Dr. Jake Kushner – Medical Nutrition Therapy for People with Type 1 Diabetes

Dr. Jake Kushner – Medical Nutrition Therapy for People with Type 1 Diabetes

November 8, 2019 2 By William Morgan


– What a pleasure it is to be here today.
On behalf of people with type I diabetes,
which has been my professional
focus and passion.
So I wanna just,
let me see back in.
Excuse me, I wanna make sure which, okay.
Just to, oh, excuse me, my
disclosure slide is gone.
Maybe my disclosure slide got trapped off.
So I’m gonna be talking
about type I diabetes today,
and again this has been
the focus of my career
and beta cell deficiency
deficiency is really
at the heart of type I
diabetes as you can see here.
There’s a profound
deficiency in beta cells
and the pancreas of a
person with type I diabetes
is on the right.
Shocking lack of insulin-producing
cells in the pancreas.
And it leaves people with type I diabetes
in a very tough space.
So I got interested in low
carb and type I diabetes
a while ago and that’s been
a source of my passion.
Okay, the slide was out of order,
but this is my disclosure.
I’m a consultant for Sanofi
and Lexicon and KNOW Foods.
And I’m now switched from academia
to Service Medical director
for McNair Interests,
which is a private equity
group with investments
and areas related to type I diabetes
and other chronic illnesses.
So type I diabetes is a serious problem.
And pediatricians like myself
would often see patients
like this and up to 100 years ago,
it was a devastating diagnosis.
So these children would arrive emaciated,
parents dreading the possibility
that it could be diabetes
and they would,
unfortunately, be told that
there is nothing available.
But with the discovery of
insulin by Banting and Best,
this really miraculous thing occurred
where you could begin to
inject and replace insulin
for these people who live with type I.
And you’d see these incredible stories.
This is the same child
on the right as the one
you see on the left.
So it was remarkable and transformative.
There were ticker tape
parades for Banting and Best
who won the Nobel Prize.
And at that time it was considered a cure
for type I diabetes.
Unfortunately we now know
that insulin is a treatment,
it’s not a cure.
And there’s really a
very significant burden
that’s born by people
who live with type I.
And in the years after the diagnosis of,
discovery of insulin,
people began to suffer
from unforeseen complications.
And this is a case series
from the Joslin Clinic
in the decades immediately following
the discovery of insulin.
You can see these patients are suffering
from all of the classic
conditions that we now believe
to be the complications of diabetes:
calcified arteries, retinitis proliferans,
high blood pressure, and proteinuria.
So this is macro and microvascular disease
manifesting in the
vessels and in the kidney.
And unfortunately, insulin-treated
type I diabetes patients
had very high rates of
mortality even into the ’90s.
And this was devastating.
So if you think about this,
a large fraction of patients
who were diagnosed with type I diabetes
around the time of, that
we put the man on the moon,
those people would still have
dramatically foreshortened lifespans.
I was born in ’65, so I’m 53.
I don’t have type I
diabetes, but if I did,
I would have been diagnosed
somewhere around ’73.
So you can see that I would
then, in my virtual diabetes,
would be 45 years in.
So let’s look at the
people who are 45 years
into a diagnosis of type I diabetes.
And you can see that at least a third
would have expired by now.
Perhaps even 40%.
Devastating.
So this was really terrible.
And an amazing thing
happened which was the,
Dr. Joslin and others had been advocating
for a proper control clinical trial
to try to determine whether tight control
could approve outcomes
for people with type I.
And the answer thankfully is yes.
So now what we live with
is a different landscape
of type I diabetes.
We don’t think that complications
are a foregone conclusion
and we do everything we
can to support people
who live with type I diabetes.
It’s millions of people worldwide,
1.25 million Americans at least.
Possibly doubled.
We could talk about that at the break.
Injected insulins: the
only available therapy.
There’s a high burden of illness.
It’s very challenging to keep blood sugars
in a normal range.
There’s risk of excessive
weight gain and hypoglycemia
with increased insulin.
And frequent hypoglycemia,
typically one to two episodes
per week but some people
have half a dozen.
And there’s a major risk of
life threatening complications
potentially preventable with tight control
as shown by the DCCT:
the Diabetes Control Complication Trial.
So it’s a challenge for people like myself
who support those who live with type I.
And it’s a challenge for
those who live with type I
and their families.
And definitive therapies, I
guess what you would call cures
are a long ways off, and I
wanna try to explain why.
There’s been a big question,
one with basic science knowledge translate
to improve type I diabetes outcomes.
And sadly, I’m here to
tell you that it’s a long
and winding road.
And I’m a physician scientist.
I’ve been running a basic
science research lab
in beta cell biology
and type I diabetes now
for more than 15 years.
And I’ve been involved in
the field for more than 20.
I think we’re probably a long ways off
from what you would think of as a cure.
And there’s a lot of
different areas that people
are investigating including
this idea of beta cell
regeneration finding some
way to regrow the beta cells
within the pancreas of
people who live with type I
or also stem cell therapy.
And the idea of somehow
finding some magic cell
that can produce quite a bit of insulin
that would replace the
cells that are lost,
or potentially also…
I’m sorry, my pointer is non-responsive.
I’m gonna keep trying here.
Oh, okay.
Immunotherapy is another one
and advanced technologies.
So immunotherapy has been popular,
this idea of infusing various things
that would modulate the immune system
either T cells or B
cells or both, or TRECs.
But this far all of
those trials have failed
their primary endpoint.
So they’re not able to
permanently induce tolerance.
They can only temporarily
slow the destruction
of the beta cells.
And then finally advance
technologies have been
somewhat of a disappointment.
We had imagined that you
just strapped this machine
on somebody and infuse
insulin in a regulated manner
but the sad truth is that it takes so long
for what you eat to influence
what your glucose is
to then influence what the machine senses
to then influence how
much insulin to deliver.
That it’s sort of like driving a car
that’s like a 100 feet
long from the very back
down a highway really fast.
And you’re making these
sort of fishtailing changes
but you’re not able to make
those changes fast enough.
And so what you see even in people who run
automated insulin delivery is
quite a bit of glucose flux.
Okay, well, I’ve published
on beta cell regeneration
for most of my career
and about 10 years ago,
we had preliminary findings
in a paper that was ultimately
published just last year
that describes how beta cells
persist in T1D pancreata
without evidence for ongoing
beta cell turnover and regeneration.
I’m not gonna show you that work here
except to say that for me
this observation precipitated
what my wife calls a professional crisis.
And I didn’t buy red sports
car and I didn’t get a tattoo,
but I really did worry
about what I was doing
in my career.
And my fear was that my
efforts to regrow beta cells
might be unsuccessful and
I might never really know
the impact of my work to advance humanity.
And so I began thinking about myself more
as a physician and less as a scientist.
And I’ve spent quite a bit of time
reorienting myself towards that.
I would also say that
stem cells in particular
have proven to be a disappointment.
And this is a commentary that
we wrote in cell stem cell
about a paper that was
published by Doug Melton
and another one that was
published by Tim Kieffer
and we’re a long ways off
from being able to take
embryonic stem cells,
turn them into bonafide
insulin-secreting cells
and then safely put them
into a human being and make
sure that they don’t get
immediately destroyed
and that they don’t cause
other metabolic problems.
I would be surprised if
this could be achieved
in my lifetime.
So what are we gonna do?
I don’t know.
I mean traditionally
we’re not doing that well.
So this is data from the T1D exchange,
and it shows you that most
people with T1D failed
to achieve glycemic targets.
We’d like to get their A1Cs
under seven if they’re adults.
We’d like to get the A1Cs of
kids under seven and a half.
And moreover, it’s not getting better;
it’s getting worse.
What?
Yes, it’s actually getting worse.
So the data on the left
is those who are enrolled
in this cohort from 2010 to 2012.
And the right, these blue
bars, that’s current data.
So we’re not making progress
with whatever we’re doing.
And moreover, there’s
excess cardiovascular death
in typically treated type I.
And I’m a relentlessly
positive optimistic person,
almost to a fault,
but I wanted to show you something scary.
This is New England article that describes
cohorts of people with type I diabetes.
And it sort of slices
them by hemoglobin A1C.
You can see that it’s going from the top
of A1Cs less than 6 to the
bottom greater than 9.7.
And those who have A1Cs
in between 7.9 and 8.7
have an increased hazard
ratio for death of any cost
of 3.11 fold non-diabetic population.
So there’s a lot at stake here.
We have to do more to
support these people.
And cardiovascular
death apparently is 4.4.
And you can see that
it increases with A1C.
And moreover, we know there’s
socioeconomic disparity
so some of the poorest
people in the population
are gonna be an incredibly high risk
for cardiovascular death.
We gotta do something.
Okay, so, I’m gonna,
all right.
I wanna take you on a tour
through glucose homeostasis
to talk about the role of the beta cell
and why carbohydrates are
really so important in type I.
So the islet, as you can
see, the big round structure
and what makes insulin of course,
which acts upon the skeletal
muscle to drive glucose
in the skeletal muscle.
And it also acts upon the liver
to suppress hepatic gluconeogenesis.
And it also acts upon the
fat ultimately driving
fatty acids in to promote adipogenesis.
So this pathway gets really
altered in type I diabetes.
And part of the reason
is you have very little
endogenous production of insulin
and you try to replace it
with exogenous insulin,
and it’s incredibly crude
whether it’s a pump or a pen in this case.
You just can’t figure out
how much insulin to give
and you’re making a guess.
And so if you take food, say, for instance
Snackwell’s devil food cookie cakes,
which are fat free and you can
(audience laughs)
and you get a big bolus of carbohydrate,
then all of a sudden you
need a whole bunch of insulin
to drive that carbohydrate
in the skeletal muscle.
But the same is also true in liver.
And you can get a whole
bunch of insulin action
upon the liver and the
same is also true in fat.
And you’re gonna promote
quite a bit of adipogenesis
and ultimately these folks
end up quite overweight.
And so we know that tight
control is associated
with obesity in type I
diabetes and that’s associated
with adverse cardiovascular outcomes
in people with type I diabetes.
So we get a problem because we’re not able
to physiologically
replace this key hormone
that’s necessary for life.
I’m showing you this.
This is a table that was handed out
at one children’s hospital
and it’s identical
to the kinds of tables that are handed out
throughout the country to
parents of nearly diagnosed
children with type I diabetes.
And so in this case imagine
yourself, the parent
of a teenage boy who’s just been diagnosed
with type I diabetes and
you have a well meaning
nutritionist who explains
that your child needs
2,300 kcals per day
and for breakfast she’ll consume
75 grams of carbohydrates.
105 for lunch, a 15-gram
carbohydrate snack,
and 120 gram carbohydrate dinner,
and a 15-gram snack at bedtime.
So what does that do?
What’s that like?
Unfortunately, it’s
incredibly difficult to do.
And the reason is you don’t really know
the number of carbohydrates
nor do you know
the transit time in the
gut where the impact
of the fats that you’re consuming,
and you end up making this random guess
as they call this.
It’s a wild guess.
And it’s probably plus
or minus 50 or 100%.
So you’re, like, I don’t know.
And people with type I diabetes
are classic for saying,
you know what, I had no idea,
I guessed 50, I guessed 25.
Because you can’t walk around
with a gram scale, right?
And I know people who have done this.
My friend Kelly would go into restaurants
with a measuring cup in her
purse when she was pregnant
and she was trying to achieve euglycemia.
But even that isn’t good enough.
And even a gram scale and
measuring cup is not enough.
So you’ll see glucoses
that will rise and fall
throughout the day.
This is data from a
continuous glucose monitor.
This is a Dexcom read out.
And you can see the average
glucose of this person is 204,
but the standard deviation is 90,
and there’s also a psychological impact.
So imagine yourself on this
roller coaster right going down
and you don’t know is in the middle,
like in the middle the afternoon,
you don’t know if you’re gonna
end up with a blood glucose
of 100 or 50 or 30.
And it’s terrifying and it causes really,
it’s a huge cognitive load.
It’s a burden to have to think about
’cause you’re never quite
sure what your sugars are.
Okay, so I’ve gotten
interested in low carb
mostly out of desperation.
And as a physician,
my thought was I had to
find something different.
So I started thinking about this
and I started asking questions,
and what I realized was that
many people didn’t know the answer.
So I asked like, why do we even prescribe
a lot of carbohydrates?
And I found the standards
of medical care in diabetes
and what it basically says is,
well, there’s limited research
concerning the amount of fat
for individuals with diabetes,
but into the medicine
has defined an acceptable
macronutrient distribution range
of total fat as 20 to 35%.
And I thought, well, what is that?
What is that advice?
And so, I was curious about this
and I actually went and
tried to understand this.
I’m trying to advance slides.
Oh, and by the way, this
advice is still here
and it hasn’t gone away.
So this is the American
Diabetes Association
and we’re still prescribing quite a bit of
macronutrient distribution
that includes quite a few carbs
and not that much fat.
So the DRI is published
by the Institute of Medicine back in 2002
and this is really
where a lot of the dogma
around carbohydrate balance comes from.
And I wanna take you
through some of the logic
that’s present within it.
It’s about 350 pages.
It’s remarkably lucid.
It has a tremendous amount in it.
It’s written by some very smart people
and it describes how there’s
a huge amount of plasticity
in our bodies to adapt to
different macronutrients,
but unfortunately, the DRI
has at the end of it lookup tables.
And so everybody says, I
don’t have time to read it.
It’s 350 pages.
Just tell me what it says.
So they go to the lookup tables.
So the lookup tables were designed
essentially as a compromise
around something that,
and I believe the lookup tables
never should have been issued
and I wanna tell you why.
So what they say is that you have to have
this acceptable macronutrient
distribution range.
And what they’re saying is,
if you get too many carbs,
you’re gonna have low HDL,
you’re gonna have high triglycerides,
you’re gonna have more LDL particles,
you’re gonna have increased
cardiovascular risks
and so that’s bad.
On the other hand, they say,
if you eat too much fat,
well, you’re gonna have
more dietary energy,
you’re gonna gain weight,
you’re gonna have more saturated fat
and therefore, you will have
increased cardiovascular risk.
And so they’re thinking
that these two extremes
are each associated with
cardiovascular risk.
And so, their logic is
they try to find a balance
in between the two
based on the apparent risk for,
for coronary heart disease
that may occur on a low diets
and based on the risk of
increased energy intake,
and therefore, obesity in the
consumption of high-fat diets,
the AMDR of fat and carbohydrate
is estimated to be 20 to 35
and 45 to 65% of energy respectively.
So they prescribe this and
this is why we eat what we it,
but it’s based on false logic.
And part of it is this idea
that as you eat more fat,
you will gain more weight.
That is true in rodents
who also consume a lot of carbohydrate,
the so-called high-fat chow,
but it’s most certainly not true in man.
So do dietary fats influence health?
I read this amazing paper
that Dr. Menti just mentioned
and I just thought it was wonderful
and I was blown away by it.
And I began to read more and
more things in the field,
really shocked to discover
that saturated fat
was not associated with increased death.
And moreover that, if anything,
so trans fats might be, but interestingly,
it’s really industrial trans fats
that are associated with cardiac disease.
And ultimately ruminant
trans fats seem to be neutral
or at least not a strong signal.
And amazingly, type two diabetes,
these ruminant trans fats were protective.
So that made me think that the
evidence around saturated fat
really needed to be re-examined
for people with diabetes.
And so, are there innovative
dietary interventions?
Yeah.
So, Dr. Richard Bernstein has
been a pioneer in this field
and he’s really an amazing person.
He’s still in it.
He’s still involved in the field.
He’s active and he has
type I diabetes himself
and he’s written this book that describes
a wonderful approach
to living with diabetes
and it’s gaining more and more attention.
So I know people who have followed it.
In the field of pediatric endocrinology,
this book is not at all taught.
It’s considered to be a
scary, dangerous thing.
And I only learned about it
through my friend, Kelly,
who has type I diabetes herself
and she was trying to find
an innovative approach
to achieve euglycemia.
And once I read it, I mean, I was hooked.
So what do you actually
do if you’re doing this?
Well, this is a picture
of my friend, Marshall,
and his standard poodles
you can see down there on his feet.
And we were having lunch,
this is last month,
and he’s eating smoked
salmon and some avocado
and some aioli that he made
himself and some low carb bread,
and that’s a very typical lunch for him.
He has type I diabetes.
He’s had it for nearly 30 years
and his blood sugars are quite good.
As you can see here, this is
postprandial by about an hour,
his blood sugar was 87, which is awesome.
And he took very little insulin.
When I talked to Marshall
about type I diabetes and low carb,
we’ve sort of been working together.
He’s a close friend.
He’s the son of one of my
oldest closest friends.
After he started playing with low carb,
he said to me something amazing.
He said, I always figured
that I was gonna die
from type I diabetes.
And when I learned about low carb
and learned how powerful
it was, I actually realized
that I might be able
to live a normal life.
And that’s pretty amazing.
And it changed the way I think about
working with people with type I.
So I showed you this CGM tracing.
This is an 18-year-old patient
who’s had type I diabetes
for more than 10 years.
This is a high carb day,
and this is the same person
now on low carb (chuckles).
So it’s really amazing.
And you can see that there’s
very little glucose flux
so she’s able to cruise throughout the day
with no fear of hypoglycemia
and a lot less effort.
Here’s a 23-year-old with
type I diabetes for 12 years
on a high carb day,
and again, these huge
roller coaster’s quite scary
with a couple episodes below
normal in a low carb day.
So, really dramatic.
And here’s a 22-year-old
who’s only had type I diabetes for a year.
Low carb since diagnosis.
Basically flat blood sugars.
And it makes me wonder whether
immediately going on low carb
might allow you to preserve
beta cell function.
And I don’t know the answer.
We have to try to figure this out.
So how about low carb and
automated insulin delivery?
And I wanna tell you about
a guy named AdrianLxM
and he is a developer for a do-it yourself
automated pancreas system
that works through the android phone
and so that’s called Android APS.
And so these folks are
hacking their phones
to operate their insulin pumps
to use continuous glucose monitoring data.
And here’s his glucose tracing.
This is over, as you can see,
the time scale is
completely different here.
So this is several days.
And you can see, on a high carb day,
there’s quite a bit of flux
and on low carb, almost none.
So I actually think that
automated insulin delivery
will wildly synergize with low carb
and part of it is that it’s
much closer to the kinetics.
You get roller coasters with low carb,
but they’re slower roller coasters
and they’re the kinds of roller
coasters that might easily
be matched by the kinetics
of a computer-controlled
exogenous insulin.
But time will tell.
We need to do these experiments.
So there is this wonderful
paper that’s just come out
and this is in pediatrics
and it includes, by the
way, Dr. Sarah Holbrook,
who’s gonna come right after me
and a bunch of other folks here.
And so, what is this paper?
This is a description of a
cohort of a Facebook group
of people who are followers
of Dr. Richard Bernstein
and they were able to achieve
a Hemoglobin A1C average of 5.67%,
which according to
pediatric endocrinologist
like myself is impossible.
We just don’t see it.
And moreover, they were
generally happy and healthy
and very enthusiastic
about what they had done
and what their lives were like.
It’s called Type One Grit.
It’s on Facebook.
It’s quite a neat thing.
Okay, The New York Times wrote about this
and there was a lot of excitement.
I love this.
I do this so that I can be healthy.
Andrew, who lives with his parents
in Jacksonville, Florida said
when I eventually move
out and go to college,
I’m gonna keep it up because
I know I’m on the right path.
Now, that’s pretty exciting.
There was a comment from three
major players in the field,
Beth Mayer-Davis, Lori
Laffel, and John Buse.
And they wrote a comment
basically saying that
although it may be true
that very low carb diets can be useful,
we find the study to fall well short
of this level of scientific
evidence that merits the media
and professional attention
it seems to have garnered.
The online community
was not a general type
I diabetes community,
rather this is a community
following a specific type of low carb
as promoted by the authors type I book.
And there’s a general concern here
that the individuals in the
cohort believe in the approach
and therefore, that
would bias the outcome.
(audience laughs)
So it’s really kind,
and that promulgating
such methodologically weak
although enticing data
broadly through the media
creates a risk that patients or providers
may pursue such plans without
adequate insulin adjustment
resulting in serious
issues for hypoglycemia
as well as risk in
nutritional deficiencies.
So this is the kind of stigma
that low carb will have
to overcome over time
to ultimately advance.
Okay, so Ludwig et al
wrote a very nice thing
and they basically said,
we don’t think the
suppression of information
is a good idea.
Low carb treatment was used
before the discovery of insulin
and we would love to
ultimately see studies.
So will low carb violate
nutrition consensus guidelines?
Well, the answer is yes.
(audience laughs)
Clearly.
And so, so this is the ISPAD guidelines.
This is the International
Society of Pediatric
and Adolescent Diabetes
and they are crystal clear that it would
at least according to their dogma.
And they say there is
international agreement
that carbohydrate should not be restricted
in children, adolescent type I diabetes
as it may result deleterious
effects on growth.
So I’m not sure about this.
It seems hyperbolic, but they
are very strong that it would
On the other hand, when they
say healthy grains, etcetera.
If you look at the American
Diabetes Association,
it’s far easier.
I’m gonna skip this stuff.
The American Diabetes Association
has basically backed off quite a bit
and they have this lovely statement.
Studies examine the ideal
amount of carbohydrate intake
for people with diabetes are inconclusive
and the amount of dietary fat
is controversial (chuckles).
So that leaves some wiggle room for us.
And my hope is that, over time,
we will begin to carry
out some proper studies.
But, again, they don’t seem
to be precise in saying that
you have to eat a certain
number of carbohydrates.
They say it’s inconclusive
and Mediterranean food might be helpful.
So I think, again, there’s
a lot of wiggle room
in the American Diabetes Association.
It’s not as prescriptive as it used to be.
There’s room for experimentation.
Let’s see.
Let’s do the experiments
and let’s find out.
They’re a lot less dogmatic
than they used to be.
They say it should be individualized.
My hope is that we can individualize
and determine the impact.
So I’m gonna skip this, some resources.
Well, I mentioned Dr. Bernstein’s book
and I would also mention this
terrific book by Adam Brown
called “Bright Spots & Landmines”.
And then I wanna just briefly talk about
the potential impact
for low carb and type I
on disease burden and
control, acute complications,
growth and development,
synergy with automated insulin delivery,
specific low carb strategies,
and lipid and cholesterol,
cardiovascular metabolism,
and all these other factors.
And when we design clinical trials,
and they will eventually
happen, I promise you.
In my lifetime, there
will be clinical trials
testing these things
with the stuff on the top
as the primary outcome
and the other ones has secondary outcomes.
And we’ll do this in lots of
different populations of people
and we’ll be able to measure
the impact of low carb
relative to some of these other therapies.
Okay, so why is so little knowledge?
Well, this is tough
and I think there’s unrealistic
timelines for the cure
and there’s also communication
barriers in between adults
who live with type I and key stakeholders,
i.e. maybe parents of young children.
There’s not a lot of
communication back and forth.
There’s lack of T1D
Nutrition Research funding
and there’s incorrect assumptions.
My favorite is the one,
people with type I diabetes
need the best nutrition
for the general population
and must follow IOM, AMDRs.
So where do we go from here?
Ultimately, it’s about
building a consensus
and trying to advance science.
So, how do we do this?
Low carb research funding.
We have to have more
funding and better studies.
We have to advocate for
better nutrition standards.
Please support the nutrition coalition.
We need to recruit adult T1D peers
to service volunteers in diabetes clinics.
That we need to foster
psychology collaborations
to test the impact of
nutrition on mental health.
We need to increase access to
continuous glucose monitors
and ketone testing.
They’re gonna be essential.
And then ultimately advocacy,
mentoring, stewardship
and local reinforcement.
And I’m gonna close with a
picture of some friends of mine.
We had a potluck.
And this is a low carb type
I diabetes potluck in Houston
and there was followers
of the Type One Grit Facebook community
and we were there to support
each other, share recipes
and just have fun.
And I think it’s gonna
require building community
to advance this and ultimately serve
the whole population
of people with type I.
So, thanks so much.
(audience applauds)
– Thank you very much.
We’re gonna have a 20-minute break
and reconvene to hear Dr. Sarah Holbrook.