Ep 83 Diabetes: Short & Sweet

have home blood glucose monitoring. So I was out doing yard work and my dad came home for lunch and they called me in the house and said, go in the bathroom, and I want you to use the restroom on this litmus paper. And I went to the restroom urinated on the litmus paper and it turned bright blue, which I knew and my parents knew them that I was a diabetic. So I got diagnosed in the summer before sixth grade. So I started a new middle school. I had one other classmate that was also a diabetic,

but I was really embarrassed to tell anybody. I didn't want anybody to know. So if I had a low blood sugar, I wouldn't want to tell anybody, so I would wait until I was like in a dead sweat and almost out of it. My teacher would say something because she would keep orange juice in her desk, but I did not want to be called out or tell anybody.

I didn't want to be different than anybody. It was not until I was a nurse working in a hospital that I had a friend that was also on a pump, you know, and we started talking and I loved talking about it, and I loved educating. And I found even now that I'm a school nurse, talking to kids with diabetes and letting them see that you can live a

normal life. You're not any different than anybody else. You can do anything you want and live with this disease, but you have to acknowledge it and take care of it is huge and I love playing that role now. So growing up, my friends were very understanding. You know. You would go over and parents would be very scared to have you over because they were like, oh, gosh, she's a diabetic. How do we take care of someone with diabetes? And my mom would say, she can take care of it, she knows.

you wanted, you just couldn't have sugar. It was one shot a day. It was all long acting insulin. It was beef and pork based insulin back then. So control was not good being ten number one, but also you know, just no way to monitor what you're doing. You peed on a Keto strip that showed glucose and keytnes and then you went to the doctor and had blood work done, and he always said, you're not in control, you're awful. You're going to be dead before you're thirty. You know,

you've got to take care of yourself. So it was not a good thing to hear when you're you know, eleven years old and eleven years old, so I was never well controlled. At sixteen, I went into a diabetic coma for four days. During that they found that I was immune to the beef and pork insulin, and thankfully at that time they had developed the humuline insulin, so they put me on humuline in our MPH, which is a buffer long acting insulin, and humline R, which is

a regular, short acting insulin. But even then it was just two shots a day. Everything was still based on you know, sugars, not carbs. Really, the concept was not there yet for that. So when I was in college, I was in DKA, like every semester or strength too much. You think you're taking your two shots a day, you're gonna be fine. When I was nineteen years old in nineteen eighty seven, I told my mom, I think I'm dying. I don't feel good. I feel horrible. She said, you're

a lazy teenager. And I found a doctor and I said, I don't feel good. I'm taking my insulin. I don't feel good. He put me in the hospital right away, and I was immune to all buffered insulin. So in nineteen eighty seven my life changed forever because I got placed on an insulin pump. I have been under tight control ever since. I just think it's come a long way. I think pump therapy. Now I'm on a censor. They cannot with censor therapy so that reach your blood sugar

all the time. You have so much more freedom now, Just coming from someone from forty three years of having diabetes, I will never complain that I have it like it is part of me, It's who I am. But diabetes is huge. It changes every aspect of your life. You have to think about everything before you do it. You just have to be prepared for high blood sugars, low blood sugars. You have to be able to have a

positive attitude and not ignore it. You can't ignore it, and you have to take care of yourself.

We never ca we never do. Before we dive into the episode, I have one more piece of exciting business, and that is that if you think back to our organ transplant episode, like many months ago, we had on two incredible guests, Carol and Betsy, who shared their first hand accounts with us, and their book titled The Insider's Guide to Living Kidney Donation, is now available, so go check it out. We'll put a link in that episode's show notes and on our website and stuff awesome.

So let's start with some basic physiology. When a person eats, like a meal, Okay, when you just take a meal, you chew up your food, you swallow it, you digest it, It goes through your small intestine, blah blah blah, breaks down into simple sugars. Proteins break down into amino acids. We absorb them through our gut. Right, we've covered that a lot on this podcast because we've talked about a lot.

and some other tissues. And it turns out, for reasons that we'll talk about later on, it's very important for our bodies to keep really tight control on our plasma glucose levels. So the amount of sugar in your blood has to be really tightly controlled so that it doesn't.

eat way too much all at once. So our body has to have mechanisms to store excess glucose like right after we eat a meal, and then also to liberate glucose from storage so that it's available in our bloodstream when we haven't eaten or when we're fasting, and it has to be able to do this in a very narrow window of healthy plasma glucose levels. We can't let the blood sugars get too high, and they also can't get too low. So the question is how do we do this in our bodies?

of four major effects. Number one, what it does is suppress the release of glucose from the liver, which is one of the main storage sites for extra sugar. It also turns on glucose transporters on our muscle tissue and our adipose tissue, so that that glucose can actually get into our cells and then be stored or used. And it also stimulates glycogen synthesis, which is the way that our body stores glucose.

adventure a little bit here. Okay, er, okay, are you ready for this, because there's two things that we still need to understand. We need to understand why it's a problem that glucose levels get too high, Like what is it that's happening? Why is that problematic? And then we also need to know how does diabetes actually happen, like what is the essential problem in this pathway with insulin and glucose? Right, So, which do you want to go over first?

So type one diabetes is an autoimmune condition where our bodies start to make antibodies against our own pancreas as beta cells, which are so important because they produce and secrete insulin, and these antibodies destroy those beta cells.

But which viruses, great question, We don't know. People have proposed, like name a virus. It's probably been proposed as a potential cause, especially viruses that are really common epstein bar definitely, CMV absolutely all of us. Next one influenza, Yeah, influenza I think has been on that list too, But nothing that's like a strong association to be able to pin

down one specif virus. Yeah. But in short, because of this, type one diabetes results from a complete inability to make insulin, So no insulin in your body means nothing to bring down those blood glucose levels, nothing to signal your body to store that glucose or allow that glucose into our

cells so that we can actually use it. And for the most part, this disease tends to happen on a pretty quick timescale, especially when it happens in kids or adolescents, like the process of starting to generate these antibodies and then the slow destruction of these beta cells and then the onset of diabetes symptoms happens pretty rapidly. It can happen in adults as well, and then it tends to be a bit slower of a course, and we don't

know why. Okay, So that's type one diabetes and kind of the underlying causes.

So what does that really mean? Right? It means that in general, people with type two diabetes have either one or both of two different problems going on. Problem one, like I said, their beta cells are not making enough insulin for whatever reason, they just stop being able to produce enough insulin or secrete that insulin into this bloodstream. Or problem number two, their tissues become resistant to these effects. So then the pancreas secretes more and more insulin. So

what we actually see is a hyper insulinemia. That means you have a lot of insulin in your bloodstream, but it's not being used properly and so it's not effective. And therefore you still have too much glucose in your bloodstream.

So the way that I like to think of it, and again this is very simplified, but I think it's kind of a just a nice framework to have, is that as you start to have this increase in insulin resistance, so your tissues are down regulating the amount of receptors that they have so that the glucose can't get into the tissues, you have an increase in insulin resistance, and your pancreas recognizes this and it's like, gosh, we have

just so much glucose running around. So your pancreas is working really hard, like working overtime, to make more and more insulin, and that then causes your tissues to become even more desensitized to that insulin because they're just overloaded.

It's like insulin overload, there's so much of it. So then your pancreas makes even more and then eventually your pancreas is just exhausted because it's been working overtime for so long that it starts to just give up and then either making cruddy insulin or just not making insulin or not secreting it. Like, what's the point You're not going to even respond to it, I'm gonna quit. So now you have both problem one and problem to problem to exacerbating problem one and causing this vicious cycle.

higher than what is considered typical baseline glucose. And so some of those people will then progress to type two diabetes, some people won't, and some people have like both problems going on. Some people maybe have only a little of one. So type two diabetes is very complicated.

especially with type one diabetes. However, all of these symptoms that I'm going to talk about can happen with type one or type two diabetes. But because type one tends to happen faster and type two tends to be a much longer course, the more acute symptoms tend to happen more in type one diabetes, and the chronic complications can

happen in both, but certainly in type two diabetes. So classically, somebody with diabetes presents with what is often called the three p's, that is, polyurea, polydipsia, and polyph phasia, and also weight loss. So what do those mean and how does it happen? So as your blood glucose levels rise, eventually your kidney, which is responsible for filtering everything in your blood, just can't filter all of that glucose and get it back into your bloodstream because there's just so

much of it. So your kidney starts excreting glucose. After your blood levels reach about one point eighty.

in thirst, like unquenchable thirst. And at the same time, the lack of insulin in your body, which is driving all of this, essentially means that your body is unable to use any of the glucose that you have in your bloodstream. So while you technically have plenty of fuel, your body thinks that it's in starvation mode, and so it switches to what's called catabolic metabolism, and that is breaking down your tissues to use for fuel, which leads

to major hunger. That is polyphasia the third P. But despite this, you see weight loss because you're literally eating your own body tissues to use as fuel, really really bad things, very bad things. And then you have other symptoms like fatigue unsurprising because this is taking a major toll on your body, blurry vision, muscle cramps because you're

electric lights are way out of whack, et cetera. And when this gets very severe, which happens in about twenty to forty percent of cases in people like presenting for the first time with something like type one diabetes, it's called diabetic keto acidosis.

then starts this process of ketogenesis. Ketones can be used by the brain as an alternative source of fuel. However, they are an acid and therefore lead to the blood becoming acidotic, which because of dehydration, is compounded by lactic acidosis, which then further worsens kidney function, which makes it even harder to excrete those keto acids because that's one of your kidney's jobs. And this acidemia can eventually lead to

brain damage. And on top of that, your body compensates via respiration to try and make your blood alkalolotic by something called cousmall breathing, which is essentially hyperventilation, which can then lead to coma and death.

well as blood vessels. So the question is like how exactly do these complications occur, and that is probably the subject of many different PhDs worth of research, But in general, chronically having way too much glucose in your bloodstream leads

to a state of chronic inflammation. This then leads to the production of reactive oxygen species, which we've talked about a number of times on the podcast, which are basically things that then cause a bunch of tissue damage, especially in blood vessels, causing vascular injury, and that can lead

to all of those complications that you mentioned, Aaron. So it has major effects on the kidneys, especially if you think about it, this is where all of that glucose is going and the kidneys are filtering everything in your bloodstream, so kidney damage is a major one. Blindness is caused from retinopathy where you have damage to the nerves of the eye and also increased blood vessel formation that leads

to increased pressures behind the eye. The peripheral neuropathies, which can lead to a loss of sensation that can then lead to injuries that are complicated by poor perfusion because those blood vessels are damaged, So then those ulcers don't heal because they don't have any blood flow, so then they become gangrenous, and then yes, you have to do amputations.

can lead to a whole host of problems. So, yeah, diabetes affects every part of your body. It has the greatest effects and the earliest effects on small blood vessels.

standard history that I usually cover for a disease. You know, things like early writings, increasing recognition of the condition, and medical advancements, especially when it comes to diabetes, the discovery of insulin, you know, all the things that like completely changed the landscape of diabetes, especially in the twentieth century.

And then for part two, I really want to go through the other transformation that diabetes went through around that same time, and that is the social perception or portrayal of the disease, especially focusing on the US.

of a treatment for a symptom of the disease. So quote a medicine to drive away the passing of too much urine, and in the sixth century BCE, the Hindu physician Sushruda described a disease of honey urine which could be detected either through tasting it directly or by observing ants gathering around a pool of urine ooh yeah. And the word diabetes itself comes from the second century CE, when the ancient Greek physician Aretaeus coined it from the

Greek word for to run through or pipe like. He also described the disease as quote melting down of the flesh and limbs into urine, and the word melodis, from the Latin word for honey or sweet, was added later on to again indicate the sweetness of the urine. Galen around the same time as Aretaeus described it as quote diarrhea of urine, and Avicenna in the tenth century CE wrote a thorough description of the disease and its complications. So the sweetness of the urine had long been recognized.

The sweet pea was people were very familiar with it, but it wasn't until the sixteen hundreds that a physician in Liverpool named Matthew Dobson realized that it was actually sugar causing the sweetness. He made the observation when treating a patient who was urinating fifteen liders of fluid a day. Oh, so to like, because I think when we say, oh, you pee a lot, like, what does that actually mean? Right? And so this person was peeing fifteen leaders of fluid a day. That is.

germ theory in the history of diabetes, oh okay. But as researchers and clinicians learned about infectious diseases and applied that knowledge to prevention, a lot of chronic diseases grew more visible as morbidity and mortality from infectious diseases dropped right and when they did, they grabbed some research attention

to themselves. So from the middle of the eighteen hundreds it was increasingly recognized that the pancreas played some role in the disease, thanks to the rise in autopsies that had been happening that showed that damaged pancreases were often found in people with diabetes, and in eighteen eighty nine at the University of Strasbourg, two researchers named Oscar Minkowski and Joseph von Mehring showed this experimentally that the pancreas was involved when they induced diabetes in a dog after

removing its pancreas, and it was all over that like, peeing everywhere in the lab and I'll do it. Minkowski was like, what's going on. I'm so annoyed. This dog is house trained. Why is it peeing everywhere? Oh my gosh, it has diabetes. But how exactly was the pancreas involved

was happening? Additional experiments removing part of the pancreas or grafting bits of a pancreas, showed eventually that the pancreas seemed to have two secretions, one external that seemed to help with digestion and one internal that went right into the bloodstream to help with carbohydrate regulation. But where did

the internal secretion come from? In nineteen oh one, Eugene Opie at Johns Hopkins showed that damage to the islets of Langerhans, which were named for their discoverer, that that damage prevented the production of this internal secretion, which then led researchers to speculate that if this internal secretion, which by the way, was totally hypothetical at the time, if it could be isolated, it could potentially be used to treat diabetes.

and disruptions in the production of these hormones could then lead to certain diseases, especially once like you know, germ theory was like, all right, let's do the low hanging fruit. We got all these diseases, Okay, what are all these now? Like, yeah, what's happening? And then in the eighteen nineties it was found that giving someone like thyroid extract could actually help treat some conditions. So in this line of reasoning, it you know, made sense that pancreous extract could possibly do

the same. But early experiments with these pancreous extracts that were performed around the very early nineteen hundreds on humans had you know, mixed results. If I'm unsurprising, if I'm feeling generous, yep, okay, And if I'm not feeling generous, I would say mostly harmful and sometimes outright dangerous okay. But in any case, they didn't really suggest that this was like a good path forward, like this was not

the clear way to go. So what was well, Despite the growing visibility of diabetes and all these advancements in understanding its pathology and being able to diagnose it, one area that was sorely lacking was in treatment. Throughout the seventeen hundreds and much of the eighteen hundreds, the leading treatments for diabetes were basically the same things that you would use to treat anything, right, Bleed them and shoot them up with opium like that boom. If you know

how to do those things, you're a doctor. In the seventeen hundreds, and there are very few diseases that would actually benefit from bleeding, but they do exist hemochromatosis, but diabetes was not one of these. Yeah, and opium, of course, that isn't going to make diabetes or many things better.

for the disease. But there was one thing that seemed to slow the progression of the disease maybe even though it did nothing to cure it. Starvation diets. Yeah. Yeah, So during the eighteen seventy Siege of Paris, when food was rationed and many people were near starvation, one doctor noticed that the urine of some of his patients with diabetes had dropped in their glucose levels, and that their

symptoms had begun to improve a little bit. So the logical step was, well, if we severely limit the caloric intake of people with diabetes, we can reduce the symptoms of the disease. And this was the opposite of previous thinking, which was like, oh, this person is losing weight, we need to feed them more, right, right, So, after this observation, starvation diets really kind of got their start. And it

wasn't always strictly starvation. You know, some diets were just no carb diets, some were just certain carbs like oats only, but in general they were calorie cutting, with most diets restricting you to fewer than five hundred calories a day. Oh my, yeah, that is not a lot.

told to fast. And the last record of this patient showed her weighing sixty pounds, less than thirty kilograms before she broke her fasting diet and died shortly after.

So the need for effective treatment was very obvious and incredibly pressing, even more so since cases seemed to be on the rise, and so far the only thing that had showed any real promise were the experiments with pancreas extracts that I had mentioned earlier. Despite their limited success. In particular, the work of two researchers, Georg Zulezer from Germany and Nikolay Pelescue from Romania, showed that there might

be something in it. In nineteen o six in Berlin, Zulzer had treated some humans with pancreatic extract but the side effects produced were like really severe and so we had to stop the project. And ten years later, in nineteen sixteen, Paulescu had succeeded in treating a diabetic dog with a solution of pancreatic extract, like it lowered its

blood sugar levels. Just okay, super cool, promising, But his work was disrupted by World War One when he was called to service, and by the time he got back he picked up his work again, but like funds were super limited and he was working almost by himself, so

it was just kind of like hard to get things moving. Yeah, and neither zules or Paulescu would end up getting the recognition they felt they deserved for their role in one of the most monumental and one of the most contentious medical advancements in the twentieth century, the discovery of insulin.

of years before World War One broke out. He joined up, he helped treat combat soldiers, and after the war was over, he tried unsuccessfully to get a permanent position at the Toronto Hospital where he did his residency in orthopedic medicine. So he decided that he was gonna move to London, Ontario set up a private practice. But it was really pretty unsuccessful, like he couldn't quite get it off the ground.

And in fact, it seemed like a lot of areas in his life were just like filled with struggle and strife and uncertainty, like he was always on and off again with his fiance, and he seemed like he was always sending out like job applications. He seemed like desperate for a change of scenery or a change of pace

in his career. Late one October night in nineteen twenty, while trying to fall asleep and what seems like, as he described stress spiraling y yeah, absolutely, his mind drifted to a paper that he had recently read to prep for a lecture that he was giving on like I think carbohydrate regulation. And this paper, which was written by Moses Baron, discussed the role of the islets of Langerhans in the internal secretion of the pancreas and its possible

role in diabetes. And he turned the idea over and over in his mind and kept thinking about it and came up with what he thought was the solution to the problem, like a way to isolate that internal pancreatic secretion and it would involve surgical removal of degenerated pancreases and dogs and extraction of the secretion from those pancreases.

And the next time he was on campus, he brought up the idea to a professor at the university where he was affiliated, and the professor was like, you know, no, like sorry, but we just don't have the resources for that. And also there's no one at the university here that knows enough about it to be able to help you. But hang on a second. There happens to be somebody visiting who might and that somebody turned out to be JJ R. McLeod visiting from the University of Toronto, who

was an expert in diabetes and carbohydrate metabolism. So Banting met with McLeod. McLeod wasn't like super impressed by Banting, who had a lot of enthusiasm and confidence, but that confidence wasn't really backed by like a lot of background reading on the subject. He was just like, I'm gonna do this and it's gonna be great.

up your practice and your affiliation here. And also like there's kind of a low chance that you would be successful, because you know, this is not a new problem, like people have tried this before. So Bantin gave it some time and thought and decided to give it a go. But after the other job applications that he had sent out had fallen through, and after his fiance had dumped him yet again, so he was like, you know what I lose, I'm getting out of here. So so yeah,

so we packed up his apartment. He headed to Toronto and got there in April nineteen twenty one, and apparently he had done no more reading on the subject in the meantime, oh or not, my goodness, not very much, because when he met with McLeod, McLeod was like, Okay, so I think this is how the experiments should go. We'll start with this, and then we'll do this, and then we'll do this. Let's you know, see how we begin.

He showed him how to do the procedures et cetera, and then he was like, also, you know, maybe you should read these papers, read these books, get a little more background in it. And then McLeod headed back to

Scotland where he was from for the summer break. But before he did that, he gave Banting an undergraduate research assistant named Charles Best to help on the project, and he kind of spent a little bit of time, like a month and a half or so, kind of walking them through these surgical procedures that they would use on

the dogs. The experimental plan went a little something like this. First, Banting and Best would get practice Banting on performing the pancreatectomies and Best using the blood and urine tests, and both of them observing what diabetes and dogs look like

like the course of disease. And then Banting would ligate the pancreatic ducks in other dogs, allow them to recover while they're pancreas's atrophied, and then reoperate on these dogs, removing their degenerated pancreases and extracting the internal secretion from them, which he would then inject into the dogs that had been made diabetic from the complete removal of their pancreas.

just fly. I everyone I cook would be like like, nope, you are getting your research whatever credit. Yeah, you're not allowed to do research at this university anymore or any ever again, yes or any Yeah. But finally, finally, after many failures, things began looking up. They were able to successfully extract the secretion from the pancreas injected into depancreatized diabetic dogs and bring them back from the brink of death and out of a diabetic coma by rapidly dropping

their blood sugar. This was like thrilling yeah, and Banting was quick to see and believe in the potential of this extract for the treatment of diabetes and humans. But McLeod, who was now back from his trip, he was urging a bit more caution. He was like, all right, why don't we just try repeating these experiments first, making sure we have like good you know, sample size, and we'll

publish the results. See if we can refine the process and make sure that like we know exactly what we're doing and that other people can replicate it.

the university. He was just sort of there, and so he said to McLoud, you know what you're gonna pay me, You're gonna give me another assistant to take care of the dogs, and you're gonna have repairs done to the operating room. And McLoud was like, okay, that's actually you're asking for quite a lot, and other research at the university would suffer if, you know, if I were to give all of this to you. And Banting's like, I

am gonna walk away from this. This is you know, blah blah blah, and so McLoud was like, you know what, Okay, fine, you're right, your work does show promise. Let's let's keep it going. So this meeting might be where we first see the tension rise between Banting and McLeod. And at this point Best was already aware of Banting's tendency to be scornful, disparaging, you know, impatient, and quick to anger. He had been yelled at at least once for dirty glassware.

But this might be this might have been the first time that McLeod saw it in action, And this meeting might also have been when the seed of hate was playing in Banting form a cloud. Yeah, it's like really a toxic It's a whole toxic story and toxic place.

But at this meeting, during his presentation, Banting like totally flubbed it. He was a terrible speaker. He stumbled over the results and it got so bad that McLoud Cloud had to keep like stepping in to clarify something or to include a crucial detail that Banting had left out. And he answered questions and then to add you know, insult to injury, or at least as perceived by Banting. McLeod kept saying, we we extracted this and we injected that.

Banting was fuming there. He was I can only imagine just like standing up there in front of the who's who of diabetes researchers in North America and basically not being able to string a coherent sentence together while your supervisor is taking what is perceived to be taking all the credit from you.

So anyway, I don't want to get too much into the whole, like.

clinical trial in January of nineteen twenty two. So just you know, from April nineteen twenty one when Banting arrived to Toronto to the first clinical trial January of nineteen

twenty two, that's very fast, too fast, I mean. So the first person to ever receive this pancreatic extract was Leonard Thompson, a fourteen year old boy who on admission weighed only sixty five pounds, whose hair was falling out, abdomen distended breath smelling of actone, and who was on a diet of four hundred and fifty calories a day.

So the trial was deemed premature and there was a rush to make a more pure sample, something that Banting took upon himself to make like a competition with Callup, who was like, I don't this doesn't need to be a competition, Like, can't we just work on this?

to be transparent with each other about research developments. I mean, they didn't become friends or anything, but you know, at least like for now, it seemed to have de escalated. But in any case, the animosity and drama was there to stay. I mean, wow, it wasn't going anywhere. I again, I can't even get into it all like, there's a great book, I'll recommend that kind of you're just like

what he said that. Yeah, And so, beginning in the spring of nineteen twenty two, the lab group began publishing their results. But the important thing is that the popular press picked it up, and that generated a lot of hype among the many people who lived with diabetes. It was in one of these first publications that was a big comprehensive one from April nineteen twenty two, that the

term insulin was first used. And there's no record as to like why or how they chose that word, but it's based on the Latin route for island, referring to the islets of Langerhans.

production process and patent it. And so even though McLeod Banting in Best were reluctant to patent it on principle, they wanted to stop other people from creating a monopoly, and so they filed this type of patent that would prevent that from happening.

soul ability or license to try to manufacture this new insulin. Yeah, but you know, the drama of discovery, the incredible tension among the researchers, the difficulties in streamlining or fine tuning the production process. All of these problems were overshadowed by the absolutely enormous impact that insulin was having on the lives of people with diabetes. A lot of accounts at the time describe the drug, describe insulin as miraculous, and

it's kind of hard to disagree with that. Yeah, Like a sixteen year old boy brought out of a diabetic coma from an insulin injection, the first time that had ever happened. A bedridden child jumping around the room hours after being given insulin. Perhaps the most famous patient from the time was Elizabeth Hughes, who was daughter of the US Secretary of State, who kept journals of her life pre and post insulin, And at the time of her first insulin shot, the fifteen year old Elizabeth weighed less

than fifty pounds. That's like twenty two kilograms. It's yeah, and she was close to death. A few weeks after receiving her first insulin shot, she gained ten pounds. Wow, and a lot of health problems resolved for her, and she went on to live like a healthy and relatively long life. And there were a million more stories just like these. Insulin saved and continues to save so very

many people from what was absolutely a death sentence. Yeah, it kind of reminds me a lot of like the stories of when antibiotics were first developed and first introduced, and it was like it was raculous. It was coming back from the brink of death. It must have been unbelievable to witness. So who was responsible for insulence development?

And who gets the credit? And are the answers to those questions the same, Well, it depends on who you ask, right, If you ask Banting, it was Banting with a little help from Best. If you ask McLeod, it was McLeod Banting and Callop. If you ask Paulescu, it was poulsq And if you ask the Nobel Prize committee, it was Banting and McLoud. So in nineteen twenty three the two were awarded the Nobel Prize. Banting was only thirty two

at the time. Oh yeah, gosh at the time. I think he was the youngest for like physiology and medicine or whatever the grouping was at the time. But Banting was furious. He could not believe that his and McLeod's name were both on the prize.

Probably not. Would Banting have gotten there without McLeod or

without call Up probably not. All these tensions and credit debates aside, though, the important thing is that insulin was now available, and just in the way that blood transfusions for hemophilia turned that disease from an acute disease to a chronic one, insulin prolonged the lives of those with diabetes, but it was also not a cure, and the long term consequences of diabetes, particularly type one, were emerging, such as kidney disease and retinopathy and all the ones that

you've already discussed in the biology. So I'm not going to go through these next things in detail. But following the discovery and production of insulin, a lot of other important developments occurred. Frederick Sanger discovered that insulin was a protein and described its structure, for which he was awarded a Nobel Prize in nineteen fifty eight, his first of two yep and Dorothy Hodgkin, whose name you might remember

from our antibiotics episode and our radiation episodes. So she used X ray crystallography to work out the three D structure of insulin. A lot of research focused on treatments for the long term consequences of diabetes, such as kidney disease and ulcers and kidney transplants, and some really important work was done by Priscilla White on reducing perinatal mortality in people with diabetes by introducing sex hormones treatment, which

hugely increased survival of the babies. And there was yet another Nobel Prize for diabetes research co awarded to Rosslyn Yallow in nineteen seventy seven for developing the radio amino assay to measure the concentration of hormones like insulin, vitamins, viruses, enzymes, and lots more stuff in humans. Genetic engineering allowed for the mass production of biosynthetic insulin, and I think we might have touched on that briefly in our Ecoli episode.

It was basically like engineering ecoli to just like pump make a ton of insulin that sounds vaguely familiar, and then the threat of bovine sponge offormencephalopathy in bovine derived insulin and kind of put for like this switch towards human insulin. And then insulin pumps were developed, and since the nineteen seventies they've shrunk in size considerably and increased

their capabilities considerably. In nineteen seventy nine, diabetes was officially divided into two types, insulin dependent diabetes melodice and non insulin dependent diabetes melodus, or type one and type two as they were called beginning in nineteen ninety five and in the late nineteen seventies is also when gestational diabetes and what was called maturity onset diabetes of the young were also recognized. There have been too many developments to

even mention. This year twenty twenty one marks the one hundred year anniversary of insulin, and over that time diabetes has un under gone a huge transformation in terms of our understanding of the disease and our ability to treat it. But the story isn't over because alongside these medical developments, diabetes was going through another kind of transformation in the twentieth century, a social transformation. If you will, Okay, Diabetes

Part two, I promise this is a lot shorter. So I know I've been talking for ages.

so like what do you expect? You deserve this? These are the consequences for your actions, And this I think reflects a huge problem, not just in showing like a complete absence of empathy, but also in revealing a general lack of understanding about the multifaceted nature of this disease and refusing to acknowledge the institutional drivers that increase the

risk of diabetes. Yeah. So, when I was prepping for this episode, I read a book called Diabetes, A History of Race and Disease by Arlene Marsha Tuckman, where I learned that it's kind of like always been this way, Like there's always been sort of this Oh well, these are the consequences of your actions, or like, oh, this is a personal disease, like this is something that you did, right.

It's always been very much like a blame the individual or the identity of the individual, kind of a disease with a particular trait or group at fault being the main thing that has changed over the decades. I had no idea before researching this episode, but it turns out that diabetes started out as a quote like Jewish disease in the late eighteen hundreds, when the visibility of diabetes and other chronic diseases was increasing as infectious diseases declined.

Diabetes was literally given the name quote the Jewish disease in Europe because of the supposed high prevalence of the disease among Jewish people, and the reason for this high prevalence varied based on the individual views of the person you ask or the person who was writing this article.

It could be because of the long years of cruel persecution faced by Jewish people that led to this high levels of stress, or it was because they overindulged in ate rich foods, or maybe it's because they had a quote nervous disposition, or it was just a way of saying that this disease had you know, foreign roots, since the immigration of Jewish people from Eastern Europe was really

high during this period. But whatever the perceived reason or stated reason at the time, this association grew global and it became entrenched in medical literature and in the minds of practicing doctors for decades, so like from the late eighteen hundreds to like a few decades into the twentieth century. Huh, yeah, was there actually an association, I mean without any quality statistics from the time. We can't say for sure, but

it seems unlikely. It seems that it was more bad statistics turned into common knowledge and then like helped along by confirmation bias. Like definitely a citation needed moment, and that was a big problem that just kept being repeated in the literature without any citation or citing someone who just said, it's really highly prevalent in Jewish people. And even if there were numbers in these articles, was the categorization of you know, Jewish and non Jewish even helpful?

Was it meaningful? Both groups were very heterogeneous. So drawing those lines was really a way of kind of like pushing a certain narrative. The way that you draw the lines is definitely like you have a bit of forethought about what statements you want to make when the numbers all kind of fall out, right, Like what's important to you about those divisions? And often you know, as it

is now, but as it was back then. You know, those divisions were a way of saying that something about your race, or your background, or your culture made you more likely to have this disease. And we see this theme, you know, race presented as an explanation for disease again and again in the history of diabetes, with Black Americans and the Native Americans and Mexican Americans and so on.

And certainly the use of racial categories and epidemiological studies can be very helpful, but they're helpful for confronting and trying to understand institutional racism and inequalities in health care or access. Not to further the myth of race as a biological construct and yet erin and yet aarin Okay, so from its reputation as a you know, quote Jewish

disease in the late eighteen hundreds. Diabetes slowly began to be viewed as a disease of man moral failing, especially in the years following World War One, which were a period of economic growth and increase in consumables and big cultural shifts, leading to culturally conservative people shouting that, like, the increasing rates of diabetes were a sign of moral decay, of this like gluttonous, over indulgent society that has no

self control. The shifting from a Jewish disease to like a more general sign of you know, moral decay or whatever also happened as more studies were done to show that there wasn't actually much of a difference in terms of stats, right, and this moral failing or over indulgence or just the rate of diabetes, it had a class structure to it. Diabetes had shifted its reputation to one

of middle and upper class and generally white people. In fact, it was thought and published in medical journals that black people were immune to diabetes. What it was literally in medical journals, Well, they are known to be immune. Same was said about Native Americans also, So why did people think they were immune to diabetes?

this lower prevalence were given or written about in racist terms. Right, Black people didn't have the quote like nervous strain or quote mental strength for diabetes.

erin it is yeah, it's all about the narrative. But then here comes another shift, right, another transformation of diabetes. So when actual statistics introduced in the nineteen twenties showed that rates of diabetes didn't differ much between black and white Americans, but do you know what did? Mortality rates

from diabetes. And another factor that contributed to the overall growing visibility of diabetes among black Americans was the increase in black medical doctors who wanted to help improve the

health of the communities that they served. And what many of these doctors saw was also reflected in the stats from the time and also from today that as poverty increased, the rates of diabetes rose, and that diabetes in general seemed to be on the rise in the nineteen thirties and estimated half a million to two million people in the US were living with the disease, and it rose to be the ninth lead and cause of death in the US in nineteen thirty six, which is up from

the twenty seventh in eighteen ninety. The development of insulin in the early nineteen twos ties helped out a bit with like the management of diabetes, but a lifetime of injections was still costly and long term effects were still present. And also, since this is an episode of TPWK, why I have to mention eugenics. So here we go obligated eugenesis. As you might guess, we're not a fan of insulin saying that it would increase the numbers of unfit people in society.

did some people get it in others not? Why were we seeing an increase in the US In nineteen sixty two, James Neil thought he might have the answer. Have you heard of the thrifty genotype? Yeah? Okay, it's basically this idea proposed by Neil that this thrifty genotype would have helped early humans live through periods of unpredictable food availability, so you would store more fat in times of plenty

to prepare for times of famine. But in the US and other developed countries where diabetes was on the rise, there weren't really these times of famine, and so the thrifty genotype went from good to bad. It began to backfire. And at first this thrifty genotype hypothesis was just used to explain a global growth in diabetes prevalence, but with recent reports showing a disproportionately high rate of diabetes among some Native American groups, it became used in this colonial

narrative of quote primitive and quote advanced societies. And in this narrative, some Native American groups were said to be more prone to develop diabetes because they were quote primitive people who were rushed into quote you know, modern living conditions and they were unequipped to deal with the diet and lifestyle.

to ignore their own role in the cycle of poverty, in the impact of displacement, genocide, and federal policies that lead to higher rates of disease, not just diabetes. Speaking of the federal government, in the nineteen eighties, a nationwide study called the Heckler Report investigated racial and ethnic health disparities in the US, and what they found was that diabetes, specifically type two and mortality from diabetes occurred at disproportionately

high rates among non white people. The report framed diabetes as I quote disease of minority groups. It barely acknowledged the role that poverty played, but rather it emphasized the racial and ethnicity differences and to some degree, sex differences.

This continued the long tradition of attributing diabetes to a moral failing or personal quality, or to a certain racial or ethnic background, all the while ignoring the role that poverty and other factors like food, deserts, like the ability to be active, that all of these things can play. Diabetes is such a nuanced disease, but it seems as though somehow we struggle still to make sense of that nuance and present it in a way that is like, oh, okay,

there are multiple parts to this story. So I've rambled on and on, and Aaron, why don't you bring me up to speed and what's happening with diabetes today?

more of your question of the wyat and how oh good? So, according to the International Diabetes Federation, in twenty nineteen, diabetes and this is all types of diabetes, of which generally ninety percent or so are type two and five to ten percent type one, and then gestational and the other types of diabetes account for the other percentages. So in twenty nineteen, diabetes caused four point two million deaths worldwide

and four hundred and sixty three million adults. This is just adults between age twenty and seventy nine were estimated to be living with diabetes, and that number is likely to rise to up to seven hundred million by twenty forty five because both type one and type two diabetes have been increasing, right, and it gets a little worse. The true disease burden, especially for type two diabetes, is likely a gross underestimation because one in three people who

have diabetes are underdiagnosed. That's over two hundred million people WHOA. Yeah, And then if you also account for all of the people who have impaired fasting glucose or what sometimes is called pre diabetes, the vast majority of those people have no idea that that's what's happening inside of their bodies.

of these are unsurprisingly very expensive, and there are of course major economic and social hurdles for people living with diabetes in low and middle income countries, but also across the globe, including here in the US. For example, insulin prices in the US are truly an abomination. In twenty eighteen, a unit of insulin was ninety eight dollars and seventy cents in the US, compared to eight dollars and eighty one cents.

on the horizon. I usually talk about whatever's going on in terms of research, and a lot of times I feel like I've been like, ohh, there's not much going on and it's like depressing. But today I don't have a lot of very specific things to go over. But that's because there is so much research going on in terms of diabetes that there's simply too much ground to cover, which is amazing. That means that there's so many people working on so many different aspects of this in terms

of new treatments. When we look at type one diabetes in general, and I apologize if there's even newer things that I have missed, but in general, the treatment is still just insulin, and while that sounds simple, it's a very complex to kind of get regimens and know how

much you have to give, et cetera. But some incredible advancements for type one diabetes or insulin dependent type two diabetes is the development of continuous glucose monitors and like you mentioned, increasingly small and easy to use insulin pumps that can keep much tighter control of that glucose, which can then prevent the development of complications.

But now because we know that insulin resistance is a big component, there's other types of treatments that are targeting tissues to make them more susceptible to the effects.

either type two or type one diabetes. But one of the biggest questions, Aaron, that you kept asking me was the why the how, especially when it comes to type two diabetes. And so, like I mentioned, both type one

and type two diabetes have a genetic component. Type two diabetes has a much stronger genetic component, meaning if you have a first degree relative with type two diabetes, you are much more likely to develop type two diabetes yourself than you are if you had someone with type one diabetes to develop type one.

The things that we know that are the most strongly associated are sedentary lifestyle, which is essentially just means not getting a lot of physical activity throughout the day. Another is diet, So having a diet that's really high in sugars that are like the kind that you find in soda is really strongly associated with type two diabetes. And then the one that cited the most frequently is obesity.

So BMI is the indicator that we use to classify obesity and obesity in the US at least, is considered a disease, which is then also considered a risk factor for diabetes, among other things, type two diabetes specifically. And BMI is not just in my opinion, but also in my opinion, not a good indicator of health. Not only does BMI not take into account things like muscle mass or the distribution of adipose tissue, whether it's central and around your organs versus on your life eggs, or arms,

et cetera. BMI also ignores so many of the social determinants of health that play into the overall risks of diabetes and so many other diseases. So be am I an obesity In general, it's not a good indicator, but in the literature it is considered a risk factor for type two diabetes.

it's not, it's really not. Again, that still doesn't address this underlying question, but it does give us a much better target right for the like mechanistic cause, did you.

plays a huge role. But I think too, Aaron, getting back to what you were saying in the last part of your history section, is it's so important, especially in a disease like diabetes, when we're talking about things like these modifiable risk factors, to not lose sight of the environment that we are in and these structures of government of our society that force us into this environment where we can't do physical activity because we're sitting at a desk at our jobs for ten hours a day and

then we're driving in our car an hour each way to work, and then we can't afford to buy fresh leafy greens because they go bad in twenty minutes in your fridge, and also they don't taste that good. Like, there are so many things that play into this. It's not an individual choice, it's so much bigger than that.

And then I also read, as I mentioned earlier, Diabetes, A History of Race and Disease by Arlene Marcia Tuckman, and finally Diabetes The Biography by Robert Tattersall.

from twenty nineteen. They're both really interesting, very detailed papers, and we'll post all of these sources for this episode and every episode on our website. This podcast will kill you dot Com.