Jeff Volek, Ph.D. – Keto-adaptation Counteracts Insulin Resistance and Reverses Type-2 Diabetes (Transcript)

Intro
[Music]
okay well Thank You Angela and it’s great to be here thank you David for
that deep dive into cholesterol and heart disease was very eye-opening
I apologize might think I lost my voice yesterday was so exciting talking to so many people but I hope I could make it
through that hour here I just wanted to quickly thank to epi genex and other
sponsors and dominic and Angela especially for coordinating this event it’s really I think the highlight of the
year in terms of low carb conferences so thank you so my talk is on keto
adaptation insulin resistance and type 2 diabetes and I want to take a little
Keto-Adaptation Counteracts Insulin Resistance & Reverses Type 2 Diabetes
time to explore those terms and flesh them out a bit more especially Aikido adaptation which I think familiar term
to many of you but it is a term that captures the complex diverse processes
that occur when we restrict carbohydrates in our diet and it’s anything but trivial so I want to talk a
bit more about what keto adaptation means and what’s happening in the body
and insulin resistance is also a term that’s very common but very complicated
in terms of underlying cellular events that account for insulin resistance and
of course type 2 diabetes is huge problem and I want to tie these all together in the talk today so just
quickly to update you if you aren’t familiar with some of the real
statistics on type-2 diabetes it’s scary it’s a true epidemic and really pandemic
because this is not something unique to the u.s. we have a worldwide plague
that’s spreading across the country it is about twelve thirteen percent of the
population in the u.s. so we’re talking about 30 million people with type 2 diabetes and it’s really even more
Diabetes is a Pandemic The scientific consensus is such that diabetes is a chronic disease that is irreversible.
prevalent in many the country’s China has about a hundred million type 2 diabetics and India’s
clothes so this is as no continent that spared from this disease in the u.s. to
it it’s much higher prevalence in older folks so we have about 25 percent of
adults over the age of 65 had type 2 diabetes so a huge amount of personal
suffering happening in these folks but it’s also a huge economic burden we have
in the u.s. we spend about two hundred and forty or fifty billion dollars
managing diabetes alone and that’s the cost of managing diabetes and also the
the cost of lost productivity as a result of diabetes so it’s expensive
disease that we can definitely save people’s lives and save a heck of a lot
of money through nutritional approaches just like keto adaptation and if you
look at the pipeline of people that are at risk of developing type 2 diabetes it’s huge so we need to really do
something about this this is a paper from Journal of American Medical Association just published in 2015 that
shows one-half of adults in the US have pre-diabetes I don’t know if if you
appreciated that I certainly didn’t think we were quite at that level of pre-diabetes but that’s the new normal
the average person now actually has prediabetes so that’s the problem and
here’s the solution it’s keto adaptation and keto adaptation is a term that my good friend Steve
Finney coined back in the early 80s it was a toxic term for him he suffered a
lot of just being ostracized really from a scientific field medical field because
he was studying keto adaptation and and I think yet this turn was one that very
accurately captures this very complex process it is a process that occurs over time it explains how our bodies adapt to
a situation where we have very low glucose availability and we not only
survive I would argue we actually thrive okay who’s the mic there okay I’ll be
Insulin Resistance & Keto-Adaptation: Opposite Ends of a Phenotypic Continuum Ubiquitous amounts of carbs is the predominant environmental
back so you can think of keto adaptation
as the opposite end of this continuum where on the other end we have the
insulin resistance syndrome that was initially described by Gerald reven
several decades ago and we have a lot of accumulating evidence that this insulin
resistance syndrome is associated with a whole range of metabolic dysregulation
that are associated in general with chronic disease and higher risk for for
many chronic diseases so at the other end of this continuum we have Quito adaptation which takes on a whole range
of physical metabolic characteristics itself but are robustly associated with
good health and we know that there’s a strong genetic component to the insulin
resistance syndrome and we also know that the key to adapted phenotype is something that’s highly conserved highly
evolved but it’s really the carbohydrates in our diet that are driving us audio expertise please yeah
being were being sabotaged by the American Heart Association and the
American Diabetes Association well I
wish I had a voice that projected better but if there’s an another microphone
it’d be great so it’s pretty clear that
increases in carbohydrate in general drive a great majority of people to the insulin resistant phenotype whereas
removing a lot of those carbohydrates from our diet moves us toward the key to
adapted phenotype and so just scratching
the surface here in terms of keto adaptation what keto adaptation requires
is that we be in a state of nutritional ketosis and that really requires we have
blood circulating ketone levels that are probably above 0.5 maybe closer to 1 up
to maybe 3 or 4 milli molar and if we’re in that state of ketosis for several
weeks we start to make a lot of these adaptations that are associated with the
key to adapted phenotype and at the very so essence of this is a switching of
metabolism over to burning primarily fat and ketones
as our primary fuel sources okay and
it’s just worth saying that as humans you know throughout evolution this has been something that is highly conserved
we have a absolute remarkable capacity to use fat for fuel that I think we’ve
underestimated in the past and it’s really it’s not the ketones that are triggering a lot of the key to
adaptation process they’re certainly involved and that’s an important outcome but it’s the reduction in carbohydrate
and the reduction in insulin levels that are a driving force in initiating the key to Adam keto adapted phenotype and
it’s this enhanced ability to burn fat and burn ketones for fuel that underlies
a lot of the positive health effects that we see it’s not the only factor certainly there’s a growing literature
base on ketones themselves having important epigenetic and signaling
effects so let’s just provide some of
the evidence here that humans can adapt to low carbohydrate intake and burn more
fat and one of the non-invasive relatively easy ways we can assess this
is through indirect calorimetry and look at the ratio of co2 produced and to
oxygen consumed and when we do this we cannot just not only measure energy
Keto-Adaptation = Fat Burning Zone
expenditure by looking at oxygen consumption we can also look at the substrate use so when you’re burning
exclusively fatty acids for fuel you have a ratio of co2 produced oxygen consumed to 0.7 and if you’re burning
all carbs you have a respiratory exchange ratio of 1 and clearly when you
eat high carbs you are biasing your metabolism and making it dependent on carbs for fuel in your RQ is closer to 1
when your key to adapted your R cues are much closer to 0.7 and you consistently
see people register resting even submaximal respiratory exchange ratios of 0.7 0.7
1.7 – so here’s a study that we completed a couple years ago we haven’t
actually published this re our data but it we we fed people diets that were
ketogenic initially and then we incrementally added carbohydrate back after three weeks so we actually tracked
these people out for several months and you see the RER goes down dramatically
on the ketogenic diet as you’d expect and as you add carbs back in roughly 50
75 gram increments you see a very linear increase in the respiratory exchange
ratio so carbs are the driving factor that controls fat burning and this
occurs not just in pre-diabetic individuals in the prior study these were relatively sedentary obese
individuals with metabolic syndrome the same adaptations occur to an even greater extent in healthy athletes and
Keto-Adaptation in Endurance Athletes
this was a classic paper by Steve Finney back in the early 80s in high-level
cyclists who he put on a ketogenic diet for four weeks and the really the most
remarkable change here was their fuel use you can see the respiratory exchange
ratio was around point eight three that indicates about a 50/50 mix of carbs and
fat and that’s after four weeks of keto adaptation down to a level that
indicating almost exclusive use of fat when they’re exercising at more or less
race pace so about 65% vo2 max or just under them and we recently replicated
that in our faster study cohort that was a group of very elite ultra endurance athletes who’d been key to adapted for
Peak Fat Burning in Keto-Adapted Endurance Athletes
much longer on average almost two years and they showed absolutely remarkable rates of fat oxidation two times the
level of fat oxidation in their high carb counterparts and they were I mean these are very good athletes – in the
high carb group that are very good fat burners but we you know we literally shattered that
rate of fat burning with keto adaptation so that’s a fundamental adaptation that
occurs across the spectrum of levels of insulin resistance going from insulin
resistant to very insulin sensitive people see that metabolic adaptation we
also in the faster cohort took muscle biopsies from those athletes and did a
metabolomic analysis and you see a very
Skeletal Muscle Metabolome
robust change in a large number of metabolites so with this type of Olmec approach
we’re able to quantify close to 400 known metabolites at rest and when we
looked at the difference between the low-carb keto adapted and high carb athletes we see that about a third or
almost a third of those metabolites are significantly different and when you
look at the pathways involved the clearly fatty acid oxidation is a
pathway that’s significantly different but also carbohydrate availability and
there’s some alterations and amino acid metabolism as well but of the top ten
metabolites that works most significant in this cohort you see that half of them
I think five of these are related to acyl carnitine which are related to
fatty acid oxidation and ketogenesis beta hydroxy butyrate and isoforms of
butyrate in the same cohort we in the same muscle biopsy sample different
Keto-adaptation awakens highly evolved genes put to sleep when we eat carbs
piece of muscle we did a full transcriptome analysis so this is a
super powerful technique that allows us to look at gene expression levels so
mRNA levels and with this deep sequencing we’re able to capture all
known genes so in one example we can look at over 25,000 genes
and just to give you evidence here that keto adaptation is associated with
epigenetic effects which was discussed yesterday we’re seeing a set of genes
that are upregulated and some genes down regulated but most of the significant
ones were upregulated in the key to adapted phenotype here in these athletes many of them related to metabolism as
you’d expect but also mitochondrial adaptations and I’ll just show you three
of the top genes so this is the top genes out of 25,000 that were most
Top Genes Showing Differential Expression HADHA
significant and you see a gene here that’s coding for an enzyme it’s the
first enzyme in the pathway of ketone production ketogenesis and you can see
the individual expression levels they’re quite dramatically different between the groups not entirely unexpected right
keto adapted phenotype is associated with higher levels of ketogenesis what’s
interesting to me and a bit of a head-scratcher is this is skeletal muscle we’re looking at and we think you
know ketones are produced in the liver exclusively so why is the muscle up
regulating a gene involved in ketogenesis i’m not sure maybe the muscle is the source of ketones but
again not unexpected here’s a gene that codes for the Tri functional protein which is involved in the oxidation of
fatty acids again individual expression levels there show dramatic difference
and the third one here is pretty interesting too this is an a gene that codes for an enzyme and that’s very
important in regulating glycogen metabolism so glycogen would be expected
to be impacted by keto adaptation for sure so three of metabolic genes here out of 25,000 that were the most
significant all relating to metabolism so this is a really complex process of
keto adaptation if you look at the far end of this diagram there’s a lot of
great things that happen in the key to adapted state in terms of promoting robust health and promoting resiliency
The Keto-Adapted Phenotype
and perhaps performance how that happens is anything but trivial and if you’re a reductionist
I’m sorry there’s no real single pathway here that’s predominant clearly ketones
are important metabolically as well as non metabolically and I really should update this figure it’s not just the
ketones that are driving the key to adapted phenotype it’s the reduction in carbs too and the
lower insulin levels are very important and it’s a combination of these stimuli that are promoting really broad spectrum
changes in physiology I can’t think of a process that’s not affected by keto adaptation so let’s talk a little bit
about insulin resistance again a very common term now and over half of adults in the US are suffering from some degree
of insulin resistance but the textbook definition here is it’s a diminished
ability of a given concentration of insulin to exert its normal biological
effect and you know as the name implies it’s it’s a resistance to the normal
effect that insulin has in cells but what I would point out is that insulin
has a heck of a lot of effects in cells and and we shouldn’t oversimplify it by
just focusing on one of those functions like glucose uptake but it is the hallmark of type 2 diabetes and we often
associate it appropriately with an inability to metabolize carbohydrate so
here’s what insulin does I mean it’s it’s fantastically complex the insulin
Insulin is a Pleiotropic Hormone
binds to a receptor on this surface causes auto phosphorylation and a whole
range of intracellular signaling pathways are engaged and many a
scientists have made career studying single pathways involved in the insulin
signaling Network and a lot of the pharmaceutical work targeting insulin
resistance is focused on some of these kinase ha’s in different pathways so
there’s been tremendous amount of effort trying to understand insulin resistance
and yet we have no drug that really works well at targeting any of these pathways and you all know insulin
functions in carbohydrate metabolism by promoting glucose uptake into cells
postprandial e skeletal muscle accounts for about 80 percent of the insulin stimulated glucose uptake but insulin
Insulin and Carbohydrate Metabolism
also works on the liver to inhibit glucose output so if you’re resistant to
insulin at the skeletal muscle or hepatic level you’re not seeing those
effects so that’s why glucose accumulates in the blood both from lack of uptake and lack of inhibition of
hepatic glucose output but equally important to insulins anabolic roles you
Insulin is the most important physiological inhibitor of lipolysis
often hear described as an anabolic hormone which it is is its anti
catabolic effects and that I would argue there that they’re even more important than the anabolic effects and so insulin
has really important roles on lipid metabolism especially lipolysis or fat
breakdown and this is the association of insulin and fat breakdown it’s not a linear relationship
it’s a curvilinear relationship where if you’re eating a high carb diet and you’re you’re raising your insulin level
that’s having an immediate impact on fat breakdown and lipolysis verses a
ketogenic diet which consistently lowers insulin levels even a little bit
dramatically changes where you land on this curve and is associated with much higher rates of fat burning and this is
a relatively immediate type of mechanism so it doesn’t necessarily take months to
see this insulins effects are exquisitely sensitive and they’re they’re rather rapid in terms of its
response so insulin has a lot of functions you know we just mentioned
briefly this role in skeletal muscle and the liver in terms of glucose metabolism but also inhibits lipolysis it affects
vascular tone and effects nitric oxide synthesis
for example in endothelial cells through a same pi3 kinase pathway that promotes
glucose uptake so when insulin is working properly it’s doing a lot of things and insulin shouldn’t be
demonized you know we don’t need to declare a war on insulin if you don’t have insulin you’re not gonna live very
long we need insulin so it is an important hormone but we shouldn’t be
over stimulating it either and relying on it to perform all these functions but
basically when you’re resistant to insulin you have some defect in that
Insulin Resistance Reduced ability of peripheral tissues to respond properly to insulin
insulin signaling pathway that results in these normal functions so you you have a garbled message and you end up
with the opposite effects occuring so you have accelerated lipolysis and
decreases in glucose uptake accelerated a padded glucose output decreases in vasodilation from lower nitric oxide
levels etc so this is why the insulin resistance syndrome and metabolic syndrome has such diverse features and
biomarkers associated with it because this insulin resistance can occur in different tissues in different pathways
and manifest in many different ways in different people so the traditional
progression of insulin resistance and this is a bit of an oversimplification goes something like this where early
stages of insulin resistance the body may be able to compensate by secreting more insulin and maintain sugar
eventually hyperinsulinemia is inadequate to over come the insulin
resistance at the peripheral tissue level and you end up with high blood sugar and high insulin and that can
continue on and actually you know have a pancreatic cell burnout and have low
insulin and then you know this is the conventional view that it’s a
progressive chronic disease that ends in diabetes and if we look though at the
beginning of this it’s often taught and believe that it’s so be city driving
this phenomenon I would argue that obesity is not the dry that it occurs in parallel but it’s a
excessive intake of carbohydrate that’s driving the insulin resistance in driving the obesity in parallel and and
they they do kind of exacerbate each other but we often see dramatic
improvements and insulin resistance before a lot of weight loss occurs and you can also have insulin resistance and
be lean so obesity is not the driving factor now if we look at other characteristics that have been well
Accumulation of TG and other lipid intermediates in IR Muscle
studied and identified in insulin resistance one characteristic is there’s higher triglyceride levels in an insulin
resistant muscle so you see muscle triglycerides correlated with different
measures of insulin resistance in glucose uptake but of course there’s just always exceptions to the rule and
athletes here kind of destroy this nice linear relationship because they also
tend to have higher triglycerides and we think this also occurs in the key to adapted phenotype so it’s unlikely
triglycerides themselves you know the triglyceride pool with in skeletal
muscle that’s available for energy use is not the pathological feature but
there have been several lipid derivatives that have been identified as
being important in insulin resistance and these include Strom ceramides in a
Cell at diacylglycerol rather and people have
spent a lot of time chasing down the specific mechanisms here this is one of the prevailing theories that these these
fatty acid derivatives cause serine phosphorylation of important upstream
regulators in the insulin resistant insulin signaling pathway like irs-1 and
that in turn causes impaired translocation of the glute 4
transporters to the membrane that are needed to bring glucose into cells there’s a lot of interest in these types
of pathways and how increases in fat fatty acid availability contribute to
insulin resistance I did want to just quickly mention exercise has been studied quite
Single bout of aerobic exercise increases insulin sensitivity
extensively in the context of insulin resistance and it’s been known for close to 40 years now that a single bout of
exercise can improve insulin sensitivity and one of the gold standard ways of measuring insulin sensitivity is to do a
hyperinsulinemic glucose hyperinsulinemic clamp where you
basically infuse insulin generally at a high level and then simultaneously
infuse glucose at a variable rate to maintain glycaemia and the more insulin
sensitive are the more you can you can infuse higher rates of glucose the more
insulin resistant you are the less you can and may infuse glucose to maintain
glycemia so you can see here after exercise there is a improvement in
insulin sensitivity at any given concentration of of insulin and that’s
measured by glucose uptake here there the rate of glucose infusion to maintain
glycemia and this is a pretty reproducible effect it’s it’s occurs at
a local level and whatever tissue was activated by the exercise but it is
transient it’s it’s pretty short-lived probably last somewhere between 24 and
48 hours after exercise so exercise is helpful for promoting improvements and
ends insulin sensitivity and here they just measured glucose area under the curve after a glucose tolerance test but
you can see it’s last for at least a couple days after a single bout of exercise there’s also a lot of work
“Metabolic Inflexibility” in Obesity and T2D
showing metabolic and flexibility in insulin resistant muscle where they just don’t they aren’t able to convert back
and forth between using glucose and fat under different stimuli whether that’s exercise or epinephrine infusion so
insulin resistant muscle has an impaired ability to oxidize fat
when your fasted or when you’re restricting carbohydrate acutely now
this can be repaired obviously in the end if you go through a keto adaptation process there’s a lot of work showing
impaired mitochondrial functioning both structure and function of mitochondria
Characteristics of Insulin Resistant Muscle: Mitochondria
are impaired there’s fewer smaller mitochondria with less oxidative capabilities and there’s just a general
decrease in oxidative capabilities within skeletal muscle so as I was
saying there’s a lot of interest in studying the mechanisms of insulin resistance but it’s almost exclusively
focused on the proteins in this insulin signaling pathway in trying to find the
defects in in that pathway and targeting them with drugs or interestingly the
mechanism that exercises has to improve insulin sensitivity seems to be separate
from the pathways that are impaired in insulin resistance so that’s why exercise works but there there’s some
Keto-Adaptation, Membrane Status, & Insulin Resistance
very provocative data suggesting the fatty acid composition of membranes is critically important in insulin
resistance this is a paper that was published over two decades ago three oh three decades ago two and a half decades
ago doing math quick up here but it’s been relatively ignored but it has been
validated in a couple other studies so this was a study that looked at fatty acid composition in skeletal muscle and
correlated that to insulin sensitivity is measured by insulin levels as well as
the clamp technique and if you focus
here and the highlighted rows the correlation of this is twenty carbon
four double bonds that’s a rack Adana Kassadin skeletal muscle was
significantly correlated to the level of insulin sensitivity and you see that the far right the
our value there is 0.76 and if you look at the ratio of arachidonic acid to its
precursor dye homo gamma linolenic acid you’d have a
correlation coefficient of 0.8 4 so that’s saying we can explain almost 3/4
of the variability and insulin sensitivity by these two simple fatty
acids in phospholipids of skeletal muscle that’s extraordinary when you
look at how complex the phenotype of insulin resistance is so just to give
Essential Fatty Acids
you a very quick debrief here on fatty acid nomenclature and essential
specifically essential fatty acid synthesis so these are our polyunsaturated essential fatty acids we
have the omega-3 omega-6 pathways and the arachidonic acid is the essential
fatty acid on the omega-6 side so that’s the 20 carbon 4 double bonds in its
immediate precursor as I mentioned was d GLA so those are the two fatty acids
that were most highly correlated with insulin sensitivity which makes one
wonder what happens to these fatty acids on a ketogenic diet and that’s something
that fascinated Steve Finney many decades ago and he convinced me it was
important to pursue that question about 10 years ago – and we’ve done a lot of work in you know answering that question
so just very quickly arachidonic acid is generally thought to be a bad fatty acid
and that’s an inaccurate oversimplification for sure arachidonic
acid because one of the reasons it’s has a strong connotation of being bad is
because it is the precursor for pro-inflammatory eicosanoids when it’s
acted upon by oxygen aces like cyclooxygenase and lipo oxygenation etc
compared to EPA eh-eh on the omega-3 side but
arachidonic acid can also be metabolized not enzymatically so whenever we have a
lot of oxidative stress and free radicals being formed these reactive oxygen species interact with the double
bonds on fatty acids so arachidonic acid is one of the most highly unsaturated fatty acids and so it’s a prime target
for our OS and when that happens you essentially have degradation of the fatty acids and you generate ISO
prostates so this was one of our first studies looking at fatty acid composition and
the I mean the short story cliff notes here is there’s a few biomarkers you can
measure that are more consistently altered by a ketogenic diet than arachidonic acid so here we see the
relative percent of arachidonic acid in the phospholipid fraction of blood
increase from eleven point five to thirteen point seven percent that’s a huge increase in the percent weight of
that fatty acid in phospho a little bit of blood we followed that up with
another well controlled feeding study we actually had two ketogenic diets in this study one they varied in fat composition
but both significantly elevated arachidonic acid and it basically occurs
in all the lipid fractions that we’ve looked at so far so we’ve isolated triglyceride phospholipid cholesterol
ester and you know phospholipids the primary fraction where you see the
highly unsaturated fatty acids but it occurs in the other fractions as well and you know again on the surface one
might won’t think that if you have more arachidonic acid you have more potential to form inflammatory markers and we saw
just the opposite in this paper we published back in 2008 the higher the
arachidonic acid was the greater the reduction in all of these
pro-inflammatory cytokines and adhesion molecules so this is the negative
correlation meaning again higher the arachidonic acid went the lower CRP went the lower il-6 went
the lower all these inflammatory markers were so this is completely opposite to what you’d expect and we actually
measured ISO prostates which is a stable marker indicating enhanced degradation
A Ketogenic Diet emphasizing MUFA and n-3 PUFA decreases oxidative stress
of arachidonic acid and it was in fact lower on the ketogenic diets than the
high carb diets and then in our most recent long-term feeding study where we
incrementally headed carbs we measured arachidonic acid and d GLA as well when
they were key to adapted and under increasing doses of carbohydrate and
here’s what we see blue line is arachidonic acid it Peaks when you’re on a ketogenic diet and as
you had carbs in it incrementally comes back down and you see just the opposite with T GLA so we think this might be
important in promoting insulin sensitivity we have some evidence that’s
increasing in skeletal muscle as well and you know this is a pretty
provocative theory anyway as to one way in which the ketogenic diet might
promote enhanced insulin sensitivity I should mention just to kind of
complete that story of arachidonic acid what we think is happening is the ketogenic diet is associated with less
oxidative stress less generation of our OS and if that’s the case you’re seeing
less degradation of arachidonic acid so that’s the primary mechanism by which
it’s increasing and all these lipid fractions is we’re seeing less our OS
mediated destruction of that fatty acid so it’s better protected in the membrane and if it’s not being acted upon by
oxygen aces arachidonic acid in membranes contributes to membrane fluidity and a lot of other important
cellular functions so when we overeat carbs we develop pre-diabetes and
eventually diabetes or at least a lot of us do and you’ve all seen the different you know seemingly disparate
markers you know that define the metabolic syndrome and just to show you
how keto adaptation effects these you know there’s a lot of studies now we
reviewed the literature back ten years ago dr. Fineman and I wrote this review
paper in 2005 ish I think it was and in
Dr Fernandez Fineman fini and myself updated that a few years later there’s
just an enormous amount of literature showing low-carb ketogenic diets are more effective than low-fat diets ed
impacting all the features of metabolic syndrome or insulin resistant syndrome
or phenotype so it really targets all of those markers and there’s a lot of
studies done on weight loss now such that we have meta-analysis the latest one plus one probably one of the better
meta-analysis because it really tried to look specifically at ketogenic diets all
show ketogenic diets do better for weight loss and cardiovascular markers
this was one of the studies we did again many years ago now in a group of
pre-diabetic individuals all the markers get better on ketogenic versus low fat and we could talk about any of these
specific markers but this is a pretty consistent uniform response that you see
if you have a well formulated ketogenic diet but what about type-2 diabetes there’s there’s less data in type-2
Effects of diet composition and ketosis on glycemia during very-low-energy-diet therapy in obese patients with non- insulin-dependent diabetes melitus
diabetes but there was really some important work done that maybe doesn’t always get cited but the early work was
very well controlled but very short-term so these are these next two studies are
actually feeding studies in patient metabolic Ward studies this was from
Barry governor back in 1996 put a group of obese type 2 diabetics on a ketogenic
diet very low in calories 650 but then had a matched caloric group
had a little bit higher carbs 94 grams of carbs saw weight loss in both groups
but only the ketogenic diet with 24 grams of carbs had you know the level of
ketones increased significantly in a 2-3 millimolar range and even though this is
short term three weeks they saw dramatic improvements in glycaemia and they were
actually measured hepatic glucose output in these participants and showed a
significant reduction in hepatic glucose output and interestingly the level of
ketosis was correlated to the level of hepatic glucose suppression so I suggest
that ketones may be playing an important role in improving hepatic insulin sensitivity in blocking you know having
its normal function of blocking glucose output or inhibiting glucose output and
the other really impressive study was
also even shorter two-week study but again metabolic Ward feeding study of a
ketogenic diet and type 2 diabetics and just after two weeks saw a significant
reduction in a1c and they actually measured insulin sensitivity using the
clamp procedure and showed a 75% improvement in insulin sensitivity after just two weeks so the footprints have
been in the sand for a long time but the question that comes up from these types
of data are well can anybody maintain this long term and we don’t have a lot
of great studies that specifically address that question but probably the best study out there right now is from
Kuwait and doctor – cheese group where they put a group of obese individuals on
what I would call a very well formulated ketogenic diet and they understood the importance of fat and so it was
scientifically designed I would say relative to some of the other formulations you see in the literature
but he had a group of those obese subjects that were diabetic so the the high
glucose group is shown in black there and tracked these people for just over a
year and showed continued well they showed dramatic weight loss initially but continued weight loss up to a year
and also dramatic improvement in glucose initially that was sustained out past a
year so this is some pretty strong evidence that diabetes can be reversed
and can occur at least over a year period and this has really been the
motivation for Verta health which is a company that I’m
involved with and founded with Steve Finney and Sami incan in and we are
really dedicated to reversing diabetes all across the planet and millions and
millions of folks and it’s based on a lot of the science that shows keto
adaptation is associated with reversal of diabetes but it’s much more than than
that it’s a very technological company that is using basically technology to
help people sustain a diet that keeps them in nutritional ketosis and keto
adapted as being a science driven company we have a large clinical study
underway at the Indiana University Health System and that’s being managed
Virta Study
by Sarah Hallberg whose fantastic physician and real leader in diabetes
management using ketogenic diets I can’t cheer a lot of the data we have
generated from this study but we do have a poster that will be presented this evening and it’s showing the interim
three-month data or just under three month data it’s very impressive and it’s
a two-year study though that were underway now with full enrollment and
actually a majority of patients are past a year and we have a lot of that data in which I can’t share with you now but I
think it’s fair to say we’re very enthusiastic about the results past a
year so this is really exciting that we can have a tool that can be scaled and
help a lot of folks that are struggling with diabetes so in summary it’s clear to me that keto
adaptation is really the key to reversing type 2 diabetes and we’re not talking about impacting a small number
of people here if we just look at the u.s. it’s apparent with the guidelines
we have today only a small percentage of us are able to maintain health on that maybe a quarter of us at best so 100
million and/or more people would be much better off restricting carbs or keto
adapting so in summary type 2 diabetes is really a carbohydrate intolerant
Summary
state yes there’s a red Ettore and environmental factors involved but at
its core it manifests as a carbohydrate intolerance state so when we take the carbs away everything gets better we can
reverse many cases of type 2 diabetes and in that regard it’s a strong word
and I’m not sure it’s appropriate yet but I think we’re getting very close to being able to say that we can cure type
2 diabetes in some people as long as we can keep them carb restricted and
normalize all the signs and symptoms of the disease so thank you very much we
happy to take questions you