have high levels

there triglycerides in your blood the

level of HDL that good protective LDL is

high or it ought be high and you don't

have elevated blood sugar levels so in

essence this is good healthy so absence

of what we call metabolic syndrome

metabolic syndrome to a doctor has five

features if you have three of those five

I will diagnose you with metabolic

syndrome that includes if you have

weight around your abdomen if you're

fasting glucose is over five point six

if your blood pressure is over 135 and

85 if your triglycerides are over one

point five if your HDL is less than one

if you take three of those boxes you

have metabolic syndrome now the

interesting thing is that each one of

those problems is caused by resistance

to insulin every one and you'll notice

that LDL doesn't form part of that

definition that's because we know just

looking at LDL level per se it's not

that good so we're going to take a bit

of a tour and have a look at each of

those five features and have a look at

how insulin parlays into those this is a

DEXA scan of one of my patients and what

you can note is that there's this yellow

here this is fat this is an pattern of

abdominal obesity this is the bad stuff

this is the stuff that's associated with

risk of heart disease and we also know

very clearly that as your level of

insulin

there's a strong correlation with

increased body weight so insulin is

implicated in obesity so how does it

actually causes obesity so we know that

it does make the fat cells bigger but

let's have another look at that

mechanism here so this is a slide that

you've seen already today but we're just

for the sake of completeness run through

it again so if you want to make that fat

cell bigger you have to stuff more in

and the things that you want to put in

if we that was the goal would be a

triglyceride here and glucose because

when the glucose and fatty acids from

the triglycerides are inside the cell

they combine to form the storage form of

fat which is called a triglyceride

now this driver's robe molecule is too

big to diffuse across the cell membrane

it's not going anywhere so for it to be

made small enough so that the fatty

acids can cross over this membrane here

we need to cleave it and that's where

something called lipoprotein lipase

comes into its own and it's no

coincidence that you give a little bit

of insulin and the activity of this

enzyme here increases substantially

insulin also acts on this transporter

here what we call the glute 4

transporter this is like a gate that

glucose uses to get into the fat cell if

you have an increase in your insulin

level it opens the gate glucose goes in

and the end result is that you've now

stored fast and the fat cell is bigger

now to add insult to injury if you want

to burn the fat you have to repeat this

process in Reverse where you first break

this complex molecule down and you do

that using something called hormone

sensitive lipase

what does insulin do to to action of

this wipes it out so there's a triple

effect there if you have elevated

insulin levels very very clear that that

elevated insulin leads to increased fat

size so let's have a look at number two

elevated blood pressure it's been

clearly shown that elevated insulin

levels correlate with increases in blood

pressure so on this graph you can see

here from the top line this is what

happens if you give people insulin on

the bottom one that's what happens if

you don't so what you can see is a clear

causative mechanism of insulin in

increasing their blood pressure and this

is something which we see every week in

clinic once people start the low carb

diet the insulin levels fall what

happens we have to reduce their blood

pressure medications that they're

invariably on otherwise they feel dizzy

it will overshoot so you control insulin

levels you can absolutely can control

blood pressure now this is the most well

known mechanism that insulin resistance

can cause change in blood pressure

essentially if you end up with a fatty

liver you damage your liver you increase

the amount of uric acid that's produced

and that uric acid inhibits the action

of something called nitric oxide and the

job of nitric oxide is to cause the

blood vessels to relax that reduces your

blood pressure now while this is the

most well known mechanism it's not the

most important model to understand the

major cause of hypertension we have to

understand a key concept and that's it

fluid follows salt wherever it is in the

body if you increase the amount of salt

you have in the blood that will draw

fluid to it we've all probably come

across this in chemistry classes in

school now insulin does a magnificent

job at telling the kidneys to hold on to

salt so having a look here this is a

example of the structure of the kidneys

so this is where the blood come passes

through here in and out here and some of

the fluid from the blood gets what we

call filtered here and that fluid passes

through this tube you'll all the way

down here until eventually it passes out

into the urine and what you can see here

is that these four sites here insulin

draws salt back out of that potential

urine and pushes it back into the blood

so in a state of excess insulin our

bodies are doing everything they can to

hold on to salt

now this explains a couple of things so

first of all essential hypertension that

type of high blood pressure that your

doctor said we don't know why you get it

you just get it if you speak to the

smart doctors their renal doctors

they're the ones who understand this

stuff they will tell you that high blood

pressure essential hypertension is an

insulin dependent state what does that

mean you don't have high insulin levels

you're probably not going to have high

blood pressure and this also explains

something else ever heard of the Kyoto

flu back in the 70s used to be called

the Atkins flu they didn't really know

what was going on back then but we do

now so we understand it's due to salt

balance but it's this is the mechanism

why if you something on a low

carbohydrate diet your body will not

hold on to that salt that it once was

because your insulin levels have dropped

so you'll end up with a temporary period

of salt deficiency until your body can

re adapt to that

remember fluid follows salt you lower

the salt level in your blood you lower

your blood volume you lower your blood

pressure you're probably going to feel

dizzy and we know that amongst other

things that dizziness is one of the key

features of what we see in the keto flu

now as an aside there's a lot of concern

about salt and I just like to present

this paper here so big paper published

in the New England Journal of Medicine

over a hundred thousand participants

followed them up for almost four years

and they mentioned how much salt was

coming out in the urine versus your

chance of dying something we call all

cause mortality so this is the graph so

what we can see here is running up the

side here this is your chance of dying

from any cause and on the bottom here

this is how much salt you are excreting

in your urine so we can assume that your

salt intake must have been at least that

much and what we see here is that the

lowest level of mortality was somewhere

between four and six grams of salt a day

if you had less salt than that look what

happens to your risk of all-cause

mortality if you're got two

to Seoul today that's about double the

risk of dying from any cause so when

we're talking about salt it's critically

important especially if you're on a

ketogenic diet because you have to

understand ketogenic diet means low

levels of insulin your body's not

holding on to that salt so a lot of

people will actually find that to avoid

the symptoms that kiddo flu they

actually need to increase their salt

intake into the diet now let's move on

to another of these features of the

metabolic syndrome triglycerides now

clearly all the epidemiological data out

there says if you have a high level of

triglycerides in your blood your risk of

heart disease is increased and this

graph here demonstrates their

association with diabetes and by proxy

insulin levels if you have high levels

of insulin as seen in diabetes you have

high levels of triglycerides now to

understand why you have high levels

their triglycerides we first of all have

to understand that the liver can store

glucose as glycogen but only up to a

point a hundred grams after you flood

the liver with sugar and it reaches its

capacity it has nowhere to go it can't

be stored so instead what happens is it

starts this process called de novo

lipogenesis de novo lipogenesis means

you'll produce fat you'll produce

triglycerides and this is a very elegant

study where they said we're going to

give people more carbohydrate than they

can burn and we'll see what happens

so on day two here you'll see that they

burnt that much of the carbohydrate and

they test they measured that through

some fancy techniques and they turned

this much carbohydrate into glycogen

stores now what happened on the next day

because their stores were quite full

they probably burned a little bit of

glycogen but there wasn't that much room

so they burnt a bit they burn a bit more

actually they stored a vinous glycogen

but then they started to produce fat and

as the days went on and you can imagine

that this is happening everyday to

people on this day

an australian diet they're giving their

bodies more carbohydrates than they need

and this process lipogenesis making

triglycerides is occurring you put in

more carbs than you can and because you

have insulin resistance that other

tissues the sugar can't be taken up that

effectively in them in the muscle

anymore it has to go somewhere

part of it goes here and it forms fat so

if we have a look here this is a liver

we make this fat de novo lipogenesis so

what happens then it gets exported

remember these V LDL particles from the

last lecture they're holding

triglycerides enters the circulation

Bank you now have increased

triglycerides in your circulation now

having a look at HDL this relates to

triglycerides we know HDL is good if you

have high levels of HDL it is a very

good indicator that your risk of heart

disease is reduced now the problem is

that we can see the triglycerides can be

taken up by the HDL molecules and

through various pathways

if the HDL molecules take up too much

progress all right it ends up leading to

their breakdown their catabolism hence a

reduction in HDL so the same mechanism

that causes an increase in triglycerides

also eventually leads to a reduction in

your HDL level so finally we come to

Step five of the metabolic syndrome

elevated blood sugar level now again

this is clearly related to insulin

resistance so what we're seeing here is

a graph across the lifespan theoretical

demonstrating how insulin is becoming

more and more resistant what this means

is it doesn't work as well as it used to

work so the compensatory response of the

body is to release more insulin for the

same effect and if we have a look at

what happens as the insulin resistance

is occurring this line here is fasting

plasma glucose we can see that fasting

plasma glucose increases now to

appreciate how this resistant causes

have to understand that the insulin is

what actually draws the sugar out of the

circulation and in a normal situation

where insulin is working it does this

quite nicely it goes into the liver

plunk a bit into the muscle take a

little bit into the fat sure and you're

not left with an excess amount of sugar

in the bloodstream but if insulin stops

working as effectively you still take a

bit of sugar up but not as much what

you're left with is a large amount of

sugar still residing within the blood

vessels so I thought I'd now go back

this is the features of metabolic

syndrome and clearly they're all caused

by insulin resistance so let's have a

look at some modern research done about

33 years ago because we've got a really

good practice in medicine of ignoring

good studies and good science this study

took ten diabetic Aborigines who all met

the criteria for metabolic syndrome they

lived in urban areas and they were

recruited for a seven week trial where

they went to live a traditional

lifestyle eating a traditional diet and

this was conducted in the Punta Shan

community about an hour's light plane

flight north of Derby so what happened

so short answer things got better this

is a graph here showing their blood

glucose level their fasting blood

glucose level on average at the start of

trial was eleven point six after seven

weeks just seven weeks it went down to

six point six their triglyceride level

at the start was 4.0 - and after seven

weeks it went down to one point one five

huge reductions what about their body

weight we saw a large reduction in their

body weight a main reduction in their

BMI went from twenty seven point two

down to twenty four point five so you're

probably wondering what is it in this

traditional diet that led to these very

impressive results well I did a bit of

research and when I actually looked into

the literature a bit deeper it appears

that the indigenous population has

always

valued fat in the diet this here is a

witchetty grub

67% fat and considered a delicacy so

when I have looked at the data from this

study and I plotted it and I compared it

to the NHMRC recommended diet so this is

a diet here that fits within their

recommended macronutrient intake I

compare it to a typical high-fat

low-carbohydrate diet which I use for my

patients and I think you can see that

the diet used in this study is far far

closer to a low carbohydrate diet

it's almost opposite of the diet that's

suitable and recommended by the NHMRC so

I just want to try and present a view of

the totality of evidence here so I'm

going to present a series of

meta-analysis now the way these studies

work is that each line here represents

an entire study and the results are it's

called a forest plot and the results are

shown here on the end and this point

here represents the average results and

the length of this line represents a

narrow bar so this large dot down here

represents an average of all the results

so when we have a look at low-carb diets

and weight loss across the board the

science says they help you lose weight

we apply this same methodology to

looking at triglycerides again down the

bottom they help you lose weight they

help you lose stroke lower your

triglycerides your HDL well look at

these big increase in the good HDL what

happens to blood pressure

well blood pressure goes down and we

know exactly why's that salt effect in

the kidneys and finally we get a

reduction in the blood glucose level as

well as we can see from this point down

here so we're now just going to take a

little bit of a detour and have a look

at what causes

insulin resistance clearly it's not good

clearly it's doing us a lot of harm so

I'm going to also take you through a bit

of a journey on some of the patient

results that we've seen in the clinic

over the last few years so the first

point here is a visceral fat fat in the

liver leads to insulin resistance and

we've now started to figure out the

pathway as hell

this is retinol binding protein for you

don't need to know the name but you do

need to know that it correlates very

well with body mass index correlates

very well

insulin index and it's been implicated

as a causal mechanism of insulin

resistance it's produced by fatty livers

so here's what happens and this is

grossly simplified but we might present

the science at a conference in the

future you have a high carbohydrate diet

and in particular fructose is implicated

here as most of you all know and that

leads to fat accumulation the visceral

fat and around the liver that then

directly leads to an increase in this

retinol binding protein for and through

various mechanisms this is the molecule

which actually contributes to insulin

resistance now I think you can see the

problem here because we know that

insulin resistance leads to fat

accumulation this is a rust and rather

nasty cycle here and the only way to

deal with it is to eliminate

carbohydrates from the diet so I was

always impressed in the clinic where not

have people come in and not be morbidly

/ obese so sometimes be 130 hundred and

forty hundred and fifty hundred and

sixty kilograms and neither lose maybe

ten percent of their body weight they'll

still be grossly overweight but their

blood tests looked very very good they

look so much better than they were

before and this is why this is a DEXA

scan of that same patient you saw

earlier you can see the fat around the

viscera here a repeat scan six months

later after only about nine percent

weight loss and we can see the visceral

fat is all but dissolved so the fat that

you lose first on a ketogenic diet

is the bad stuff this is magnificent so

a very modest degree of weight loss is

going to be beneficial for your health

now if we actually have a look at this

in another way I can assess liver health

through blood tests which I do in my

clinic so what you need to understand

about liver cells is that they've got

chemicals and constituents inside them

that aren't really found anywhere else

in the body in high levels and if you

damage that liver cell it will release

the contents into the circulation where

we can detect it with a blood test and

if we see certain chemicals that we know

are particular to liver cells in the

circulation that infers that there's a

degree of damage happening to the liver

so what we're having a look at here I

won't you have a look at this bottom

line on the line all the doctors in the

audience know that alt relates to liver

health look what happens before a

low-carb diet and after a low-carb diet

the liver gets healthier now this is

probably one of the most important tests

I do in the clinic and call it the

glucose tolerance insulin response test

what happens is that you have a blood

test and following that you have a drink

at half an hour are not shown here one

hour and two hours we then repeat blood

tests but rather than testing only

glucose which is the standard test done

we also measure your insulin level and

this is really really important because

the pattern of insulin the height of

insulin is very predictive of your

future health outcomes this was a really

nice study published several years ago

and the main finding from this study was

that the peak insulin depending on

whether occurred at 30 60 or 90 minutes

was very predictive of your chance of

developing diabetes over the next 11

years so in this first group you can see

your chairs are becoming diabetic over

10 years not so bad

what happens if you're a pattern for

almost a 1m2 chance of developing

diabetes understanding your insulin

profile is essential to understanding

your health so let's have a look at

real-world patience these are actual

patient results

so we can see here looking at the

insulin we have a pic of insulin

occurring at the one hour mark so we'll

just ignore the glucose for a moment

so what pattern of insulin is that

that's a pattern three percent chance of

progressing to diabetes over the next 11

years 15 percent what about this

individual their insulin levels are not

as high doesn't look as bad right

but it's the duration and the timing and

the peak which is also essential we can

see here it's constantly going up

there's no peak in the first two hours

chance of progression to diabetes in the

next 10 years or so about one in two so

we can also get some other interesting

insights from this type of testing in

our patients so this patient came to me

and they were caught in a pattern of

cyclical eating so those of you who are

now ketogenic think back to when you

used to eat tabs come morning tea time

you would hunt down a small child if you

needed to to get something so why is

that so something I see not infrequently

in my patients is something called

reactive hypoglycemia so you'd think

that if you stuffed 75 grams of glucose

into the circulation that your sugar

should be high and should stay high but

not in everybody in this individual you

can see they overshot they released

insulin and that insulin overcorrected

the sugar that was put in throughout the

two-hour mark they left with a blood

glucose level of 1.1 in this situation

you're going to feel lousy all the

doctors in the audience are probably

wondering what happened to this patient

they find they did not die

but at this point in time this patient

was going to crave carbohydrates now

you've seen bowl and a half a crunchy

nut cornflakes coupler up and goes is

the same as this blood test if you start

off your day with that healthy breakfast

for this individual that means they'll

be caught on a cycle of reactive eating

trying to restore their blood glucose

levels back to normal so in this

situation this is a revelation for this

patient you stop putting that rubbish in

at the side of the day your blood sugar

levels stabilize and that's exactly what

happened now one other point is that

because we do the testing so depending

on who you are we'll do the half now

testing as well as a one hour testing

but something we see not infrequently is

an elevated one hour test or a half an

hour blood sugar with a normal two hour

test now a blood sugar of over eleven

point one at any point time during this

test is consistent with the diagnosis of

diabetes so I suspect there's a lot of

stuff even if we were only measuring

glucose if we included the one hour

marker into the standard test it would

be a whole lot more diagnostic so we've

talked about the insulin resistance that

tends to develop over a long period of

time and so what essentially happens

this was very well covered by Doron is

that over time insulin gradually rises

to compensate for the resistance but

there reaches a point where it can't

compensate any longer and then your

blood sugar starts to rise and then

several years after that your insulin

secretion reaches a peak now this is

what is in common parlance known as

pancreatic burnout now I'm going to tell

you what causes this so you've all seen

before in my previous lecture what

happens when sugar attaches to proteins

glycated them that leads to the

formation of something called advanced

glycosylated end-products

that leads to

swinging proteins and basically D

functions it well this very process has

been shown to happen in the cells of the

pancreas that make insulin now I don't

know if you think that's ironic or not

but the sugar which the insulin is

trying to control will actually kill the

cells that release the insulin now one

of the exciting things that we see

though is that this process if you don't

get to a too late

he is partially reversible and I can

actually test people's ability to

secrete insulin I measure something

called C peptide and what we're seeing

is that we have been doing it for very

long but the data looks relatively

promising at the moment that we're

starting to see a restoration of

people's ability to secrete more insulin

over time it's taking several months but

it looks quite exciting at the moment so

let's think about this chart of insulin

resistance and compare it to patients

we've actually seen in the clinic so

these are actual patients which I've

seen so here we see we're right down the

left hand side healthy days blood

Sugar's low insulin slow ten what

happens now blood Sugar's low but you

can see that insulin is now come up to

83 this is not diagnostic of anything

this individual would go and have

standard testing and be told they have

nothing to worry about it's at this

point that they might be told they have

pre-diabetes because their blood sugar

here has started to come up off the

baseline but you can see here the

insolence even higher and the final

stage is now blood Sugar's eleven point

four that's diagnostic of diabetes at

two hours this patient would be told

that they have diabetes but have look at

the insulin the insulin is actually not

that high this is demonstrating how the

capacity of the pancreas to secrete

insulin actually gets damaged when it's

exposed to sustained elevated blood

sugar levels and your insulin level will

then drop so here's a good news we can

fix this and you can fix it in a

relatively short period of time this

patient

over about three months have a look at

the one our level of insulin there big

drop this patient again some quite

reasonable drops even more weight loss

this patient again some very impressive

drops so we can actually reverse this

insulin resistance we can test it we can

prove it thank you