What is best diet for metabolic syndrome
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
