WEBVTT - Ep 83 Diabetes: Short & Sweet 0:00:02.520 --> 0:00:06.000 Hi, I'm Carla Williamson. I am a Type one diabetic 0:00:06.559 --> 0:00:10.360 forty three years this August. I was diagnosed in nineteen 0:00:10.400 --> 0:00:14.800 seventy seven. I was drinking all the time. I couldnot 0:00:14.840 --> 0:00:17.440 get enough water. My mom said I would go from 0:00:17.480 --> 0:00:20.400 a water fountain, drink a coke, then drink milk. I 0:00:20.400 --> 0:00:24.320 couldn't get enough. I was losing weight. My dad was 0:00:24.320 --> 0:00:27.320 a Type one diabetic also, and my mom had recognized 0:00:27.360 --> 0:00:30.760 the symptoms pretty early, and back then they did not 0:00:30.920 --> 0:00:34.320 have home blood glucose monitoring. So I was out doing 0:00:34.400 --> 0:00:36.559 yard work and my dad came home for lunch and 0:00:37.080 --> 0:00:39.000 they called me in the house and said, go in 0:00:39.040 --> 0:00:41.239 the bathroom, and I want you to use the restroom 0:00:41.280 --> 0:00:45.640 on this litmus paper. And I went to the restroom 0:00:46.240 --> 0:00:49.960 urinated on the litmus paper and it turned bright blue, 0:00:50.360 --> 0:00:53.600 which I knew and my parents knew them that I 0:00:53.680 --> 0:00:56.560 was a diabetic. So I got diagnosed in the summer 0:00:56.600 --> 0:00:59.480 before sixth grade. So I started a new middle school. 0:01:00.200 --> 0:01:02.960 I had one other classmate that was also a diabetic, 0:01:03.440 --> 0:01:07.000 but I was really embarrassed to tell anybody. I didn't 0:01:07.000 --> 0:01:09.959 want anybody to know. So if I had a low 0:01:10.000 --> 0:01:12.360 blood sugar, I wouldn't want to tell anybody, so I 0:01:12.360 --> 0:01:14.640 would wait until I was like in a dead sweat 0:01:14.680 --> 0:01:17.759 and almost out of it. My teacher would say something 0:01:17.800 --> 0:01:20.120 because she would keep orange juice in her desk, but 0:01:20.160 --> 0:01:24.040 I did not want to be called out or tell anybody. 0:01:24.160 --> 0:01:27.039 I didn't want to be different than anybody. It was 0:01:27.160 --> 0:01:30.160 not until I was a nurse working in a hospital 0:01:30.160 --> 0:01:32.440 that I had a friend that was also on a pump, 0:01:33.120 --> 0:01:36.319 you know, and we started talking and I loved talking 0:01:36.360 --> 0:01:40.520 about it, and I loved educating. And I found even 0:01:40.760 --> 0:01:43.440 now that I'm a school nurse, talking to kids with 0:01:43.480 --> 0:01:46.560 diabetes and letting them see that you can live a 0:01:46.560 --> 0:01:49.640 normal life. You're not any different than anybody else. You 0:01:49.680 --> 0:01:53.040 can do anything you want and live with this disease, 0:01:53.080 --> 0:01:55.120 but you have to acknowledge it and take care of 0:01:55.160 --> 0:01:58.960 it is huge and I love playing that role now. 0:01:59.800 --> 0:02:04.560 So growing up, my friends were very understanding. You know. 0:02:04.640 --> 0:02:07.480 You would go over and parents would be very scared 0:02:07.520 --> 0:02:09.320 to have you over because they were like, oh, gosh, 0:02:09.320 --> 0:02:12.600 she's a diabetic. How do we take care of someone 0:02:12.639 --> 0:02:16.040 with diabetes? And my mom would say, she can take 0:02:16.080 --> 0:02:17.239 care of it, she knows. 0:02:17.080 --> 0:02:17.639 What to do. 0:02:18.560 --> 0:02:21.079 My parents handed me the disease at ten years old 0:02:21.080 --> 0:02:23.240 and said, this is yours. You're going to live with 0:02:23.360 --> 0:02:25.160 the rest of your life. You've got to learn to 0:02:25.160 --> 0:02:28.240 make good decisions. So I got out of the hospital 0:02:28.320 --> 0:02:30.120 on a Monday, and I was at a sleepover on 0:02:30.160 --> 0:02:34.200 a Friday. So I was always given freedoms and good 0:02:34.280 --> 0:02:38.240 or bad, I don't know, but to handle this disease. 0:02:38.760 --> 0:02:42.720 Back in nineteen seventy seven, it's so different than it 0:02:42.800 --> 0:02:45.880 is now. Everything was no sugar. You could eat anything 0:02:45.919 --> 0:02:48.560 you wanted, you just couldn't have sugar. It was one 0:02:48.600 --> 0:02:52.280 shot a day. It was all long acting insulin. It 0:02:52.360 --> 0:02:56.079 was beef and pork based insulin back then. So control 0:02:56.400 --> 0:03:01.240 was not good being ten number one, but also you know, 0:03:01.480 --> 0:03:04.840 just no way to monitor what you're doing. You peed 0:03:04.919 --> 0:03:08.640 on a Keto strip that showed glucose and keytnes and 0:03:08.680 --> 0:03:10.840 then you went to the doctor and had blood work done, 0:03:10.840 --> 0:03:14.640 and he always said, you're not in control, you're awful. 0:03:15.120 --> 0:03:17.520 You're going to be dead before you're thirty. You know, 0:03:17.600 --> 0:03:20.480 you've got to take care of yourself. So it was 0:03:20.560 --> 0:03:22.799 not a good thing to hear when you're you know, 0:03:22.919 --> 0:03:25.760 eleven years old and eleven years old, so I was 0:03:25.800 --> 0:03:30.079 never well controlled. At sixteen, I went into a diabetic 0:03:30.120 --> 0:03:33.720 coma for four days. During that they found that I 0:03:33.760 --> 0:03:37.120 was immune to the beef and pork insulin, and thankfully 0:03:37.160 --> 0:03:41.480 at that time they had developed the humuline insulin, so 0:03:41.960 --> 0:03:46.040 they put me on humuline in our MPH, which is 0:03:46.040 --> 0:03:49.520 a buffer long acting insulin, and humline R, which is 0:03:49.520 --> 0:03:52.960 a regular, short acting insulin. But even then it was 0:03:53.000 --> 0:03:55.960 just two shots a day. Everything was still based on 0:03:56.800 --> 0:04:00.800 you know, sugars, not carbs. Really, the concept was not 0:04:00.920 --> 0:04:04.320 there yet for that. So when I was in college, 0:04:04.600 --> 0:04:08.520 I was in DKA, like every semester or strength too much. 0:04:08.960 --> 0:04:10.920 You think you're taking your two shots a day, you're 0:04:10.960 --> 0:04:13.800 gonna be fine. When I was nineteen years old in 0:04:13.920 --> 0:04:16.680 nineteen eighty seven, I told my mom, I think I'm dying. 0:04:16.800 --> 0:04:19.880 I don't feel good. I feel horrible. She said, you're 0:04:19.880 --> 0:04:23.919 a lazy teenager. And I found a doctor and I said, 0:04:24.080 --> 0:04:26.920 I don't feel good. I'm taking my insulin. I don't 0:04:26.960 --> 0:04:29.520 feel good. He put me in the hospital right away, 0:04:29.560 --> 0:04:33.920 and I was immune to all buffered insulin. So in 0:04:34.040 --> 0:04:36.600 nineteen eighty seven my life changed forever because I got 0:04:36.640 --> 0:04:39.719 placed on an insulin pump. I have been under tight 0:04:39.760 --> 0:04:43.040 control ever since. I just think it's come a long way. 0:04:43.279 --> 0:04:47.560 I think pump therapy. Now I'm on a censor. They 0:04:47.640 --> 0:04:49.920 cannot with censor therapy so that reach your blood sugar 0:04:49.960 --> 0:04:52.640 all the time. You have so much more freedom now, 0:04:53.240 --> 0:04:56.520 Just coming from someone from forty three years of having diabetes, 0:04:56.880 --> 0:04:59.200 I will never complain that I have it like it 0:04:59.400 --> 0:05:02.920 is part of me, It's who I am. But diabetes 0:05:03.040 --> 0:05:07.159 is huge. It changes every aspect of your life. You 0:05:07.240 --> 0:05:09.960 have to think about everything before you do it. You 0:05:10.080 --> 0:05:12.240 just have to be prepared for high blood sugars, low 0:05:12.240 --> 0:05:15.120 blood sugars. You have to be able to have a 0:05:15.160 --> 0:05:18.640 positive attitude and not ignore it. You can't ignore it, 0:05:18.680 --> 0:05:19.880 and you have to take care of yourself. 0:06:04.680 --> 0:06:08.799 Thank you so much Carla for coming on and chatting 0:06:08.839 --> 0:06:11.000 with us. We really appreciate it. 0:06:11.320 --> 0:06:11.800 We do. 0:06:13.040 --> 0:06:16.480 Hi. I'm Erin Welsh and I'm erin Almond Updyke and 0:06:16.560 --> 0:06:18.599 this is this podcast will kill you. 0:06:19.600 --> 0:06:23.039 Yeah, this is this is going to be a good episode. 0:06:23.160 --> 0:06:26.520 Erin, I think so. I think it's I mean, we 0:06:26.560 --> 0:06:29.520 say this every time, this is this podcast and we 0:06:29.560 --> 0:06:31.920 are excited about this episode and it's going to be 0:06:31.960 --> 0:06:35.560 a good one. And we can't wait to get into it. 0:06:36.080 --> 0:06:38.560 Yeah, you know, we're going to try and keep it 0:06:38.600 --> 0:06:40.080 short and sweet, right. 0:06:41.200 --> 0:06:43.880 Yeah, but we will fail in our attempt. 0:06:46.800 --> 0:06:49.400 Should we start off with a quarantini? 0:06:49.920 --> 0:06:50.599 Let's do it? 0:06:51.200 --> 0:06:52.760 What are we drinking this week? 0:06:52.920 --> 0:06:57.880 Erin this week, I can barely hold in the laughter. 0:06:59.000 --> 0:07:03.760 This week we are drinking the aptly named sweet pea 0:07:04.560 --> 0:07:05.320 sweet pee. 0:07:05.800 --> 0:07:08.000 It's spelled p ee. 0:07:08.760 --> 0:07:12.440 Yeah, get Aaron. Do you want to explain why we're 0:07:12.480 --> 0:07:13.560 calling it sweet pea? 0:07:14.080 --> 0:07:16.840 Well, I'll explain a lot in the biology section. 0:07:18.240 --> 0:07:22.720 But that is one of the hallmark symptoms of diabetes Melodie, 0:07:23.240 --> 0:07:26.280 which is the topic of today, and that's having excess 0:07:26.320 --> 0:07:28.760 glucose or sugar in your pee. 0:07:29.240 --> 0:07:36.200 Yeah, it's true. But unlike that pea sweet pea, the 0:07:36.320 --> 0:07:41.000 Quarantini and Placebarita does not have any sugar in it. 0:07:41.520 --> 0:07:43.040 No, it's diabetes friendly. 0:07:43.440 --> 0:07:47.160 Yeah. The thing is, we were, you know, researching, okay, 0:07:47.240 --> 0:07:50.920 what are good cocktails for people with diabetes, and you know, 0:07:51.040 --> 0:07:52.840 again and again it kind of came up as like 0:07:53.160 --> 0:07:56.120 no sugar, you know, pretty simple stuff, and so what 0:07:56.160 --> 0:07:58.040 we wanted to do was kind of keep it simple 0:07:58.080 --> 0:08:01.800 and approachable. And it's actually one of my favorite like 0:08:01.920 --> 0:08:04.920 go to drinks. It's a vodka soda. 0:08:05.200 --> 0:08:08.640 It's a vodka soda. And if you want the plasiburrita version, 0:08:08.960 --> 0:08:10.920 it's a soda water with lime. Yeah. 0:08:11.000 --> 0:08:13.400 And the thing is, you know, you can really, you know, 0:08:13.480 --> 0:08:15.680 spice it up or flavor it up however you want 0:08:15.680 --> 0:08:18.400 to do it right. You can use infused vodka. You 0:08:18.440 --> 0:08:21.600 can use lemon or a different kind of fruit instead 0:08:21.600 --> 0:08:24.040 of lime. You can do anything you want. You can 0:08:24.080 --> 0:08:28.640 do stevia syrup or whatever. But you know, as a baseline, 0:08:29.000 --> 0:08:30.200 start with a vodka soda. 0:08:30.640 --> 0:08:31.440 Yeah, do that. 0:08:32.120 --> 0:08:34.440 If you need a full recipe, we will post one 0:08:34.559 --> 0:08:36.720 on our website. This podcast will kill You dot Com 0:08:36.760 --> 0:08:39.000 and all of our social media channels. 0:08:39.160 --> 0:08:42.880 So more business. On our website, you can also find 0:08:43.040 --> 0:08:46.480 things like transcripts. You can find things like a link 0:08:46.520 --> 0:08:50.280 to our Goodreads list, to our bookshop dot org affiliate account. 0:08:50.840 --> 0:08:55.640 You can find all of the references to past episodes, 0:08:55.880 --> 0:08:58.439 promo codes for all of the things we talk about 0:08:58.480 --> 0:08:59.200 in the ads. 0:09:00.120 --> 0:09:03.679 Saren oh everything everything you need this podcast will kill 0:09:03.720 --> 0:09:04.439 You dot Com? 0:09:04.600 --> 0:09:07.960 Oh yeah, merchant music. Two more things. I feel like 0:09:08.120 --> 0:09:11.920 at this point in the season and in our podcasting career, 0:09:11.960 --> 0:09:15.040 we should have that part down, but shall we don't? 0:09:15.520 --> 0:09:19.240 We never ca we never do. Before we dive into 0:09:19.280 --> 0:09:22.240 the episode, I have one more piece of exciting business, 0:09:22.559 --> 0:09:24.960 and that is that if you think back to our 0:09:25.040 --> 0:09:29.080 organ transplant episode, like many months ago, we had on 0:09:29.120 --> 0:09:32.920 two incredible guests, Carol and Betsy, who shared their first 0:09:32.960 --> 0:09:37.679 hand accounts with us, and their book titled The Insider's 0:09:37.679 --> 0:09:41.520 Guide to Living Kidney Donation, is now available, so go 0:09:41.840 --> 0:09:45.480 check it out. We'll put a link in that episode's 0:09:45.520 --> 0:09:48.720 show notes and on our website and stuff awesome. 0:09:50.280 --> 0:09:55.520 Should we dive into this probably long episode, let's do it, Okay, 0:09:55.960 --> 0:10:22.679 right after this break. So here's the thing about diabetes, 0:10:22.800 --> 0:10:25.960 arin We always say that we're not experts on any 0:10:26.000 --> 0:10:29.720 of the topics that we cover, true, and it's still 0:10:29.800 --> 0:10:34.400 true here today. So certainly there are probably going to 0:10:34.440 --> 0:10:38.199 be like endocrinologists or PhDs in biochemistry. 0:10:37.440 --> 0:10:39.680 Who are, like, you're mussing crucial pieces. 0:10:40.640 --> 0:10:43.520 We're focusing here on the broad strokes, folks. So what 0:10:43.600 --> 0:10:46.800 I'm hoping that listeners come away with by the end 0:10:46.800 --> 0:10:50.480 of this episode is an understanding from the biology side 0:10:50.559 --> 0:10:54.960 of what insulin is and what it normally does, what 0:10:55.280 --> 0:11:00.320 the essential underlying problems are in diabetes, whatever type we 0:11:00.360 --> 0:11:04.800 talk about, and why you see the complications that you see. 0:11:04.960 --> 0:11:08.640 So those are the three main pictures. Okay, excellent, all right, 0:11:09.559 --> 0:11:13.679 So let's start with some basic physiology. When a person eats, 0:11:13.760 --> 0:11:16.360 like a meal, Okay, when you just take a meal, 0:11:16.880 --> 0:11:19.040 you chew up your food, you swallow it, you digest it, 0:11:19.040 --> 0:11:22.040 It goes through your small intestine, blah blah blah, breaks 0:11:22.080 --> 0:11:26.319 down into simple sugars. Proteins break down into amino acids. 0:11:26.320 --> 0:11:29.600 We absorb them through our gut. Right, we've covered that 0:11:29.679 --> 0:11:32.160 a lot on this podcast because we've talked about a lot. 0:11:32.040 --> 0:11:33.880 Of gut bugs. 0:11:34.200 --> 0:11:37.280 But usually that's where we end the conversation is after 0:11:37.320 --> 0:11:41.839 things get absorbed or don't get absorbed into our bloodstream. 0:11:42.000 --> 0:11:42.840 So now we're going. 0:11:42.760 --> 0:11:46.760 To talk about everything that happens after that. So in 0:11:46.800 --> 0:11:51.080 our bloodstream, these nutrients, sugars, amino acids, fatty acids. These 0:11:51.120 --> 0:11:54.040 are what our cells use for energy so that we can. 0:11:53.920 --> 0:11:56.160 Live and grow and exist. 0:11:56.600 --> 0:11:59.160 And one of those sources of energy that our cells 0:11:59.240 --> 0:12:02.600 use is glucus, which is a single sugar, like a 0:12:02.600 --> 0:12:07.160 one sugar molecule. A lot of tissues use other sources 0:12:07.160 --> 0:12:10.600 of energy more than glucose, but some of our tissues, 0:12:10.600 --> 0:12:16.480 including our brain, can pretty much only use glucose, and 0:12:16.520 --> 0:12:18.600 the way that this gets to our tissues is through 0:12:18.679 --> 0:12:22.960 our bloodstream, and so that's what we call plasma glucose. 0:12:23.160 --> 0:12:25.840 That's like the primary source of fuel for our brain 0:12:26.040 --> 0:12:29.600 and some other tissues. And it turns out, for reasons 0:12:29.640 --> 0:12:33.680 that we'll talk about later on, it's very important for 0:12:33.760 --> 0:12:37.560 our bodies to keep really tight control on our plasma 0:12:37.600 --> 0:12:40.520 glucose levels. So the amount of sugar in your blood 0:12:41.000 --> 0:12:43.800 has to be really tightly controlled so that it doesn't. 0:12:43.520 --> 0:12:46.400 Go too high or too low. 0:12:46.600 --> 0:12:49.959 But the problem then is that the majority of our 0:12:50.120 --> 0:12:54.240 intake of energy, like when we eat, happens in discrete 0:12:54.320 --> 0:12:57.800 time periods. It's not like we're eating continuously throughout the day. 0:12:57.840 --> 0:13:00.680 We have periods like overnight where we don't eat at all, 0:13:01.000 --> 0:13:03.760 and then periods like I don't know, Thanksgiving, where we 0:13:03.800 --> 0:13:07.600 eat way too much all at once. So our body 0:13:07.679 --> 0:13:12.000 has to have mechanisms to store excess glucose like right 0:13:12.040 --> 0:13:15.199 after we eat a meal, and then also to liberate 0:13:15.280 --> 0:13:18.880 glucose from storage so that it's available in our bloodstream 0:13:18.960 --> 0:13:22.600 when we haven't eaten or when we're fasting, and it 0:13:22.679 --> 0:13:24.320 has to be able to do this in a very 0:13:24.559 --> 0:13:28.960 narrow window of healthy plasma glucose levels. We can't let 0:13:29.000 --> 0:13:31.439 the blood sugars get too high, and they also can't 0:13:31.440 --> 0:13:36.040 get too low. So the question is how do we 0:13:36.120 --> 0:13:38.200 do this in our bodies? 0:13:39.040 --> 0:13:41.080 The answer is insulin. 0:13:41.640 --> 0:13:44.800 Whatever can we have like a trumpet play? 0:13:44.840 --> 0:13:47.840 Whenever I say insulin in this episode, that would be 0:13:47.880 --> 0:13:48.840 a lot of trumpeting. 0:13:48.960 --> 0:13:50.839 I would think way too many trumpets. 0:13:52.480 --> 0:13:56.479 So, insulin is a peptide that is synthesized in the pancreas. 0:13:56.720 --> 0:14:00.880 Your pancreas is just a really incredible organ It excretes 0:14:01.040 --> 0:14:04.680 a lot of digestive enzymes that allow the breakdown of nutrients, 0:14:05.400 --> 0:14:08.719 and then a whole range of different hormones that enter 0:14:08.760 --> 0:14:11.440 the blood stream and have a variety of effects. But 0:14:11.520 --> 0:14:15.760 one of these major hormones is insulin, and it's secreted 0:14:15.840 --> 0:14:19.960 specifically by these cells called beta cells in response to 0:14:20.240 --> 0:14:27.560 elevated blood glucose levels. And insulin has three or kind 0:14:27.600 --> 0:14:31.920 of four major effects. Number one, what it does is 0:14:32.000 --> 0:14:35.560 suppress the release of glucose from the liver, which is 0:14:35.600 --> 0:14:40.000 one of the main storage sites for extra sugar. It 0:14:40.040 --> 0:14:44.600 also turns on glucose transporters on our muscle tissue and 0:14:44.640 --> 0:14:48.400 our adipose tissue, so that that glucose can actually get 0:14:48.440 --> 0:14:52.640 into our cells and then be stored or used. And 0:14:52.720 --> 0:14:57.160 it also stimulates glycogen synthesis, which is the way that 0:14:57.200 --> 0:14:59.440 our body stores glucose. 0:15:00.240 --> 0:15:02.000 And it does so much. 0:15:03.040 --> 0:15:07.720 It also inhibits the release of free fatty acids, which 0:15:07.760 --> 0:15:10.760 are another one of the major forms of energy that 0:15:10.800 --> 0:15:14.800 our body uses, and it stimulates those to be stored instead, 0:15:14.920 --> 0:15:18.360 so we store fat when we have insulin secretion. 0:15:18.840 --> 0:15:19.680 Okay, gotcha? 0:15:19.880 --> 0:15:22.000 All right, that was a lot I know. 0:15:23.320 --> 0:15:27.320 But the like TLDR of all of that is that 0:15:27.560 --> 0:15:31.000 insulin is a hormone that is secreted when glucose levels 0:15:31.040 --> 0:15:36.240 are high. An insulin's role is to decrease plasma or 0:15:36.320 --> 0:15:38.720 blood levels of glucose in our bodies. 0:15:39.640 --> 0:15:43.320 This is like flashback from teaching IB one fifty or 0:15:43.520 --> 0:15:45.040 one or whatever it is. 0:15:45.400 --> 0:15:50.600 Yeah, it's like way back intro bio biokem oh, yeah, 0:15:50.640 --> 0:15:54.400 but I haven't even gotten to diabetes, right, So the 0:15:54.480 --> 0:15:59.440 question is what is diabetes? And at its core, diabetes 0:15:59.560 --> 0:16:02.760 is a pro problem of insulin. I think that a 0:16:02.760 --> 0:16:05.600 lot of people think of diabetes in terms of glucose, 0:16:05.760 --> 0:16:07.480 they're like diabetes. 0:16:06.920 --> 0:16:09.440 Sugar blah blah blah. 0:16:09.560 --> 0:16:13.360 But diabetes is a problem of insulin. So if insulin's 0:16:13.440 --> 0:16:18.080 normal function is to decrease blood levels of glucose, and 0:16:18.160 --> 0:16:22.960 diabetes is a problem where insulin isn't working correctly, then 0:16:23.360 --> 0:16:26.680 the problem in diabetes is you have too much glucose 0:16:27.000 --> 0:16:31.920 in your bloodstream. H right, Right, So now the episode's 0:16:31.960 --> 0:16:35.480 over and you understand everything about diabetes, uh huh, Okay, 0:16:37.280 --> 0:16:40.120 obviously that's not true. We're going to choose your own 0:16:40.160 --> 0:16:43.000 adventure a little bit here. Okay, er, okay, are you 0:16:43.120 --> 0:16:46.320 ready for this, because there's two things that we still 0:16:46.360 --> 0:16:50.040 need to understand. We need to understand why it's a 0:16:50.120 --> 0:16:53.040 problem that glucose levels get too high, Like what is 0:16:53.080 --> 0:16:56.160 it that's happening? Why is that problematic? And then we 0:16:56.240 --> 0:16:59.600 also need to know how does diabetes actually happen, like 0:17:00.480 --> 0:17:03.600 what is the essential problem in this pathway with insulin 0:17:03.680 --> 0:17:06.800 and glucose? Right, So, which do you want to go 0:17:06.840 --> 0:17:07.479 over first? 0:17:08.800 --> 0:17:09.119 Well? 0:17:10.000 --> 0:17:13.120 I think the problems. 0:17:12.960 --> 0:17:17.840 Okay, like what happens with the problem with insulin? Yeah, exactly, Okay, great, 0:17:18.560 --> 0:17:23.280 great answer. Erin everyone is probably well aware that there 0:17:23.280 --> 0:17:27.160 are multiple different types of diabetes, which have a number 0:17:27.160 --> 0:17:29.080 of different names that I'm guessing you're probably going to 0:17:29.160 --> 0:17:31.160 go into and a little bit right erin. 0:17:31.200 --> 0:17:35.959 I mean only actually very briefly. Okay, that's fine for 0:17:36.080 --> 0:17:39.280 most of the history, I just say diabetes. 0:17:39.600 --> 0:17:40.600 Oh, that's fair. 0:17:41.280 --> 0:17:44.800 Well, the different types of diabetes, it is really important 0:17:44.840 --> 0:17:47.840 to understand the distinctions between them, so we'll. 0:17:47.560 --> 0:17:48.640 Go over it here. 0:17:49.440 --> 0:17:52.320 But essentially, the way that we classify it today is 0:17:52.600 --> 0:17:56.840 type one diabetes, type two diabetes, and then there's like 0:17:56.960 --> 0:18:00.679 gestational diabetes, and there's a few other more rare, so 0:18:00.720 --> 0:18:02.760 we're going to focus on type one and type two. 0:18:04.119 --> 0:18:09.200 So type one diabetes in general results from a destruction 0:18:09.720 --> 0:18:14.960 of the beta cells of the pancreas, usually from auto antibodies. 0:18:15.119 --> 0:18:20.200 So type one diabetes is an autoimmune condition where our 0:18:20.240 --> 0:18:24.639 bodies start to make antibodies against our own pancreas as 0:18:24.720 --> 0:18:27.960 beta cells, which are so important because they produce and 0:18:28.000 --> 0:18:32.439 secrete insulin, and these antibodies destroy those beta cells. 0:18:33.480 --> 0:18:38.520 What do we know of the triggers for this autoimmune reaction? 0:18:39.160 --> 0:18:46.639 Really good question, arin we don't, okay, So there is 0:18:46.680 --> 0:18:51.600 a genetic component to type one diabetes, However, what is 0:18:51.680 --> 0:18:56.760 interesting is that the genetic links with type one diabetes, 0:18:57.200 --> 0:19:00.879 it's not like a hereditary disease. Genetic links are not 0:19:01.000 --> 0:19:04.840 nearly as strong actually as in type two diabetes, for example. 0:19:05.200 --> 0:19:06.000 Oh interesting. 0:19:06.440 --> 0:19:10.280 Yeah, So while there are these genetic factors that certainly 0:19:10.280 --> 0:19:15.040 play a role, it's also environmental factors, and we don't 0:19:15.119 --> 0:19:18.440 know exactly what those environmental factors are that then lead 0:19:18.520 --> 0:19:21.479 to this autoimmune disease. There's a lot of thought that 0:19:21.560 --> 0:19:26.240 maybe it's viral involvement, like in people with certain susceptible genotypes, 0:19:26.560 --> 0:19:32.000 exposure to certain viruses or certain other environmental conditions trigger 0:19:32.160 --> 0:19:35.800 this autoimmune response that then leads to type one diabetes. 0:19:36.359 --> 0:19:41.280 But which viruses, great question, We don't know. People have proposed, 0:19:41.320 --> 0:19:44.000 like name a virus. It's probably been proposed as a 0:19:44.040 --> 0:19:48.040 potential cause, especially viruses that are really common epstein bar definitely, 0:19:48.119 --> 0:19:53.960 CMV absolutely all of us. Next one influenza, Yeah, influenza 0:19:54.000 --> 0:19:56.959 I think has been on that list too, But nothing 0:19:57.040 --> 0:19:59.240 that's like a strong association to be able to pin 0:19:59.320 --> 0:20:05.680 down one specif virus. Yeah. But in short, because of this, 0:20:06.040 --> 0:20:10.800 type one diabetes results from a complete inability to make insulin, 0:20:11.200 --> 0:20:14.480 So no insulin in your body means nothing to bring 0:20:14.600 --> 0:20:18.280 down those blood glucose levels, nothing to signal your body 0:20:18.320 --> 0:20:21.840 to store that glucose or allow that glucose into our 0:20:21.880 --> 0:20:26.000 cells so that we can actually use it. And for 0:20:26.040 --> 0:20:28.520 the most part, this disease tends to happen on a 0:20:28.560 --> 0:20:33.040 pretty quick timescale, especially when it happens in kids or adolescents, 0:20:34.040 --> 0:20:38.480 like the process of starting to generate these antibodies and 0:20:38.520 --> 0:20:41.040 then the slow destruction of these beta cells and then 0:20:41.040 --> 0:20:45.760 the onset of diabetes symptoms happens pretty rapidly. It can 0:20:45.880 --> 0:20:48.480 happen in adults as well, and then it tends to 0:20:48.480 --> 0:20:50.840 be a bit slower of a course, and we don't 0:20:50.840 --> 0:20:54.320 know why. Okay, So that's type one diabetes and kind 0:20:54.320 --> 0:20:55.840 of the underlying causes. 0:20:57.160 --> 0:20:58.439 You look like you have a question. 0:20:58.800 --> 0:21:00.720 Well, I don't know if it's something that you're going 0:21:00.800 --> 0:21:04.680 to go over in the other path of m choose 0:21:04.720 --> 0:21:05.480 my own adventure. 0:21:05.640 --> 0:21:07.800 Well, okay, then let's wait, and if you still have 0:21:07.880 --> 0:21:09.080 it at the end, then ask it. 0:21:09.240 --> 0:21:12.320 Okay, just like, hold all questions till the end of 0:21:12.359 --> 0:21:14.160 the presentation, please. 0:21:14.920 --> 0:21:16.360 And then it'll be more of a comment. 0:21:16.800 --> 0:21:19.840 Yep, all right. 0:21:19.920 --> 0:21:22.360 So type two diabetes is. 0:21:22.320 --> 0:21:27.320 A bit more complicated than that. Type two diabetes results 0:21:27.359 --> 0:21:32.960 from a combination of different things, including beta cell dysfunction, 0:21:33.680 --> 0:21:35.840 but not necessarily destruction. 0:21:36.640 --> 0:21:41.000 What's the difference between dysfunction and disruption, just like producing 0:21:41.160 --> 0:21:42.119 less insulin? 0:21:42.720 --> 0:21:46.800 Right, yeah, so either producing like not great insulin or 0:21:46.880 --> 0:21:50.080 just not being able to produce enough insulin or making 0:21:50.119 --> 0:21:53.720 insulin but not being able to secrete it. Whereas in 0:21:53.800 --> 0:22:00.000 type one diabetes, your beta cells are obliterated, They're gone, right, Okay, Yeah, 0:22:00.480 --> 0:22:04.880 So it's a combination of beta cell dysfunction and insulin resistance. 0:22:05.160 --> 0:22:09.160 So you have insulin, you're making insulin, but your tissues 0:22:09.200 --> 0:22:11.800 are not responding to it the way that they're supposed to. 0:22:13.080 --> 0:22:17.159 So what does that really mean? Right? It means that 0:22:17.240 --> 0:22:20.040 in general, people with type two diabetes have either one 0:22:20.200 --> 0:22:24.280 or both of two different problems going on. Problem one, 0:22:24.320 --> 0:22:26.800 like I said, their beta cells are not making enough 0:22:26.840 --> 0:22:29.840 insulin for whatever reason, they just stop being able to 0:22:30.440 --> 0:22:35.600 produce enough insulin or secrete that insulin into this bloodstream. 0:22:36.240 --> 0:22:40.879 Or problem number two, their tissues become resistant to these effects. 0:22:41.080 --> 0:22:45.719 So then the pancreas secretes more and more insulin. So 0:22:45.760 --> 0:22:49.440 what we actually see is a hyper insulinemia. That means 0:22:49.520 --> 0:22:52.679 you have a lot of insulin in your bloodstream, but 0:22:52.760 --> 0:22:57.000 it's not being used properly and so it's not effective. 0:22:57.080 --> 0:23:00.600 And therefore you still have too much glucose in your bloodstream. 0:23:01.000 --> 0:23:03.160 So you just have like a bunch of like insulin 0:23:03.280 --> 0:23:06.679 and glucose, you know, circulating around. So what does it 0:23:06.800 --> 0:23:11.280 mean that your tissues are no longer responding to insulin 0:23:11.440 --> 0:23:13.520 in the right way? Like what's going on there? 0:23:13.800 --> 0:23:14.639 Yeah, good question. 0:23:14.800 --> 0:23:17.919 A whole bunch of different things. In part, it's that 0:23:18.119 --> 0:23:21.720 you actually can see down regulation of the number of 0:23:21.960 --> 0:23:26.920 glucose receptors on tissues. So glucose has to be actively 0:23:26.920 --> 0:23:30.560 transported into your skeletal muscle and your adipose tissue. It 0:23:30.600 --> 0:23:33.280 can't just like legle its way in there. And so 0:23:33.520 --> 0:23:37.159 in type two diabetes, you can have less receptors on 0:23:37.240 --> 0:23:42.119 those cells, like they progressively get lower, or like a 0:23:42.119 --> 0:23:43.800 whole host of other things can happen. 0:23:43.800 --> 0:23:45.240 But that's kind of the main ones. 0:23:46.560 --> 0:23:49.000 But why, Okay, we'll get to the why. 0:23:49.280 --> 0:23:53.840 Okay, hopefully maybe maybe Okay, okay, we'll approach the why. 0:23:54.400 --> 0:23:58.639 But yeah, we'll we'll slowly get to the y. But 0:23:58.760 --> 0:24:01.440 one question, because because in many. 0:24:01.080 --> 0:24:05.040 Cases we actually see both of these things happening simultaneously. 0:24:05.680 --> 0:24:09.160 So then there comes this question of which comes first. 0:24:10.520 --> 0:24:12.119 So the way that I like to think of it, 0:24:12.200 --> 0:24:15.400 and again this is very simplified, but I think it's 0:24:15.480 --> 0:24:18.560 kind of a just a nice framework to have, is 0:24:18.600 --> 0:24:22.359 that as you start to have this increase in insulin resistance, 0:24:22.760 --> 0:24:28.840 so your tissues are down regulating the amount of receptors 0:24:28.880 --> 0:24:31.880 that they have so that the glucose can't get into 0:24:31.920 --> 0:24:35.800 the tissues, you have an increase in insulin resistance, and 0:24:35.800 --> 0:24:39.240 your pancreas recognizes this and it's like, gosh, we have 0:24:39.359 --> 0:24:42.720 just so much glucose running around. So your pancreas is 0:24:42.760 --> 0:24:46.639 working really hard, like working overtime, to make more and 0:24:46.760 --> 0:24:51.520 more insulin, and that then causes your tissues to become 0:24:51.640 --> 0:24:55.399 even more desensitized to that insulin because they're just overloaded. 0:24:55.480 --> 0:24:58.560 It's like insulin overload, there's so much of it. So 0:24:58.600 --> 0:25:01.720 then your pancreas makes even more and then eventually your 0:25:01.720 --> 0:25:05.440 pancreas is just exhausted because it's been working overtime for 0:25:05.480 --> 0:25:07.919 so long that it starts to just give up and 0:25:07.960 --> 0:25:11.280 then either making cruddy insulin or just not making insulin 0:25:11.359 --> 0:25:13.520 or not secreting it. Like, what's the point You're not 0:25:13.560 --> 0:25:16.280 going to even respond to it, I'm gonna quit. So 0:25:16.359 --> 0:25:20.240 now you have both problem one and problem to problem 0:25:20.320 --> 0:25:23.560 to exacerbating problem one and causing this vicious cycle. 0:25:24.520 --> 0:25:27.159 What's the timeline for that to happen? 0:25:27.720 --> 0:25:30.520 That's a good question, and it's hard to put an 0:25:30.520 --> 0:25:34.200 actual timeline on it, especially because when you look at 0:25:34.240 --> 0:25:37.600 like a population level, there are a whole lot of 0:25:37.600 --> 0:25:40.840 people who have what is sometimes called pre diabetes or 0:25:40.960 --> 0:25:43.679 just I forget the other proper term for it, but 0:25:43.720 --> 0:25:48.439 it's like increased fasting glucose levels where they have this 0:25:48.840 --> 0:25:53.919 higher than what is considered typical baseline glucose. And so 0:25:54.600 --> 0:25:57.200 some of those people will then progress to type two diabetes, 0:25:57.240 --> 0:26:00.920 some people won't, and some people have like both problems 0:26:00.920 --> 0:26:03.240 going on. Some people maybe have only a little of one. 0:26:03.280 --> 0:26:06.760 So type two diabetes is very complicated. 0:26:06.960 --> 0:26:11.400 Interesting, and so when it comes to type two, part 0:26:11.400 --> 0:26:14.800 of the problem is like the resistance seems like the 0:26:14.800 --> 0:26:18.720 biggest part to target for treatment, right, Like how do 0:26:18.760 --> 0:26:23.000 you reduce resistance because it seems like that's sort of 0:26:23.000 --> 0:26:27.080 what's contributing to the pancreas just being overloaded and like poof, 0:26:27.160 --> 0:26:28.280 I can't do this anymore. 0:26:28.840 --> 0:26:31.600 Yeah, that's a good thought, and we actually have a 0:26:31.680 --> 0:26:34.040 lot of medicines that do exactly that to try and 0:26:34.320 --> 0:26:37.240 make your tissues more sensitive to the effects of insulin, 0:26:38.480 --> 0:26:42.040 and that is for some people, really good treatment for diabetes. 0:26:42.960 --> 0:26:46.320 But we'll just have to keep talking because there's more 0:26:46.440 --> 0:26:47.520 to the story. 0:26:48.480 --> 0:26:53.000 Excellent, love that song, my favorite track. 0:26:53.119 --> 0:26:55.840 I just made it up just right off the top 0:26:55.880 --> 0:26:58.040 of my head. All right, So now let's talk Now 0:26:58.040 --> 0:27:01.960 that we understand the underlying problem with these two different 0:27:02.000 --> 0:27:06.040 types of diabetes, let's talk about what the symptoms of 0:27:06.119 --> 0:27:08.639 these diseases are, and then we'll finally get to that 0:27:08.800 --> 0:27:10.879 second part of the Choose your Own adventure, which is 0:27:10.960 --> 0:27:15.200 like understanding why this high glucose is a problem, because 0:27:15.200 --> 0:27:21.520 that really is what drives the symptoms, right so classically, 0:27:21.880 --> 0:27:26.360 especially with type one diabetes. However, all of these symptoms 0:27:26.400 --> 0:27:28.320 that I'm going to talk about can happen with type 0:27:28.320 --> 0:27:32.280 one or type two diabetes. But because type one tends 0:27:32.320 --> 0:27:34.960 to happen faster and type two tends to be a 0:27:35.040 --> 0:27:40.879 much longer course, the more acute symptoms tend to happen 0:27:40.920 --> 0:27:44.840 more in type one diabetes, and the chronic complications can 0:27:44.880 --> 0:27:49.800 happen in both, but certainly in type two diabetes. So classically, 0:27:50.119 --> 0:27:53.520 somebody with diabetes presents with what is often called the 0:27:53.640 --> 0:28:01.119 three p's, that is, polyurea, polydipsia, and polyph phasia, and 0:28:01.200 --> 0:28:04.600 also weight loss. So what do those mean and how 0:28:04.600 --> 0:28:08.280 does it happen? So as your blood glucose levels rise, 0:28:08.880 --> 0:28:12.280 eventually your kidney, which is responsible for filtering everything in 0:28:12.320 --> 0:28:15.840 your blood, just can't filter all of that glucose and 0:28:15.880 --> 0:28:18.199 get it back into your bloodstream because there's just so 0:28:18.320 --> 0:28:22.200 much of it. So your kidney starts excreting glucose. After 0:28:22.359 --> 0:28:24.240 your blood levels reach about one point eighty. 0:28:24.359 --> 0:28:24.960 It just starts. 0:28:25.240 --> 0:28:28.639 You start peeing out sugar, hence the. 0:28:28.680 --> 0:28:31.119 Name I'm quarantine sweetpee. 0:28:32.680 --> 0:28:38.120 And glucose. Just like lactose does in our guts see 0:28:38.160 --> 0:28:42.920 our lactose intolerance episode. Glucose is an osmodic diuretic, so 0:28:42.960 --> 0:28:46.320 it holds onto the water along with it. So now 0:28:46.360 --> 0:28:49.840 you're peeing out a ton of water because your kidneys 0:28:49.840 --> 0:28:52.880 aren't holding onto the glucose or the water. So that's 0:28:52.880 --> 0:28:59.160 the first P polyuria, which leads unsurprisingly to massive dehydration, 0:28:59.360 --> 0:29:03.640 causing the set second P polydipsia, which means major increase 0:29:03.680 --> 0:29:09.160 in thirst, like unquenchable thirst. And at the same time, 0:29:09.400 --> 0:29:13.160 the lack of insulin in your body, which is driving 0:29:13.200 --> 0:29:16.360 all of this, essentially means that your body is unable 0:29:16.400 --> 0:29:18.680 to use any of the glucose that you have in 0:29:18.720 --> 0:29:22.800 your bloodstream. So while you technically have plenty of fuel, 0:29:23.280 --> 0:29:26.480 your body thinks that it's in starvation mode, and so 0:29:26.680 --> 0:29:31.400 it switches to what's called catabolic metabolism, and that is 0:29:31.520 --> 0:29:35.120 breaking down your tissues to use for fuel, which leads 0:29:35.160 --> 0:29:39.920 to major hunger. That is polyphasia the third P. But 0:29:40.040 --> 0:29:43.160 despite this, you see weight loss because you're literally eating 0:29:43.200 --> 0:29:47.320 your own body tissues to use as fuel, really really 0:29:47.480 --> 0:29:51.400 bad things, very bad things. And then you have other 0:29:51.480 --> 0:29:55.720 symptoms like fatigue unsurprising because this is taking a major 0:29:55.760 --> 0:29:59.600 toll on your body, blurry vision, muscle cramps because you're 0:29:59.600 --> 0:30:05.600 electric lights are way out of whack, et cetera. And 0:30:05.680 --> 0:30:10.560 when this gets very severe, which happens in about twenty 0:30:10.600 --> 0:30:14.280 to forty percent of cases in people like presenting for 0:30:14.320 --> 0:30:18.080 the first time with something like type one diabetes, it's 0:30:18.120 --> 0:30:20.040 called diabetic keto acidosis. 0:30:20.080 --> 0:30:21.479 A lot of people have probably heard of this. 0:30:23.120 --> 0:30:25.520 It is exactly what the name implies. 0:30:26.480 --> 0:30:30.000 So I just I just looked this up to clarify 0:30:30.080 --> 0:30:33.240 something and that I had popped into my head, and 0:30:34.320 --> 0:30:37.280 I remember, do you ever see the movie Steel Magnolias, 0:30:37.680 --> 0:30:39.000 you know, Julia Roberts. 0:30:39.000 --> 0:30:40.840 I have never seen Steel Magnolias. 0:30:40.880 --> 0:30:43.440 Okay, well, you know, I hope this isn't too much 0:30:43.480 --> 0:30:46.920 of a spoiler, but there's definitely Julia Roberts play someone 0:30:46.920 --> 0:30:50.440 who has type one diabetes, and there's like I thought 0:30:50.760 --> 0:30:54.760 it was a keto acidosis like attack. No, it was 0:30:54.800 --> 0:30:59.760 actually hypoglycemia. And but I need to rewatch that movie 0:31:00.320 --> 0:31:02.600 now after doing this episode. 0:31:02.760 --> 0:31:05.040 Well, you saying that just made me think of Honey, 0:31:05.160 --> 0:31:07.920 I shrunk the is it, honey, we shrunk ourselves. 0:31:08.280 --> 0:31:11.920 I think it's number three? Yeah, and number three is 0:31:11.920 --> 0:31:12.400 the baby. 0:31:12.520 --> 0:31:15.400 But I don't remember what banana. I just he needs 0:31:15.440 --> 0:31:18.360 bananas because of the potassium. But is that because he's diabetic, 0:31:18.400 --> 0:31:21.160 because you do need potassium? I think so, I don't 0:31:21.160 --> 0:31:24.640 know anyways, that that's is. 0:31:25.880 --> 0:31:29.600 There are many of them, I believe, all right. 0:31:29.680 --> 0:31:34.960 So diabetic ketoacidosis. So if you're thinking about that classic 0:31:35.040 --> 0:31:38.280 presentation that I talked about as that can kind of 0:31:38.320 --> 0:31:42.320 progress if it goes unrecognized, or if somebody has like 0:31:42.360 --> 0:31:46.960 a low level of that going on the three p's 0:31:47.720 --> 0:31:50.479 and then they get some other stressor on top of it, 0:31:50.560 --> 0:31:54.200 like an infection or just something that stresses their body out, 0:31:55.360 --> 0:31:59.320 as that person becomes even more dehydrated and just continue 0:31:59.320 --> 0:32:02.680 this process of breaking down their fat stores. Their liver 0:32:02.800 --> 0:32:07.720 then starts this process of ketogenesis. Ketones can be used 0:32:07.720 --> 0:32:12.000 by the brain as an alternative source of fuel. However, 0:32:13.080 --> 0:32:15.760 they are an acid and therefore lead to the blood 0:32:15.800 --> 0:32:23.440 becoming acidotic, which because of dehydration, is compounded by lactic acidosis, 0:32:23.840 --> 0:32:28.000 which then further worsens kidney function, which makes it even 0:32:28.040 --> 0:32:31.320 harder to excrete those keto acids because that's one of 0:32:31.320 --> 0:32:36.040 your kidney's jobs. And this acidemia can eventually lead to 0:32:36.120 --> 0:32:40.800 brain damage. And on top of that, your body compensates 0:32:41.440 --> 0:32:45.360 via respiration to try and make your blood alkalolotic by 0:32:45.600 --> 0:32:49.720 something called cousmall breathing, which is essentially hyperventilation, which can 0:32:49.800 --> 0:32:51.640 then lead to coma and death. 0:32:52.120 --> 0:32:55.800 It's very severe, Okay, So when people refer to a 0:32:55.880 --> 0:32:59.280 diabetic coma, it's ketoacidosis like it. 0:32:59.640 --> 0:33:03.640 Very often, Yes, it can be Okay, Yeah, so that's 0:33:03.720 --> 0:33:08.680 kind of the acute complications of diabetes type one or 0:33:08.720 --> 0:33:12.640 type two. But those tend to happen more in type one. 0:33:13.200 --> 0:33:16.680 But certainly somebody with undiagnosed type two diabetes might have 0:33:16.760 --> 0:33:21.640 symptoms like a little bit of polydipsia, maybe some polyuria. 0:33:21.280 --> 0:33:21.760 Et cetera. 0:33:22.920 --> 0:33:27.280 So now let's think of it in terms of long term. 0:33:28.400 --> 0:33:31.120 Why is having too much sugar in your blood bad 0:33:31.400 --> 0:33:34.760 long term? And a lot of people might know of 0:33:34.800 --> 0:33:38.600 some of the common kind of side effects of diabetes. Aaron, 0:33:38.800 --> 0:33:40.760 do you know some of them just off the top 0:33:40.760 --> 0:33:41.240 of your head. 0:33:41.600 --> 0:33:44.600 I mean, I know that kidney disease is a big problem. 0:33:44.720 --> 0:33:47.959 I know ulcers are a big problem, Like amputations are 0:33:48.000 --> 0:33:55.120 really common. Blindness or retinopathy is really common, I think, 0:33:55.280 --> 0:33:58.320 just like loss of sensation in your extremities. 0:33:58.440 --> 0:33:59.960 Yeah, yeah, peripheral neuropathy. 0:34:00.520 --> 0:34:03.960 Yeah, and all of those things that you just talked about, 0:34:04.120 --> 0:34:08.200 plus the cardiovascular risk, so risk of clots, especially in 0:34:08.239 --> 0:34:09.280 your heart or your brain. 0:34:09.760 --> 0:34:11.680 Right, heart attacks are really common too. 0:34:11.840 --> 0:34:12.600 Yeah. 0:34:12.640 --> 0:34:15.040 All of those can be split into kind of two 0:34:15.160 --> 0:34:20.400 different but very similar processes. Those are microvascular complications, so 0:34:20.600 --> 0:34:26.400 small blood vessel problems and macrovascular complications, so large blood vessels, 0:34:26.480 --> 0:34:30.799 heart brain, okay, But either way we're dealing with vascular 0:34:30.920 --> 0:34:35.480 complications and in some cases direct damage to nerves as 0:34:35.520 --> 0:34:39.399 well as blood vessels. So the question is like how 0:34:39.440 --> 0:34:44.239 exactly do these complications occur, and that is probably the 0:34:44.280 --> 0:34:49.560 subject of many different PhDs worth of research, But in general, 0:34:50.360 --> 0:34:54.120 chronically having way too much glucose in your bloodstream leads 0:34:54.160 --> 0:34:59.200 to a state of chronic inflammation. This then leads to 0:34:59.239 --> 0:35:03.319 the production of reactive oxygen species, which we've talked about 0:35:03.320 --> 0:35:06.600 a number of times on the podcast, which are basically 0:35:06.680 --> 0:35:09.880 things that then cause a bunch of tissue damage, especially 0:35:10.040 --> 0:35:13.960 in blood vessels, causing vascular injury, and that can lead 0:35:13.960 --> 0:35:16.600 to all of those complications that you mentioned, Aaron. So 0:35:16.719 --> 0:35:20.759 it has major effects on the kidneys, especially if you 0:35:20.760 --> 0:35:22.840 think about it, this is where all of that glucose 0:35:22.880 --> 0:35:25.719 is going and the kidneys are filtering everything in your bloodstream, 0:35:27.239 --> 0:35:31.600 so kidney damage is a major one. Blindness is caused 0:35:31.640 --> 0:35:34.960 from retinopathy where you have damage to the nerves of 0:35:35.000 --> 0:35:39.719 the eye and also increased blood vessel formation that leads 0:35:39.760 --> 0:35:45.720 to increased pressures behind the eye. The peripheral neuropathies, which 0:35:45.719 --> 0:35:48.319 can lead to a loss of sensation that can then 0:35:48.440 --> 0:35:53.719 lead to injuries that are complicated by poor perfusion because 0:35:53.760 --> 0:35:56.640 those blood vessels are damaged, So then those ulcers don't 0:35:56.680 --> 0:35:59.719 heal because they don't have any blood flow, so then 0:35:59.760 --> 0:36:03.000 they become gangrenous, and then yes, you have to do amputations. 0:36:03.480 --> 0:36:05.600 It seems like there are parts of the body that 0:36:05.680 --> 0:36:11.200 are more sensitive to this. Kidneys make sense because they're 0:36:11.640 --> 0:36:14.399 having a difficult time with the filtration. Heart makes sense 0:36:14.440 --> 0:36:19.080 because blood blah blah blah. What about like your stomach 0:36:19.600 --> 0:36:24.560 or like you know, other organs, I mean, what's going 0:36:24.600 --> 0:36:25.160 on with those? 0:36:25.360 --> 0:36:26.600 Yeah, great question. 0:36:27.040 --> 0:36:30.240 I think a lot of people think that diabetes, oh, 0:36:30.360 --> 0:36:34.080 your kidneys, your eyes. Diabetes is a disease that affects 0:36:34.239 --> 0:36:38.680 every single organ in your body. So your stomach, Diabetes 0:36:38.760 --> 0:36:42.040 can affect your autonomic nervous system as well as your 0:36:42.080 --> 0:36:46.080 peripheral nerves, and that damage, along with a host of 0:36:46.120 --> 0:36:49.160 other things, can lead to delayed gastric emptying. So it 0:36:49.200 --> 0:36:51.760 can cause your stomach to not be able to contract 0:36:51.840 --> 0:36:54.160 the way that it's supposed to so that you can 0:36:54.200 --> 0:36:57.239 actually get your food to empty from your stomach, which 0:36:57.280 --> 0:37:00.840 can lead to a whole host of problems. So, yeah, 0:37:00.960 --> 0:37:04.600 diabetes affects every part of your body. It has the 0:37:04.640 --> 0:37:08.320 greatest effects and the earliest effects on small blood vessels. 0:37:08.520 --> 0:37:09.560 That's why we see. 0:37:09.320 --> 0:37:13.640 Things like neuropathy or retinopathy because those are really small vessels. 0:37:14.440 --> 0:37:17.440 But then it also has the potential to have complications 0:37:17.440 --> 0:37:21.719 on larger vessels like your heart, your brain. It affects 0:37:22.160 --> 0:37:23.560 the entirety. 0:37:23.120 --> 0:37:23.760 Of your body. 0:37:24.360 --> 0:37:33.040 Yeah, okay, that makes sense, and that's the biology of diabetes. Erin, uh, 0:37:33.080 --> 0:37:37.440 did we get to the why? I've been waiting? 0:37:37.719 --> 0:37:39.360 I know you have been waiting. 0:37:40.960 --> 0:37:44.319 We don't have a great answer to the why, but 0:37:45.560 --> 0:37:49.480 I have a guess as to the answer in our 0:37:49.680 --> 0:37:52.000 current events section, so we'll just have to wait. 0:37:52.080 --> 0:37:54.400 Oh okay, all right, okay. 0:37:55.080 --> 0:37:58.120 So Aaron, tell me what do we know about this? 0:37:58.280 --> 0:38:00.760 I assume it's been with us since forever. 0:38:02.600 --> 0:38:38.600 Yeah, let's start back at forever right after this break. 0:38:39.440 --> 0:38:44.000 All right, So this is a long episode so far. 0:38:45.520 --> 0:38:48.400 I'm going to add to that. I'm going to do 0:38:48.440 --> 0:38:52.279 something a little bit different for this episode, and that 0:38:52.480 --> 0:38:57.440 is to divide the history section into two parts, not 0:38:57.719 --> 0:39:01.840 like sequential chapters, you know, like happened and then this happened, 0:39:02.000 --> 0:39:05.920 but more like parallel histories in a way awesome. And 0:39:06.000 --> 0:39:08.440 for this first part, I'm going to focus on the 0:39:08.480 --> 0:39:11.680 standard history that I usually cover for a disease. You know, 0:39:11.800 --> 0:39:16.440 things like early writings, increasing recognition of the condition, and 0:39:16.600 --> 0:39:20.799 medical advancements, especially when it comes to diabetes, the discovery 0:39:20.840 --> 0:39:24.000 of insulin, you know, all the things that like completely 0:39:24.120 --> 0:39:28.480 changed the landscape of diabetes, especially in the twentieth century. 0:39:29.520 --> 0:39:32.080 And then for part two, I really want to go 0:39:32.200 --> 0:39:36.120 through the other transformation that diabetes went through around that 0:39:36.200 --> 0:39:40.400 same time, and that is the social perception or portrayal 0:39:40.520 --> 0:39:44.040 of the disease, especially focusing on the US. 0:39:44.560 --> 0:39:50.240 Excellent. I can't wait, alrighty. 0:39:49.880 --> 0:39:53.760 So let's begin at the beginning. It probably doesn't surprise 0:39:53.880 --> 0:39:58.200 you to know that diabetes has long been recognized by 0:39:58.320 --> 0:40:03.560 many different ancient cultures. You went through the symptoms of diabetes, 0:40:03.800 --> 0:40:08.680 and especially for the like acute symptoms, and they're pretty 0:40:08.760 --> 0:40:13.359 recognizable and unique, so it makes sense that they were 0:40:13.360 --> 0:40:17.319 written about at length for thousands of years. It was 0:40:17.440 --> 0:40:23.520 mentioned in the Ebres Papyrus, my favorite, in the form 0:40:23.600 --> 0:40:26.400 of a treatment for a symptom of the disease. So 0:40:26.600 --> 0:40:29.560 quote a medicine to drive away the passing of too 0:40:29.640 --> 0:40:33.600 much urine, and in the sixth century BCE, the Hindu 0:40:33.640 --> 0:40:38.480 physician Sushruda described a disease of honey urine which could 0:40:38.520 --> 0:40:43.319 be detected either through tasting it directly or by observing 0:40:43.400 --> 0:40:48.719 ants gathering around a pool of urine ooh yeah. And 0:40:48.760 --> 0:40:52.120 the word diabetes itself comes from the second century CE, 0:40:52.680 --> 0:40:56.279 when the ancient Greek physician Aretaeus coined it from the 0:40:56.320 --> 0:41:01.359 Greek word for to run through or pipe like. He 0:41:01.440 --> 0:41:05.200 also described the disease as quote melting down of the 0:41:05.239 --> 0:41:10.600 flesh and limbs into urine, and the word melodis, from 0:41:10.840 --> 0:41:14.680 the Latin word for honey or sweet, was added later 0:41:14.760 --> 0:41:19.360 on to again indicate the sweetness of the urine. Galen 0:41:19.520 --> 0:41:23.200 around the same time as Aretaeus described it as quote 0:41:23.239 --> 0:41:28.440 diarrhea of urine, and Avicenna in the tenth century CE 0:41:28.680 --> 0:41:31.960 wrote a thorough description of the disease and its complications. 0:41:32.840 --> 0:41:36.319 So the sweetness of the urine had long been recognized. 0:41:36.360 --> 0:41:40.480 The sweet pea was people were very familiar with it, 0:41:41.040 --> 0:41:44.360 but it wasn't until the sixteen hundreds that a physician 0:41:44.440 --> 0:41:49.400 in Liverpool named Matthew Dobson realized that it was actually 0:41:49.480 --> 0:41:54.400 sugar causing the sweetness. He made the observation when treating 0:41:54.440 --> 0:41:58.520 a patient who was urinating fifteen liders of fluid a day. Oh, 0:41:58.840 --> 0:42:01.719 so to like, because I think when we say, oh, 0:42:01.760 --> 0:42:04.759 you pee a lot, like, what does that actually mean? Right? 0:42:04.760 --> 0:42:08.240 And so this person was peeing fifteen leaders of fluid 0:42:08.280 --> 0:42:09.759 a day. That is. 0:42:11.960 --> 0:42:12.760 Way too much. 0:42:13.600 --> 0:42:16.840 Oh yeah, we just have a little we have a 0:42:16.840 --> 0:42:17.640 little sidebar. 0:42:18.360 --> 0:42:20.640 Yeah, to do a little calculation. 0:42:21.440 --> 0:42:23.520 Who was really boring, So we had to cut it. 0:42:23.640 --> 0:42:28.279 But for reference, a typical amount of urine output is 0:42:28.320 --> 0:42:33.719 between eight hundred and about two thousand millileaders or two 0:42:33.880 --> 0:42:36.719 leaders a day a day. 0:42:38.880 --> 0:42:44.200 Yeah, ooh yeah, so we've been talking about sweet pea 0:42:44.840 --> 0:42:49.360 and yeah, I mean people did have to taste it like. 0:42:49.400 --> 0:42:53.279 That was how a lot of the diagnoses were made, 0:42:53.880 --> 0:42:58.160 you know, mostly were made, but at least one doctor 0:42:59.000 --> 0:43:05.000 successfully fermented the urine to produce what he described as 0:43:05.040 --> 0:43:08.120 like a weak beer urine beer. Yeah. 0:43:08.160 --> 0:43:09.480 That should have been our quarantine. 0:43:09.719 --> 0:43:14.120 That should have been our quarantini. And this taste test 0:43:14.280 --> 0:43:18.600 remained the main way of diagnosing someone with diabetes until 0:43:18.640 --> 0:43:22.600 the eighteen hundreds, when chemical tests were developed to detect 0:43:22.680 --> 0:43:27.000 and measure glucose in the urine, much to many physicians relief. 0:43:27.120 --> 0:43:32.200 I am sure around the time that these tests were developed, 0:43:32.280 --> 0:43:36.120 the medical world was undergoing a pretty big transformation in 0:43:36.200 --> 0:43:40.680 terms of our understanding of disease. Yes, I'm bringing up 0:43:40.719 --> 0:43:45.600 germ theory in the history of diabetes, oh okay. But 0:43:45.880 --> 0:43:50.360 as researchers and clinicians learned about infectious diseases and applied 0:43:50.360 --> 0:43:54.520 that knowledge to prevention, a lot of chronic diseases grew 0:43:54.640 --> 0:43:59.560 more visible as morbidity and mortality from infectious diseases dropped 0:44:00.520 --> 0:44:04.280 right and when they did, they grabbed some research attention 0:44:04.360 --> 0:44:08.320 to themselves. So from the middle of the eighteen hundreds 0:44:08.760 --> 0:44:12.520 it was increasingly recognized that the pancreas played some role 0:44:12.560 --> 0:44:15.759 in the disease, thanks to the rise in autopsies that 0:44:15.880 --> 0:44:20.800 had been happening that showed that damaged pancreases were often 0:44:20.840 --> 0:44:25.359 found in people with diabetes, and in eighteen eighty nine 0:44:25.840 --> 0:44:30.719 at the University of Strasbourg, two researchers named Oscar Minkowski 0:44:30.840 --> 0:44:34.960 and Joseph von Mehring showed this experimentally that the pancreas 0:44:35.040 --> 0:44:39.800 was involved when they induced diabetes in a dog after 0:44:40.200 --> 0:44:44.200 removing its pancreas, and it was all over that like, 0:44:44.280 --> 0:44:47.279 peeing everywhere in the lab and I'll do it. Minkowski 0:44:47.400 --> 0:44:49.759 was like, what's going on. I'm so annoyed. This dog 0:44:49.880 --> 0:44:52.560 is house trained. Why is it peeing everywhere? Oh my gosh, 0:44:52.600 --> 0:44:59.560 it has diabetes. But how exactly was the pancreas involved 0:45:00.160 --> 0:45:05.080 was happening? Additional experiments removing part of the pancreas or 0:45:05.160 --> 0:45:10.799 grafting bits of a pancreas, showed eventually that the pancreas 0:45:10.800 --> 0:45:16.799 seemed to have two secretions, one external that seemed to 0:45:16.840 --> 0:45:21.399 help with digestion and one internal that went right into 0:45:21.440 --> 0:45:26.560 the bloodstream to help with carbohydrate regulation. But where did 0:45:26.560 --> 0:45:31.560 the internal secretion come from? In nineteen oh one, Eugene 0:45:31.640 --> 0:45:35.640 Opie at Johns Hopkins showed that damage to the islets 0:45:35.680 --> 0:45:39.640 of Langerhans, which were named for their discoverer, that that 0:45:39.760 --> 0:45:45.520 damage prevented the production of this internal secretion, which then 0:45:46.040 --> 0:45:50.600 led researchers to speculate that if this internal secretion, which 0:45:50.680 --> 0:45:54.080 by the way, was totally hypothetical at the time, if 0:45:54.080 --> 0:45:57.160 it could be isolated, it could potentially be used to 0:45:57.239 --> 0:45:58.439 treat diabetes. 0:45:58.600 --> 0:45:59.760 This is so cool. 0:46:00.600 --> 0:46:04.319 It is amazing that people I just can't believe like 0:46:04.360 --> 0:46:07.279 the pancreas, like the functions of the pancreas at a 0:46:07.320 --> 0:46:10.759 time when like bioassays were non existent. 0:46:11.280 --> 0:46:13.799 Right, it's just people being so. 0:46:15.280 --> 0:46:20.440 Kind of intuitive or or maybe it's deductive. I don't know, 0:46:20.560 --> 0:46:22.920 but it's just it's smarter than me. 0:46:25.440 --> 0:46:26.680 I'm so impressed by it. 0:46:27.000 --> 0:46:30.480 Well, I think also, you know, to give a little 0:46:30.480 --> 0:46:36.480 bit more historical context, at the time, this wasn't necessarily 0:46:36.719 --> 0:46:40.680 as huge a leap in thinking as we are looking 0:46:40.719 --> 0:46:43.560 at it to be right, This was actually in line 0:46:43.640 --> 0:46:46.800 with a lot of other medical advancements that were happening 0:46:47.280 --> 0:46:51.640 showing how certain organs produced hormones, like the field of 0:46:51.840 --> 0:46:55.319 you know, endochronology was kind of burgeoning at this time, 0:46:55.840 --> 0:47:00.000 and that it was recognized that these hormones regulated bodily functions, 0:47:00.520 --> 0:47:04.759 and disruptions in the production of these hormones could then 0:47:04.880 --> 0:47:09.200 lead to certain diseases, especially once like you know, germ 0:47:09.239 --> 0:47:11.840 theory was like, all right, let's do the low hanging fruit. 0:47:12.160 --> 0:47:16.320 We got all these diseases, Okay, what are all these now? Like, yeah, 0:47:16.800 --> 0:47:21.600 what's happening? And then in the eighteen nineties it was 0:47:21.640 --> 0:47:25.759 found that giving someone like thyroid extract could actually help 0:47:25.880 --> 0:47:30.080 treat some conditions. So in this line of reasoning, it 0:47:30.440 --> 0:47:34.440 you know, made sense that pancreous extract could possibly do 0:47:34.520 --> 0:47:40.600 the same. But early experiments with these pancreous extracts that 0:47:40.640 --> 0:47:44.480 were performed around the very early nineteen hundreds on humans 0:47:44.560 --> 0:47:48.799 had you know, mixed results. If I'm unsurprising, if I'm 0:47:48.840 --> 0:47:52.960 feeling generous, yep, okay, And if I'm not feeling generous, 0:47:52.960 --> 0:47:57.280 I would say mostly harmful and sometimes outright dangerous okay. 0:47:57.360 --> 0:47:59.840 But in any case, they didn't really suggest that this 0:48:00.200 --> 0:48:03.680 was like a good path forward, like this was not 0:48:03.800 --> 0:48:09.040 the clear way to go. So what was well, Despite 0:48:09.080 --> 0:48:13.279 the growing visibility of diabetes and all these advancements in 0:48:13.480 --> 0:48:18.200 understanding its pathology and being able to diagnose it, one 0:48:18.280 --> 0:48:23.680 area that was sorely lacking was in treatment. Throughout the 0:48:23.719 --> 0:48:26.680 seventeen hundreds and much of the eighteen hundreds, the leading 0:48:26.719 --> 0:48:30.040 treatments for diabetes were basically the same things that you 0:48:30.080 --> 0:48:33.760 would use to treat anything, right, Bleed them and shoot 0:48:33.800 --> 0:48:37.680 them up with opium like that boom. If you know 0:48:37.719 --> 0:48:39.640 how to do those things, you're a doctor. In the 0:48:39.680 --> 0:48:44.440 seventeen hundreds, and there are very few diseases that would 0:48:44.480 --> 0:48:49.759 actually benefit from bleeding, but they do exist hemochromatosis, but 0:48:49.840 --> 0:48:54.040 diabetes was not one of these. Yeah, and opium, of course, 0:48:54.600 --> 0:48:58.800 that isn't going to make diabetes or many things better. 0:48:59.680 --> 0:48:59.719 No. 0:49:00.880 --> 0:49:06.560 No. Diabetes was generally viewed as a disease of downhill progress, 0:49:07.280 --> 0:49:11.279 and for someone diagnosed with what was then known as 0:49:11.400 --> 0:49:15.960 acute or juvenile onset diabetes now type one, the life 0:49:16.000 --> 0:49:20.800 expectancy following diagnosis was like one to three years. Often 0:49:20.840 --> 0:49:25.239 it was months. It wasn't that much longer for those 0:49:25.360 --> 0:49:29.040 with what was viewed as the chronic form either. It 0:49:29.120 --> 0:49:35.520 was essentially a death sentence. Like across the board, medications 0:49:35.560 --> 0:49:38.919 and tinctures and infusions seemed to be of no help 0:49:38.960 --> 0:49:43.200 for the disease. But there was one thing that seemed 0:49:43.200 --> 0:49:48.240 to slow the progression of the disease maybe even though 0:49:48.280 --> 0:49:55.080 it did nothing to cure it. Starvation diets. Yeah. Yeah, 0:49:56.280 --> 0:49:59.800 So during the eighteen seventy Siege of Paris, when food 0:49:59.880 --> 0:50:03.680 was rationed and many people were near starvation, one doctor 0:50:03.760 --> 0:50:06.160 noticed that the urine of some of his patients with 0:50:06.280 --> 0:50:10.640 diabetes had dropped in their glucose levels, and that their 0:50:10.680 --> 0:50:15.120 symptoms had begun to improve a little bit. So the 0:50:15.200 --> 0:50:19.080 logical step was, well, if we severely limit the caloric 0:50:19.160 --> 0:50:22.799 intake of people with diabetes, we can reduce the symptoms 0:50:22.840 --> 0:50:27.080 of the disease. And this was the opposite of previous thinking, 0:50:27.120 --> 0:50:29.319 which was like, oh, this person is losing weight, we 0:50:29.360 --> 0:50:33.520 need to feed them more, right, right, So, after this observation, 0:50:33.680 --> 0:50:36.640 starvation diets really kind of got their start. And it 0:50:36.760 --> 0:50:41.120 wasn't always strictly starvation. You know, some diets were just 0:50:41.280 --> 0:50:45.400 no carb diets, some were just certain carbs like oats only, 0:50:46.080 --> 0:50:50.040 but in general they were calorie cutting, with most diets 0:50:50.080 --> 0:50:53.279 restricting you to fewer than five hundred calories a day. 0:50:53.680 --> 0:50:56.479 Oh my, yeah, that is not a lot. 0:50:56.640 --> 0:50:59.600 That is no, you can't live on that long term. 0:50:59.320 --> 0:51:04.200 But exactly, yeah, I mean, and these starvation diets did 0:51:04.200 --> 0:51:07.399 seem to work, like to a degree. I mean, they 0:51:07.440 --> 0:51:10.360 did nothing at all to cure or even effectively treat 0:51:10.360 --> 0:51:13.680 the disease, but they did in some cases just like 0:51:13.880 --> 0:51:18.799 slow the progression and help manage these glucose levels. But 0:51:18.880 --> 0:51:24.960 the stories are horrifying, right. For instance, one woman forty 0:51:25.000 --> 0:51:28.719 three years old was admitted to the hospital in nineteen sixteen, 0:51:29.200 --> 0:51:34.120 weighing seventy nine pounds or thirty six kilograms, and was 0:51:34.200 --> 0:51:37.600 told to fast. And the last record of this patient 0:51:37.680 --> 0:51:42.560 showed her weighing sixty pounds, less than thirty kilograms before 0:51:42.640 --> 0:51:46.240 she broke her fasting diet and died shortly after. 0:51:46.840 --> 0:51:48.040 Oh my goodness. 0:51:48.200 --> 0:51:50.640 And another really sad story is of a twelve year 0:51:50.680 --> 0:51:54.480 old boy with diabetes. Already blind from the disease, he 0:51:54.600 --> 0:51:56.960 was brought to the hospital so that his food could 0:51:57.000 --> 0:52:01.319 be closely monitored and his calories even more restricted. His 0:52:01.400 --> 0:52:04.799 weight dropped to forty pounds, but the blood glucose didn't 0:52:04.800 --> 0:52:07.879 seem to be dropping, and so he they cut even 0:52:07.960 --> 0:52:09.680 more and he died of starvation. 0:52:10.320 --> 0:52:11.440 Oh my god. 0:52:12.560 --> 0:52:16.000 So these starvation diets, in addition to slowly killing you, 0:52:16.320 --> 0:52:20.360 were also largely unachievable for most people with diabetes because 0:52:20.840 --> 0:52:24.440 they require the time and the money to monitor and 0:52:24.560 --> 0:52:27.880 weigh each individual food item and rest and it was 0:52:28.000 --> 0:52:32.719 just like not a reality. Yeah, So, going into the 0:52:32.760 --> 0:52:37.360 twentieth century, the available treatments for diabetes were really more 0:52:37.560 --> 0:52:41.960 of a choice among evils, right, die of diabetes or 0:52:42.040 --> 0:52:45.600 of starvation or of opium addiction, just like take your pick. 0:52:46.960 --> 0:52:50.680 So the need for effective treatment was very obvious and 0:52:50.719 --> 0:52:54.560 incredibly pressing, even more so since cases seemed to be 0:52:54.719 --> 0:52:58.319 on the rise, and so far the only thing that 0:52:58.400 --> 0:53:02.000 had showed any real promise were the experiments with pancreas 0:53:02.040 --> 0:53:06.200 extracts that I had mentioned earlier. Despite their limited success. 0:53:07.520 --> 0:53:12.959 In particular, the work of two researchers, Georg Zulezer from 0:53:13.000 --> 0:53:17.799 Germany and Nikolay Pelescue from Romania, showed that there might 0:53:18.000 --> 0:53:22.080 be something in it. In nineteen o six in Berlin, 0:53:22.480 --> 0:53:26.560 Zulzer had treated some humans with pancreatic extract but the 0:53:26.600 --> 0:53:29.920 side effects produced were like really severe and so we 0:53:29.960 --> 0:53:33.440 had to stop the project. And ten years later, in 0:53:33.520 --> 0:53:38.600 nineteen sixteen, Paulescu had succeeded in treating a diabetic dog 0:53:38.719 --> 0:53:42.879 with a solution of pancreatic extract, like it lowered its 0:53:42.880 --> 0:53:47.520 blood sugar levels. Just okay, super cool, promising, But his 0:53:47.640 --> 0:53:50.239 work was disrupted by World War One when he was 0:53:50.280 --> 0:53:54.080 called to service, and by the time he got back 0:53:55.239 --> 0:53:58.040 he picked up his work again, but like funds were 0:53:58.080 --> 0:54:01.680 super limited and he was working almost by himself, so 0:54:01.760 --> 0:54:05.400 it was just kind of like hard to get things moving. Yeah, 0:54:05.440 --> 0:54:10.040 and neither zules or Paulescu would end up getting the 0:54:10.080 --> 0:54:14.279 recognition they felt they deserved for their role in one 0:54:14.280 --> 0:54:18.280 of the most monumental and one of the most contentious 0:54:18.920 --> 0:54:23.680 medical advancements in the twentieth century, the discovery of insulin. 0:54:24.320 --> 0:54:27.520 Insulin do that horn again? 0:54:31.680 --> 0:54:36.520 In fact, like this, the history of this discovery continues 0:54:36.600 --> 0:54:41.440 to be like a fairly debated topic in medical history, 0:54:41.560 --> 0:54:44.120 like who should get credit for it? And so I'm 0:54:44.120 --> 0:54:46.400 just going to do the best I can to navigate 0:54:47.440 --> 0:54:52.880 those tensions. Yeah, So let's meet one of the central 0:54:52.960 --> 0:54:57.880 characters of this story, Frederick Banting born in Ontario in 0:54:57.920 --> 0:55:01.760 eighteen ninety one. He began med school just a couple 0:55:01.760 --> 0:55:05.160 of years before World War One broke out. He joined up, 0:55:05.200 --> 0:55:08.600 he helped treat combat soldiers, and after the war was over, 0:55:09.239 --> 0:55:12.799 he tried unsuccessfully to get a permanent position at the 0:55:12.800 --> 0:55:17.040 Toronto Hospital where he did his residency in orthopedic medicine. 0:55:18.120 --> 0:55:22.280 So he decided that he was gonna move to London, 0:55:22.360 --> 0:55:27.360 Ontario set up a private practice. But it was really 0:55:27.880 --> 0:55:32.040 pretty unsuccessful, like he couldn't quite get it off the ground. 0:55:32.760 --> 0:55:35.240 And in fact, it seemed like a lot of areas 0:55:35.280 --> 0:55:38.520 in his life were just like filled with struggle and 0:55:38.600 --> 0:55:44.319 strife and uncertainty, like he was always on and off 0:55:44.360 --> 0:55:48.600 again with his fiance, and he seemed like he was 0:55:48.600 --> 0:55:51.680 always sending out like job applications. He seemed like desperate 0:55:51.680 --> 0:55:54.000 for a change of scenery or a change of pace 0:55:54.120 --> 0:55:58.960 in his career. Late one October night in nineteen twenty, 0:55:59.520 --> 0:56:03.120 while trying to fall asleep and what seems like, as 0:56:03.120 --> 0:56:11.240 he described stress spiraling y yeah, absolutely, his mind drifted 0:56:11.239 --> 0:56:13.840 to a paper that he had recently read to prep 0:56:13.920 --> 0:56:16.000 for a lecture that he was giving on like I 0:56:16.040 --> 0:56:20.640 think carbohydrate regulation. And this paper, which was written by 0:56:20.640 --> 0:56:24.640 Moses Baron, discussed the role of the islets of Langerhans 0:56:24.800 --> 0:56:27.960 in the internal secretion of the pancreas and its possible 0:56:28.040 --> 0:56:32.920 role in diabetes. And he turned the idea over and 0:56:33.000 --> 0:56:36.239 over in his mind and kept thinking about it and 0:56:36.440 --> 0:56:39.360 came up with what he thought was the solution to 0:56:39.400 --> 0:56:43.400 the problem, like a way to isolate that internal pancreatic 0:56:43.440 --> 0:56:49.200 secretion and it would involve surgical removal of degenerated pancreases 0:56:49.239 --> 0:56:53.120 and dogs and extraction of the secretion from those pancreases. 0:56:54.280 --> 0:56:57.240 And the next time he was on campus, he brought 0:56:57.400 --> 0:57:00.520 up the idea to a professor at the university where 0:57:00.560 --> 0:57:05.080 he was affiliated, and the professor was like, you know, no, 0:57:05.680 --> 0:57:09.279 like sorry, but we just don't have the resources for that. 0:57:10.080 --> 0:57:13.200 And also there's no one at the university here that 0:57:13.960 --> 0:57:15.920 knows enough about it to be able to help you. 0:57:17.480 --> 0:57:21.400 But hang on a second. There happens to be somebody 0:57:21.520 --> 0:57:26.680 visiting who might and that somebody turned out to be 0:57:26.880 --> 0:57:32.080 JJ R. McLeod visiting from the University of Toronto, who 0:57:32.120 --> 0:57:38.320 was an expert in diabetes and carbohydrate metabolism. So Banting 0:57:38.440 --> 0:57:43.160 met with McLeod. McLeod wasn't like super impressed by Banting, 0:57:43.840 --> 0:57:49.400 who had a lot of enthusiasm and confidence, but that 0:57:49.560 --> 0:57:54.120 confidence wasn't really backed by like a lot of background 0:57:54.160 --> 0:57:57.240 reading on the subject. He was just like, I'm gonna 0:57:57.240 --> 0:57:58.560 do this and it's gonna be great. 0:57:59.000 --> 0:58:01.200 Oh and we've met those. 0:58:01.560 --> 0:58:04.080 Yeah, And McLeod was like, you know, people have spent 0:58:04.120 --> 0:58:08.360 their entire careers working on this problem. Do you know 0:58:08.400 --> 0:58:11.160 about these people? Do you know the work that they've done. 0:58:11.840 --> 0:58:16.920 But over the conversation, McLeod became more and more convinced 0:58:16.960 --> 0:58:20.880 and became eventually interested enough to say, Okay, you know what, 0:58:21.040 --> 0:58:25.880 sure come to the University of Toronto whenever, and you know, 0:58:26.160 --> 0:58:28.520 we can try to set something up, but you know, 0:58:28.680 --> 0:58:32.280 think carefully about this decision because it would mean giving 0:58:32.360 --> 0:58:36.760 up your practice and your affiliation here. And also like 0:58:36.840 --> 0:58:39.800 there's kind of a low chance that you would be successful, 0:58:40.040 --> 0:58:43.920 because you know, this is not a new problem, like 0:58:44.120 --> 0:58:48.320 people have tried this before. So Bantin gave it some 0:58:48.400 --> 0:58:51.760 time and thought and decided to give it a go. 0:58:52.640 --> 0:58:56.080 But after the other job applications that he had sent 0:58:56.160 --> 0:58:59.280 out had fallen through, and after his fiance had dumped 0:58:59.320 --> 0:59:02.640 him yet again, so he was like, you know what 0:59:04.040 --> 0:59:08.160 I lose, I'm getting out of here. So so yeah, 0:59:08.240 --> 0:59:11.040 so we packed up his apartment. He headed to Toronto 0:59:11.200 --> 0:59:16.000 and got there in April nineteen twenty one, and apparently 0:59:16.120 --> 0:59:18.760 he had done no more reading on the subject in 0:59:18.800 --> 0:59:21.800 the meantime, oh or not, my goodness, not very much, 0:59:21.960 --> 0:59:26.680 because when he met with McLeod, McLeod was like, Okay, 0:59:26.720 --> 0:59:29.760 so I think this is how the experiments should go. 0:59:30.840 --> 0:59:32.480 We'll start with this, and then we'll do this, and 0:59:32.520 --> 0:59:35.000 then we'll do this. Let's you know, see how we begin. 0:59:35.120 --> 0:59:37.920 He showed him how to do the procedures et cetera, 0:59:38.920 --> 0:59:41.720 and then he was like, also, you know, maybe you 0:59:41.720 --> 0:59:46.080 should read these papers, read these books, get a little 0:59:46.080 --> 0:59:49.400 more background in it. And then McLeod headed back to 0:59:49.480 --> 0:59:53.040 Scotland where he was from for the summer break. But 0:59:53.200 --> 0:59:58.240 before he did that, he gave Banting an undergraduate research 0:59:58.240 --> 1:00:02.040 assistant named Charles Best to help on the project, and 1:00:02.240 --> 1:00:04.520 he kind of spent a little bit of time, like 1:00:04.560 --> 1:00:06.440 a month and a half or so, kind of walking 1:00:06.480 --> 1:00:09.160 them through these surgical procedures that they would use on 1:00:09.240 --> 1:00:16.320 the dogs. The experimental plan went a little something like this. First, 1:00:16.640 --> 1:00:20.920 Banting and Best would get practice Banting on performing the 1:00:20.960 --> 1:00:28.240 pancreatectomies and Best using the blood and urine tests, and 1:00:28.480 --> 1:00:32.640 both of them observing what diabetes and dogs look like 1:00:32.640 --> 1:00:36.720 like the course of disease. And then Banting would ligate 1:00:36.760 --> 1:00:40.480 the pancreatic ducks in other dogs, allow them to recover 1:00:40.640 --> 1:00:45.440 while they're pancreas's atrophied, and then reoperate on these dogs, 1:00:45.560 --> 1:00:51.120 removing their degenerated pancreases and extracting the internal secretion from them, 1:00:51.440 --> 1:00:55.040 which he would then inject into the dogs that had 1:00:55.080 --> 1:00:58.680 been made diabetic from the complete removal of their pancreas. 1:00:59.040 --> 1:00:59.600 Huh. 1:01:00.120 --> 1:01:02.920 It didn't need like it was later realized that the 1:01:03.120 --> 1:01:06.400 atrophy didn't need to happen, but that's yeah, that was 1:01:06.520 --> 1:01:09.080 what they thought needed to happen first. 1:01:09.640 --> 1:01:12.480 It's interesting that that that part of it worked. 1:01:14.000 --> 1:01:17.800 I know, well, you know, and it it It didn't 1:01:17.840 --> 1:01:24.960 really work at first. It things got off to a 1:01:25.200 --> 1:01:27.000 really rocky start. 1:01:27.960 --> 1:01:32.680 And it's really sad because a lot of dogs died 1:01:33.280 --> 1:01:37.040 in the course of this experiment and in many other experiments, 1:01:37.560 --> 1:01:41.640 especially after the surgeries, which you know, keep in mind 1:01:41.800 --> 1:01:45.720 these were the days pre antibiotic, so like they would 1:01:45.800 --> 1:01:52.200 just die of sepsis, good surgeries, no, no, And in fact, 1:01:52.720 --> 1:01:57.640 so many dogs died that they began to like buy 1:01:57.800 --> 1:02:01.800 dogs off of the street because they had almost depleted 1:02:01.840 --> 1:02:06.040 the store of university dogs. Like this would not fly nowadays, 1:02:06.080 --> 1:02:09.760 just fly. I everyone I cook would be like like, nope, 1:02:10.720 --> 1:02:14.800 you are getting your research whatever credit. Yeah, you're not 1:02:14.840 --> 1:02:17.360 allowed to do research at this university anymore or any 1:02:17.440 --> 1:02:22.680 ever again, yes or any Yeah. But finally, finally, after 1:02:22.840 --> 1:02:27.360 many failures, things began looking up. They were able to 1:02:27.400 --> 1:02:32.800 successfully extract the secretion from the pancreas injected into depancreatized 1:02:32.800 --> 1:02:36.520 diabetic dogs and bring them back from the brink of 1:02:36.680 --> 1:02:40.880 death and out of a diabetic coma by rapidly dropping 1:02:40.880 --> 1:02:47.160 their blood sugar. This was like thrilling yeah, and Banting 1:02:47.360 --> 1:02:50.800 was quick to see and believe in the potential of 1:02:50.800 --> 1:02:55.680 this extract for the treatment of diabetes and humans. But McLeod, 1:02:55.720 --> 1:02:58.960 who was now back from his trip, he was urging 1:02:59.000 --> 1:03:00.880 a bit more caution. He was like, all right, why 1:03:00.880 --> 1:03:04.400 don't we just try repeating these experiments first, making sure 1:03:04.400 --> 1:03:08.440 we have like good you know, sample size, and we'll 1:03:08.480 --> 1:03:11.480 publish the results. See if we can refine the process 1:03:11.560 --> 1:03:14.400 and make sure that like we know exactly what we're 1:03:14.400 --> 1:03:16.200 doing and that other people can replicate it. 1:03:16.880 --> 1:03:18.800 Oh, I don't like where this is going. 1:03:18.880 --> 1:03:24.200 By your tone, it's there's so much drama, it's it's 1:03:24.280 --> 1:03:27.720 absurd and I won't even go into it all. But 1:03:27.760 --> 1:03:32.760 so Banting was like not really, he was like not' 1:03:32.920 --> 1:03:35.240 I don't want to have to wait for this. But 1:03:35.240 --> 1:03:37.720 but also he didn't really have a lot of like 1:03:37.800 --> 1:03:41.560 bargaining power. Banting had been working these past few months 1:03:41.760 --> 1:03:45.240 with like on no salary, on no official position with 1:03:45.240 --> 1:03:48.440 the university. He was just sort of there, and so 1:03:48.520 --> 1:03:51.480 he said to McLoud, you know what you're gonna pay me, 1:03:52.240 --> 1:03:54.600 You're gonna give me another assistant to take care of 1:03:54.640 --> 1:03:58.120 the dogs, and you're gonna have repairs done to the 1:03:58.160 --> 1:04:02.560 operating room. And McLoud was like, okay, that's actually you're 1:04:02.600 --> 1:04:05.080 asking for quite a lot, and other research at the 1:04:05.160 --> 1:04:08.640 university would suffer if, you know, if I were to 1:04:08.680 --> 1:04:12.440 give all of this to you. And Banting's like, I 1:04:12.520 --> 1:04:15.720 am gonna walk away from this. This is you know, 1:04:15.760 --> 1:04:19.360 blah blah blah, and so McLoud was like, you know what, Okay, fine, 1:04:19.800 --> 1:04:22.960 you're right, your work does show promise. Let's let's keep 1:04:23.000 --> 1:04:28.600 it going. So this meeting might be where we first 1:04:28.680 --> 1:04:34.080 see the tension rise between Banting and McLeod. And at 1:04:34.080 --> 1:04:37.360 this point Best was already aware of Banting's tendency to 1:04:37.400 --> 1:04:43.120 be scornful, disparaging, you know, impatient, and quick to anger. 1:04:43.760 --> 1:04:47.320 He had been yelled at at least once for dirty glassware. 1:04:48.160 --> 1:04:50.760 But this might be this might have been the first 1:04:50.800 --> 1:04:56.360 time that McLeod saw it in action, And this meeting 1:04:56.680 --> 1:04:59.680 might also have been when the seed of hate was 1:04:59.680 --> 1:05:04.480 playing in Banting form a cloud. Yeah, it's like really 1:05:04.560 --> 1:05:08.520 a toxic It's a whole toxic story and toxic place. 1:05:08.960 --> 1:05:12.680 Oh my gosh, yeah, but that seed of hate. 1:05:12.840 --> 1:05:17.840 It bloomed like wild that December of nineteen twenty one, 1:05:18.320 --> 1:05:23.560 at the Annual Physiological Society meeting, Banting and Best were 1:05:23.680 --> 1:05:26.480 due to present their research on the internal secretion of 1:05:26.520 --> 1:05:30.240 the pancreas, which had progressed since the summer with the 1:05:30.320 --> 1:05:33.960 use of pancreas is from cal fetuses and then alcohol 1:05:34.080 --> 1:05:38.120 for extraction from whole fresh pancreas, and things were taking 1:05:38.160 --> 1:05:41.760 along and all of their results were pointing towards successful 1:05:41.800 --> 1:05:44.919 treatment of diabetes in the animals that they were working with. 1:05:46.160 --> 1:05:51.720 But at this meeting, during his presentation, Banting like totally 1:05:51.760 --> 1:05:56.080 flubbed it. He was a terrible speaker. He stumbled over 1:05:56.120 --> 1:06:00.240 the results and it got so bad that McLoud Cloud 1:06:00.640 --> 1:06:05.000 had to keep like stepping in to clarify something or 1:06:05.080 --> 1:06:08.040 to include a crucial detail that Banting had left out. 1:06:08.440 --> 1:06:12.840 And he answered questions and then to add you know, 1:06:13.120 --> 1:06:16.120 insult to injury, or at least as perceived by Banting. 1:06:16.920 --> 1:06:21.880 McLeod kept saying, we we extracted this and we injected that. 1:06:22.760 --> 1:06:29.280 Banting was fuming there. He was I can only imagine 1:06:29.360 --> 1:06:32.800 just like standing up there in front of the who's 1:06:32.840 --> 1:06:37.520 who of diabetes researchers in North America and basically not 1:06:37.600 --> 1:06:40.919 being able to string a coherent sentence together while your 1:06:41.040 --> 1:06:46.280 supervisor is taking what is perceived to be taking all 1:06:46.360 --> 1:06:47.720 the credit from you. 1:06:48.400 --> 1:06:52.000 I can one hundred percent imagine that, and it is 1:06:52.280 --> 1:06:53.160 so cringe. 1:06:53.600 --> 1:06:59.240 It is really yeah, And that's and so Banting like 1:06:59.440 --> 1:07:02.360 he didn't He wasn't the type to just silently fume. 1:07:03.040 --> 1:07:06.520 He was like ranting and raving to all of his friends, 1:07:07.000 --> 1:07:10.520 like McLeod is a horrible person, he's stealing all my results, 1:07:10.520 --> 1:07:13.760 blah blah blah. It like really became very bad. And 1:07:14.880 --> 1:07:18.720 I will say, in defense of McLeod, anyone else who 1:07:19.000 --> 1:07:22.080 worked with him doesn't describe him that way. It seems 1:07:22.120 --> 1:07:24.720 like Banting was the only one to sort of accuse 1:07:24.840 --> 1:07:31.800 him of being incredibly territorial or taking credit or stealing credit. 1:07:32.560 --> 1:07:36.000 So anyway, I don't want to get too much into 1:07:36.040 --> 1:07:36.680 the whole, like. 1:07:37.480 --> 1:07:40.479 You know, India lab drama, right, Yeah. 1:07:40.560 --> 1:07:44.880 And at this point it was the entire lab like 1:07:45.000 --> 1:07:48.600 McLeod had shifted gears, like these results were super promising, 1:07:48.720 --> 1:07:52.480 and so McLeod was like, you know what, everyone, almost 1:07:52.480 --> 1:07:54.720 everyone in this lab is going to start working on 1:07:54.800 --> 1:08:01.240 this pancreaus problem, and he also brought on eventually a 1:08:01.320 --> 1:08:05.840 visiting biochemist by the name of James Collop, who was 1:08:05.920 --> 1:08:10.360 added to speed up the extraction and purification process. And 1:08:10.400 --> 1:08:13.520 so things were happening quickly now, with the first human 1:08:13.560 --> 1:08:17.040 clinical trial in January of nineteen twenty two. So just 1:08:17.360 --> 1:08:21.360 you know, from April nineteen twenty one when Banting arrived 1:08:21.560 --> 1:08:25.160 to Toronto to the first clinical trial January of nineteen 1:08:25.200 --> 1:08:30.519 twenty two, that's very fast, too fast, I mean. So 1:08:30.600 --> 1:08:34.720 the first person to ever receive this pancreatic extract was 1:08:34.960 --> 1:08:38.760 Leonard Thompson, a fourteen year old boy who on admission 1:08:38.840 --> 1:08:43.599 weighed only sixty five pounds, whose hair was falling out, 1:08:43.880 --> 1:08:48.840 abdomen distended breath smelling of actone, and who was on 1:08:48.920 --> 1:08:51.840 a diet of four hundred and fifty calories a day. 1:08:52.160 --> 1:08:53.600 Oh my gracious. 1:08:53.880 --> 1:08:57.920 On January eleventh, Leonard received the first injection, which led 1:08:57.920 --> 1:09:01.120 to a twenty five percent reduction in blood sugar and 1:09:01.160 --> 1:09:05.200 a slight reduction in urine glucose. But overall the results 1:09:05.240 --> 1:09:09.439 weren't like super promising, especially since the impurities in the 1:09:09.479 --> 1:09:14.639 extract led to like an absess forming at the injection site. 1:09:14.880 --> 1:09:19.000 So the trial was deemed premature and there was a 1:09:19.120 --> 1:09:22.960 rush to make a more pure sample, something that Banting 1:09:23.280 --> 1:09:26.959 took upon himself to make like a competition with Callup, 1:09:27.040 --> 1:09:29.559 who was like, I don't this doesn't need to be 1:09:29.600 --> 1:09:32.640 a competition, Like, can't we just work on this? 1:09:33.160 --> 1:09:33.360 Yeah? 1:09:34.160 --> 1:09:40.719 Tensions mounted Callop one he like found a better purification process, 1:09:41.200 --> 1:09:44.559 and the new, more purified extract was injected into Leonard 1:09:44.600 --> 1:09:47.479 with much better results on January twenty third. 1:09:47.880 --> 1:09:48.559 Oh wow. 1:09:49.360 --> 1:09:53.599 But a few days before then, before this injection happened, 1:09:54.160 --> 1:09:58.400 Banting and Callop had gotten into a fight that was 1:09:58.560 --> 1:10:04.320 at least verbal and possibly physical. Oh my, because accounts differ. 1:10:05.120 --> 1:10:08.280 When Callup announced, he walked into the room and announced 1:10:08.280 --> 1:10:13.720 that he a fine tuned the purification protocol. B was 1:10:13.800 --> 1:10:16.759 going to keep it a secret from Banting in Best 1:10:17.080 --> 1:10:20.400 and not reveal any part of it, and see that 1:10:20.520 --> 1:10:23.160 he was going to file a patent on it under 1:10:23.240 --> 1:10:24.200 his name alone. 1:10:24.800 --> 1:10:27.040 Oh my, gracious. 1:10:27.160 --> 1:10:31.680 And apparently McLeod had okayed all of this. What so 1:10:31.880 --> 1:10:37.040 then this led to I would imagine a huge yelling 1:10:37.080 --> 1:10:41.000 match among most, if not all parties, Banting and Best 1:10:41.040 --> 1:10:44.519 and McLeod and call Up. I mean, the battle lines 1:10:44.560 --> 1:10:48.760 were very clearly drawn, with those two groups on you know, 1:10:48.880 --> 1:10:50.960 banting a best on one side, call Up and McLeod 1:10:51.000 --> 1:10:54.719 on the other. And then a ceasefire of sorts came 1:10:54.920 --> 1:10:58.320 in the form of a signed agreement that none of 1:10:58.360 --> 1:11:01.280 them would patent the process and that they would have 1:11:01.400 --> 1:11:05.160 to be transparent with each other about research developments. I mean, 1:11:05.200 --> 1:11:09.040 they didn't become friends or anything, but you know, at 1:11:09.120 --> 1:11:12.080 least like for now, it seemed to have de escalated. 1:11:13.360 --> 1:11:16.240 But in any case, the animosity and drama was there 1:11:16.280 --> 1:11:20.679 to stay. I mean, wow, it wasn't going anywhere. I again, 1:11:20.720 --> 1:11:22.840 I can't even get into it all like, there's a 1:11:22.840 --> 1:11:25.479 great book, I'll recommend that kind of you're just like 1:11:25.720 --> 1:11:33.000 what he said that. Yeah, And so, beginning in the 1:11:33.040 --> 1:11:36.560 spring of nineteen twenty two, the lab group began publishing 1:11:36.600 --> 1:11:40.519 their results. But the important thing is that the popular 1:11:40.640 --> 1:11:43.880 press picked it up, and that generated a lot of 1:11:44.000 --> 1:11:48.320 hype among the many people who lived with diabetes. It 1:11:48.439 --> 1:11:51.840 was in one of these first publications that was a 1:11:51.880 --> 1:11:55.320 big comprehensive one from April nineteen twenty two, that the 1:11:55.400 --> 1:11:58.680 term insulin was first used. And there's no record as 1:11:58.680 --> 1:12:02.160 to like why or how they chose that word, but 1:12:02.200 --> 1:12:05.120 it's based on the Latin route for island, referring to 1:12:05.160 --> 1:12:06.840 the islets of Langerhans. 1:12:07.120 --> 1:12:08.439 Okay, okay, okay. 1:12:08.880 --> 1:12:11.519 It was clear to everyone in the field that this 1:12:11.640 --> 1:12:15.559 research marked a new era for diabetes research and treatment. 1:12:16.560 --> 1:12:19.080 It would certainly be a bad time for things to 1:12:19.360 --> 1:12:20.479 fall apart, wouldn't it. 1:12:21.200 --> 1:12:22.560 Oh, Aaron. 1:12:24.200 --> 1:12:30.839 So Banting had begun to drink heavily and several times decided, 1:12:30.880 --> 1:12:33.960 you know what, I'm I'm quitting this whole thing. I 1:12:33.960 --> 1:12:36.479 don't want to be a part of this anymore, until 1:12:36.560 --> 1:12:39.920 best you know, talked him out of it and call up. 1:12:40.040 --> 1:12:43.280 On the other hand, was having, you know, more like 1:12:43.479 --> 1:12:47.320 lab centric problems. He had lost the knack for insulin production. 1:12:47.600 --> 1:12:50.439 He like couldn't he couldn't figure out. He was like, 1:12:50.520 --> 1:12:53.720 whatever I was doing before is no longer working for me, 1:12:53.840 --> 1:12:55.360 and I don't know why what. 1:12:55.880 --> 1:12:56.479 That's weird. 1:12:57.000 --> 1:12:59.559 It's weird, and it's bad because it led to this 1:12:59.680 --> 1:13:03.040 in slin famine among the people who had already received 1:13:03.080 --> 1:13:08.479 injections and were needing those to help regulate their blood sugar. 1:13:09.880 --> 1:13:13.960 And then MacLeod was simultaneously worried about the lives of 1:13:14.080 --> 1:13:17.000 the people who needed that insulin, and he was also 1:13:17.160 --> 1:13:20.280 worried that someone else was going to figure out the 1:13:20.360 --> 1:13:25.280 production process and patent it. And so even though McLeod 1:13:25.360 --> 1:13:28.840 Banting in Best were reluctant to patent it on principle, 1:13:29.520 --> 1:13:32.920 they wanted to stop other people from creating a monopoly, 1:13:33.479 --> 1:13:36.200 and so they filed this type of patent that would 1:13:36.680 --> 1:13:37.879 prevent that from happening. 1:13:38.200 --> 1:13:38.519 Okay. 1:13:39.000 --> 1:13:41.720 McLeod also realized that if they wanted to turn this 1:13:41.800 --> 1:13:45.960 insulin into an actual medical product that people could reliably 1:13:46.439 --> 1:13:49.080 get their hands on, they needed to get a pharmaceutical 1:13:49.120 --> 1:13:52.880 company involved, which is how Eli Lilly came to be 1:13:52.960 --> 1:13:57.040 so closely associated with insulin. It was someone from Eli 1:13:57.080 --> 1:13:59.439 Lilly at that very first meeting and they were like 1:13:59.640 --> 1:14:04.599 working very closely with the Toronto team to get the 1:14:04.640 --> 1:14:12.160 soul ability or license to try to manufacture this new insulin. Yeah, 1:14:12.439 --> 1:14:17.559 but you know, the drama of discovery, the incredible tension 1:14:17.760 --> 1:14:22.960 among the researchers, the difficulties in streamlining or fine tuning 1:14:23.000 --> 1:14:28.599 the production process. All of these problems were overshadowed by 1:14:28.640 --> 1:14:33.080 the absolutely enormous impact that insulin was having on the 1:14:33.120 --> 1:14:37.400 lives of people with diabetes. A lot of accounts at 1:14:37.400 --> 1:14:42.439 the time describe the drug, describe insulin as miraculous, and 1:14:42.520 --> 1:14:45.519 it's kind of hard to disagree with that. Yeah, Like 1:14:45.680 --> 1:14:48.520 a sixteen year old boy brought out of a diabetic 1:14:48.560 --> 1:14:51.479 coma from an insulin injection, the first time that had 1:14:51.520 --> 1:14:56.400 ever happened. A bedridden child jumping around the room hours 1:14:56.439 --> 1:15:00.920 after being given insulin. Perhaps the most famous patient from 1:15:01.280 --> 1:15:04.519 the time was Elizabeth Hughes, who was daughter of the 1:15:04.600 --> 1:15:07.920 US Secretary of State, who kept journals of her life 1:15:08.200 --> 1:15:11.320 pre and post insulin, And at the time of her 1:15:11.360 --> 1:15:15.160 first insulin shot, the fifteen year old Elizabeth weighed less 1:15:15.200 --> 1:15:22.320 than fifty pounds. That's like twenty two kilograms. It's yeah, 1:15:22.360 --> 1:15:26.759 and she was close to death. A few weeks after 1:15:26.800 --> 1:15:31.040 receiving her first insulin shot, she gained ten pounds. Wow, 1:15:31.040 --> 1:15:33.720 and a lot of health problems resolved for her, and 1:15:33.760 --> 1:15:37.280 she went on to live like a healthy and relatively 1:15:37.320 --> 1:15:41.880 long life. And there were a million more stories just 1:15:42.120 --> 1:15:46.559 like these. Insulin saved and continues to save so very 1:15:46.600 --> 1:15:50.760 many people from what was absolutely a death sentence. Yeah, 1:15:51.240 --> 1:15:53.519 it kind of reminds me a lot of like the 1:15:53.600 --> 1:15:58.200 stories of when antibiotics were first developed and first introduced, 1:15:58.439 --> 1:16:01.799 and it was like it was raculous. It was coming 1:16:01.840 --> 1:16:05.280 back from the brink of death. It must have been 1:16:05.960 --> 1:16:13.440 unbelievable to witness. So who was responsible for insulence development? 1:16:13.840 --> 1:16:17.280 And who gets the credit? And are the answers to 1:16:17.320 --> 1:16:22.400 those questions the same, Well, it depends on who you ask, right, 1:16:22.800 --> 1:16:26.280 If you ask Banting, it was Banting with a little 1:16:26.320 --> 1:16:30.080 help from Best. If you ask McLeod, it was McLeod 1:16:30.160 --> 1:16:34.839 Banting and Callop. If you ask Paulescu, it was poulsq 1:16:36.160 --> 1:16:39.200 And if you ask the Nobel Prize committee, it was 1:16:39.280 --> 1:16:43.559 Banting and McLoud. So in nineteen twenty three the two 1:16:43.760 --> 1:16:47.479 were awarded the Nobel Prize. Banting was only thirty two 1:16:47.560 --> 1:16:51.720 at the time. Oh yeah, gosh at the time. I 1:16:51.720 --> 1:16:54.400 think he was the youngest for like physiology and medicine 1:16:54.479 --> 1:16:57.879 or whatever the grouping was at the time. But Banting 1:16:58.120 --> 1:17:03.240 was furious. He could not believe that his and McLeod's 1:17:03.320 --> 1:17:05.400 name were both on the prize. 1:17:05.720 --> 1:17:06.839 Oh goodness. 1:17:07.240 --> 1:17:11.640 He believed it should have been him and Best, and 1:17:11.720 --> 1:17:13.639 so at first he was like, you know what, I'm 1:17:13.640 --> 1:17:16.160 going to refuse this prize. I don't want anything to 1:17:16.200 --> 1:17:19.759 do with it. And then eventually he was like, Actually, 1:17:19.800 --> 1:17:21.280 what I'm going to do is I'm going to split 1:17:21.320 --> 1:17:24.920 it with best men. That's what he did, and McLeod 1:17:25.120 --> 1:17:28.320 in turn decided that he was going to split it 1:17:28.360 --> 1:17:33.080 with Callop. Okay, I don't know who deserves it, honestly, 1:17:33.280 --> 1:17:37.519 I mean, does paulsc you deserve some credit? Absolutely sole credit? 1:17:37.600 --> 1:17:42.200 Probably not. Would Banting have gotten there without McLeod or 1:17:42.240 --> 1:17:47.120 without call Up probably not. All these tensions and credit 1:17:47.160 --> 1:17:50.280 debates aside, though, the important thing is that insulin was 1:17:50.320 --> 1:17:53.920 now available, and just in the way that blood transfusions 1:17:53.920 --> 1:17:57.559 for hemophilia turned that disease from an acute disease to 1:17:57.600 --> 1:18:01.920 a chronic one, insulin prolonged the lives of those with diabetes, 1:18:02.320 --> 1:18:04.880 but it was also not a cure, and the long 1:18:04.960 --> 1:18:09.840 term consequences of diabetes, particularly type one, were emerging, such 1:18:09.840 --> 1:18:13.040 as kidney disease and retinopathy and all the ones that 1:18:13.080 --> 1:18:16.920 you've already discussed in the biology. So I'm not going 1:18:17.000 --> 1:18:20.879 to go through these next things in detail. But following 1:18:20.920 --> 1:18:24.160 the discovery and production of insulin, a lot of other 1:18:24.240 --> 1:18:28.920 important developments occurred. Frederick Sanger discovered that insulin was a 1:18:28.960 --> 1:18:32.400 protein and described its structure, for which he was awarded 1:18:32.439 --> 1:18:35.680 a Nobel Prize in nineteen fifty eight, his first of 1:18:35.760 --> 1:18:41.759 two yep and Dorothy Hodgkin, whose name you might remember 1:18:41.880 --> 1:18:46.960 from our antibiotics episode and our radiation episodes. So she 1:18:47.120 --> 1:18:49.840 used X ray crystallography to work out the three D 1:18:49.920 --> 1:18:55.040 structure of insulin. A lot of research focused on treatments 1:18:55.040 --> 1:18:58.400 for the long term consequences of diabetes, such as kidney 1:18:58.400 --> 1:19:03.879 disease and ulcers and kidney transplants, and some really important 1:19:03.920 --> 1:19:08.160 work was done by Priscilla White on reducing perinatal mortality 1:19:08.320 --> 1:19:13.160 in people with diabetes by introducing sex hormones treatment, which 1:19:13.280 --> 1:19:17.880 hugely increased survival of the babies. And there was yet 1:19:17.920 --> 1:19:22.439 another Nobel Prize for diabetes research co awarded to Rosslyn 1:19:22.520 --> 1:19:26.360 Yallow in nineteen seventy seven for developing the radio amino 1:19:26.439 --> 1:19:33.240 assay to measure the concentration of hormones like insulin, vitamins, viruses, enzymes, 1:19:33.320 --> 1:19:38.720 and lots more stuff in humans. Genetic engineering allowed for 1:19:38.800 --> 1:19:42.800 the mass production of biosynthetic insulin, and I think we 1:19:42.880 --> 1:19:45.479 might have touched on that briefly in our Ecoli episode. 1:19:45.520 --> 1:19:49.479 It was basically like engineering ecoli to just like pump 1:19:49.560 --> 1:19:53.360 make a ton of insulin that sounds vaguely familiar, and 1:19:53.400 --> 1:19:58.839 then the threat of bovine sponge offormencephalopathy in bovine derived 1:19:58.840 --> 1:20:02.040 insulin and kind of put for like this switch towards 1:20:02.400 --> 1:20:08.760 human insulin. And then insulin pumps were developed, and since 1:20:08.800 --> 1:20:13.240 the nineteen seventies they've shrunk in size considerably and increased 1:20:13.280 --> 1:20:19.320 their capabilities considerably. In nineteen seventy nine, diabetes was officially 1:20:19.320 --> 1:20:25.639 divided into two types, insulin dependent diabetes melodice and non 1:20:25.680 --> 1:20:30.040 insulin dependent diabetes melodus, or type one and type two 1:20:30.200 --> 1:20:34.240 as they were called beginning in nineteen ninety five and 1:20:34.400 --> 1:20:37.840 in the late nineteen seventies is also when gestational diabetes 1:20:38.120 --> 1:20:42.040 and what was called maturity onset diabetes of the young 1:20:43.400 --> 1:20:48.280 were also recognized. There have been too many developments to 1:20:48.560 --> 1:20:54.080 even mention. This year twenty twenty one marks the one 1:20:54.200 --> 1:20:59.560 hundred year anniversary of insulin, and over that time diabetes 1:20:59.600 --> 1:21:02.920 has un under gone a huge transformation in terms of 1:21:02.960 --> 1:21:06.639 our understanding of the disease and our ability to treat it. 1:21:07.560 --> 1:21:12.600 But the story isn't over because alongside these medical developments, 1:21:12.920 --> 1:21:17.160 diabetes was going through another kind of transformation in the 1:21:17.200 --> 1:21:24.880 twentieth century, a social transformation. If you will, Okay, Diabetes 1:21:24.920 --> 1:21:27.519 Part two, I promise this is a lot shorter. So 1:21:28.880 --> 1:21:30.639 I know I've been talking for ages. 1:21:31.200 --> 1:21:32.160 I've been enjoying it. 1:21:32.600 --> 1:21:38.720 Okay, good. I hope that remains true. So I can 1:21:38.800 --> 1:21:42.880 only speak for the US or my experience in the US, 1:21:43.160 --> 1:21:46.599 but in many things that I've read or seen on TV, 1:21:47.200 --> 1:21:50.840 or I've heard in the classroom, there's this sense that 1:21:51.000 --> 1:21:55.960 diabetes type two in particular is a personal choice, with 1:21:56.040 --> 1:22:00.880 this tinge of morality surrounding it in some ways to 1:22:00.920 --> 1:22:04.360 how STIs are talked about, like oh, you did these things, 1:22:04.400 --> 1:22:06.840 so like what do you expect? You deserve this? These 1:22:06.880 --> 1:22:11.639 are the consequences for your actions, And this I think 1:22:11.880 --> 1:22:15.280 reflects a huge problem, not just in showing like a 1:22:15.360 --> 1:22:20.200 complete absence of empathy, but also in revealing a general 1:22:20.360 --> 1:22:24.719 lack of understanding about the multifaceted nature of this disease 1:22:25.640 --> 1:22:30.720 and refusing to acknowledge the institutional drivers that increase the 1:22:30.880 --> 1:22:35.160 risk of diabetes. Yeah. So, when I was prepping for 1:22:35.200 --> 1:22:39.799 this episode, I read a book called Diabetes, A History 1:22:39.840 --> 1:22:44.080 of Race and Disease by Arlene Marsha Tuckman, where I 1:22:44.200 --> 1:22:48.080 learned that it's kind of like always been this way, 1:22:48.200 --> 1:22:52.240 Like there's always been sort of this Oh well, these 1:22:52.240 --> 1:22:54.760 are the consequences of your actions, or like, oh, this 1:22:54.800 --> 1:22:59.320 is a personal disease, like this is something that you did, right. 1:23:00.520 --> 1:23:04.000 It's always been very much like a blame the individual 1:23:04.160 --> 1:23:07.439 or the identity of the individual, kind of a disease 1:23:08.120 --> 1:23:11.720 with a particular trait or group at fault being the 1:23:11.760 --> 1:23:15.639 main thing that has changed over the decades. I had 1:23:15.680 --> 1:23:19.280 no idea before researching this episode, but it turns out 1:23:19.439 --> 1:23:23.799 that diabetes started out as a quote like Jewish disease 1:23:25.280 --> 1:23:28.840 in the late eighteen hundreds, when the visibility of diabetes 1:23:28.880 --> 1:23:33.600 and other chronic diseases was increasing as infectious diseases declined. 1:23:34.320 --> 1:23:39.200 Diabetes was literally given the name quote the Jewish disease 1:23:39.760 --> 1:23:43.800 in Europe because of the supposed high prevalence of the 1:23:43.800 --> 1:23:47.639 disease among Jewish people, and the reason for this high 1:23:47.680 --> 1:23:51.920 prevalence varied based on the individual views of the person 1:23:52.000 --> 1:23:54.639 you ask or the person who was writing this article. 1:23:55.920 --> 1:23:59.200 It could be because of the long years of cruel 1:23:59.240 --> 1:24:03.360 persecution faced by Jewish people that led to this high 1:24:03.400 --> 1:24:07.519 levels of stress, or it was because they overindulged in 1:24:07.680 --> 1:24:10.479 ate rich foods, or maybe it's because they had a 1:24:10.600 --> 1:24:14.160 quote nervous disposition, or it was just a way of 1:24:14.200 --> 1:24:18.120 saying that this disease had you know, foreign roots, since 1:24:18.160 --> 1:24:21.719 the immigration of Jewish people from Eastern Europe was really 1:24:21.840 --> 1:24:26.840 high during this period. But whatever the perceived reason or 1:24:26.920 --> 1:24:31.880 stated reason at the time, this association grew global and 1:24:31.920 --> 1:24:35.679 it became entrenched in medical literature and in the minds 1:24:35.720 --> 1:24:38.880 of practicing doctors for decades, so like from the late 1:24:38.960 --> 1:24:44.000 eighteen hundreds to like a few decades into the twentieth century. Huh, yeah, 1:24:45.520 --> 1:24:50.919 was there actually an association, I mean without any quality 1:24:50.960 --> 1:24:54.760 statistics from the time. We can't say for sure, but 1:24:54.880 --> 1:24:59.920 it seems unlikely. It seems that it was more bad 1:25:00.080 --> 1:25:05.000 statistics turned into common knowledge and then like helped along 1:25:05.040 --> 1:25:11.280 by confirmation bias. Like definitely a citation needed moment, and 1:25:11.560 --> 1:25:13.799 that was a big problem that just kept being repeated 1:25:13.840 --> 1:25:17.479 in the literature without any citation or citing someone who 1:25:17.640 --> 1:25:23.640 just said, it's really highly prevalent in Jewish people. And 1:25:23.720 --> 1:25:26.760 even if there were numbers in these articles, was the 1:25:26.800 --> 1:25:31.400 categorization of you know, Jewish and non Jewish even helpful? 1:25:31.640 --> 1:25:37.840 Was it meaningful? Both groups were very heterogeneous. So drawing 1:25:37.880 --> 1:25:40.720 those lines was really a way of kind of like 1:25:40.880 --> 1:25:43.400 pushing a certain narrative. The way that you draw the 1:25:43.520 --> 1:25:47.080 lines is definitely like you have a bit of forethought 1:25:47.120 --> 1:25:50.679 about what statements you want to make when the numbers 1:25:50.680 --> 1:25:53.120 all kind of fall out, right, Like what's important to 1:25:53.160 --> 1:25:58.200 you about those divisions? And often you know, as it 1:25:58.280 --> 1:26:00.360 is now, but as it was back then. You know, 1:26:00.479 --> 1:26:03.679 those divisions were a way of saying that something about 1:26:03.720 --> 1:26:06.760 your race, or your background, or your culture made you 1:26:06.840 --> 1:26:11.320 more likely to have this disease. And we see this theme, 1:26:11.920 --> 1:26:15.519 you know, race presented as an explanation for disease again 1:26:15.800 --> 1:26:20.360 and again in the history of diabetes, with Black Americans 1:26:20.479 --> 1:26:23.960 and the Native Americans and Mexican Americans and so on. 1:26:25.320 --> 1:26:30.439 And certainly the use of racial categories and epidemiological studies 1:26:30.439 --> 1:26:33.680 can be very helpful, but they're helpful for confronting and 1:26:33.760 --> 1:26:38.639 trying to understand institutional racism and inequalities in health care 1:26:38.760 --> 1:26:43.120 or access. Not to further the myth of race as 1:26:43.120 --> 1:26:50.160 a biological construct and yet erin and yet aarin Okay, 1:26:50.240 --> 1:26:53.759 so from its reputation as a you know, quote Jewish 1:26:53.800 --> 1:26:57.920 disease in the late eighteen hundreds. Diabetes slowly began to 1:26:58.000 --> 1:27:01.920 be viewed as a disease of man moral failing, especially 1:27:01.960 --> 1:27:04.720 in the years following World War One, which were a 1:27:04.760 --> 1:27:09.240 period of economic growth and increase in consumables and big 1:27:09.280 --> 1:27:14.200 cultural shifts, leading to culturally conservative people shouting that, like, 1:27:14.479 --> 1:27:17.960 the increasing rates of diabetes were a sign of moral decay, 1:27:18.479 --> 1:27:21.920 of this like gluttonous, over indulgent society that has no 1:27:22.000 --> 1:27:26.120 self control. The shifting from a Jewish disease to like 1:27:26.160 --> 1:27:29.920 a more general sign of you know, moral decay or 1:27:29.960 --> 1:27:34.400 whatever also happened as more studies were done to show 1:27:34.479 --> 1:27:37.519 that there wasn't actually much of a difference in terms 1:27:37.520 --> 1:27:42.240 of stats, right, and this moral failing or over indulgence 1:27:42.960 --> 1:27:45.599 or just the rate of diabetes, it had a class 1:27:45.640 --> 1:27:49.880 structure to it. Diabetes had shifted its reputation to one 1:27:50.040 --> 1:27:56.040 of middle and upper class and generally white people. In fact, 1:27:56.439 --> 1:28:00.599 it was thought and published in medical journals that black 1:28:00.640 --> 1:28:05.360 people were immune to diabetes. What it was literally in 1:28:05.800 --> 1:28:09.080 medical journals, Well, they are known to be immune. Same 1:28:09.320 --> 1:28:15.200 was said about Native Americans also, So why did people 1:28:15.200 --> 1:28:16.840 think they were immune to diabetes? 1:28:19.479 --> 1:28:24.080 I don't know, Aaron, Why, I mean, we don't know 1:28:24.160 --> 1:28:27.559 for sure, we can speculate it's likely that it had 1:28:28.320 --> 1:28:31.040 a large part to do with a lack of access 1:28:31.520 --> 1:28:33.800 to primary care physician or hospitals. 1:28:34.320 --> 1:28:38.439 So like doctors just simply weren't seeing diabetes and black 1:28:38.439 --> 1:28:43.000 people because they weren't treating black people. And it's also 1:28:43.080 --> 1:28:46.040 possible that doctors simply were like, well, I'm not going 1:28:46.120 --> 1:28:49.599 to test the urine of a black person because they're immune. 1:28:49.640 --> 1:28:52.800 I read that in the literature, so there's no point 1:28:52.840 --> 1:28:57.080 in even testing you for diabetes. But the reasons for 1:28:57.120 --> 1:29:02.200 this lower prevalence were given or written about in racist terms. Right, 1:29:02.360 --> 1:29:05.720 Black people didn't have the quote like nervous strain or 1:29:05.800 --> 1:29:07.920 quote mental strength for diabetes. 1:29:08.560 --> 1:29:12.639 What I know it is, what does that even mean? 1:29:13.320 --> 1:29:18.439 Basically, what I gather from this is that people wanted 1:29:18.479 --> 1:29:21.880 diabetes to mean whatever they wanted it to mean. Yeah, 1:29:22.000 --> 1:29:25.519 they couldn't find a cause, They couldn't explain why it happened, 1:29:26.040 --> 1:29:28.200 and so then they looked around and thought, Okay, what 1:29:28.320 --> 1:29:31.000 is the narrative I want to push. Yeah, it all 1:29:31.080 --> 1:29:35.360 had to do with just like individual biases, societal biases, 1:29:35.600 --> 1:29:40.639 and you know, racist ideals. It's yeah, it's so weird 1:29:40.800 --> 1:29:45.240 erin it is yeah, it's all about the narrative. But 1:29:45.400 --> 1:29:50.240 then here comes another shift, right, another transformation of diabetes. 1:29:50.880 --> 1:29:55.320 So when actual statistics introduced in the nineteen twenties showed 1:29:55.360 --> 1:29:59.880 that rates of diabetes didn't differ much between black and 1:30:00.040 --> 1:30:05.160 white Americans, but do you know what did? Mortality rates 1:30:05.320 --> 1:30:11.880 from diabetes. And another factor that contributed to the overall 1:30:12.000 --> 1:30:16.720 growing visibility of diabetes among black Americans was the increase 1:30:16.880 --> 1:30:21.360 in black medical doctors who wanted to help improve the 1:30:21.400 --> 1:30:24.800 health of the communities that they served. And what many 1:30:24.840 --> 1:30:28.400 of these doctors saw was also reflected in the stats 1:30:28.439 --> 1:30:33.920 from the time and also from today that as poverty increased, 1:30:34.040 --> 1:30:38.040 the rates of diabetes rose, and that diabetes in general 1:30:38.160 --> 1:30:42.200 seemed to be on the rise in the nineteen thirties 1:30:42.240 --> 1:30:45.439 and estimated half a million to two million people in 1:30:45.479 --> 1:30:48.760 the US were living with the disease, and it rose 1:30:48.840 --> 1:30:51.040 to be the ninth lead and cause of death in 1:30:51.120 --> 1:30:53.960 the US in nineteen thirty six, which is up from 1:30:54.000 --> 1:30:58.920 the twenty seventh in eighteen ninety. The development of insulin 1:30:59.040 --> 1:31:01.519 in the early nineteen twos ties helped out a bit 1:31:01.640 --> 1:31:06.040 with like the management of diabetes, but a lifetime of 1:31:06.080 --> 1:31:10.400 injections was still costly and long term effects were still present. 1:31:11.520 --> 1:31:14.599 And also, since this is an episode of TPWK, why 1:31:14.840 --> 1:31:20.560 I have to mention eugenics. So here we go obligated eugenesis. 1:31:20.640 --> 1:31:23.320 As you might guess, we're not a fan of insulin 1:31:23.880 --> 1:31:27.360 saying that it would increase the numbers of unfit people 1:31:27.840 --> 1:31:28.800 in society. 1:31:30.560 --> 1:31:33.920 I saw it coming here. It still hurts every time. 1:31:33.920 --> 1:31:39.400 Every time. But a huge problem with the eugenesis arguments, 1:31:39.560 --> 1:31:42.439 you know, besides the fact that they're terrible and they 1:31:42.439 --> 1:31:45.360 were making judgments on who should or should not reproduce, 1:31:46.400 --> 1:31:49.640 was that no one could predict who would get diabetes. 1:31:49.800 --> 1:31:54.360 Right still, you know it is true today the how 1:31:54.479 --> 1:31:57.519 of diabetes was beginning to be worked out, but the 1:31:57.600 --> 1:32:02.840 why had not yet been answered and still isn't really 1:32:03.479 --> 1:32:09.439 fully answerable. We'll get back to it arin, Well, why 1:32:09.479 --> 1:32:12.559 did some people get it in others not? Why were 1:32:12.600 --> 1:32:16.479 we seeing an increase in the US In nineteen sixty two, 1:32:17.080 --> 1:32:21.200 James Neil thought he might have the answer. Have you 1:32:21.240 --> 1:32:26.360 heard of the thrifty genotype? Yeah? Okay, it's basically this 1:32:26.479 --> 1:32:30.640 idea proposed by Neil that this thrifty genotype would have 1:32:30.680 --> 1:32:35.200 helped early humans live through periods of unpredictable food availability, 1:32:35.680 --> 1:32:38.439 so you would store more fat in times of plenty 1:32:38.560 --> 1:32:42.479 to prepare for times of famine. But in the US 1:32:42.560 --> 1:32:45.679 and other developed countries where diabetes was on the rise, 1:32:46.000 --> 1:32:49.400 there weren't really these times of famine, and so the 1:32:49.439 --> 1:32:53.680 thrifty genotype went from good to bad. It began to backfire. 1:32:54.920 --> 1:32:59.240 And at first this thrifty genotype hypothesis was just used 1:32:59.240 --> 1:33:03.960 to explain a global growth in diabetes prevalence, but with 1:33:04.120 --> 1:33:09.240 recent reports showing a disproportionately high rate of diabetes among 1:33:09.320 --> 1:33:14.200 some Native American groups, it became used in this colonial 1:33:14.439 --> 1:33:20.920 narrative of quote primitive and quote advanced societies. And in 1:33:20.960 --> 1:33:23.519 this narrative, some Native American groups were said to be 1:33:23.680 --> 1:33:28.160 more prone to develop diabetes because they were quote primitive 1:33:28.200 --> 1:33:31.920 people who were rushed into quote you know, modern living 1:33:31.960 --> 1:33:35.280 conditions and they were unequipped to deal with the diet 1:33:35.360 --> 1:33:36.120 and lifestyle. 1:33:36.320 --> 1:33:41.240 That is such a mischaracterization of yeah I can't. 1:33:41.600 --> 1:33:44.920 Yeah, yeah, I mean, it's it's quite the turn from 1:33:45.280 --> 1:33:48.920 diabetes as a mark of civilized society that was popular 1:33:48.960 --> 1:33:53.320 earlier in the century, and the thrifty genotype hypothesis is 1:33:53.360 --> 1:33:58.160 not well supported at all, I should note despite it 1:33:58.240 --> 1:34:03.720 continuing to be pushed by some people Jared Diamond, but 1:34:05.560 --> 1:34:09.000 by couching the high prevalence of diabetes in certain Native 1:34:09.000 --> 1:34:14.840 American groups in biological or genetic terms or concepts, it 1:34:14.960 --> 1:34:18.519 made and continues to make it possible for the government 1:34:18.680 --> 1:34:21.639 to ignore their own role in the cycle of poverty, 1:34:21.800 --> 1:34:26.320 in the impact of displacement, genocide, and federal policies that 1:34:27.040 --> 1:34:32.600 lead to higher rates of disease, not just diabetes. Speaking 1:34:32.640 --> 1:34:38.320 of the federal government, in the nineteen eighties, a nationwide 1:34:38.360 --> 1:34:42.599 study called the Heckler Report investigated racial and ethnic health 1:34:42.640 --> 1:34:46.840 disparities in the US, and what they found was that diabetes, 1:34:47.040 --> 1:34:52.320 specifically type two and mortality from diabetes occurred at disproportionately 1:34:52.439 --> 1:34:58.920 high rates among non white people. The report framed diabetes 1:34:59.320 --> 1:35:06.840 as I quote disease of minority groups. It barely acknowledged 1:35:06.880 --> 1:35:12.080 the role that poverty played, but rather it emphasized the 1:35:12.240 --> 1:35:17.240 racial and ethnicity differences and to some degree, sex differences. 1:35:18.040 --> 1:35:23.280 This continued the long tradition of attributing diabetes to a 1:35:23.360 --> 1:35:27.280 moral failing or personal quality, or to a certain racial 1:35:27.400 --> 1:35:31.040 or ethnic background, all the while ignoring the role that 1:35:31.160 --> 1:35:36.320 poverty and other factors like food, deserts, like the ability 1:35:36.400 --> 1:35:40.040 to be active, that all of these things can play. 1:35:41.040 --> 1:35:46.400 Diabetes is such a nuanced disease, but it seems as 1:35:46.439 --> 1:35:51.080 though somehow we struggle still to make sense of that 1:35:51.200 --> 1:35:55.840 nuance and present it in a way that is like, oh, okay, 1:35:56.000 --> 1:36:02.200 there are multiple parts to this story. So I've rambled 1:36:02.280 --> 1:36:08.200 on and on, and Aaron, why don't you bring me 1:36:08.280 --> 1:36:10.599 up to speed and what's happening with diabetes today? 1:36:11.200 --> 1:36:14.519 I'll do my best erin, let's take a quick break first. 1:36:43.800 --> 1:36:46.439 Why don't we just start straight in with the numbers. 1:36:47.080 --> 1:36:50.360 We'll get right to it, and then we'll go through 1:36:51.720 --> 1:36:55.760 advances and treatment and then hopefully answer a little bit 1:36:55.880 --> 1:37:02.120 more of your question of the wyat and how oh good? So, 1:37:02.760 --> 1:37:09.920 according to the International Diabetes Federation, in twenty nineteen, diabetes 1:37:09.960 --> 1:37:13.679 and this is all types of diabetes, of which generally 1:37:13.960 --> 1:37:17.400 ninety percent or so are type two and five to 1:37:17.439 --> 1:37:21.840 ten percent type one, and then gestational and the other 1:37:21.880 --> 1:37:26.519 types of diabetes account for the other percentages. So in 1:37:26.560 --> 1:37:34.759 twenty nineteen, diabetes caused four point two million deaths worldwide 1:37:35.560 --> 1:37:39.600 and four hundred and sixty three million adults. This is 1:37:39.760 --> 1:37:44.599 just adults between age twenty and seventy nine were estimated 1:37:44.640 --> 1:37:48.639 to be living with diabetes, and that number is likely 1:37:48.720 --> 1:37:51.840 to rise to up to seven hundred million by twenty 1:37:51.960 --> 1:37:55.080 forty five because both type one and type two diabetes 1:37:55.120 --> 1:37:59.120 have been increasing, right, and it gets a little worse. 1:38:00.479 --> 1:38:05.120 The true disease burden, especially for type two diabetes, is 1:38:05.240 --> 1:38:09.760 likely a gross underestimation because one in three people who 1:38:09.840 --> 1:38:18.200 have diabetes are underdiagnosed. That's over two hundred million people WHOA. Yeah, 1:38:18.240 --> 1:38:21.160 And then if you also account for all of the 1:38:21.200 --> 1:38:25.280 people who have impaired fasting glucose or what sometimes is 1:38:25.280 --> 1:38:29.000 called pre diabetes, the vast majority of those people have 1:38:29.520 --> 1:38:32.200 no idea that that's what's happening inside of their bodies. 1:38:33.120 --> 1:38:36.799 Hmm okay, and a good. 1:38:36.640 --> 1:38:39.000 Proportion of those people may go on to develop type 1:38:39.000 --> 1:38:47.240 two diabetes a little worse than that. While there's a 1:38:47.240 --> 1:38:51.160 lot of variation in both incidents and prevalence of both 1:38:51.200 --> 1:38:55.559 types of diabetes across the globe, like different prevalences in 1:38:55.600 --> 1:39:00.000 different areas, overall, more than eighty percent of people currently 1:39:00.120 --> 1:39:03.439 living with type two diabetes are currently living in low 1:39:03.600 --> 1:39:07.679 or middle income countries, which, especially as we talk about 1:39:07.680 --> 1:39:11.559 the new developments in treatment poses additional challenges because most 1:39:11.600 --> 1:39:17.479 of these are unsurprisingly very expensive, and there are of 1:39:17.520 --> 1:39:21.479 course major economic and social hurdles for people living with 1:39:21.520 --> 1:39:24.799 diabetes in low and middle income countries, but also across 1:39:24.840 --> 1:39:30.040 the globe, including here in the US. For example, insulin 1:39:30.080 --> 1:39:35.040 prices in the US are truly an abomination. In twenty eighteen, 1:39:35.520 --> 1:39:38.960 a unit of insulin was ninety eight dollars and seventy 1:39:39.000 --> 1:39:42.240 cents in the US, compared to eight dollars and eighty 1:39:42.320 --> 1:39:43.360 one cents. 1:39:43.600 --> 1:39:45.320 In thirty two other countries. 1:39:46.600 --> 1:39:50.519 And while diabetes is certainly not exclusively a disease of 1:39:50.600 --> 1:39:54.040 low income, when you consider not only the price of insulin, 1:39:54.320 --> 1:39:56.679 but the price, like I already said, of so many 1:39:56.720 --> 1:39:59.720 of the newer and in some cases better drugs for 1:39:59.760 --> 1:40:05.520 type two diabetes that are also incredibly expensive, Diabetes certainly 1:40:05.960 --> 1:40:10.160 contributes to the cycle of poverty across the globe. So 1:40:10.320 --> 1:40:13.400 that's all the bad news, and I know there's a 1:40:13.439 --> 1:40:17.599 lot of it, but there's at least some good news 1:40:17.680 --> 1:40:21.599 on the horizon. I usually talk about whatever's going on 1:40:21.760 --> 1:40:25.160 in terms of research, and a lot of times I 1:40:25.160 --> 1:40:27.679 feel like I've been like, ohh, there's not much going 1:40:27.720 --> 1:40:31.200 on and it's like depressing. But today I don't have 1:40:31.280 --> 1:40:34.080 a lot of very specific things to go over. But 1:40:34.200 --> 1:40:38.400 that's because there is so much research going on in 1:40:38.479 --> 1:40:41.920 terms of diabetes that there's simply too much ground to cover, 1:40:42.280 --> 1:40:44.880 which is amazing. That means that there's so many people 1:40:44.920 --> 1:40:50.040 working on so many different aspects of this in terms 1:40:50.040 --> 1:40:54.160 of new treatments. When we look at type one diabetes 1:40:55.080 --> 1:40:58.000 in general, and I apologize if there's even newer things 1:40:58.040 --> 1:41:00.240 that I have missed, but in general, the treatment is 1:41:00.280 --> 1:41:03.840 still just insulin, and while that sounds simple, it's a 1:41:04.040 --> 1:41:07.400 very complex to kind of get regimens and know how 1:41:07.479 --> 1:41:11.320 much you have to give, et cetera. But some incredible 1:41:11.320 --> 1:41:15.840 advancements for type one diabetes or insulin dependent type two 1:41:15.920 --> 1:41:20.840 diabetes is the development of continuous glucose monitors and like 1:41:20.920 --> 1:41:26.000 you mentioned, increasingly small and easy to use insulin pumps 1:41:26.000 --> 1:41:30.599 that can keep much tighter control of that glucose, which 1:41:30.640 --> 1:41:33.120 can then prevent the development of complications. 1:41:33.200 --> 1:41:34.400 So that's incredible. 1:41:35.880 --> 1:41:40.120 When it comes to type two diabetes, Oh my gracious, 1:41:41.320 --> 1:41:43.599 the number of new drugs. I think there's a new 1:41:43.640 --> 1:41:48.680 one every day, and a lot of them. Like we 1:41:48.840 --> 1:41:50.960 kind of touched on a bit before are touching on 1:41:51.040 --> 1:41:57.160 different mechanisms of diabetes control. So previously things were just 1:41:57.280 --> 1:42:00.480 working on increasing the amount of insulin that people secrete. 1:42:00.880 --> 1:42:04.120 But now because we know that insulin resistance is a 1:42:04.120 --> 1:42:08.559 big component, there's other types of treatments that are targeting 1:42:08.600 --> 1:42:11.320 tissues to make them more susceptible to the effects. 1:42:11.920 --> 1:42:13.680 There's a lot of really cool stuff. 1:42:13.439 --> 1:42:15.479 Going on with type two diabetes treatment. 1:42:15.600 --> 1:42:17.240 Yeah, that's interesting, it's. 1:42:17.240 --> 1:42:18.160 Very very cool. 1:42:19.880 --> 1:42:23.280 There's also so much work being done to better understand 1:42:23.360 --> 1:42:27.760 the genetic components of both types of diabetes. So I 1:42:27.800 --> 1:42:29.720 want to kind of stick with that for just a 1:42:29.800 --> 1:42:33.559 moment and then we'll wrap up. So, both type one 1:42:33.560 --> 1:42:37.800 and type two diabetes have genetic links, but it's not 1:42:37.840 --> 1:42:40.000 like any of the genetic disorders that we've covered in 1:42:40.000 --> 1:42:43.679 the past, or it's like a single gene. It's many 1:42:43.680 --> 1:42:47.840 different genes, and it's not a strong genetic component for 1:42:47.960 --> 1:42:51.640 either type two or type one diabetes. But one of 1:42:51.640 --> 1:42:54.800 the biggest questions, Aaron, that you kept asking me was 1:42:55.320 --> 1:42:58.559 the why the how, especially when it comes to type 1:42:58.560 --> 1:43:02.760 two diabetes. And so, like I mentioned, both type one 1:43:02.800 --> 1:43:06.840 and type two diabetes have a genetic component. Type two 1:43:06.920 --> 1:43:11.280 diabetes has a much stronger genetic component, meaning if you 1:43:11.479 --> 1:43:15.040 have a first degree relative with type two diabetes, you 1:43:15.080 --> 1:43:18.200 are much more likely to develop type two diabetes yourself 1:43:19.040 --> 1:43:21.760 than you are if you had someone with type one 1:43:21.760 --> 1:43:23.320 diabetes to develop type one. 1:43:23.600 --> 1:43:26.320 That makes sense, uh huh okay, So there's a much. 1:43:26.240 --> 1:43:30.599 Stronger genetic component to type two diabetes, but it's not 1:43:30.800 --> 1:43:34.840 a single gene. It's very multivariate, and just like with 1:43:34.960 --> 1:43:38.720 type one diabetes, there's also a huge amount of environmental 1:43:39.040 --> 1:43:42.800 components that go into the development of type two diabetes. 1:43:43.640 --> 1:43:46.880 And some of these are what are often called modifiable 1:43:46.960 --> 1:43:50.640 risk factors, and these are factors in the environment that 1:43:50.680 --> 1:43:53.720 can change and that can lead to risk of diabetes. 1:43:54.000 --> 1:43:56.200 The things that we know that are the most strongly 1:43:56.200 --> 1:44:01.519 associated are sedentary lifestyle, which is essentially just means not 1:44:01.640 --> 1:44:05.360 getting a lot of physical activity throughout the day. Another 1:44:05.680 --> 1:44:09.639 is diet, So having a diet that's really high in 1:44:10.439 --> 1:44:12.280 sugars that are like the kind that you find in 1:44:12.360 --> 1:44:17.639 soda is really strongly associated with type two diabetes. And 1:44:17.680 --> 1:44:20.800 then the one that cited the most frequently is obesity. 1:44:22.320 --> 1:44:26.120 So BMI is the indicator that we use to classify 1:44:26.439 --> 1:44:30.759 obesity and obesity in the US at least, is considered 1:44:30.840 --> 1:44:35.040 a disease, which is then also considered a risk factor 1:44:35.360 --> 1:44:40.639 for diabetes, among other things, type two diabetes specifically. And 1:44:40.960 --> 1:44:44.720 BMI is not just in my opinion, but also in 1:44:44.800 --> 1:44:49.400 my opinion, not a good indicator of health. Not only 1:44:49.400 --> 1:44:53.040 does BMI not take into account things like muscle mass 1:44:53.560 --> 1:44:57.519 or the distribution of adipose tissue, whether it's central and 1:44:57.560 --> 1:45:00.920 around your organs versus on your life eggs, or arms, 1:45:00.960 --> 1:45:05.439 et cetera. BMI also ignores so many of the social 1:45:05.520 --> 1:45:08.680 determinants of health that play into the overall risks of 1:45:08.840 --> 1:45:13.240 diabetes and so many other diseases. So be am I 1:45:13.479 --> 1:45:16.840 an obesity In general, it's not a good indicator, but 1:45:17.040 --> 1:45:19.439 in the literature it is considered a risk factor for 1:45:19.600 --> 1:45:20.560 type two diabetes. 1:45:21.520 --> 1:45:27.960 M Mechanistically, what is it about those things that causes 1:45:28.240 --> 1:45:33.599 insulin resistance and like a faulty production of insulin? 1:45:33.920 --> 1:45:37.760 Yeah, and that is the question that we still absolutely 1:45:37.840 --> 1:45:41.880 do not know the answer to. But here's something exciting, 1:45:42.320 --> 1:45:45.080 and it still doesn't address the question of why those 1:45:45.240 --> 1:45:49.280 risk factors then lead to this. But I found a 1:45:49.320 --> 1:45:53.640 couple of articles that are really promising on the underlying 1:45:53.680 --> 1:45:58.479 mechanism before you even get to insulin resistance, and that 1:45:58.600 --> 1:46:00.679 is dysfunction in the brain itself. 1:46:01.520 --> 1:46:02.160 Huh. 1:46:02.240 --> 1:46:06.680 So, dysfunction in the hypothalamus that was treated with a 1:46:06.720 --> 1:46:12.680 single dose of something called fibroblast growth factor resulted in 1:46:12.920 --> 1:46:18.479 mice in sustained diabetes remission a single dose. So these 1:46:18.520 --> 1:46:23.400 papers were basically suggesting that what happens, for whatever reason, 1:46:23.520 --> 1:46:27.800 from this genetic susceptibility and these environmental factors is that 1:46:27.880 --> 1:46:32.360 the effect on the hypothalamus in your brain is to 1:46:32.479 --> 1:46:36.040 increase your body's set point for what is an okay 1:46:36.160 --> 1:46:39.120 level of glucose That is. 1:46:39.600 --> 1:46:41.960 Super interesting, isn't it fascinating? 1:46:42.760 --> 1:46:45.880 And so then by giving this dose of this FGF one, 1:46:46.000 --> 1:46:49.559 what they were doing was lowering back that set point 1:46:49.600 --> 1:46:53.639 to something more like one twenty instead of like two 1:46:54.000 --> 1:46:57.800 hundred or whatever. So then your pancreas doesn't have to 1:46:58.040 --> 1:47:03.000 compensate to try an increase insulin because your body, your 1:47:03.040 --> 1:47:05.760 brain is telling your body it's okay to let my 1:47:05.760 --> 1:47:08.160 blood glucose get this high, and your pancrease is like, no, 1:47:08.200 --> 1:47:12.479 it's not, it's really not. Again, that still doesn't address 1:47:12.520 --> 1:47:17.040 this underlying question, but it does give us a much 1:47:17.200 --> 1:47:23.280 better target right for the like mechanistic cause, did you. 1:47:23.400 --> 1:47:26.680 Come across anything about epigenetics. 1:47:26.760 --> 1:47:30.040 I mean, epigenetics is a huge part of this, right, 1:47:30.080 --> 1:47:33.760 and that's but no, I didn't read any papers about it, 1:47:33.840 --> 1:47:36.599 and so I don't know like what those mechanisms are. 1:47:37.120 --> 1:47:38.599 But with any of these. 1:47:38.400 --> 1:47:44.120 Like polygenic and gene and environment things, I think epigenetics 1:47:44.120 --> 1:47:47.240 plays a huge role. But I think too, Aaron, getting 1:47:47.240 --> 1:47:49.280 back to what you were saying in the last part 1:47:49.320 --> 1:47:53.720 of your history section, is it's so important, especially in 1:47:53.760 --> 1:47:56.880 a disease like diabetes, when we're talking about things like 1:47:57.040 --> 1:48:00.880 these modifiable risk factors, to not lose sight of the 1:48:01.120 --> 1:48:05.520 environment that we are in and these structures of government 1:48:05.840 --> 1:48:10.559 of our society that force us into this environment where 1:48:10.800 --> 1:48:13.120 we can't do physical activity because we're sitting at a 1:48:13.160 --> 1:48:15.240 desk at our jobs for ten hours a day and 1:48:15.280 --> 1:48:17.800 then we're driving in our car an hour each way 1:48:17.840 --> 1:48:20.639 to work, and then we can't afford to buy fresh 1:48:20.720 --> 1:48:23.040 leafy greens because they go bad in twenty minutes in 1:48:23.080 --> 1:48:25.559 your fridge, and also they don't taste that good. Like, 1:48:25.800 --> 1:48:29.800 there are so many things that play into this. It's 1:48:29.920 --> 1:48:33.559 not an individual choice, it's so much bigger than that. 1:48:34.760 --> 1:48:40.880 Yeah, it's it's a really multifaceted yeah, like issue and discussion. 1:48:40.520 --> 1:48:45.799 And again BMI is a bad indicator. Hoof. 1:48:46.400 --> 1:48:52.840 Well yeah, don't get me started on that one. So 1:48:52.960 --> 1:48:55.880 that is diabetes. 1:48:55.880 --> 1:48:59.400 In brief, in brief, you know, short and sweet. We 1:48:59.560 --> 1:49:01.759 kept it nice, long and sweet. 1:49:02.120 --> 1:49:02.519 Yeah. 1:49:03.200 --> 1:49:08.120 Sources, so I will mention I basically relied on three books. 1:49:08.600 --> 1:49:12.639 The first one is The Discovery of Insulin by Michael Bliss. 1:49:12.800 --> 1:49:15.519 I feel like it's a really well researched and even 1:49:15.560 --> 1:49:19.040 handed look at you credit for the discovery of insulin. 1:49:19.439 --> 1:49:23.200 And apparently there's also a mini series about this story 1:49:23.479 --> 1:49:27.479 called Glory Enough for All. I think it's on YouTube. 1:49:28.040 --> 1:49:31.680 And then I also read, as I mentioned earlier, Diabetes, 1:49:31.760 --> 1:49:34.839 A History of Race and Disease by Arlene Marcia Tuckman, 1:49:35.640 --> 1:49:39.600 and finally Diabetes The Biography by Robert Tattersall. 1:49:40.120 --> 1:49:40.640 Awesome. 1:49:41.200 --> 1:49:44.240 The vast majority of my biology for the first time 1:49:44.280 --> 1:49:47.719 in forever, came from a single textbook, so big shout 1:49:47.720 --> 1:49:52.200 out to the Principles of Diabetes Melodis by Poritzky editor, 1:49:53.520 --> 1:49:57.120 and then a few other papers here and there for 1:49:57.200 --> 1:50:00.200 a little bit of specifics and if you're interested in 1:50:00.240 --> 1:50:05.240 that brain glucose research. I have two papers, one from 1:50:05.360 --> 1:50:10.360 Nature Communications twenty twenty and another from Diabetes that was 1:50:10.360 --> 1:50:14.679 from twenty nineteen. They're both really interesting, very detailed papers, 1:50:14.800 --> 1:50:17.680 and we'll post all of these sources for this episode 1:50:17.680 --> 1:50:21.000 and every episode on our website. This podcast will kill 1:50:21.040 --> 1:50:21.719 you dot Com. 1:50:22.360 --> 1:50:26.040 Thank you again so much, Carla for coming on and 1:50:26.120 --> 1:50:28.559 chatting with us. We really appreciate it. 1:50:29.000 --> 1:50:30.240 Yeah, thank you so much. 1:50:31.439 --> 1:50:34.400 And thank you to Bloodmobile for providing the music for 1:50:34.560 --> 1:50:36.800 this episode and all of our episodes. 1:50:37.080 --> 1:50:39.639 Thank you to the Exactly Right Network, of whom we're 1:50:39.760 --> 1:50:41.080 very proud to be a part. 1:50:41.479 --> 1:50:45.240 And thank you to you listeners for listening to this 1:50:45.520 --> 1:50:46.600 very long episode. 1:50:46.840 --> 1:50:49.800 Is a real doozy and what it is. 1:50:50.520 --> 1:50:55.040 And thanks also especially to all of our supporters on Patreon. 1:50:55.360 --> 1:50:59.160 We love you and appreciate you. I mean the depth 1:50:59.200 --> 1:51:00.639 of our appreciation and knows. 1:51:00.520 --> 1:51:02.280 No bounds, no bounds whatsoever. 1:51:04.280 --> 1:51:08.360 Okay, Well, until next time, wash your hands. 1:51:08.160 --> 1:51:09.320 You filthy animals. 1:51:14.280 --> 1:51:14.320 M