Speaker 1: Hi, I'm Carla Williamson. I am a Type one diabetic
Speaker 1: forty three years this August. I was diagnosed in nineteen
Speaker 1: seventy seven. I was drinking all the time. I couldnot
Speaker 1: get enough water. My mom said I would go from
Speaker 1: a water fountain, drink a coke, then drink milk. I
Speaker 1: couldn't get enough. I was losing weight. My dad was
Speaker 1: a Type one diabetic also, and my mom had recognized
Speaker 1: the symptoms pretty early, and back then they did not
Speaker 1: have home blood glucose monitoring. So I was out doing
Speaker 1: yard work and my dad came home for lunch and
Speaker 1: they called me in the house and said, go in
Speaker 1: the bathroom, and I want you to use the restroom
Speaker 1: on this litmus paper. And I went to the restroom
Speaker 1: urinated on the litmus paper and it turned bright blue,
Speaker 1: which I knew and my parents knew them that I
Speaker 1: was a diabetic. So I got diagnosed in the summer
Speaker 1: before sixth grade. So I started a new middle school.
Speaker 1: I had one other classmate that was also a diabetic,
Speaker 1: but I was really embarrassed to tell anybody. I didn't
Speaker 1: want anybody to know. So if I had a low
Speaker 1: blood sugar, I wouldn't want to tell anybody, so I
Speaker 1: would wait until I was like in a dead sweat
Speaker 1: and almost out of it. My teacher would say something
Speaker 1: because she would keep orange juice in her desk, but
Speaker 1: I did not want to be called out or tell anybody.
Speaker 1: I didn't want to be different than anybody. It was
Speaker 1: not until I was a nurse working in a hospital
Speaker 1: that I had a friend that was also on a pump,
Speaker 1: you know, and we started talking and I loved talking
Speaker 1: about it, and I loved educating. And I found even
Speaker 1: now that I'm a school nurse, talking to kids with
Speaker 1: diabetes and letting them see that you can live a
Speaker 1: normal life. You're not any different than anybody else. You
Speaker 1: can do anything you want and live with this disease,
Speaker 1: but you have to acknowledge it and take care of
Speaker 1: it is huge and I love playing that role now.
Speaker 1: So growing up, my friends were very understanding. You know.
Speaker 1: You would go over and parents would be very scared
Speaker 1: to have you over because they were like, oh, gosh,
Speaker 1: she's a diabetic. How do we take care of someone
Speaker 1: with diabetes? And my mom would say, she can take
Speaker 1: care of it, she knows.
Speaker 2: What to do.
Speaker 1: My parents handed me the disease at ten years old
Speaker 1: and said, this is yours. You're going to live with
Speaker 1: the rest of your life. You've got to learn to
Speaker 1: make good decisions. So I got out of the hospital
Speaker 1: on a Monday, and I was at a sleepover on
Speaker 1: a Friday. So I was always given freedoms and good
Speaker 1: or bad, I don't know, but to handle this disease.
Speaker 1: Back in nineteen seventy seven, it's so different than it
Speaker 1: is now. Everything was no sugar. You could eat anything
Speaker 1: you wanted, you just couldn't have sugar. It was one
Speaker 1: shot a day. It was all long acting insulin. It
Speaker 1: was beef and pork based insulin back then. So control
Speaker 1: was not good being ten number one, but also you know,
Speaker 1: just no way to monitor what you're doing. You peed
Speaker 1: on a Keto strip that showed glucose and keytnes and
Speaker 1: then you went to the doctor and had blood work done,
Speaker 1: and he always said, you're not in control, you're awful.
Speaker 1: You're going to be dead before you're thirty. You know,
Speaker 1: you've got to take care of yourself. So it was
Speaker 1: not a good thing to hear when you're you know,
Speaker 1: eleven years old and eleven years old, so I was
Speaker 1: never well controlled. At sixteen, I went into a diabetic
Speaker 1: coma for four days. During that they found that I
Speaker 1: was immune to the beef and pork insulin, and thankfully
Speaker 1: at that time they had developed the humuline insulin, so
Speaker 1: they put me on humuline in our MPH, which is
Speaker 1: a buffer long acting insulin, and humline R, which is
Speaker 1: a regular, short acting insulin. But even then it was
Speaker 1: just two shots a day. Everything was still based on
Speaker 1: you know, sugars, not carbs. Really, the concept was not
Speaker 1: there yet for that. So when I was in college,
Speaker 1: I was in DKA, like every semester or strength too much.
Speaker 1: You think you're taking your two shots a day, you're
Speaker 1: gonna be fine. When I was nineteen years old in
Speaker 1: nineteen eighty seven, I told my mom, I think I'm dying.
Speaker 1: I don't feel good. I feel horrible. She said, you're
Speaker 1: a lazy teenager. And I found a doctor and I said,
Speaker 1: I don't feel good. I'm taking my insulin. I don't
Speaker 1: feel good. He put me in the hospital right away,
Speaker 1: and I was immune to all buffered insulin. So in
Speaker 1: nineteen eighty seven my life changed forever because I got
Speaker 1: placed on an insulin pump. I have been under tight
Speaker 1: control ever since. I just think it's come a long way.
Speaker 1: I think pump therapy. Now I'm on a censor. They
Speaker 1: cannot with censor therapy so that reach your blood sugar
Speaker 1: all the time. You have so much more freedom now,
Speaker 1: Just coming from someone from forty three years of having diabetes,
Speaker 1: I will never complain that I have it like it
Speaker 1: is part of me, It's who I am. But diabetes
Speaker 1: is huge. It changes every aspect of your life. You
Speaker 1: have to think about everything before you do it. You
Speaker 1: just have to be prepared for high blood sugars, low
Speaker 1: blood sugars. You have to be able to have a
Speaker 1: positive attitude and not ignore it. You can't ignore it,
Speaker 1: and you have to take care of yourself.
Speaker 2: Thank you so much Carla for coming on and chatting
Speaker 2: with us. We really appreciate it.
Speaker 3: We do.
Speaker 2: Hi. I'm Erin Welsh and I'm erin Almond Updyke and
Speaker 2: this is this podcast will kill you.
Speaker 4: Yeah, this is this is going to be a good episode.
Speaker 2: Erin, I think so. I think it's I mean, we
Speaker 2: say this every time, this is this podcast and we
Speaker 2: are excited about this episode and it's going to be
Speaker 2: a good one. And we can't wait to get into it.
Speaker 3: Yeah, you know, we're going to try and keep it
Speaker 3: short and sweet, right.
Speaker 2: Yeah, but we will fail in our attempt.
Speaker 3: Should we start off with a quarantini?
Speaker 2: Let's do it?
Speaker 3: What are we drinking this week?
Speaker 2: Erin this week, I can barely hold in the laughter.
Speaker 2: This week we are drinking the aptly named sweet pea
Speaker 2: sweet pee.
Speaker 3: It's spelled p ee.
Speaker 2: Yeah, get Aaron. Do you want to explain why we're
Speaker 2: calling it sweet pea?
Speaker 3: Well, I'll explain a lot in the biology section.
Speaker 4: But that is one of the hallmark symptoms of diabetes Melodie,
Speaker 4: which is the topic of today, and that's having excess
Speaker 4: glucose or sugar in your pee.
Speaker 2: Yeah, it's true. But unlike that pea sweet pea, the
Speaker 2: Quarantini and Placebarita does not have any sugar in it.
Speaker 3: No, it's diabetes friendly.
Speaker 2: Yeah. The thing is, we were, you know, researching, okay,
Speaker 2: what are good cocktails for people with diabetes, and you know,
Speaker 2: again and again it kind of came up as like
Speaker 2: no sugar, you know, pretty simple stuff, and so what
Speaker 2: we wanted to do was kind of keep it simple
Speaker 2: and approachable. And it's actually one of my favorite like
Speaker 2: go to drinks. It's a vodka soda.
Speaker 4: It's a vodka soda. And if you want the plasiburrita version,
Speaker 4: it's a soda water with lime. Yeah.
Speaker 2: And the thing is, you know, you can really, you know,
Speaker 2: spice it up or flavor it up however you want
Speaker 2: to do it right. You can use infused vodka. You
Speaker 2: can use lemon or a different kind of fruit instead
Speaker 2: of lime. You can do anything you want. You can
Speaker 2: do stevia syrup or whatever. But you know, as a baseline,
Speaker 2: start with a vodka soda.
Speaker 3: Yeah, do that.
Speaker 4: If you need a full recipe, we will post one
Speaker 4: on our website. This podcast will kill You dot Com
Speaker 4: and all of our social media channels.
Speaker 2: So more business. On our website, you can also find
Speaker 2: things like transcripts. You can find things like a link
Speaker 2: to our Goodreads list, to our bookshop dot org affiliate account.
Speaker 2: You can find all of the references to past episodes,
Speaker 2: promo codes for all of the things we talk about
Speaker 2: in the ads.
Speaker 4: Saren oh everything everything you need this podcast will kill
Speaker 4: You dot Com?
Speaker 2: Oh yeah, merchant music. Two more things. I feel like
Speaker 2: at this point in the season and in our podcasting career,
Speaker 2: we should have that part down, but shall we don't?
Speaker 2: We never ca we never do. Before we dive into
Speaker 2: the episode, I have one more piece of exciting business,
Speaker 2: and that is that if you think back to our
Speaker 2: organ transplant episode, like many months ago, we had on
Speaker 2: two incredible guests, Carol and Betsy, who shared their first
Speaker 2: hand accounts with us, and their book titled The Insider's
Speaker 2: Guide to Living Kidney Donation, is now available, so go
Speaker 2: check it out. We'll put a link in that episode's
Speaker 2: show notes and on our website and stuff awesome.
Speaker 4: Should we dive into this probably long episode, let's do it, Okay,
Speaker 4: right after this break. So here's the thing about diabetes,
Speaker 4: arin We always say that we're not experts on any
Speaker 4: of the topics that we cover, true, and it's still
Speaker 4: true here today. So certainly there are probably going to
Speaker 4: be like endocrinologists or PhDs in biochemistry.
Speaker 3: Who are, like, you're mussing crucial pieces.
Speaker 4: We're focusing here on the broad strokes, folks. So what
Speaker 4: I'm hoping that listeners come away with by the end
Speaker 4: of this episode is an understanding from the biology side
Speaker 4: of what insulin is and what it normally does, what
Speaker 4: the essential underlying problems are in diabetes, whatever type we
Speaker 4: talk about, and why you see the complications that you see.
Speaker 4: So those are the three main pictures. Okay, excellent, all right,
Speaker 4: So let's start with some basic physiology. When a person eats,
Speaker 4: like a meal, Okay, when you just take a meal,
Speaker 4: you chew up your food, you swallow it, you digest it,
Speaker 4: It goes through your small intestine, blah blah blah, breaks
Speaker 4: down into simple sugars. Proteins break down into amino acids.
Speaker 4: We absorb them through our gut. Right, we've covered that
Speaker 4: a lot on this podcast because we've talked about a lot.
Speaker 3: Of gut bugs.
Speaker 4: But usually that's where we end the conversation is after
Speaker 4: things get absorbed or don't get absorbed into our bloodstream.
Speaker 3: So now we're going.
Speaker 4: To talk about everything that happens after that. So in
Speaker 4: our bloodstream, these nutrients, sugars, amino acids, fatty acids. These
Speaker 4: are what our cells use for energy so that we can.
Speaker 3: Live and grow and exist.
Speaker 4: And one of those sources of energy that our cells
Speaker 4: use is glucus, which is a single sugar, like a
Speaker 4: one sugar molecule. A lot of tissues use other sources
Speaker 4: of energy more than glucose, but some of our tissues,
Speaker 4: including our brain, can pretty much only use glucose, and
Speaker 4: the way that this gets to our tissues is through
Speaker 4: our bloodstream, and so that's what we call plasma glucose.
Speaker 4: That's like the primary source of fuel for our brain
Speaker 4: and some other tissues. And it turns out, for reasons
Speaker 4: that we'll talk about later on, it's very important for
Speaker 4: our bodies to keep really tight control on our plasma
Speaker 4: glucose levels. So the amount of sugar in your blood
Speaker 4: has to be really tightly controlled so that it doesn't.
Speaker 3: Go too high or too low.
Speaker 4: But the problem then is that the majority of our
Speaker 4: intake of energy, like when we eat, happens in discrete
Speaker 4: time periods. It's not like we're eating continuously throughout the day.
Speaker 4: We have periods like overnight where we don't eat at all,
Speaker 4: and then periods like I don't know, Thanksgiving, where we
Speaker 4: eat way too much all at once. So our body
Speaker 4: has to have mechanisms to store excess glucose like right
Speaker 4: after we eat a meal, and then also to liberate
Speaker 4: glucose from storage so that it's available in our bloodstream
Speaker 4: when we haven't eaten or when we're fasting, and it
Speaker 4: has to be able to do this in a very
Speaker 4: narrow window of healthy plasma glucose levels. We can't let
Speaker 4: the blood sugars get too high, and they also can't
Speaker 4: get too low. So the question is how do we
Speaker 4: do this in our bodies?
Speaker 3: The answer is insulin.
Speaker 4: Whatever can we have like a trumpet play?
Speaker 2: Whenever I say insulin in this episode, that would be
Speaker 2: a lot of trumpeting.
Speaker 3: I would think way too many trumpets.
Speaker 4: So, insulin is a peptide that is synthesized in the pancreas.
Speaker 4: Your pancreas is just a really incredible organ It excretes
Speaker 4: a lot of digestive enzymes that allow the breakdown of nutrients,
Speaker 4: and then a whole range of different hormones that enter
Speaker 4: the blood stream and have a variety of effects. But
Speaker 4: one of these major hormones is insulin, and it's secreted
Speaker 4: specifically by these cells called beta cells in response to
Speaker 4: elevated blood glucose levels. And insulin has three or kind
Speaker 4: of four major effects. Number one, what it does is
Speaker 4: suppress the release of glucose from the liver, which is
Speaker 4: one of the main storage sites for extra sugar. It
Speaker 4: also turns on glucose transporters on our muscle tissue and
Speaker 4: our adipose tissue, so that that glucose can actually get
Speaker 4: into our cells and then be stored or used. And
Speaker 4: it also stimulates glycogen synthesis, which is the way that
Speaker 4: our body stores glucose.
Speaker 3: And it does so much.
Speaker 4: It also inhibits the release of free fatty acids, which
Speaker 4: are another one of the major forms of energy that
Speaker 4: our body uses, and it stimulates those to be stored instead,
Speaker 4: so we store fat when we have insulin secretion.
Speaker 2: Okay, gotcha?
Speaker 3: All right, that was a lot I know.
Speaker 4: But the like TLDR of all of that is that
Speaker 4: insulin is a hormone that is secreted when glucose levels
Speaker 4: are high. An insulin's role is to decrease plasma or
Speaker 4: blood levels of glucose in our bodies.
Speaker 2: This is like flashback from teaching IB one fifty or
Speaker 2: one or whatever it is.
Speaker 4: Yeah, it's like way back intro bio biokem oh, yeah,
Speaker 4: but I haven't even gotten to diabetes, right, So the
Speaker 4: question is what is diabetes? And at its core, diabetes
Speaker 4: is a pro problem of insulin. I think that a
Speaker 4: lot of people think of diabetes in terms of glucose,
Speaker 4: they're like diabetes.
Speaker 3: Sugar blah blah blah.
Speaker 4: But diabetes is a problem of insulin. So if insulin's
Speaker 4: normal function is to decrease blood levels of glucose, and
Speaker 4: diabetes is a problem where insulin isn't working correctly, then
Speaker 4: the problem in diabetes is you have too much glucose
Speaker 4: in your bloodstream. H right, Right, So now the episode's
Speaker 4: over and you understand everything about diabetes, uh huh, Okay,
Speaker 4: obviously that's not true. We're going to choose your own
Speaker 4: adventure a little bit here. Okay, er, okay, are you
Speaker 4: ready for this, because there's two things that we still
Speaker 4: need to understand. We need to understand why it's a
Speaker 4: problem that glucose levels get too high, Like what is
Speaker 4: it that's happening? Why is that problematic? And then we
Speaker 4: also need to know how does diabetes actually happen, like
Speaker 4: what is the essential problem in this pathway with insulin
Speaker 4: and glucose? Right, So, which do you want to go
Speaker 4: over first?
Speaker 3: Well?
Speaker 2: I think the problems.
Speaker 4: Okay, like what happens with the problem with insulin? Yeah, exactly, Okay, great,
Speaker 4: great answer. Erin everyone is probably well aware that there
Speaker 4: are multiple different types of diabetes, which have a number
Speaker 4: of different names that I'm guessing you're probably going to
Speaker 4: go into and a little bit right erin.
Speaker 2: I mean only actually very briefly. Okay, that's fine for
Speaker 2: most of the history, I just say diabetes.
Speaker 3: Oh, that's fair.
Speaker 4: Well, the different types of diabetes, it is really important
Speaker 4: to understand the distinctions between them, so we'll.
Speaker 3: Go over it here.
Speaker 4: But essentially, the way that we classify it today is
Speaker 4: type one diabetes, type two diabetes, and then there's like
Speaker 4: gestational diabetes, and there's a few other more rare, so
Speaker 4: we're going to focus on type one and type two.
Speaker 4: So type one diabetes in general results from a destruction
Speaker 4: of the beta cells of the pancreas, usually from auto antibodies.
Speaker 4: So type one diabetes is an autoimmune condition where our
Speaker 4: bodies start to make antibodies against our own pancreas as
Speaker 4: beta cells, which are so important because they produce and
Speaker 4: secrete insulin, and these antibodies destroy those beta cells.
Speaker 2: What do we know of the triggers for this autoimmune reaction?
Speaker 4: Really good question, arin we don't, okay, So there is
Speaker 4: a genetic component to type one diabetes, However, what is
Speaker 4: interesting is that the genetic links with type one diabetes,
Speaker 4: it's not like a hereditary disease. Genetic links are not
Speaker 4: nearly as strong actually as in type two diabetes, for example.
Speaker 2: Oh interesting.
Speaker 4: Yeah, So while there are these genetic factors that certainly
Speaker 4: play a role, it's also environmental factors, and we don't
Speaker 4: know exactly what those environmental factors are that then lead
Speaker 4: to this autoimmune disease. There's a lot of thought that
Speaker 4: maybe it's viral involvement, like in people with certain susceptible genotypes,
Speaker 4: exposure to certain viruses or certain other environmental conditions trigger
Speaker 4: this autoimmune response that then leads to type one diabetes.
Speaker 4: But which viruses, great question, We don't know. People have proposed,
Speaker 4: like name a virus. It's probably been proposed as a
Speaker 4: potential cause, especially viruses that are really common epstein bar definitely,
Speaker 4: CMV absolutely all of us. Next one influenza, Yeah, influenza
Speaker 4: I think has been on that list too, But nothing
Speaker 4: that's like a strong association to be able to pin
Speaker 4: down one specif virus. Yeah. But in short, because of this,
Speaker 4: type one diabetes results from a complete inability to make insulin,
Speaker 4: So no insulin in your body means nothing to bring
Speaker 4: down those blood glucose levels, nothing to signal your body
Speaker 4: to store that glucose or allow that glucose into our
Speaker 4: cells so that we can actually use it. And for
Speaker 4: the most part, this disease tends to happen on a
Speaker 4: pretty quick timescale, especially when it happens in kids or adolescents,
Speaker 4: like the process of starting to generate these antibodies and
Speaker 4: then the slow destruction of these beta cells and then
Speaker 4: the onset of diabetes symptoms happens pretty rapidly. It can
Speaker 4: happen in adults as well, and then it tends to
Speaker 4: be a bit slower of a course, and we don't
Speaker 4: know why. Okay, So that's type one diabetes and kind
Speaker 4: of the underlying causes.
Speaker 3: You look like you have a question.
Speaker 2: Well, I don't know if it's something that you're going
Speaker 2: to go over in the other path of m choose
Speaker 2: my own adventure.
Speaker 4: Well, okay, then let's wait, and if you still have
Speaker 4: it at the end, then ask it.
Speaker 2: Okay, just like, hold all questions till the end of
Speaker 2: the presentation, please.
Speaker 3: And then it'll be more of a comment.
Speaker 2: Yep, all right.
Speaker 3: So type two diabetes is.
Speaker 4: A bit more complicated than that. Type two diabetes results
Speaker 4: from a combination of different things, including beta cell dysfunction,
Speaker 4: but not necessarily destruction.
Speaker 2: What's the difference between dysfunction and disruption, just like producing
Speaker 2: less insulin?
Speaker 4: Right, yeah, so either producing like not great insulin or
Speaker 4: just not being able to produce enough insulin or making
Speaker 4: insulin but not being able to secrete it. Whereas in
Speaker 4: type one diabetes, your beta cells are obliterated, They're gone, right, Okay, Yeah,
Speaker 4: So it's a combination of beta cell dysfunction and insulin resistance.
Speaker 4: So you have insulin, you're making insulin, but your tissues
Speaker 4: are not responding to it the way that they're supposed to.
Speaker 4: So what does that really mean? Right? It means that
Speaker 4: in general, people with type two diabetes have either one
Speaker 4: or both of two different problems going on. Problem one,
Speaker 4: like I said, their beta cells are not making enough
Speaker 4: insulin for whatever reason, they just stop being able to
Speaker 4: produce enough insulin or secrete that insulin into this bloodstream.
Speaker 4: Or problem number two, their tissues become resistant to these effects.
Speaker 4: So then the pancreas secretes more and more insulin. So
Speaker 4: what we actually see is a hyper insulinemia. That means
Speaker 4: you have a lot of insulin in your bloodstream, but
Speaker 4: it's not being used properly and so it's not effective.
Speaker 4: And therefore you still have too much glucose in your bloodstream.
Speaker 2: So you just have like a bunch of like insulin
Speaker 2: and glucose, you know, circulating around. So what does it
Speaker 2: mean that your tissues are no longer responding to insulin
Speaker 2: in the right way? Like what's going on there?
Speaker 3: Yeah, good question.
Speaker 4: A whole bunch of different things. In part, it's that
Speaker 4: you actually can see down regulation of the number of
Speaker 4: glucose receptors on tissues. So glucose has to be actively
Speaker 4: transported into your skeletal muscle and your adipose tissue. It
Speaker 4: can't just like legle its way in there. And so
Speaker 4: in type two diabetes, you can have less receptors on
Speaker 4: those cells, like they progressively get lower, or like a
Speaker 4: whole host of other things can happen.
Speaker 3: But that's kind of the main ones.
Speaker 4: But why, Okay, we'll get to the why.
Speaker 2: Okay, hopefully maybe maybe Okay, okay, we'll approach the why.
Speaker 3: But yeah, we'll we'll slowly get to the y. But
Speaker 3: one question, because because in many.
Speaker 4: Cases we actually see both of these things happening simultaneously.
Speaker 4: So then there comes this question of which comes first.
Speaker 4: So the way that I like to think of it,
Speaker 4: and again this is very simplified, but I think it's
Speaker 4: kind of a just a nice framework to have, is
Speaker 4: that as you start to have this increase in insulin resistance,
Speaker 4: so your tissues are down regulating the amount of receptors
Speaker 4: that they have so that the glucose can't get into
Speaker 4: the tissues, you have an increase in insulin resistance, and
Speaker 4: your pancreas recognizes this and it's like, gosh, we have
Speaker 4: just so much glucose running around. So your pancreas is
Speaker 4: working really hard, like working overtime, to make more and
Speaker 4: more insulin, and that then causes your tissues to become
Speaker 4: even more desensitized to that insulin because they're just overloaded.
Speaker 4: It's like insulin overload, there's so much of it. So
Speaker 4: then your pancreas makes even more and then eventually your
Speaker 4: pancreas is just exhausted because it's been working overtime for
Speaker 4: so long that it starts to just give up and
Speaker 4: then either making cruddy insulin or just not making insulin
Speaker 4: or not secreting it. Like, what's the point You're not
Speaker 4: going to even respond to it, I'm gonna quit. So
Speaker 4: now you have both problem one and problem to problem
Speaker 4: to exacerbating problem one and causing this vicious cycle.
Speaker 2: What's the timeline for that to happen?
Speaker 4: That's a good question, and it's hard to put an
Speaker 4: actual timeline on it, especially because when you look at
Speaker 4: like a population level, there are a whole lot of
Speaker 4: people who have what is sometimes called pre diabetes or
Speaker 4: just I forget the other proper term for it, but
Speaker 4: it's like increased fasting glucose levels where they have this
Speaker 4: higher than what is considered typical baseline glucose. And so
Speaker 4: some of those people will then progress to type two diabetes,
Speaker 4: some people won't, and some people have like both problems
Speaker 4: going on. Some people maybe have only a little of one.
Speaker 4: So type two diabetes is very complicated.
Speaker 2: Interesting, and so when it comes to type two, part
Speaker 2: of the problem is like the resistance seems like the
Speaker 2: biggest part to target for treatment, right, Like how do
Speaker 2: you reduce resistance because it seems like that's sort of
Speaker 2: what's contributing to the pancreas just being overloaded and like poof,
Speaker 2: I can't do this anymore.
Speaker 4: Yeah, that's a good thought, and we actually have a
Speaker 4: lot of medicines that do exactly that to try and
Speaker 4: make your tissues more sensitive to the effects of insulin,
Speaker 4: and that is for some people, really good treatment for diabetes.
Speaker 4: But we'll just have to keep talking because there's more
Speaker 4: to the story.
Speaker 2: Excellent, love that song, my favorite track.
Speaker 4: I just made it up just right off the top
Speaker 4: of my head. All right, So now let's talk Now
Speaker 4: that we understand the underlying problem with these two different
Speaker 4: types of diabetes, let's talk about what the symptoms of
Speaker 4: these diseases are, and then we'll finally get to that
Speaker 4: second part of the Choose your Own adventure, which is
Speaker 4: like understanding why this high glucose is a problem, because
Speaker 4: that really is what drives the symptoms, right so classically,
Speaker 4: especially with type one diabetes. However, all of these symptoms
Speaker 4: that I'm going to talk about can happen with type
Speaker 4: one or type two diabetes. But because type one tends
Speaker 4: to happen faster and type two tends to be a
Speaker 4: much longer course, the more acute symptoms tend to happen
Speaker 4: more in type one diabetes, and the chronic complications can
Speaker 4: happen in both, but certainly in type two diabetes. So classically,
Speaker 4: somebody with diabetes presents with what is often called the
Speaker 4: three p's, that is, polyurea, polydipsia, and polyph phasia, and
Speaker 4: also weight loss. So what do those mean and how
Speaker 4: does it happen? So as your blood glucose levels rise,
Speaker 4: eventually your kidney, which is responsible for filtering everything in
Speaker 4: your blood, just can't filter all of that glucose and
Speaker 4: get it back into your bloodstream because there's just so
Speaker 4: much of it. So your kidney starts excreting glucose. After
Speaker 4: your blood levels reach about one point eighty.
Speaker 3: It just starts.
Speaker 4: You start peeing out sugar, hence the.
Speaker 3: Name I'm quarantine sweetpee.
Speaker 4: And glucose. Just like lactose does in our guts see
Speaker 4: our lactose intolerance episode. Glucose is an osmodic diuretic, so
Speaker 4: it holds onto the water along with it. So now
Speaker 4: you're peeing out a ton of water because your kidneys
Speaker 4: aren't holding onto the glucose or the water. So that's
Speaker 4: the first P polyuria, which leads unsurprisingly to massive dehydration,
Speaker 4: causing the set second P polydipsia, which means major increase
Speaker 4: in thirst, like unquenchable thirst. And at the same time,
Speaker 4: the lack of insulin in your body, which is driving
Speaker 4: all of this, essentially means that your body is unable
Speaker 4: to use any of the glucose that you have in
Speaker 4: your bloodstream. So while you technically have plenty of fuel,
Speaker 4: your body thinks that it's in starvation mode, and so
Speaker 4: it switches to what's called catabolic metabolism, and that is
Speaker 4: breaking down your tissues to use for fuel, which leads
Speaker 4: to major hunger. That is polyphasia the third P. But
Speaker 4: despite this, you see weight loss because you're literally eating
Speaker 4: your own body tissues to use as fuel, really really
Speaker 4: bad things, very bad things. And then you have other
Speaker 4: symptoms like fatigue unsurprising because this is taking a major
Speaker 4: toll on your body, blurry vision, muscle cramps because you're
Speaker 4: electric lights are way out of whack, et cetera. And
Speaker 4: when this gets very severe, which happens in about twenty
Speaker 4: to forty percent of cases in people like presenting for
Speaker 4: the first time with something like type one diabetes, it's
Speaker 4: called diabetic keto acidosis.
Speaker 3: A lot of people have probably heard of this.
Speaker 4: It is exactly what the name implies.
Speaker 2: So I just I just looked this up to clarify
Speaker 2: something and that I had popped into my head, and
Speaker 2: I remember, do you ever see the movie Steel Magnolias,
Speaker 2: you know, Julia Roberts.
Speaker 4: I have never seen Steel Magnolias.
Speaker 2: Okay, well, you know, I hope this isn't too much
Speaker 2: of a spoiler, but there's definitely Julia Roberts play someone
Speaker 2: who has type one diabetes, and there's like I thought
Speaker 2: it was a keto acidosis like attack. No, it was
Speaker 2: actually hypoglycemia. And but I need to rewatch that movie
Speaker 2: now after doing this episode.
Speaker 4: Well, you saying that just made me think of Honey,
Speaker 4: I shrunk the is it, honey, we shrunk ourselves.
Speaker 2: I think it's number three? Yeah, and number three is
Speaker 2: the baby.
Speaker 4: But I don't remember what banana. I just he needs
Speaker 4: bananas because of the potassium. But is that because he's diabetic,
Speaker 4: because you do need potassium? I think so, I don't
Speaker 4: know anyways, that that's is.
Speaker 2: There are many of them, I believe, all right.
Speaker 4: So diabetic ketoacidosis. So if you're thinking about that classic
Speaker 4: presentation that I talked about as that can kind of
Speaker 4: progress if it goes unrecognized, or if somebody has like
Speaker 4: a low level of that going on the three p's
Speaker 4: and then they get some other stressor on top of it,
Speaker 4: like an infection or just something that stresses their body out,
Speaker 4: as that person becomes even more dehydrated and just continue
Speaker 4: this process of breaking down their fat stores. Their liver
Speaker 4: then starts this process of ketogenesis. Ketones can be used
Speaker 4: by the brain as an alternative source of fuel. However,
Speaker 4: they are an acid and therefore lead to the blood
Speaker 4: becoming acidotic, which because of dehydration, is compounded by lactic acidosis,
Speaker 4: which then further worsens kidney function, which makes it even
Speaker 4: harder to excrete those keto acids because that's one of
Speaker 4: your kidney's jobs. And this acidemia can eventually lead to
Speaker 4: brain damage. And on top of that, your body compensates
Speaker 4: via respiration to try and make your blood alkalolotic by
Speaker 4: something called cousmall breathing, which is essentially hyperventilation, which can
Speaker 4: then lead to coma and death.
Speaker 2: It's very severe, Okay, So when people refer to a
Speaker 2: diabetic coma, it's ketoacidosis like it.
Speaker 4: Very often, Yes, it can be Okay, Yeah, so that's
Speaker 4: kind of the acute complications of diabetes type one or
Speaker 4: type two. But those tend to happen more in type one.
Speaker 4: But certainly somebody with undiagnosed type two diabetes might have
Speaker 4: symptoms like a little bit of polydipsia, maybe some polyuria.
Speaker 3: Et cetera.
Speaker 4: So now let's think of it in terms of long term.
Speaker 4: Why is having too much sugar in your blood bad
Speaker 4: long term? And a lot of people might know of
Speaker 4: some of the common kind of side effects of diabetes. Aaron,
Speaker 4: do you know some of them just off the top
Speaker 4: of your head.
Speaker 2: I mean, I know that kidney disease is a big problem.
Speaker 2: I know ulcers are a big problem, Like amputations are
Speaker 2: really common. Blindness or retinopathy is really common, I think,
Speaker 2: just like loss of sensation in your extremities.
Speaker 3: Yeah, yeah, peripheral neuropathy.
Speaker 4: Yeah, and all of those things that you just talked about,
Speaker 4: plus the cardiovascular risk, so risk of clots, especially in
Speaker 4: your heart or your brain.
Speaker 2: Right, heart attacks are really common too.
Speaker 3: Yeah.
Speaker 4: All of those can be split into kind of two
Speaker 4: different but very similar processes. Those are microvascular complications, so
Speaker 4: small blood vessel problems and macrovascular complications, so large blood vessels,
Speaker 4: heart brain, okay, But either way we're dealing with vascular
Speaker 4: complications and in some cases direct damage to nerves as
Speaker 4: well as blood vessels. So the question is like how
Speaker 4: exactly do these complications occur, and that is probably the
Speaker 4: subject of many different PhDs worth of research, But in general,
Speaker 4: chronically having way too much glucose in your bloodstream leads
Speaker 4: to a state of chronic inflammation. This then leads to
Speaker 4: the production of reactive oxygen species, which we've talked about
Speaker 4: a number of times on the podcast, which are basically
Speaker 4: things that then cause a bunch of tissue damage, especially
Speaker 4: in blood vessels, causing vascular injury, and that can lead
Speaker 4: to all of those complications that you mentioned, Aaron. So
Speaker 4: it has major effects on the kidneys, especially if you
Speaker 4: think about it, this is where all of that glucose
Speaker 4: is going and the kidneys are filtering everything in your bloodstream,
Speaker 4: so kidney damage is a major one. Blindness is caused
Speaker 4: from retinopathy where you have damage to the nerves of
Speaker 4: the eye and also increased blood vessel formation that leads
Speaker 4: to increased pressures behind the eye. The peripheral neuropathies, which
Speaker 4: can lead to a loss of sensation that can then
Speaker 4: lead to injuries that are complicated by poor perfusion because
Speaker 4: those blood vessels are damaged, So then those ulcers don't
Speaker 4: heal because they don't have any blood flow, so then
Speaker 4: they become gangrenous, and then yes, you have to do amputations.
Speaker 2: It seems like there are parts of the body that
Speaker 2: are more sensitive to this. Kidneys make sense because they're
Speaker 2: having a difficult time with the filtration. Heart makes sense
Speaker 2: because blood blah blah blah. What about like your stomach
Speaker 2: or like you know, other organs, I mean, what's going
Speaker 2: on with those?
Speaker 3: Yeah, great question.
Speaker 4: I think a lot of people think that diabetes, oh,
Speaker 4: your kidneys, your eyes. Diabetes is a disease that affects
Speaker 4: every single organ in your body. So your stomach, Diabetes
Speaker 4: can affect your autonomic nervous system as well as your
Speaker 4: peripheral nerves, and that damage, along with a host of
Speaker 4: other things, can lead to delayed gastric emptying. So it
Speaker 4: can cause your stomach to not be able to contract
Speaker 4: the way that it's supposed to so that you can
Speaker 4: actually get your food to empty from your stomach, which
Speaker 4: can lead to a whole host of problems. So, yeah,
Speaker 4: diabetes affects every part of your body. It has the
Speaker 4: greatest effects and the earliest effects on small blood vessels.
Speaker 3: That's why we see.
Speaker 4: Things like neuropathy or retinopathy because those are really small vessels.
Speaker 4: But then it also has the potential to have complications
Speaker 4: on larger vessels like your heart, your brain. It affects
Speaker 4: the entirety.
Speaker 3: Of your body.
Speaker 2: Yeah, okay, that makes sense, and that's the biology of diabetes. Erin, uh,
Speaker 2: did we get to the why? I've been waiting?
Speaker 3: I know you have been waiting.
Speaker 4: We don't have a great answer to the why, but
Speaker 4: I have a guess as to the answer in our
Speaker 4: current events section, so we'll just have to wait.
Speaker 2: Oh okay, all right, okay.
Speaker 4: So Aaron, tell me what do we know about this?
Speaker 4: I assume it's been with us since forever.
Speaker 5: Yeah, let's start back at forever right after this break.
Speaker 2: All right, So this is a long episode so far.
Speaker 2: I'm going to add to that. I'm going to do
Speaker 2: something a little bit different for this episode, and that
Speaker 2: is to divide the history section into two parts, not
Speaker 2: like sequential chapters, you know, like happened and then this happened,
Speaker 2: but more like parallel histories in a way awesome. And
Speaker 2: for this first part, I'm going to focus on the
Speaker 2: standard history that I usually cover for a disease. You know,
Speaker 2: things like early writings, increasing recognition of the condition, and
Speaker 2: medical advancements, especially when it comes to diabetes, the discovery
Speaker 2: of insulin, you know, all the things that like completely
Speaker 2: changed the landscape of diabetes, especially in the twentieth century.
Speaker 2: And then for part two, I really want to go
Speaker 2: through the other transformation that diabetes went through around that
Speaker 2: same time, and that is the social perception or portrayal
Speaker 2: of the disease, especially focusing on the US.
Speaker 3: Excellent. I can't wait, alrighty.
Speaker 2: So let's begin at the beginning. It probably doesn't surprise
Speaker 2: you to know that diabetes has long been recognized by
Speaker 2: many different ancient cultures. You went through the symptoms of diabetes,
Speaker 2: and especially for the like acute symptoms, and they're pretty
Speaker 2: recognizable and unique, so it makes sense that they were
Speaker 2: written about at length for thousands of years. It was
Speaker 2: mentioned in the Ebres Papyrus, my favorite, in the form
Speaker 2: of a treatment for a symptom of the disease. So
Speaker 2: quote a medicine to drive away the passing of too
Speaker 2: much urine, and in the sixth century BCE, the Hindu
Speaker 2: physician Sushruda described a disease of honey urine which could
Speaker 2: be detected either through tasting it directly or by observing
Speaker 2: ants gathering around a pool of urine ooh yeah. And
Speaker 2: the word diabetes itself comes from the second century CE,
Speaker 2: when the ancient Greek physician Aretaeus coined it from the
Speaker 2: Greek word for to run through or pipe like. He
Speaker 2: also described the disease as quote melting down of the
Speaker 2: flesh and limbs into urine, and the word melodis, from
Speaker 2: the Latin word for honey or sweet, was added later
Speaker 2: on to again indicate the sweetness of the urine. Galen
Speaker 2: around the same time as Aretaeus described it as quote
Speaker 2: diarrhea of urine, and Avicenna in the tenth century CE
Speaker 2: wrote a thorough description of the disease and its complications.
Speaker 2: So the sweetness of the urine had long been recognized.
Speaker 2: The sweet pea was people were very familiar with it,
Speaker 2: but it wasn't until the sixteen hundreds that a physician
Speaker 2: in Liverpool named Matthew Dobson realized that it was actually
Speaker 2: sugar causing the sweetness. He made the observation when treating
Speaker 2: a patient who was urinating fifteen liders of fluid a day. Oh,
Speaker 2: so to like, because I think when we say, oh,
Speaker 2: you pee a lot, like, what does that actually mean? Right?
Speaker 2: And so this person was peeing fifteen leaders of fluid
Speaker 2: a day. That is.
Speaker 3: Way too much.
Speaker 2: Oh yeah, we just have a little we have a
Speaker 2: little sidebar.
Speaker 3: Yeah, to do a little calculation.
Speaker 2: Who was really boring, So we had to cut it.
Speaker 4: But for reference, a typical amount of urine output is
Speaker 4: between eight hundred and about two thousand millileaders or two
Speaker 4: leaders a day a day.
Speaker 2: Yeah, ooh yeah, so we've been talking about sweet pea
Speaker 2: and yeah, I mean people did have to taste it like.
Speaker 2: That was how a lot of the diagnoses were made,
Speaker 2: you know, mostly were made, but at least one doctor
Speaker 2: successfully fermented the urine to produce what he described as
Speaker 2: like a weak beer urine beer. Yeah.
Speaker 3: That should have been our quarantine.
Speaker 2: That should have been our quarantini. And this taste test
Speaker 2: remained the main way of diagnosing someone with diabetes until
Speaker 2: the eighteen hundreds, when chemical tests were developed to detect
Speaker 2: and measure glucose in the urine, much to many physicians relief.
Speaker 2: I am sure around the time that these tests were developed,
Speaker 2: the medical world was undergoing a pretty big transformation in
Speaker 2: terms of our understanding of disease. Yes, I'm bringing up
Speaker 2: germ theory in the history of diabetes, oh okay. But
Speaker 2: as researchers and clinicians learned about infectious diseases and applied
Speaker 2: that knowledge to prevention, a lot of chronic diseases grew
Speaker 2: more visible as morbidity and mortality from infectious diseases dropped
Speaker 2: right and when they did, they grabbed some research attention
Speaker 2: to themselves. So from the middle of the eighteen hundreds
Speaker 2: it was increasingly recognized that the pancreas played some role
Speaker 2: in the disease, thanks to the rise in autopsies that
Speaker 2: had been happening that showed that damaged pancreases were often
Speaker 2: found in people with diabetes, and in eighteen eighty nine
Speaker 2: at the University of Strasbourg, two researchers named Oscar Minkowski
Speaker 2: and Joseph von Mehring showed this experimentally that the pancreas
Speaker 2: was involved when they induced diabetes in a dog after
Speaker 2: removing its pancreas, and it was all over that like,
Speaker 2: peeing everywhere in the lab and I'll do it. Minkowski
Speaker 2: was like, what's going on. I'm so annoyed. This dog
Speaker 2: is house trained. Why is it peeing everywhere? Oh my gosh,
Speaker 2: it has diabetes. But how exactly was the pancreas involved
Speaker 2: was happening? Additional experiments removing part of the pancreas or
Speaker 2: grafting bits of a pancreas, showed eventually that the pancreas
Speaker 2: seemed to have two secretions, one external that seemed to
Speaker 2: help with digestion and one internal that went right into
Speaker 2: the bloodstream to help with carbohydrate regulation. But where did
Speaker 2: the internal secretion come from? In nineteen oh one, Eugene
Speaker 2: Opie at Johns Hopkins showed that damage to the islets
Speaker 2: of Langerhans, which were named for their discoverer, that that
Speaker 2: damage prevented the production of this internal secretion, which then
Speaker 2: led researchers to speculate that if this internal secretion, which
Speaker 2: by the way, was totally hypothetical at the time, if
Speaker 2: it could be isolated, it could potentially be used to
Speaker 2: treat diabetes.
Speaker 3: This is so cool.
Speaker 2: It is amazing that people I just can't believe like
Speaker 2: the pancreas, like the functions of the pancreas at a
Speaker 2: time when like bioassays were non existent.
Speaker 3: Right, it's just people being so.
Speaker 4: Kind of intuitive or or maybe it's deductive. I don't know,
Speaker 4: but it's just it's smarter than me.
Speaker 3: I'm so impressed by it.
Speaker 2: Well, I think also, you know, to give a little
Speaker 2: bit more historical context, at the time, this wasn't necessarily
Speaker 2: as huge a leap in thinking as we are looking
Speaker 2: at it to be right, This was actually in line
Speaker 2: with a lot of other medical advancements that were happening
Speaker 2: showing how certain organs produced hormones, like the field of
Speaker 2: you know, endochronology was kind of burgeoning at this time,
Speaker 2: and that it was recognized that these hormones regulated bodily functions,
Speaker 2: and disruptions in the production of these hormones could then
Speaker 2: lead to certain diseases, especially once like you know, germ
Speaker 2: theory was like, all right, let's do the low hanging fruit.
Speaker 2: We got all these diseases, Okay, what are all these now? Like, yeah,
Speaker 2: what's happening? And then in the eighteen nineties it was
Speaker 2: found that giving someone like thyroid extract could actually help
Speaker 2: treat some conditions. So in this line of reasoning, it
Speaker 2: you know, made sense that pancreous extract could possibly do
Speaker 2: the same. But early experiments with these pancreous extracts that
Speaker 2: were performed around the very early nineteen hundreds on humans
Speaker 2: had you know, mixed results. If I'm unsurprising, if I'm
Speaker 2: feeling generous, yep, okay, And if I'm not feeling generous,
Speaker 2: I would say mostly harmful and sometimes outright dangerous okay.
Speaker 2: But in any case, they didn't really suggest that this
Speaker 2: was like a good path forward, like this was not
Speaker 2: the clear way to go. So what was well, Despite
Speaker 2: the growing visibility of diabetes and all these advancements in
Speaker 2: understanding its pathology and being able to diagnose it, one
Speaker 2: area that was sorely lacking was in treatment. Throughout the
Speaker 2: seventeen hundreds and much of the eighteen hundreds, the leading
Speaker 2: treatments for diabetes were basically the same things that you
Speaker 2: would use to treat anything, right, Bleed them and shoot
Speaker 2: them up with opium like that boom. If you know
Speaker 2: how to do those things, you're a doctor. In the
Speaker 2: seventeen hundreds, and there are very few diseases that would
Speaker 2: actually benefit from bleeding, but they do exist hemochromatosis, but
Speaker 2: diabetes was not one of these. Yeah, and opium, of course,
Speaker 2: that isn't going to make diabetes or many things better.
Speaker 1: No.
Speaker 2: No. Diabetes was generally viewed as a disease of downhill progress,
Speaker 2: and for someone diagnosed with what was then known as
Speaker 2: acute or juvenile onset diabetes now type one, the life
Speaker 2: expectancy following diagnosis was like one to three years. Often
Speaker 2: it was months. It wasn't that much longer for those
Speaker 2: with what was viewed as the chronic form either. It
Speaker 2: was essentially a death sentence. Like across the board, medications
Speaker 2: and tinctures and infusions seemed to be of no help
Speaker 2: for the disease. But there was one thing that seemed
Speaker 2: to slow the progression of the disease maybe even though
Speaker 2: it did nothing to cure it. Starvation diets. Yeah. Yeah,
Speaker 2: So during the eighteen seventy Siege of Paris, when food
Speaker 2: was rationed and many people were near starvation, one doctor
Speaker 2: noticed that the urine of some of his patients with
Speaker 2: diabetes had dropped in their glucose levels, and that their
Speaker 2: symptoms had begun to improve a little bit. So the
Speaker 2: logical step was, well, if we severely limit the caloric
Speaker 2: intake of people with diabetes, we can reduce the symptoms
Speaker 2: of the disease. And this was the opposite of previous thinking,
Speaker 2: which was like, oh, this person is losing weight, we
Speaker 2: need to feed them more, right, right, So, after this observation,
Speaker 2: starvation diets really kind of got their start. And it
Speaker 2: wasn't always strictly starvation. You know, some diets were just
Speaker 2: no carb diets, some were just certain carbs like oats only,
Speaker 2: but in general they were calorie cutting, with most diets
Speaker 2: restricting you to fewer than five hundred calories a day.
Speaker 2: Oh my, yeah, that is not a lot.
Speaker 4: That is no, you can't live on that long term.
Speaker 2: But exactly, yeah, I mean, and these starvation diets did
Speaker 2: seem to work, like to a degree. I mean, they
Speaker 2: did nothing at all to cure or even effectively treat
Speaker 2: the disease, but they did in some cases just like
Speaker 2: slow the progression and help manage these glucose levels. But
Speaker 2: the stories are horrifying, right. For instance, one woman forty
Speaker 2: three years old was admitted to the hospital in nineteen sixteen,
Speaker 2: weighing seventy nine pounds or thirty six kilograms, and was
Speaker 2: told to fast. And the last record of this patient
Speaker 2: showed her weighing sixty pounds, less than thirty kilograms before
Speaker 2: she broke her fasting diet and died shortly after.
Speaker 3: Oh my goodness.
Speaker 2: And another really sad story is of a twelve year
Speaker 2: old boy with diabetes. Already blind from the disease, he
Speaker 2: was brought to the hospital so that his food could
Speaker 2: be closely monitored and his calories even more restricted. His
Speaker 2: weight dropped to forty pounds, but the blood glucose didn't
Speaker 2: seem to be dropping, and so he they cut even
Speaker 2: more and he died of starvation.
Speaker 3: Oh my god.
Speaker 2: So these starvation diets, in addition to slowly killing you,
Speaker 2: were also largely unachievable for most people with diabetes because
Speaker 2: they require the time and the money to monitor and
Speaker 2: weigh each individual food item and rest and it was
Speaker 2: just like not a reality. Yeah, So, going into the
Speaker 2: twentieth century, the available treatments for diabetes were really more
Speaker 2: of a choice among evils, right, die of diabetes or
Speaker 2: of starvation or of opium addiction, just like take your pick.
Speaker 2: So the need for effective treatment was very obvious and
Speaker 2: incredibly pressing, even more so since cases seemed to be
Speaker 2: on the rise, and so far the only thing that
Speaker 2: had showed any real promise were the experiments with pancreas
Speaker 2: extracts that I had mentioned earlier. Despite their limited success.
Speaker 2: In particular, the work of two researchers, Georg Zulezer from
Speaker 2: Germany and Nikolay Pelescue from Romania, showed that there might
Speaker 2: be something in it. In nineteen o six in Berlin,
Speaker 2: Zulzer had treated some humans with pancreatic extract but the
Speaker 2: side effects produced were like really severe and so we
Speaker 2: had to stop the project. And ten years later, in
Speaker 2: nineteen sixteen, Paulescu had succeeded in treating a diabetic dog
Speaker 2: with a solution of pancreatic extract, like it lowered its
Speaker 2: blood sugar levels. Just okay, super cool, promising, But his
Speaker 2: work was disrupted by World War One when he was
Speaker 2: called to service, and by the time he got back
Speaker 2: he picked up his work again, but like funds were
Speaker 2: super limited and he was working almost by himself, so
Speaker 2: it was just kind of like hard to get things moving. Yeah,
Speaker 2: and neither zules or Paulescu would end up getting the
Speaker 2: recognition they felt they deserved for their role in one
Speaker 2: of the most monumental and one of the most contentious
Speaker 2: medical advancements in the twentieth century, the discovery of insulin.
Speaker 3: Insulin do that horn again?
Speaker 2: In fact, like this, the history of this discovery continues
Speaker 2: to be like a fairly debated topic in medical history,
Speaker 2: like who should get credit for it? And so I'm
Speaker 2: just going to do the best I can to navigate
Speaker 2: those tensions. Yeah, So let's meet one of the central
Speaker 2: characters of this story, Frederick Banting born in Ontario in
Speaker 2: eighteen ninety one. He began med school just a couple
Speaker 2: of years before World War One broke out. He joined up,
Speaker 2: he helped treat combat soldiers, and after the war was over,
Speaker 2: he tried unsuccessfully to get a permanent position at the
Speaker 2: Toronto Hospital where he did his residency in orthopedic medicine.
Speaker 2: So he decided that he was gonna move to London,
Speaker 2: Ontario set up a private practice. But it was really
Speaker 2: pretty unsuccessful, like he couldn't quite get it off the ground.
Speaker 2: And in fact, it seemed like a lot of areas
Speaker 2: in his life were just like filled with struggle and
Speaker 2: strife and uncertainty, like he was always on and off
Speaker 2: again with his fiance, and he seemed like he was
Speaker 2: always sending out like job applications. He seemed like desperate
Speaker 2: for a change of scenery or a change of pace
Speaker 2: in his career. Late one October night in nineteen twenty,
Speaker 2: while trying to fall asleep and what seems like, as
Speaker 2: he described stress spiraling y yeah, absolutely, his mind drifted
Speaker 2: to a paper that he had recently read to prep
Speaker 2: for a lecture that he was giving on like I
Speaker 2: think carbohydrate regulation. And this paper, which was written by
Speaker 2: Moses Baron, discussed the role of the islets of Langerhans
Speaker 2: in the internal secretion of the pancreas and its possible
Speaker 2: role in diabetes. And he turned the idea over and
Speaker 2: over in his mind and kept thinking about it and
Speaker 2: came up with what he thought was the solution to
Speaker 2: the problem, like a way to isolate that internal pancreatic
Speaker 2: secretion and it would involve surgical removal of degenerated pancreases
Speaker 2: and dogs and extraction of the secretion from those pancreases.
Speaker 2: And the next time he was on campus, he brought
Speaker 2: up the idea to a professor at the university where
Speaker 2: he was affiliated, and the professor was like, you know, no,
Speaker 2: like sorry, but we just don't have the resources for that.
Speaker 2: And also there's no one at the university here that
Speaker 2: knows enough about it to be able to help you.
Speaker 2: But hang on a second. There happens to be somebody
Speaker 2: visiting who might and that somebody turned out to be
Speaker 2: JJ R. McLeod visiting from the University of Toronto, who
Speaker 2: was an expert in diabetes and carbohydrate metabolism. So Banting
Speaker 2: met with McLeod. McLeod wasn't like super impressed by Banting,
Speaker 2: who had a lot of enthusiasm and confidence, but that
Speaker 2: confidence wasn't really backed by like a lot of background
Speaker 2: reading on the subject. He was just like, I'm gonna
Speaker 2: do this and it's gonna be great.
Speaker 4: Oh and we've met those.
Speaker 2: Yeah, And McLeod was like, you know, people have spent
Speaker 2: their entire careers working on this problem. Do you know
Speaker 2: about these people? Do you know the work that they've done.
Speaker 2: But over the conversation, McLeod became more and more convinced
Speaker 2: and became eventually interested enough to say, Okay, you know what,
Speaker 2: sure come to the University of Toronto whenever, and you know,
Speaker 2: we can try to set something up, but you know,
Speaker 2: think carefully about this decision because it would mean giving
Speaker 2: up your practice and your affiliation here. And also like
Speaker 2: there's kind of a low chance that you would be successful,
Speaker 2: because you know, this is not a new problem, like
Speaker 2: people have tried this before. So Bantin gave it some
Speaker 2: time and thought and decided to give it a go.
Speaker 2: But after the other job applications that he had sent
Speaker 2: out had fallen through, and after his fiance had dumped
Speaker 2: him yet again, so he was like, you know what
Speaker 2: I lose, I'm getting out of here. So so yeah,
Speaker 2: so we packed up his apartment. He headed to Toronto
Speaker 2: and got there in April nineteen twenty one, and apparently
Speaker 2: he had done no more reading on the subject in
Speaker 2: the meantime, oh or not, my goodness, not very much,
Speaker 2: because when he met with McLeod, McLeod was like, Okay,
Speaker 2: so I think this is how the experiments should go.
Speaker 2: We'll start with this, and then we'll do this, and
Speaker 2: then we'll do this. Let's you know, see how we begin.
Speaker 2: He showed him how to do the procedures et cetera,
Speaker 2: and then he was like, also, you know, maybe you
Speaker 2: should read these papers, read these books, get a little
Speaker 2: more background in it. And then McLeod headed back to
Speaker 2: Scotland where he was from for the summer break. But
Speaker 2: before he did that, he gave Banting an undergraduate research
Speaker 2: assistant named Charles Best to help on the project, and
Speaker 2: he kind of spent a little bit of time, like
Speaker 2: a month and a half or so, kind of walking
Speaker 2: them through these surgical procedures that they would use on
Speaker 2: the dogs. The experimental plan went a little something like this. First,
Speaker 2: Banting and Best would get practice Banting on performing the
Speaker 2: pancreatectomies and Best using the blood and urine tests, and
Speaker 2: both of them observing what diabetes and dogs look like
Speaker 2: like the course of disease. And then Banting would ligate
Speaker 2: the pancreatic ducks in other dogs, allow them to recover
Speaker 2: while they're pancreas's atrophied, and then reoperate on these dogs,
Speaker 2: removing their degenerated pancreases and extracting the internal secretion from them,
Speaker 2: which he would then inject into the dogs that had
Speaker 2: been made diabetic from the complete removal of their pancreas.
Speaker 3: Huh.
Speaker 2: It didn't need like it was later realized that the
Speaker 2: atrophy didn't need to happen, but that's yeah, that was
Speaker 2: what they thought needed to happen first.
Speaker 4: It's interesting that that that part of it worked.
Speaker 6: I know, well, you know, and it it It didn't
Speaker 6: really work at first. It things got off to a
Speaker 6: really rocky start.
Speaker 2: And it's really sad because a lot of dogs died
Speaker 2: in the course of this experiment and in many other experiments,
Speaker 2: especially after the surgeries, which you know, keep in mind
Speaker 2: these were the days pre antibiotic, so like they would
Speaker 2: just die of sepsis, good surgeries, no, no, And in fact,
Speaker 2: so many dogs died that they began to like buy
Speaker 2: dogs off of the street because they had almost depleted
Speaker 2: the store of university dogs. Like this would not fly nowadays,
Speaker 2: just fly. I everyone I cook would be like like, nope,
Speaker 2: you are getting your research whatever credit. Yeah, you're not
Speaker 2: allowed to do research at this university anymore or any
Speaker 2: ever again, yes or any Yeah. But finally, finally, after
Speaker 2: many failures, things began looking up. They were able to
Speaker 2: successfully extract the secretion from the pancreas injected into depancreatized
Speaker 2: diabetic dogs and bring them back from the brink of
Speaker 2: death and out of a diabetic coma by rapidly dropping
Speaker 2: their blood sugar. This was like thrilling yeah, and Banting
Speaker 2: was quick to see and believe in the potential of
Speaker 2: this extract for the treatment of diabetes and humans. But McLeod,
Speaker 2: who was now back from his trip, he was urging
Speaker 2: a bit more caution. He was like, all right, why
Speaker 2: don't we just try repeating these experiments first, making sure
Speaker 2: we have like good you know, sample size, and we'll
Speaker 2: publish the results. See if we can refine the process
Speaker 2: and make sure that like we know exactly what we're
Speaker 2: doing and that other people can replicate it.
Speaker 4: Oh, I don't like where this is going.
Speaker 2: By your tone, it's there's so much drama, it's it's
Speaker 2: absurd and I won't even go into it all. But
Speaker 2: so Banting was like not really, he was like not'
Speaker 2: I don't want to have to wait for this. But
Speaker 2: but also he didn't really have a lot of like
Speaker 2: bargaining power. Banting had been working these past few months
Speaker 2: with like on no salary, on no official position with
Speaker 2: the university. He was just sort of there, and so
Speaker 2: he said to McLoud, you know what you're gonna pay me,
Speaker 2: You're gonna give me another assistant to take care of
Speaker 2: the dogs, and you're gonna have repairs done to the
Speaker 2: operating room. And McLoud was like, okay, that's actually you're
Speaker 2: asking for quite a lot, and other research at the
Speaker 2: university would suffer if, you know, if I were to
Speaker 2: give all of this to you. And Banting's like, I
Speaker 2: am gonna walk away from this. This is you know,
Speaker 2: blah blah blah, and so McLoud was like, you know what, Okay, fine,
Speaker 2: you're right, your work does show promise. Let's let's keep
Speaker 2: it going. So this meeting might be where we first
Speaker 2: see the tension rise between Banting and McLeod. And at
Speaker 2: this point Best was already aware of Banting's tendency to
Speaker 2: be scornful, disparaging, you know, impatient, and quick to anger.
Speaker 2: He had been yelled at at least once for dirty glassware.
Speaker 2: But this might be this might have been the first
Speaker 2: time that McLeod saw it in action, And this meeting
Speaker 2: might also have been when the seed of hate was
Speaker 2: playing in Banting form a cloud. Yeah, it's like really
Speaker 2: a toxic It's a whole toxic story and toxic place.
Speaker 3: Oh my gosh, yeah, but that seed of hate.
Speaker 2: It bloomed like wild that December of nineteen twenty one,
Speaker 2: at the Annual Physiological Society meeting, Banting and Best were
Speaker 2: due to present their research on the internal secretion of
Speaker 2: the pancreas, which had progressed since the summer with the
Speaker 2: use of pancreas is from cal fetuses and then alcohol
Speaker 2: for extraction from whole fresh pancreas, and things were taking
Speaker 2: along and all of their results were pointing towards successful
Speaker 2: treatment of diabetes in the animals that they were working with.
Speaker 2: But at this meeting, during his presentation, Banting like totally
Speaker 2: flubbed it. He was a terrible speaker. He stumbled over
Speaker 2: the results and it got so bad that McLoud Cloud
Speaker 2: had to keep like stepping in to clarify something or
Speaker 2: to include a crucial detail that Banting had left out.
Speaker 2: And he answered questions and then to add you know,
Speaker 2: insult to injury, or at least as perceived by Banting.
Speaker 2: McLeod kept saying, we we extracted this and we injected that.
Speaker 2: Banting was fuming there. He was I can only imagine
Speaker 2: just like standing up there in front of the who's
Speaker 2: who of diabetes researchers in North America and basically not
Speaker 2: being able to string a coherent sentence together while your
Speaker 2: supervisor is taking what is perceived to be taking all
Speaker 2: the credit from you.
Speaker 4: I can one hundred percent imagine that, and it is
Speaker 4: so cringe.
Speaker 2: It is really yeah, And that's and so Banting like
Speaker 2: he didn't He wasn't the type to just silently fume.
Speaker 2: He was like ranting and raving to all of his friends,
Speaker 2: like McLeod is a horrible person, he's stealing all my results,
Speaker 2: blah blah blah. It like really became very bad. And
Speaker 2: I will say, in defense of McLeod, anyone else who
Speaker 2: worked with him doesn't describe him that way. It seems
Speaker 2: like Banting was the only one to sort of accuse
Speaker 2: him of being incredibly territorial or taking credit or stealing credit.
Speaker 2: So anyway, I don't want to get too much into
Speaker 2: the whole, like.
Speaker 4: You know, India lab drama, right, Yeah.
Speaker 2: And at this point it was the entire lab like
Speaker 2: McLeod had shifted gears, like these results were super promising,
Speaker 2: and so McLeod was like, you know what, everyone, almost
Speaker 2: everyone in this lab is going to start working on
Speaker 2: this pancreaus problem, and he also brought on eventually a
Speaker 2: visiting biochemist by the name of James Collop, who was
Speaker 2: added to speed up the extraction and purification process. And
Speaker 2: so things were happening quickly now, with the first human
Speaker 2: clinical trial in January of nineteen twenty two. So just
Speaker 2: you know, from April nineteen twenty one when Banting arrived
Speaker 2: to Toronto to the first clinical trial January of nineteen
Speaker 2: twenty two, that's very fast, too fast, I mean. So
Speaker 2: the first person to ever receive this pancreatic extract was
Speaker 2: Leonard Thompson, a fourteen year old boy who on admission
Speaker 2: weighed only sixty five pounds, whose hair was falling out,
Speaker 2: abdomen distended breath smelling of actone, and who was on
Speaker 2: a diet of four hundred and fifty calories a day.
Speaker 3: Oh my gracious.
Speaker 2: On January eleventh, Leonard received the first injection, which led
Speaker 2: to a twenty five percent reduction in blood sugar and
Speaker 2: a slight reduction in urine glucose. But overall the results
Speaker 2: weren't like super promising, especially since the impurities in the
Speaker 2: extract led to like an absess forming at the injection site.
Speaker 2: So the trial was deemed premature and there was a
Speaker 2: rush to make a more pure sample, something that Banting
Speaker 2: took upon himself to make like a competition with Callup,
Speaker 2: who was like, I don't this doesn't need to be
Speaker 2: a competition, Like, can't we just work on this?
Speaker 1: Yeah?
Speaker 2: Tensions mounted Callop one he like found a better purification process,
Speaker 2: and the new, more purified extract was injected into Leonard
Speaker 2: with much better results on January twenty third.
Speaker 3: Oh wow.
Speaker 2: But a few days before then, before this injection happened,
Speaker 2: Banting and Callop had gotten into a fight that was
Speaker 2: at least verbal and possibly physical. Oh my, because accounts differ.
Speaker 2: When Callup announced, he walked into the room and announced
Speaker 2: that he a fine tuned the purification protocol. B was
Speaker 2: going to keep it a secret from Banting in Best
Speaker 2: and not reveal any part of it, and see that
Speaker 2: he was going to file a patent on it under
Speaker 2: his name alone.
Speaker 3: Oh my, gracious.
Speaker 2: And apparently McLeod had okayed all of this. What so
Speaker 2: then this led to I would imagine a huge yelling
Speaker 2: match among most, if not all parties, Banting and Best
Speaker 2: and McLeod and call Up. I mean, the battle lines
Speaker 2: were very clearly drawn, with those two groups on you know,
Speaker 2: banting a best on one side, call Up and McLeod
Speaker 2: on the other. And then a ceasefire of sorts came
Speaker 2: in the form of a signed agreement that none of
Speaker 2: them would patent the process and that they would have
Speaker 2: to be transparent with each other about research developments. I mean,
Speaker 2: they didn't become friends or anything, but you know, at
Speaker 2: least like for now, it seemed to have de escalated.
Speaker 2: But in any case, the animosity and drama was there
Speaker 2: to stay. I mean, wow, it wasn't going anywhere. I again,
Speaker 2: I can't even get into it all like, there's a
Speaker 2: great book, I'll recommend that kind of you're just like
Speaker 2: what he said that. Yeah, And so, beginning in the
Speaker 2: spring of nineteen twenty two, the lab group began publishing
Speaker 2: their results. But the important thing is that the popular
Speaker 2: press picked it up, and that generated a lot of
Speaker 2: hype among the many people who lived with diabetes. It
Speaker 2: was in one of these first publications that was a
Speaker 2: big comprehensive one from April nineteen twenty two, that the
Speaker 2: term insulin was first used. And there's no record as
Speaker 2: to like why or how they chose that word, but
Speaker 2: it's based on the Latin route for island, referring to
Speaker 2: the islets of Langerhans.
Speaker 3: Okay, okay, okay.
Speaker 2: It was clear to everyone in the field that this
Speaker 2: research marked a new era for diabetes research and treatment.
Speaker 2: It would certainly be a bad time for things to
Speaker 2: fall apart, wouldn't it.
Speaker 3: Oh, Aaron.
Speaker 2: So Banting had begun to drink heavily and several times decided,
Speaker 2: you know what, I'm I'm quitting this whole thing. I
Speaker 2: don't want to be a part of this anymore, until
Speaker 2: best you know, talked him out of it and call up.
Speaker 2: On the other hand, was having, you know, more like
Speaker 2: lab centric problems. He had lost the knack for insulin production.
Speaker 2: He like couldn't he couldn't figure out. He was like,
Speaker 2: whatever I was doing before is no longer working for me,
Speaker 2: and I don't know why what.
Speaker 3: That's weird.
Speaker 2: It's weird, and it's bad because it led to this
Speaker 2: in slin famine among the people who had already received
Speaker 2: injections and were needing those to help regulate their blood sugar.
Speaker 2: And then MacLeod was simultaneously worried about the lives of
Speaker 2: the people who needed that insulin, and he was also
Speaker 2: worried that someone else was going to figure out the
Speaker 2: production process and patent it. And so even though McLeod
Speaker 2: Banting in Best were reluctant to patent it on principle,
Speaker 2: they wanted to stop other people from creating a monopoly,
Speaker 2: and so they filed this type of patent that would
Speaker 2: prevent that from happening.
Speaker 3: Okay.
Speaker 2: McLeod also realized that if they wanted to turn this
Speaker 2: insulin into an actual medical product that people could reliably
Speaker 2: get their hands on, they needed to get a pharmaceutical
Speaker 2: company involved, which is how Eli Lilly came to be
Speaker 2: so closely associated with insulin. It was someone from Eli
Speaker 2: Lilly at that very first meeting and they were like
Speaker 2: working very closely with the Toronto team to get the
Speaker 2: soul ability or license to try to manufacture this new insulin. Yeah,
Speaker 2: but you know, the drama of discovery, the incredible tension
Speaker 2: among the researchers, the difficulties in streamlining or fine tuning
Speaker 2: the production process. All of these problems were overshadowed by
Speaker 2: the absolutely enormous impact that insulin was having on the
Speaker 2: lives of people with diabetes. A lot of accounts at
Speaker 2: the time describe the drug, describe insulin as miraculous, and
Speaker 2: it's kind of hard to disagree with that. Yeah, Like
Speaker 2: a sixteen year old boy brought out of a diabetic
Speaker 2: coma from an insulin injection, the first time that had
Speaker 2: ever happened. A bedridden child jumping around the room hours
Speaker 2: after being given insulin. Perhaps the most famous patient from
Speaker 2: the time was Elizabeth Hughes, who was daughter of the
Speaker 2: US Secretary of State, who kept journals of her life
Speaker 2: pre and post insulin, And at the time of her
Speaker 2: first insulin shot, the fifteen year old Elizabeth weighed less
Speaker 2: than fifty pounds. That's like twenty two kilograms. It's yeah,
Speaker 2: and she was close to death. A few weeks after
Speaker 2: receiving her first insulin shot, she gained ten pounds. Wow,
Speaker 2: and a lot of health problems resolved for her, and
Speaker 2: she went on to live like a healthy and relatively
Speaker 2: long life. And there were a million more stories just
Speaker 2: like these. Insulin saved and continues to save so very
Speaker 2: many people from what was absolutely a death sentence. Yeah,
Speaker 2: it kind of reminds me a lot of like the
Speaker 2: stories of when antibiotics were first developed and first introduced,
Speaker 2: and it was like it was raculous. It was coming
Speaker 2: back from the brink of death. It must have been
Speaker 2: unbelievable to witness. So who was responsible for insulence development?
Speaker 2: And who gets the credit? And are the answers to
Speaker 2: those questions the same, Well, it depends on who you ask, right,
Speaker 2: If you ask Banting, it was Banting with a little
Speaker 2: help from Best. If you ask McLeod, it was McLeod
Speaker 2: Banting and Callop. If you ask Paulescu, it was poulsq
Speaker 2: And if you ask the Nobel Prize committee, it was
Speaker 2: Banting and McLoud. So in nineteen twenty three the two
Speaker 2: were awarded the Nobel Prize. Banting was only thirty two
Speaker 2: at the time. Oh yeah, gosh at the time. I
Speaker 2: think he was the youngest for like physiology and medicine
Speaker 2: or whatever the grouping was at the time. But Banting
Speaker 2: was furious. He could not believe that his and McLeod's
Speaker 2: name were both on the prize.
Speaker 3: Oh goodness.
Speaker 2: He believed it should have been him and Best, and
Speaker 2: so at first he was like, you know what, I'm
Speaker 2: going to refuse this prize. I don't want anything to
Speaker 2: do with it. And then eventually he was like, Actually,
Speaker 2: what I'm going to do is I'm going to split
Speaker 2: it with best men. That's what he did, and McLeod
Speaker 2: in turn decided that he was going to split it
Speaker 2: with Callop. Okay, I don't know who deserves it, honestly,
Speaker 2: I mean, does paulsc you deserve some credit? Absolutely sole credit?
Speaker 2: Probably not. Would Banting have gotten there without McLeod or
Speaker 2: without call Up probably not. All these tensions and credit
Speaker 2: debates aside, though, the important thing is that insulin was
Speaker 2: now available, and just in the way that blood transfusions
Speaker 2: for hemophilia turned that disease from an acute disease to
Speaker 2: a chronic one, insulin prolonged the lives of those with diabetes,
Speaker 2: but it was also not a cure, and the long
Speaker 2: term consequences of diabetes, particularly type one, were emerging, such
Speaker 2: as kidney disease and retinopathy and all the ones that
Speaker 2: you've already discussed in the biology. So I'm not going
Speaker 2: to go through these next things in detail. But following
Speaker 2: the discovery and production of insulin, a lot of other
Speaker 2: important developments occurred. Frederick Sanger discovered that insulin was a
Speaker 2: protein and described its structure, for which he was awarded
Speaker 2: a Nobel Prize in nineteen fifty eight, his first of
Speaker 2: two yep and Dorothy Hodgkin, whose name you might remember
Speaker 2: from our antibiotics episode and our radiation episodes. So she
Speaker 2: used X ray crystallography to work out the three D
Speaker 2: structure of insulin. A lot of research focused on treatments
Speaker 2: for the long term consequences of diabetes, such as kidney
Speaker 2: disease and ulcers and kidney transplants, and some really important
Speaker 2: work was done by Priscilla White on reducing perinatal mortality
Speaker 2: in people with diabetes by introducing sex hormones treatment, which
Speaker 2: hugely increased survival of the babies. And there was yet
Speaker 2: another Nobel Prize for diabetes research co awarded to Rosslyn
Speaker 2: Yallow in nineteen seventy seven for developing the radio amino
Speaker 2: assay to measure the concentration of hormones like insulin, vitamins, viruses, enzymes,
Speaker 2: and lots more stuff in humans. Genetic engineering allowed for
Speaker 2: the mass production of biosynthetic insulin, and I think we
Speaker 2: might have touched on that briefly in our Ecoli episode.
Speaker 2: It was basically like engineering ecoli to just like pump
Speaker 2: make a ton of insulin that sounds vaguely familiar, and
Speaker 2: then the threat of bovine sponge offormencephalopathy in bovine derived
Speaker 2: insulin and kind of put for like this switch towards
Speaker 2: human insulin. And then insulin pumps were developed, and since
Speaker 2: the nineteen seventies they've shrunk in size considerably and increased
Speaker 2: their capabilities considerably. In nineteen seventy nine, diabetes was officially
Speaker 2: divided into two types, insulin dependent diabetes melodice and non
Speaker 2: insulin dependent diabetes melodus, or type one and type two
Speaker 2: as they were called beginning in nineteen ninety five and
Speaker 2: in the late nineteen seventies is also when gestational diabetes
Speaker 2: and what was called maturity onset diabetes of the young
Speaker 2: were also recognized. There have been too many developments to
Speaker 2: even mention. This year twenty twenty one marks the one
Speaker 2: hundred year anniversary of insulin, and over that time diabetes
Speaker 2: has un under gone a huge transformation in terms of
Speaker 2: our understanding of the disease and our ability to treat it.
Speaker 2: But the story isn't over because alongside these medical developments,
Speaker 2: diabetes was going through another kind of transformation in the
Speaker 2: twentieth century, a social transformation. If you will, Okay, Diabetes
Speaker 2: Part two, I promise this is a lot shorter. So
Speaker 2: I know I've been talking for ages.
Speaker 3: I've been enjoying it.
Speaker 2: Okay, good. I hope that remains true. So I can
Speaker 2: only speak for the US or my experience in the US,
Speaker 2: but in many things that I've read or seen on TV,
Speaker 2: or I've heard in the classroom, there's this sense that
Speaker 2: diabetes type two in particular is a personal choice, with
Speaker 2: this tinge of morality surrounding it in some ways to
Speaker 2: how STIs are talked about, like oh, you did these things,
Speaker 2: so like what do you expect? You deserve this? These
Speaker 2: are the consequences for your actions, And this I think
Speaker 2: reflects a huge problem, not just in showing like a
Speaker 2: complete absence of empathy, but also in revealing a general
Speaker 2: lack of understanding about the multifaceted nature of this disease
Speaker 2: and refusing to acknowledge the institutional drivers that increase the
Speaker 2: risk of diabetes. Yeah. So, when I was prepping for
Speaker 2: this episode, I read a book called Diabetes, A History
Speaker 2: of Race and Disease by Arlene Marsha Tuckman, where I
Speaker 2: learned that it's kind of like always been this way,
Speaker 2: Like there's always been sort of this Oh well, these
Speaker 2: are the consequences of your actions, or like, oh, this
Speaker 2: is a personal disease, like this is something that you did, right.
Speaker 2: It's always been very much like a blame the individual
Speaker 2: or the identity of the individual, kind of a disease
Speaker 2: with a particular trait or group at fault being the
Speaker 2: main thing that has changed over the decades. I had
Speaker 2: no idea before researching this episode, but it turns out
Speaker 2: that diabetes started out as a quote like Jewish disease
Speaker 2: in the late eighteen hundreds, when the visibility of diabetes
Speaker 2: and other chronic diseases was increasing as infectious diseases declined.
Speaker 2: Diabetes was literally given the name quote the Jewish disease
Speaker 2: in Europe because of the supposed high prevalence of the
Speaker 2: disease among Jewish people, and the reason for this high
Speaker 2: prevalence varied based on the individual views of the person
Speaker 2: you ask or the person who was writing this article.
Speaker 2: It could be because of the long years of cruel
Speaker 2: persecution faced by Jewish people that led to this high
Speaker 2: levels of stress, or it was because they overindulged in
Speaker 2: ate rich foods, or maybe it's because they had a
Speaker 2: quote nervous disposition, or it was just a way of
Speaker 2: saying that this disease had you know, foreign roots, since
Speaker 2: the immigration of Jewish people from Eastern Europe was really
Speaker 2: high during this period. But whatever the perceived reason or
Speaker 2: stated reason at the time, this association grew global and
Speaker 2: it became entrenched in medical literature and in the minds
Speaker 2: of practicing doctors for decades, so like from the late
Speaker 2: eighteen hundreds to like a few decades into the twentieth century. Huh, yeah,
Speaker 2: was there actually an association, I mean without any quality
Speaker 2: statistics from the time. We can't say for sure, but
Speaker 2: it seems unlikely. It seems that it was more bad
Speaker 2: statistics turned into common knowledge and then like helped along
Speaker 2: by confirmation bias. Like definitely a citation needed moment, and
Speaker 2: that was a big problem that just kept being repeated
Speaker 2: in the literature without any citation or citing someone who
Speaker 2: just said, it's really highly prevalent in Jewish people. And
Speaker 2: even if there were numbers in these articles, was the
Speaker 2: categorization of you know, Jewish and non Jewish even helpful?
Speaker 2: Was it meaningful? Both groups were very heterogeneous. So drawing
Speaker 2: those lines was really a way of kind of like
Speaker 2: pushing a certain narrative. The way that you draw the
Speaker 2: lines is definitely like you have a bit of forethought
Speaker 2: about what statements you want to make when the numbers
Speaker 2: all kind of fall out, right, Like what's important to
Speaker 2: you about those divisions? And often you know, as it
Speaker 2: is now, but as it was back then. You know,
Speaker 2: those divisions were a way of saying that something about
Speaker 2: your race, or your background, or your culture made you
Speaker 2: more likely to have this disease. And we see this theme,
Speaker 2: you know, race presented as an explanation for disease again
Speaker 2: and again in the history of diabetes, with Black Americans
Speaker 2: and the Native Americans and Mexican Americans and so on.
Speaker 2: And certainly the use of racial categories and epidemiological studies
Speaker 2: can be very helpful, but they're helpful for confronting and
Speaker 2: trying to understand institutional racism and inequalities in health care
Speaker 2: or access. Not to further the myth of race as
Speaker 2: a biological construct and yet erin and yet aarin Okay,
Speaker 2: so from its reputation as a you know, quote Jewish
Speaker 2: disease in the late eighteen hundreds. Diabetes slowly began to
Speaker 2: be viewed as a disease of man moral failing, especially
Speaker 2: in the years following World War One, which were a
Speaker 2: period of economic growth and increase in consumables and big
Speaker 2: cultural shifts, leading to culturally conservative people shouting that, like,
Speaker 2: the increasing rates of diabetes were a sign of moral decay,
Speaker 2: of this like gluttonous, over indulgent society that has no
Speaker 2: self control. The shifting from a Jewish disease to like
Speaker 2: a more general sign of you know, moral decay or
Speaker 2: whatever also happened as more studies were done to show
Speaker 2: that there wasn't actually much of a difference in terms
Speaker 2: of stats, right, and this moral failing or over indulgence
Speaker 2: or just the rate of diabetes, it had a class
Speaker 2: structure to it. Diabetes had shifted its reputation to one
Speaker 2: of middle and upper class and generally white people. In fact,
Speaker 2: it was thought and published in medical journals that black
Speaker 2: people were immune to diabetes. What it was literally in
Speaker 2: medical journals, Well, they are known to be immune. Same
Speaker 2: was said about Native Americans also, So why did people
Speaker 2: think they were immune to diabetes?
Speaker 7: I don't know, Aaron, Why, I mean, we don't know
Speaker 7: for sure, we can speculate it's likely that it had
Speaker 7: a large part to do with a lack of access
Speaker 7: to primary care physician or hospitals.
Speaker 2: So like doctors just simply weren't seeing diabetes and black
Speaker 2: people because they weren't treating black people. And it's also
Speaker 2: possible that doctors simply were like, well, I'm not going
Speaker 2: to test the urine of a black person because they're immune.
Speaker 2: I read that in the literature, so there's no point
Speaker 2: in even testing you for diabetes. But the reasons for
Speaker 2: this lower prevalence were given or written about in racist terms. Right,
Speaker 2: Black people didn't have the quote like nervous strain or
Speaker 2: quote mental strength for diabetes.
Speaker 3: What I know it is, what does that even mean?
Speaker 2: Basically, what I gather from this is that people wanted
Speaker 2: diabetes to mean whatever they wanted it to mean. Yeah,
Speaker 2: they couldn't find a cause, They couldn't explain why it happened,
Speaker 2: and so then they looked around and thought, Okay, what
Speaker 2: is the narrative I want to push. Yeah, it all
Speaker 2: had to do with just like individual biases, societal biases,
Speaker 2: and you know, racist ideals. It's yeah, it's so weird
Speaker 2: erin it is yeah, it's all about the narrative. But
Speaker 2: then here comes another shift, right, another transformation of diabetes.
Speaker 2: So when actual statistics introduced in the nineteen twenties showed
Speaker 2: that rates of diabetes didn't differ much between black and
Speaker 2: white Americans, but do you know what did? Mortality rates
Speaker 2: from diabetes. And another factor that contributed to the overall
Speaker 2: growing visibility of diabetes among black Americans was the increase
Speaker 2: in black medical doctors who wanted to help improve the
Speaker 2: health of the communities that they served. And what many
Speaker 2: of these doctors saw was also reflected in the stats
Speaker 2: from the time and also from today that as poverty increased,
Speaker 2: the rates of diabetes rose, and that diabetes in general
Speaker 2: seemed to be on the rise in the nineteen thirties
Speaker 2: and estimated half a million to two million people in
Speaker 2: the US were living with the disease, and it rose
Speaker 2: to be the ninth lead and cause of death in
Speaker 2: the US in nineteen thirty six, which is up from
Speaker 2: the twenty seventh in eighteen ninety. The development of insulin
Speaker 2: in the early nineteen twos ties helped out a bit
Speaker 2: with like the management of diabetes, but a lifetime of
Speaker 2: injections was still costly and long term effects were still present.
Speaker 2: And also, since this is an episode of TPWK, why
Speaker 2: I have to mention eugenics. So here we go obligated eugenesis.
Speaker 2: As you might guess, we're not a fan of insulin
Speaker 2: saying that it would increase the numbers of unfit people
Speaker 2: in society.
Speaker 3: I saw it coming here. It still hurts every time.
Speaker 2: Every time. But a huge problem with the eugenesis arguments,
Speaker 2: you know, besides the fact that they're terrible and they
Speaker 2: were making judgments on who should or should not reproduce,
Speaker 2: was that no one could predict who would get diabetes.
Speaker 2: Right still, you know it is true today the how
Speaker 2: of diabetes was beginning to be worked out, but the
Speaker 2: why had not yet been answered and still isn't really
Speaker 2: fully answerable. We'll get back to it arin, Well, why
Speaker 2: did some people get it in others not? Why were
Speaker 2: we seeing an increase in the US In nineteen sixty two,
Speaker 2: James Neil thought he might have the answer. Have you
Speaker 2: heard of the thrifty genotype? Yeah? Okay, it's basically this
Speaker 2: idea proposed by Neil that this thrifty genotype would have
Speaker 2: helped early humans live through periods of unpredictable food availability,
Speaker 2: so you would store more fat in times of plenty
Speaker 2: to prepare for times of famine. But in the US
Speaker 2: and other developed countries where diabetes was on the rise,
Speaker 2: there weren't really these times of famine, and so the
Speaker 2: thrifty genotype went from good to bad. It began to backfire.
Speaker 2: And at first this thrifty genotype hypothesis was just used
Speaker 2: to explain a global growth in diabetes prevalence, but with
Speaker 2: recent reports showing a disproportionately high rate of diabetes among
Speaker 2: some Native American groups, it became used in this colonial
Speaker 2: narrative of quote primitive and quote advanced societies. And in
Speaker 2: this narrative, some Native American groups were said to be
Speaker 2: more prone to develop diabetes because they were quote primitive
Speaker 2: people who were rushed into quote you know, modern living
Speaker 2: conditions and they were unequipped to deal with the diet
Speaker 2: and lifestyle.
Speaker 4: That is such a mischaracterization of yeah I can't.
Speaker 2: Yeah, yeah, I mean, it's it's quite the turn from
Speaker 2: diabetes as a mark of civilized society that was popular
Speaker 2: earlier in the century, and the thrifty genotype hypothesis is
Speaker 2: not well supported at all, I should note despite it
Speaker 2: continuing to be pushed by some people Jared Diamond, but
Speaker 2: by couching the high prevalence of diabetes in certain Native
Speaker 2: American groups in biological or genetic terms or concepts, it
Speaker 2: made and continues to make it possible for the government
Speaker 2: to ignore their own role in the cycle of poverty,
Speaker 2: in the impact of displacement, genocide, and federal policies that
Speaker 2: lead to higher rates of disease, not just diabetes. Speaking
Speaker 2: of the federal government, in the nineteen eighties, a nationwide
Speaker 2: study called the Heckler Report investigated racial and ethnic health
Speaker 2: disparities in the US, and what they found was that diabetes,
Speaker 2: specifically type two and mortality from diabetes occurred at disproportionately
Speaker 2: high rates among non white people. The report framed diabetes
Speaker 2: as I quote disease of minority groups. It barely acknowledged
Speaker 2: the role that poverty played, but rather it emphasized the
Speaker 2: racial and ethnicity differences and to some degree, sex differences.
Speaker 2: This continued the long tradition of attributing diabetes to a
Speaker 2: moral failing or personal quality, or to a certain racial
Speaker 2: or ethnic background, all the while ignoring the role that
Speaker 2: poverty and other factors like food, deserts, like the ability
Speaker 2: to be active, that all of these things can play.
Speaker 2: Diabetes is such a nuanced disease, but it seems as
Speaker 2: though somehow we struggle still to make sense of that
Speaker 2: nuance and present it in a way that is like, oh, okay,
Speaker 2: there are multiple parts to this story. So I've rambled
Speaker 2: on and on, and Aaron, why don't you bring me
Speaker 2: up to speed and what's happening with diabetes today?
Speaker 4: I'll do my best erin, let's take a quick break first.
Speaker 4: Why don't we just start straight in with the numbers.
Speaker 4: We'll get right to it, and then we'll go through
Speaker 4: advances and treatment and then hopefully answer a little bit
Speaker 4: more of your question of the wyat and how oh good? So,
Speaker 4: according to the International Diabetes Federation, in twenty nineteen, diabetes
Speaker 4: and this is all types of diabetes, of which generally
Speaker 4: ninety percent or so are type two and five to
Speaker 4: ten percent type one, and then gestational and the other
Speaker 4: types of diabetes account for the other percentages. So in
Speaker 4: twenty nineteen, diabetes caused four point two million deaths worldwide
Speaker 4: and four hundred and sixty three million adults. This is
Speaker 4: just adults between age twenty and seventy nine were estimated
Speaker 4: to be living with diabetes, and that number is likely
Speaker 4: to rise to up to seven hundred million by twenty
Speaker 4: forty five because both type one and type two diabetes
Speaker 4: have been increasing, right, and it gets a little worse.
Speaker 4: The true disease burden, especially for type two diabetes, is
Speaker 4: likely a gross underestimation because one in three people who
Speaker 4: have diabetes are underdiagnosed. That's over two hundred million people WHOA. Yeah,
Speaker 4: And then if you also account for all of the
Speaker 4: people who have impaired fasting glucose or what sometimes is
Speaker 4: called pre diabetes, the vast majority of those people have
Speaker 4: no idea that that's what's happening inside of their bodies.
Speaker 3: Hmm okay, and a good.
Speaker 4: Proportion of those people may go on to develop type
Speaker 4: two diabetes a little worse than that. While there's a
Speaker 4: lot of variation in both incidents and prevalence of both
Speaker 4: types of diabetes across the globe, like different prevalences in
Speaker 4: different areas, overall, more than eighty percent of people currently
Speaker 4: living with type two diabetes are currently living in low
Speaker 4: or middle income countries, which, especially as we talk about
Speaker 4: the new developments in treatment poses additional challenges because most
Speaker 4: of these are unsurprisingly very expensive, and there are of
Speaker 4: course major economic and social hurdles for people living with
Speaker 4: diabetes in low and middle income countries, but also across
Speaker 4: the globe, including here in the US. For example, insulin
Speaker 4: prices in the US are truly an abomination. In twenty eighteen,
Speaker 4: a unit of insulin was ninety eight dollars and seventy
Speaker 4: cents in the US, compared to eight dollars and eighty
Speaker 4: one cents.
Speaker 3: In thirty two other countries.
Speaker 4: And while diabetes is certainly not exclusively a disease of
Speaker 4: low income, when you consider not only the price of insulin,
Speaker 4: but the price, like I already said, of so many
Speaker 4: of the newer and in some cases better drugs for
Speaker 4: type two diabetes that are also incredibly expensive, Diabetes certainly
Speaker 4: contributes to the cycle of poverty across the globe. So
Speaker 4: that's all the bad news, and I know there's a
Speaker 4: lot of it, but there's at least some good news
Speaker 4: on the horizon. I usually talk about whatever's going on
Speaker 4: in terms of research, and a lot of times I
Speaker 4: feel like I've been like, ohh, there's not much going
Speaker 4: on and it's like depressing. But today I don't have
Speaker 4: a lot of very specific things to go over. But
Speaker 4: that's because there is so much research going on in
Speaker 4: terms of diabetes that there's simply too much ground to cover,
Speaker 4: which is amazing. That means that there's so many people
Speaker 4: working on so many different aspects of this in terms
Speaker 4: of new treatments. When we look at type one diabetes
Speaker 4: in general, and I apologize if there's even newer things
Speaker 4: that I have missed, but in general, the treatment is
Speaker 4: still just insulin, and while that sounds simple, it's a
Speaker 4: very complex to kind of get regimens and know how
Speaker 4: much you have to give, et cetera. But some incredible
Speaker 4: advancements for type one diabetes or insulin dependent type two
Speaker 4: diabetes is the development of continuous glucose monitors and like
Speaker 4: you mentioned, increasingly small and easy to use insulin pumps
Speaker 4: that can keep much tighter control of that glucose, which
Speaker 4: can then prevent the development of complications.
Speaker 3: So that's incredible.
Speaker 4: When it comes to type two diabetes, Oh my gracious,
Speaker 4: the number of new drugs. I think there's a new
Speaker 4: one every day, and a lot of them. Like we
Speaker 4: kind of touched on a bit before are touching on
Speaker 4: different mechanisms of diabetes control. So previously things were just
Speaker 4: working on increasing the amount of insulin that people secrete.
Speaker 4: But now because we know that insulin resistance is a
Speaker 4: big component, there's other types of treatments that are targeting
Speaker 4: tissues to make them more susceptible to the effects.
Speaker 3: There's a lot of really cool stuff.
Speaker 4: Going on with type two diabetes treatment.
Speaker 2: Yeah, that's interesting, it's.
Speaker 3: Very very cool.
Speaker 4: There's also so much work being done to better understand
Speaker 4: the genetic components of both types of diabetes. So I
Speaker 4: want to kind of stick with that for just a
Speaker 4: moment and then we'll wrap up. So, both type one
Speaker 4: and type two diabetes have genetic links, but it's not
Speaker 4: like any of the genetic disorders that we've covered in
Speaker 4: the past, or it's like a single gene. It's many
Speaker 4: different genes, and it's not a strong genetic component for
Speaker 4: either type two or type one diabetes. But one of
Speaker 4: the biggest questions, Aaron, that you kept asking me was
Speaker 4: the why the how, especially when it comes to type
Speaker 4: two diabetes. And so, like I mentioned, both type one
Speaker 4: and type two diabetes have a genetic component. Type two
Speaker 4: diabetes has a much stronger genetic component, meaning if you
Speaker 4: have a first degree relative with type two diabetes, you
Speaker 4: are much more likely to develop type two diabetes yourself
Speaker 4: than you are if you had someone with type one
Speaker 4: diabetes to develop type one.
Speaker 3: That makes sense, uh huh okay, So there's a much.
Speaker 4: Stronger genetic component to type two diabetes, but it's not
Speaker 4: a single gene. It's very multivariate, and just like with
Speaker 4: type one diabetes, there's also a huge amount of environmental
Speaker 4: components that go into the development of type two diabetes.
Speaker 4: And some of these are what are often called modifiable
Speaker 4: risk factors, and these are factors in the environment that
Speaker 4: can change and that can lead to risk of diabetes.
Speaker 4: The things that we know that are the most strongly
Speaker 4: associated are sedentary lifestyle, which is essentially just means not
Speaker 4: getting a lot of physical activity throughout the day. Another
Speaker 4: is diet, So having a diet that's really high in
Speaker 4: sugars that are like the kind that you find in
Speaker 4: soda is really strongly associated with type two diabetes. And
Speaker 4: then the one that cited the most frequently is obesity.
Speaker 4: So BMI is the indicator that we use to classify
Speaker 4: obesity and obesity in the US at least, is considered
Speaker 4: a disease, which is then also considered a risk factor
Speaker 4: for diabetes, among other things, type two diabetes specifically. And
Speaker 4: BMI is not just in my opinion, but also in
Speaker 4: my opinion, not a good indicator of health. Not only
Speaker 4: does BMI not take into account things like muscle mass
Speaker 4: or the distribution of adipose tissue, whether it's central and
Speaker 4: around your organs versus on your life eggs, or arms,
Speaker 4: et cetera. BMI also ignores so many of the social
Speaker 4: determinants of health that play into the overall risks of
Speaker 4: diabetes and so many other diseases. So be am I
Speaker 4: an obesity In general, it's not a good indicator, but
Speaker 4: in the literature it is considered a risk factor for
Speaker 4: type two diabetes.
Speaker 2: M Mechanistically, what is it about those things that causes
Speaker 2: insulin resistance and like a faulty production of insulin?
Speaker 4: Yeah, and that is the question that we still absolutely
Speaker 4: do not know the answer to. But here's something exciting,
Speaker 4: and it still doesn't address the question of why those
Speaker 4: risk factors then lead to this. But I found a
Speaker 4: couple of articles that are really promising on the underlying
Speaker 4: mechanism before you even get to insulin resistance, and that
Speaker 4: is dysfunction in the brain itself.
Speaker 2: Huh.
Speaker 4: So, dysfunction in the hypothalamus that was treated with a
Speaker 4: single dose of something called fibroblast growth factor resulted in
Speaker 4: mice in sustained diabetes remission a single dose. So these
Speaker 4: papers were basically suggesting that what happens, for whatever reason,
Speaker 4: from this genetic susceptibility and these environmental factors is that
Speaker 4: the effect on the hypothalamus in your brain is to
Speaker 4: increase your body's set point for what is an okay
Speaker 4: level of glucose That is.
Speaker 3: Super interesting, isn't it fascinating?
Speaker 4: And so then by giving this dose of this FGF one,
Speaker 4: what they were doing was lowering back that set point
Speaker 4: to something more like one twenty instead of like two
Speaker 4: hundred or whatever. So then your pancreas doesn't have to
Speaker 4: compensate to try an increase insulin because your body, your
Speaker 4: brain is telling your body it's okay to let my
Speaker 4: blood glucose get this high, and your pancrease is like, no,
Speaker 4: it's not, it's really not. Again, that still doesn't address
Speaker 4: this underlying question, but it does give us a much
Speaker 4: better target right for the like mechanistic cause, did you.
Speaker 2: Come across anything about epigenetics.
Speaker 4: I mean, epigenetics is a huge part of this, right,
Speaker 4: and that's but no, I didn't read any papers about it,
Speaker 4: and so I don't know like what those mechanisms are.
Speaker 3: But with any of these.
Speaker 4: Like polygenic and gene and environment things, I think epigenetics
Speaker 4: plays a huge role. But I think too, Aaron, getting
Speaker 4: back to what you were saying in the last part
Speaker 4: of your history section, is it's so important, especially in
Speaker 4: a disease like diabetes, when we're talking about things like
Speaker 4: these modifiable risk factors, to not lose sight of the
Speaker 4: environment that we are in and these structures of government
Speaker 4: of our society that force us into this environment where
Speaker 4: we can't do physical activity because we're sitting at a
Speaker 4: desk at our jobs for ten hours a day and
Speaker 4: then we're driving in our car an hour each way
Speaker 4: to work, and then we can't afford to buy fresh
Speaker 4: leafy greens because they go bad in twenty minutes in
Speaker 4: your fridge, and also they don't taste that good. Like,
Speaker 4: there are so many things that play into this. It's
Speaker 4: not an individual choice, it's so much bigger than that.
Speaker 2: Yeah, it's it's a really multifaceted yeah, like issue and discussion.
Speaker 3: And again BMI is a bad indicator. Hoof.
Speaker 4: Well yeah, don't get me started on that one. So
Speaker 4: that is diabetes.
Speaker 2: In brief, in brief, you know, short and sweet. We
Speaker 2: kept it nice, long and sweet.
Speaker 3: Yeah.
Speaker 2: Sources, so I will mention I basically relied on three books.
Speaker 2: The first one is The Discovery of Insulin by Michael Bliss.
Speaker 2: I feel like it's a really well researched and even
Speaker 2: handed look at you credit for the discovery of insulin.
Speaker 2: And apparently there's also a mini series about this story
Speaker 2: called Glory Enough for All. I think it's on YouTube.
Speaker 2: And then I also read, as I mentioned earlier, Diabetes,
Speaker 2: A History of Race and Disease by Arlene Marcia Tuckman,
Speaker 2: and finally Diabetes The Biography by Robert Tattersall.
Speaker 3: Awesome.
Speaker 4: The vast majority of my biology for the first time
Speaker 4: in forever, came from a single textbook, so big shout
Speaker 4: out to the Principles of Diabetes Melodis by Poritzky editor,
Speaker 4: and then a few other papers here and there for
Speaker 4: a little bit of specifics and if you're interested in
Speaker 4: that brain glucose research. I have two papers, one from
Speaker 4: Nature Communications twenty twenty and another from Diabetes that was
Speaker 4: from twenty nineteen. They're both really interesting, very detailed papers,
Speaker 4: and we'll post all of these sources for this episode
Speaker 4: and every episode on our website. This podcast will kill
Speaker 4: you dot Com.
Speaker 2: Thank you again so much, Carla for coming on and
Speaker 2: chatting with us. We really appreciate it.
Speaker 4: Yeah, thank you so much.
Speaker 2: And thank you to Bloodmobile for providing the music for
Speaker 2: this episode and all of our episodes.
Speaker 4: Thank you to the Exactly Right Network, of whom we're
Speaker 4: very proud to be a part.
Speaker 2: And thank you to you listeners for listening to this
Speaker 2: very long episode.
Speaker 3: Is a real doozy and what it is.
Speaker 2: And thanks also especially to all of our supporters on Patreon.
Speaker 2: We love you and appreciate you. I mean the depth
Speaker 2: of our appreciation and knows.
Speaker 4: No bounds, no bounds whatsoever.
Speaker 2: Okay, Well, until next time, wash your hands.
Speaker 3: You filthy animals.
Speaker 4: M