Selected Podcast

Insulin, from Discovery to Today

The hundredth anniversary of the discovery of insulin is cause for celebration, especially for those of us who depend on insulin to control our diabetes. Insulin formulations have come a long way since the hormone was first extracted from the pancreases of lab animals at a small lab in Canada.

The Medical Director and Co-Founder of the MarinHealth Braden Diabetes Center Dr. Linda Gaudiani is a world-class expert on the use of insulin. In this podcast, she does a deep dive on the many refinements to insulin therapy, from delivery systems like the pump and the pen, to long and short acting varieties, to the introduction of a new, once-a-week insulin.
Insulin, from Discovery to Today
Featuring:
Linda Gaudiani, MD, FACP, FACE
Dr. Gaudiani is the president of Marin Endocrine Care and Research a specialty practice in Endocrinology, Diabetology and Metabolism since 1985 and now part of the Marin Health Care District. In addition to her endocrinology practice, she co-directs the Marin Endocrine Bone Density Services. 

Learn more about Linda Gaudiani, MD, FACP, FACE
Transcription:

Bill Klaproth (Host): 2021 marks the 100 year anniversary of the discovery of insulin. So what is the history of insulin and how has insulin therapy evolved since that initial discovery? And what does the use of insulin mean for people living with diabetes? Well we're going to find out what Dr. Linda Gaudiani, Medical Director and Co-Founder of the MarinHealth Braden Diabetes Center.

This is The Healing Podcast brought to you by MarinHealth. I'm Bill Klaproth. Dr. Gaudiani, it's always a pleasure to talk with you, and on a special occasion, it's the 100 year anniversary of the discovery of insulin. So, we're looking forward to hearing from you about how insulin came about, the changes throughout the years and where we're at today. So let me start with this, Dr. Gaudiani, can you tell us a little bit about diabetes care before insulin was discovered? What was the prognosis like for people with diabetes back then?

Linda Gaudiani, MD, FACP, FACE (Guest): Thank you so much for having me, first of all. And Bill, it is always good to talk to you. And to feel like I can reach out to other folks this way. It's such a special year that's been celebrated, not only nationally, but internationally, because the discovery of insulin impacted the entire world.

And happily it was discovered in North America. It was discovered by Canadian scientists working eventually and closely with American scientists. Before that discovery, which was actually when it was came to light. And was actually sold to a company and started to produce it in,1921. There's a backstory on that. There were German and other European scientists working as early as the mid 1800s, 1860 to 1880. And they discovered that if you took the pancreas out of dogs, they developed what looked like, what they knew as Type 2 diabetes. They started getting sick and urinating and lost weight and died. I don't know the backstory as to why they were doing those pancreatectomies, but I think actually in those days, one of the things that researchers were doing was, they were removing different organs to see what would happen to animals to try to get just these answers. What do these organs do? What do they make? We didn't know any of that, then.

So, these poor animals that were sacrificed led to the first huge hint which was that when you took the pancreas out of a dog, he developed what looked like diabetes. So, then the next 20 plus years were spent, well, would it be possible if you put this material back into individuals who have diabetes, could you cure them? Remember what we're talking about is like 150 years ago. So science was very different, right? Very crude then. So, what these earliest docs did and these were two very young guys, Banting and Best were in their twenties, isn't that amazing?

One was just out of medical school and another was a researcher. And what they did was they took this pancreati from animals, the crude material. And they tried crushing and purifying it and making a crude extract. And what they found was that if that crude extract was given back to animals and eventually in experimental settings to humans, you could bring the blood sugars down. Voila.

Host: So that was 1921. That was the official discovery of insulin?

Dr. Gaudiani: That was the official discovery. That was when the, the first patent was actually sold to Eli Lilly.

Host: Wow interesting.

Dr. Gaudiani: I believe at about that time. And guess what? You've probably heard this story, but guess what that patent for all of insulin was sold for?

Host: Oh my Lord. I don't know, but I, I'm sure we're going to be like, what? No. What was it sold for?

Dr. Gaudiani: $1.

Host: Wow. How about that?

Dr. Gaudiani: a period of months, millions of doses were being given in a very short period of time. Of course, a lot of those people got sick. Remember this was not easy. This was a crude thick viscous material. And it came from animals, which meant although they didn't know this, humans were going to get immunologic reactions. So this was an extract that was given in big glass syringes with big needles, because it was thick. It had to be given under the skin because they tried taking it orally. Since it's a protein, you just adjust it. So it didn't work orally. It had to be given intravenously. A lot of people got rashes, swelling, tremendous pain at the injection site, but if I can circle back Bill, to answer another question you asked me at the beginning, what was this disease like?

The fact was this disease was completely fatal. Type 1 diabetes. Now we're talking about Type 1 diabetes, the type which usually affected only young children in those days and young adults. And they uniformly died within a few years. It was just pathetic and terrible to go back and look at the stories of those young children and young adolescents and young people. The only treatment available was to severely limit their intake of carbohydrates, since carbohydrates rapidly are metabolized to glucose. And if you could severely limit that, they could survive for short periods of time on just proteins, but essentially these children's starved and essentially got down to these incredibly thin body weights and eventually passed.

So it was even more fatal in a way than polio, which left cripples and did kill many youngsters in those days as well. But no one ever came out of Type 1 diabetes without insulin in those days.

Host: Yeah, this was brutal. So it was worth going through all of that at the time, the pain at injection point, the rashes, the illness. The immune response, right.

Dr. Gaudiani: They couldn't purify in those days. They couldn't get all the other proteins out. They could crush it. They finally made a preparation that appeared to have a lot of insulin in it, but it had other things from the pancreas in it as well, that they just couldn't purify in those days.

Host: But it was worth it. right? Because the other option is starving to death. So, let's go through this to try to get this insulin in.

Dr. Gaudiani: Exactly. There's a beautiful story I re-read, as I was thinking about this last night and today, and this story sits on my desk. I always have it there. It was published in, I think the New England, no, the Annals of Internal Medicine, and I have an old copy from 2005, but it really goes back and chronicles the story of the first American to receive insulin injections and his name was, Jim Dexterhavens. And he was, I think, 15 years old in 1915, when he got his diagnosis, just going through his growth spurt. He got up to five feet, eight inches. He weighed 80 pounds.

Host: Oh, okay.

Dr. Gaudiani: Imagine that. And his father was an executive with Eastman Kodak and was a long time friend of George Eastman. And because they were more educated and he had some friends who were doing research and calling and trying to figure out what was available. And eventually he connected with Dr. Banting in Canada. And Dr. Banting sent him some of the first insulin that he had made because he made such a big plea.

And when the father first gave his son this injection, he got violently ill. And the story is that Dr. Banting actually got on a train and came to the states to administer the following injections. And although they just didn't know the dose. Can you imagine? I mean, they had no idea how much to give. And these were children that were already very, very sick. So, they weren't just somebody with modest elevation of blood sugars, they were pre-morbid. But eventually they found the dose. They gave enough. And it's a beautiful story. It chronicles over the next few years. It wasn't all an overnight miracle. But it was a miracle. Eventually he got well enough that he gained back to about 150 pounds, went through his adolescence. Became a young man, went and got married, fathered two children and became a very famous woodcutter designing famous artistic woodcuts. And that, was a, that was an art form that was more popular in those days. So things are in museums. I think it's a beautiful story of the dedication of these researchers, who were not out there to make money on it. They were really out there to save lives. It's very inspiring.

Host: That's a great story. And that led to a Nobel prize win. Is that correct?

Dr. Gaudiani: They did, they did get the Nobel prize the discovery of insulin. And here we are, a hundred years later with mostly wonderful news. I have to say here in this time of COVID, I think we need to hear most of the good news, which is this is a completely curable disease. Diabetics now go on to lead completely full and healthy lives. It's still not easy to manage, but with the subsequent enormous modifications that have been made both to the insulins themselves and to insulin delivery systems, we now have something we never had, which is Type 1 diabetics that are living into old age, 70, 80, 90. I had a patient who lived into her nineties.

She was diagnosed as a young girl. She had her diabetes over 75 years. And I'll tell you, she was a vigorous wonderful woman with a big family, and she got one of the Joslin clinic, very rare to get their not only a 50 year metal, but their 75 year metal. The Joslin clinic, Dr. Joslin was one of the first researchers and started the first diabetes clinic in this country. And his clinic, of course is still there. The famous Joslin clinic in New York. And they now give a special gold metal to anyone who lives for 50 years with Type 1 diabetes. And they give a 75 year, not only to recognize the accomplishment of that patient and their physicians and their families, but because they're collecting data on those patients who survive to try to figure out how were these patients with this very, very difficult disease treated with pretty crude all we had insulins at the beginning and who have gone through all the various changes. What was different about them and they are still collecting that data, but it was also really moving too.

We got her metal and we gave it in my office and her children and her grandchildren, and great-grandchildren sat in the waiting room and listened to her story of what it was like and what happened to her. So there's a great history there.

Host: Okay. Okay. So let me ask you this then this may be a silly question. So Type 1 diabetes always starts in childhood, right? When adults get diabetes, is it always Type 2? Is that the delineation of that may be a silly question, but.

Dr. Gaudiani: No, it's not silly at all. There's a surprising answer. We used to think that, but that's not true. This is an unusual disease that can actually occur at any time. I've had patients as old as 91 diagnosed with Type 1 diabetes. It's extremely rare. But when a very thin patient presents with severe hyperglycemia and weight loss and their antibodies are positive, that's diagnostic of Type 1. There are special antibodies that one can measure as well as certain genetic predispositions. No one really knows what uncovers and leads to Type 1 diabetes, but we do know that there is a certain let's put genetic predisposition that's common in many, but not all of the Type 1 diabetic patients that we study.

But there may be something else that flips the switch to express the immunologic attack that occurs on the pancreas, and destroys these particular cells called the beta cells in the islets of Langerhans in the pancreas. And we luckily have a great excess of insulin, most of us, probably because it's such an important hormone. So we all have a lot more that we need. But by the time a patient really presents with severe high blood sugars, the disease has been silent for a period of time because there was that excess capacity. By the time they become hyperglycemic, that means high blood sugars, with the side effects of high blood sugars, those patients have usually lost like 90 or 95% of their insulin secretory capacity.

So that is why we can't reverse it in general, in it's, it's current stage of diagnosis. There's a big study going on called TrialNet. And increasingly when patients are diagnosed with Type 1, family members are screened. I don't want to give you the impression that universally we can screen and detect and prevent, but there are a few studies and this is being intensively studied and has been for decades, suggesting that there may be some immunologic agents that could be useful in preventing the onset in the susceptible before they have full-blown disease.

Host: Wow. Okay.

Dr. Gaudiani: The hooker is, that these medications could have side effects. So you want to be sure you're not giving a youngster medication that's going to have side effects, unless you're really sure you're preventing disease. So, this is a very, very complex issue, but to circle back, I think I wanted to make sure I've left you with the correct impression. One can't separate Type 1 and Type 2 by age, but in general, it's a disease of younger individuals. It can occur as young as six months, although that's very rare. And it can occur unusually in the eighth and ninth, decade of life, but usually in children and young adults. And young to middle age adults.

Host: Okay, well, thank you for clearing that up. I appreciate it. So you've told us the history of insulin. So can you now fast forward us through the years to present day on how insulin therapy has evolved since that initial discovery and what insulin means to people living with diabetes? I mean, it is life saving, right?

Dr. Gaudiani: It is lifesaving. And I also want to tell you, Bill that it's life saving, not only for Type 1s, but for many Type 2 patients as well, because Type 2, which we don't always get into in these discussions, but we should. Remember again, those patients, because in the past, they often succumbed to the complications of Type 2 diabetes early when it was more poorly controlled than it is now. They had heart disease. They had kidney problems, blindness, loss of vision. Now many of those complications are prevented. They're living long lives. They get into a phase of insulin deficiency, not only insulin resistance. Type 2 is marked by both insulin resistance and insulin deficiency. And when patients are living long lives, and they get to a point, the Type 2s where they need insulin too, and this is wonderful; they don't always need the same complex regimen Type 1's need, but sometimes they do need intensive insulin.

What we've learned over the decades is that a single shot of long acting insulin, which is all we had at the beginning, is not physiologic. That's not how insulin works in our own bodies. In our own bodies, our pancreas is always making a little bit of insulin all the time, even when we're not eating, just to keep our metabolism and our blood sugars stable. Glucose being the fuel for the cell, keeping it ideal. And then every time we get to a meal, our pancreas secretes an extra burst of insulin to cover the fuel that's coming from that food. The glucose, eventually things get broken down to glucose as the basic fuel.

So we have tried to mimic that with the creation of both specific insulins that have long-acting properties and can be given as a single dose or twice a day. As a basal what we call basal insulin. And now there are also a number of short acting insulins, and those are useful. And given before meals, before snacks, so that patients are able to utilize all their fuel.

Host: So these advancements give people an option. Now you said there's medication that can help regulate people over a longer period of time. And then there's also one that you can take right before meal time, to give an insulin boost.

Dr. Gaudiani: And now Bill, there are insulins coming out and they're almost here. There's a weekly insulin. That's just coming out. That's very, very exciting. That's going to be great for some patients. There is inhaled insulin. The safety long term is still being studied, but it's on the market. It's a wonderful agent as well. And it's an adjunct, in certain particular clinical situations. It provides benefit. So I think the advantage here is for Type 1s and people who have significant insulin deficiency to be seeing physicians who are familiar with these different insulins, as well as insulin delivery devices, right. In the old days, needles that our grandmothers used, had to be sterilized, about an inch and a half long. Glass syringes, down to then the development of these tiny little syringes with tiny little needles. We have insulin pens. Which are, have a little cartridge and look much like a ballpoint pen with a little needle at the end of it. And insulin can be delivered very conveniently without having to carry bottles and syringes around with those pens. There are Smart Pens that have a little computer and Bluetooth in them essentially. And they give insulin by direction according to one's blood sugar, they make some calculations and recommendations and they give insulins in even a more sophisticated way that's very helpful. And of course we have insulin pumps. Which are small devices that have a reservoir of insulin. And a patient wears that pump with a small subcutaneous needle under the skin that's taped down. And they get their insulin continuously and they do not give injections. And that usually is an automated device and most of them now, are associated with a continuous glucose monitor. So the monitor is always checking the blood sugar. It's talking to the insulin pump. The insulin pump is responding to that. And adjusting the insulin every few minutes. So that's what is called the artificial pancreas. If you've heard that word. And that's called an automated insulin device. So that's where we've gone. So it's been a big journey.

Host: Amazing. This journey hearing you talk about, basically the thick goo that they were trying to inject a hundred years ago to today with all the things you just listed, just absolutely amazing. So, let me ask you this then, last question, Dr. Gaudiani. Thank you so much for your time as always. Can you talk about the diabetes care at MarinHealth, specifically in this 100th year anniversary? Is there anything new you'd like to share with us? How has this changed the way you're treating patients today?

Dr. Gaudiani: We're lucky here. We're in a place in the country where many, many patients have insurance. Many people, most people have some access to medical care and here in Marin County and within MarinHealth, I was fortunate to be able to co-found the Braden Diabetes Center with Mr. Braden, which opened its doors just eight years ago. But I've been here now 35 years practicing even before the Braden Center. We've been, the Braden center and MarinHealth made a big effort to recognize the hundredth year of insulin this year. We've reviewed all our insulin protocols. We actually have banners and pins and we've had a series of lectures. We had an amazing Fall Fest with a speaker.

We have a Fall Fest every year with a huge academic speaker. And we had Dr. J. Scarlett who is an international speaker talk about the future of Type 1 diabetes insulin. And that was a fantastic talk in October. So we have marked that. We are trying to improve our intra hospital diabetes care all the time with our diabetes care program and our glucose management team there, as well as the outpatient team at Braden. We're opening a podiatry clinic for foot wellness, which includes patients on insulin, of course, and patients who are not on insulin. But I would say there's just more awareness and more commitment to the patients with diabetes to help them.

As we say in our motto, travel through live well with diabetes. I just want to say one thing though. This is not the case, uniformly, even in our country, much less in the world. Diabetes is a disease that's still killing many, many, many people. And unfortunately, even though insulin has been around for a hundred years, insulin access is very limited. Insulin that used to cost 60 to 50 years ago, 75 cents for a bottle, now costs $400. And many patients will need five bottles, six bottles a month if they're on full insulin. So you can imagine what happens if you don't have insurance? It's impossible.

Host: Right.

Dr. Gaudiani: So there are the most frequent cause of people dying of diabetic ketoacidosis is no access to care and unfortunately children still die of this disease. This is what is the heartbreaking thing. In diabetic ketoacidosis, not because we don't have the treatment, but because they don't have access to insulin. So this is something that's coming before Congress and my colleagues were actually talking about it this morning. We are increasingly trying to make politicians aware that insulin is not an option, it's a life necessity for many patients. And we have to do better for our patients in terms of access to care and access to supplies. It's an already an enormously difficult disease to treat at its best. But people need access to care and supplies. Of course that's expensive and complex. But I think there's more awareness Bill, that's that's the encouraging part. And many more people, including politicians are realizing this and trying to support our efforts. So, I guess the bottom line is good, but the parenthesis is there are still a whole lot more to do.

Host: Right. Well, at least people like you have identified this and are bringing it to politicians who can hopefully write policy and make changes because you're right, you said this was kind of a complex problem. Well, when you put it in this way, it's not very complex. These children need insulin right, to live.

Dr. Gaudiani: Absolutely.

Host: And access to care should be there for everyone.

Dr. Gaudiani: It should be in. And then the data is really very clear that minorities, ethnicities and ethnic disparity absolutely correlates with mortality.

Host: Health inequality in this country and around the world, quite frankly, has to be addressed. We have to talk about these things and we have to stand up and we have to fight for health equality and get these changes made. So, we all can live in a more equitable society. Especially in America.

Dr. Gaudiani: That's what we want for our children and our grandchildren. And we have to look at history, I think and realize we can't stand aside from other countries. Children from other countries will marry our children. We all come from other countries, our grandchildren will be international.

Host: That's so true.

Dr. Gaudiani: And I think just so shortsighted, not for us to recognize that. But of course these are economic decisions that are vastly complex. Nonetheless, I think we're in conversation and I want to really thank you for having a program that gives us a chance to talk about it, to talk about the positives, to talk about the progress. And to remind us all of where we still have to go and work, I'm really dedicated to this. My team is, I think MarinHealth has made huge strides in focusing on diabetes. And as opposed to 10 years ago, you know, diabetes is its own service line at MarinHealth now, both with inpatient and outpatient care that we provide at Braden and all the physicians, nurses, and health practitioners are so much more aware and have really been tremendously on board, with my efforts to improve things for our community and for the North Bay.

Host: We applaud you for that, 35 years at MarinHealth is just amazing and dedicating your life to diabetes, research and treatment and helping individuals. So just amazing. And I'm glad that we, have a format like this podcast where we can just talk and hear you tell us about the history of insulin and diabetes, because you know, we're so caught up in our day-to-day lives, it's kind of nice to sit back and hear you talk about how insulin was created and what it was like in the early days.

And what this meant for people and what it was like living with diabetes a hundred years ago, how it ravaged people's bodies, where they were basically starving to death because they cut out all carbohydrates. It's just a amazing story to hear where we were and where we are today with all of the advancements, but still, as you have told us, a lot more ground to cover. So, so important to remember that as well. We're not there yet. We're getting there, but we've got to make health more equitable for everybody so they can get this life saving care.

So thank you, Dr. Gaudiani. It's always a pleasure to talk with you. Thank you for sharing your insight and your history lesson with us. It's a very important.

Dr. Gaudiani: You summarized that so well, Bill it's an honor to be on your show again. And to hear your expertise. I know you, do so much work in this area and help get the word out to folks. And for myself, I'll just say it's been an honor taking care of patients in Marin for this long. And I can also say it's been a joy. My patients are my friends. In the old days, we didn't have pediatric endocrinologists and I used to see even the young children and now they're grown adults. They're amazing. They're parents themselves and have taught me so much about courage and persistence. So let's hope that we keep moving forward. I know that we will, and I really, really appreciate the opportunity to share some time with you this morning.

Host: Yeah, you bet. And we appreciate you. And everything you do at MarinHealth and the Braden Diabetes Center. Dr. Gaudiani thank you so much again.

Dr. Gaudiani: Thanks so much. Bye bye now. Have a great day.

Host: It's always great to talk to people that are so passionate about what they do. And that's what you find when you talk to the health professionals at MarinHealth. And once again, that was Dr. Linda Gaudiani. And for more information, you can always visit mymarinhealth.org. And if you found this podcast helpful, please share it on your social channels and check out the full podcast library for topics of interest to you. This is The Healing Podcast brought to you by MarinHealth. I'm Bill Klaproth. Thanks for listening.