– 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..

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