← Taking Control Of Your Diabetes® - The Podcast!
Taking Control Of Your Diabetes® - The Podcast!
Unlocking the Mystery of Type 1 Diabetes – The TEDDY & Cascade Studies with Michael Killiam
00:33:52
Loading summary
Transcript47 lines
- [00:00]
Michael Killiam
Foreign.
- [00:20]
Dr. Steve Edelman
Hello everyone. Welcome to the taking control of your diabetes podcast and I'm One of the two co hosts, Dr. Steve Edelman and unfortunately my good friend and colleague and co host Dr. Jeremy Pettis can't be with us today. We both have type 1 diabetes, we work at UCSD and we also work for the not for profit taking control of your diabetes. Want to remind everybody to please like and subscribe to the podcast and remember that we're videotaping all our podcasts. So there's going to be on YouTube as well as the podcast stations and look out for a lot of great videos we have set up for 2025. So today we're going to talk about the Teddy and Cascade studies. These are two 20 year long studies looking at environmental and genetic factors that lead to the development of type 1 diabetes and I could say in at risk individuals and we'll learn a lot about it. Today we have Michael Killiam, he's the director of the clinical services at Pacific Northw West Research Institute and he is one of two researchers that have been doing this very long running international. These international studies that have given us so much information on what are the risk factors leading to Type one and I would say you might agree had brought up probably more questions than answers because this is a tough area to tackle which is the cause of type 1 diabetes. Introduce yourself Michael. And my first part as you introduce yourself, what led you to spend 20 years of your professional career in this area?
- [02:11]
Michael Killiam
Okay, great. Thank you so much and thank you for having me here. I will say I got a chance to listen to some of your podcasts and I always find it a little more fascinating when you have an endocrinologist who has that real personal experience with type one. So let's see. Myself, I have, let's have it with my husband for about 31 years now. We have two grown kids. I've been living in Seattle for about 30 years. Before that I worked as a paramedic in Alabama and down in Los Angeles. Not a big fan of California, but.
- [02:51]
Dr. Steve Edelman
You know what a paramedic turns type one researcher. I love it. Well, tell us a word about your co host because I know you guys are a close group of guys that working very hard to advance the field of type 1 diabetes.
- [03:06]
Michael Killiam
Well, so I'll say, you know the, the thing that got me into this is like, you know, I decided to go back to school and look at other things and as a student started doing research and just found the idea of it and kind of the way it Worked and the puzzle of it. Very, very interesting and so very exciting that, you know, I've gotten to spend this much time doing this. I should correct you a little bit. You said, you know, one of a couple on Teddy. There are so many of us on this project. I mean, it's a huge project with six clinical centers around the world, and it's been an immense project and joy to kind of undertake as we try and understand, you know, what are those environmental factors that kind of trigger the disease? I'll step back a little bit. Kind of, you know, before Teddy started, we had, you know, some precursor studies that looked at, you know, trying to understand the disease process. And with Teddy, we were pretty clear, okay, genetics, you have to be predisposed to get type one. But then there's this black box. Something happens. And that was really what we were charged with. And I have to say, the NIDDK was very clear from day one all the way through today. It's like your first goal is to understand what are the environmental factors that trigger type 1 diabetes. And you're absolutely right. It has led to probably more questions than answers. But now we're asking better questions. The more we understand, the closer we can get to really grasping this and understanding how to prevent this disease.
- [04:49]
Dr. Steve Edelman
Yes. And when I listened to your podcast that you did in the past, you said something very important. This kind of research doesn't occur overnight. It takes time. And your advances within your study probably change direction as you learn more and more. Well, let's. Let's tell our listeners and viewers now what is the Teddy study? And it stands for the Environmental Determinants of Diabetes Study. So it's such an important study because, as you mentioned previously in your work and your publications, you get the genetic risk. Not everyone goes on to type 1 diabetes. So what can explain those that go on and those that do not?
- [05:33]
Michael Killiam
So kind of what we under. Or what we believed, our hypothesis that we wanted to test here, was that you start with genetic predisposition, and then something in the environment comes along and triggers the immune system to start the attack. The vast majority of people. I mean, there's about 5% of the people walking around who are genetically predisposed to get type 1, and the vast majority will never get type 1 at all. And so there's. There's something in, you know, in that smaller set that starts the process going. And there's a lot of different things that we looked at and we were interested in, but, you know, viruses and diet and psychosocial factors all really kind of continue to kind of bubble up to the. To the top there. And so, you know, our goal was really just to look at, you know, to follow these kids, which is, you know, an observational study for they were from birth to 15 years. The whole study is a little over 20 years, but the kids are birth to 15 years. So it's, you know, it's a lot trying to figure out and tease out kind of what's important. Unfortunately, you know, we aren't allowed to keep them in a bubble and, you know, and then test one thing at a time, like we would like. But, you know, this is where kind of the collaboration really comes into play, is that by having such a large set of participants, we're able to kind of tease out some of those more important factors. I would just say that, you know, projects like Teddy, there are several consortium projects that have been funded through projects like the Special Diabetes Program through the nidk. And it's like, you know, without that, it's like projects like this aren't possible because it's extremely expensive and time consuming to really do this and to get good quality data for this long.
- [07:28]
Dr. Steve Edelman
Yes. I mean, reading about this study, maybe you can talk about some of the challenges and what you might have been looking for when you saw these patients and collected information on them every three months. You know, from blood to urine to stool, nail clippings, even hair. But I heard that some of your participants didn't like getting their hair cut before the usual time. You've collected tremendous data, and what kind of things were you looking for? And that's a tremendous, I would say, effort on the side of your volunteers that volunteered them or their kids to be in the study. I don't know how you did it and maintain such a high level of recruitment and retention in this study.
- [08:10]
Michael Killiam
Well, I think there are a variety of reasons why it was successful, but as far as what we're looking at, in some ways, it was like really broad strokes of what can we possibly find. Obviously, there were some things that we were interested in looking at. Some previous studies had hinted at things, for example, cow's milk being a risk factor. And so that was one of the things that we wanted to look at as well. Nice thing about Teddy is that because it's large enough, we have the power to not just look at things that may trigger disease, but things that may be protective.
- [08:49]
Dr. Steve Edelman
Yes.
- [08:49]
Michael Killiam
And cow's milk was one of those. That was really kind of nice because what we found was it wasn't so much that cow's milk was a risk factor, but that breast milk was protective. And so understanding those kind of individual things, how do we keep these people for so long? I have to say that really goes down to the clinicians. I think that people join research because they, you know, one see some potential that this may help their child as well as potential that this may help future generations. But honestly, I don't think that gets you to commit for 15 years.
- [09:31]
Dr. Steve Edelman
Yes.
- [09:32]
Michael Killiam
And I think the big difference there is the clinicians that we have, the team of people, and so many. I'm constantly amazed at how many people are still on this project that were on this project when I first started. And forming those relationships with the families is really what keeps the families in. One of the things we do at the end of the study is we ask them is like, what are the things you'd be willing to do again? And what are the things that you think worked well or didn't work well? And consistently, people praise their clinician, and it's like, it's that. It's that connection that really keeps them coming back.
- [10:14]
Dr. Steve Edelman
That that's where it's at.
- [10:15]
Michael Killiam
It's.
- [10:15]
Dr. Steve Edelman
It's the relationship. And, you know, you got to have faith in who you're working with. You got to have trust, and. And the clinicians have to have empathy and understanding. So I've done clinical research my whole career, and that's it right there for recruitment and retention, for sure. Well, let's. Let's go down some of the things maybe that you guys have discovered. How about let's just start off with viruses. You know, everyone has heard of the Coxsackie B virus, and I know that certain viruses have been associated with folks coming down with type one. And the other thing I'll say is, you know, many of my patients, they're always trying to figure out why they got type one. And they'll say, yeah, I had this severe virus a few months before, and I used to say to myself, oh, they're full of it. You know, they're just trying to associate something, but they might have something there. Based on some of your research.
- [11:06]
Michael Killiam
I would say yes and no. How's that? So one of the things that we've learned is really the autoimmunity. The process of the attack on the pancreas starts often years and years before the clinical onset of diabetes. And I hear those stories, too, from our participants, where it's like, oh, I got really, really sick. And then, you know, a month later I was diagnosed, like, yeah, that's probably what put you over the edge, but, you know, your body was already destroying those cells. And that had been going on for a while. Viruses have long been looked at. Some research studies have shown, okay, look, viruses definitely. And others have gone back to test it and not really been able to see any correlation. And Teddy, we were. We were able. Because we were following these children so closely the first four years of life, every three months, we were really able to kind of look at the viruses that they were. That they were exposed to. I should also say, in addition to seeing them every three months in clinic, they also mailed in monthly stool samples. So we had lots of biological material to work with. And since viruses are shed in the stool, we were able to kind of analyze that. And I think one of the things that Teddy has found that is unique is that it's really how long that infection persists. So it's not that you get a virus, but it's how long does that stay. And so we saw that, say you have a viral exposure and we see it in one stool sample, then there may be a slightly increased risk, but it's significantly different when we see it at 60 and 90 days, there's a definite increase in the autoimmunity. And so it's how long does that viral infection persist?
- [12:59]
Dr. Steve Edelman
Yeah, and I read that the hypothesis could be that they mutate if they've been around for a long time, and that mutation somehow leads to the development of destruction of the beta cells.
- [13:11]
Michael Killiam
Well, viruses are amazing at being able to adapt. Right. And they will live inside ourselves as long as they can and just kind of hide there. And unfortunately, the beta cells are one place that certain types of viruses are attracted to.
- [13:31]
Dr. Steve Edelman
Yeah, and I love that quote. Studying viruses like stalking ghosts. Was that the right phrase? I love that, because then you can really have a picture view of what it's like. It's not easy. And anybody that's knows anything about viruses, how they mutate, right before you try to exterminate them, like the COVID virus, for example, all the different variants. So sometimes these viruses are harmless, and some others lead to the development of type 1 diabetes. What about the HLA region of the chromosome? And you might want to, if you can explain that in more lay terms, you know, because it's a complicated area.
- [14:13]
Michael Killiam
The HLA region is basically just a section of your chromosome that encodes for how your immune system responds. We talk about the antigen, say the virus are a portion of the virus being presented to the immune system. The HLA region is one of the areas that decides how your body responds to those. Unfortunately, certain HLA types also increase your risk for developing autoimmune diseases like type 1 or celiac disease. And so with Teddy, we started out with, you know, I will say because it was such an ambitious project, we really started with like the highest of the highest high risk. And so it wasn't designed to really catch everyone, but to catch those who were more likely to progress during the time that we follow them. And what we found, even that, you know, there, there are much more that we should be looking at besides just the HLA area. And so that kind of, I will, I'll give a quick plug for Cascade, that kind of build, build on Cascade there, which is our next project, which we started a few years ago. And you know, understanding, okay, these genes, each of these genes weigh a little bit differently, as well as some of them provide protection against others. And so understanding where those are and how that interplay goes to allow us to better in the future, give a risk estimate to the parents of their children of like, over their lifetime, what are their chances of developing type 1 diabetes?
- [16:02]
Dr. Steve Edelman
Yes. And as I understand it, Cascade is looking for more interventions to prevent the development of type one. I mean, I've heard you say, you know, finding the cause is one thing, but then finding an intervention is another. And is that what Cascade is about?
- [16:20]
Michael Killiam
Well, kind of, you know, Cascade, our goal is really to get, get screening to be part of the standard of care. You know, studies like Teddy have really shown us a lot, but Teddy, where it's like, you know, we did this very expensive typing. We also did a very expensive follow up. It's not, it's not practical. You know, we just, quite frankly, we don't have that many healthcare dollars to spend on it, unfortunately. And so Cascade, we were able to take some of the things that we learned and it's like, okay, what is really important here when it comes to predicting and understanding a child's risk. And so we better defined, you know, the genetic, the genes that we look at as well as kind of what the antibody schedule is. When you have a very robust antibody schedule like Teddy had, we're able to then pull out certain visits and be like, okay, at what point do you, you start losing actual cases? And so then narrow it down to really just about three visits that they need to do over childhood, which is incredible to think we were doing more than that in their first year.
- [17:36]
Dr. Steve Edelman
Well, that's what you discovered. The high risk times to do studies and look for these markers. Now I've heard you talk about modulators. And so can you talk about like vitamin D, vitamin C, omega fatty acids? And what kind of results have you gotten in terms of their role in delaying the progression to type 1 in high risk individuals?
- [18:04]
Michael Killiam
So I should start off, I'm not the nutritionist, so maybe not the perfect person. But these things help kind of, you know, vitamin D particularly will help kind of lower your immune response. And so when you have someone with a very, with autoimmunity, you know, potentially vitamin D can kind of decrease that response. And what we found is that there's, you know, just like anything there, there are huge variations in that. One of the things that we discovered was it had been, it'd been shown before, there's a vitamin D receptor gene. But one of the things that we found was that certain types of that gene, even if doesn't matter how much vitamin D supplement you get, your body can only absorb so much. The idea that we would just be able to give everyone vitamin D supplements, it's not as effective as well as potentially the amount that you'd have to give could be, could be a little toxic. But understanding kind of how these things play as well as in the different individuals and the gene and the environmental interaction there, understanding that a little bit better kind of helps us understand and develop better interventions. I think there is, I can't remember where it is right now, but I think there are a couple of studies that are looking at vitamin D intervention to kind of slow down or stop the immune response. And you know, at the point where the kids are just, I say just, but where they're antibody positive but they have no clinical signs of type 1, which in my opinion is the optimum time, that's when we want to intervene, when you still have plenty of beta cells to make enough insulin.
- [19:57]
Dr. Steve Edelman
You know, I tend to agree with you. My CGM just beeped. I'm not even sure where my phone is right now, but that's okay.
- [20:07]
Michael Killiam
In the chair next to you.
- [20:08]
Dr. Steve Edelman
In the chair next to me. Thank you. I don't want it to beep again, but you know, having diabetes for 54 fricking years. Hurry up, man. I need something for people. Already have it. Yeah, you know, I mean, I was gonna say that there are so many hypotheses out there and, you know, finding one where you can get a positive result in people early in stage. And you're talking about stage one type one diabetes. And I happen to agree with you because the earlier you intervene, the more viable beta cells you will have. So I think, as you know now, the tablizumab story, it's proved by the fda, Teasel, that's in stage two, and they already have to have abnormal glucoses. So I think our philosophy is the same. Probably most people, the earlier you can intervene, the better. But trying to identify those individuals. Now, you said that you took the very high risk patients and then looked at some of these potential causative factors. What was your definition of a high risk individual that would be put into Teddy?
- [21:19]
Michael Killiam
So the. So there is. I'm trying to think where absolute criteria was. So the idea was, if you look at risk over time, the top 10% of the people who would develop type 1 diabetes. So basically they had to have to be in the study, they had to have all both copies of genes that put them at risk. We define the genes as susceptible, resistant and neutral. And susceptible. And neutral is still at risk for diabetes, but it's not as high a risk. And so all of these children had to have really both susceptible genes. And a subset of our population obviously also had family members with type 1 diabetes. And so they had additional genes that were going on behind the scenes that we weren't necessarily looking at initially for screening.
- [22:19]
Dr. Steve Edelman
Yeah, we know having a first degree relative puts their risk 15 times higher than others. And so that's important. And then they really get into it. If you have two relatives that have type one, if you have your mother who has type one, your father or identical twin. So you took these high risk individuals and looked for triggers that either prevented them or protected them from going on to type one. Well, if you had to summarize, I know this is off the top of your head. Some of the key findings of the Teddy so far. And how many individuals were in the Teddy? Say, I believe it was 6,000. Is that right?
- [22:59]
Michael Killiam
Actually a little over 8,700. Almost 8,800.
- [23:02]
Dr. Steve Edelman
Wow. Yeah. How could you summarize what some of your findings to this point in time?
- [23:09]
Michael Killiam
Well, I think kind of going back to what we were saying before, one of the things that we've really found is that there are this. Autoimmunity starts really, really young, not just for type 1 diabetes, but also for celiac disease and also for autoimmune thyroid disease, which we were studying those diseases as well, because there is a link between them and type one, and we want to understand that link. I was amazed. Typically you look at thyroid disease and you don't expect to see anything until right around puberty, whereas we were seeing things significantly Much earlier than that. I think that's exciting. I think that provides, you know, potentially another opportunity of, you know, a way to intervene a longer time to intervene. I will. You know, other things that we looked at are there, you know, are kind of discovered is that there are different types of Type one, if you will. You know, the outcome is the same, but kind of the way you get there is very different. The younger you are, the more aggressive the autoimmune process is. And you know, we've seen, we, we saw kids who would be, you know, they would go from antibody negative to antibody positive and then Type one in a course of like three months. Whereas with, you know, with the teenagers, you don't see that it takes years. And then as you get, you know, older adults develop Type one as well, just as many adults develop Type one as children do, which is why we've gotten away from calling it juvenile diabetes. But the disease process in adults tends to be a bit slower as well. And there are a variety of factors while that may be the case, but these do tend to show up and the way that you would want to treat them and address them are different. There are other things that I thought were, we talk about viruses. Viruses, to me is pretty exciting because we know how to deal with viruses. We have a very low toxic, low toxic way of dealing with viruses. Vaccines work. And if you have, if you're able to screen all of the children and understand, you know, know the children who are at risk, then, you know, potentially you could change their recommended vaccine schedule and, you know, quickly reduce the incidence. You know, we may not get rid of Type one altogether. We, but quickly reduce the incidence without, you know, and without introducing a lot of, you know, typically it's the immunomodulators that you have to, that you'd have to use, whereas this is a much lower toxic and, you know, something they won't have to like, you know, be on for the rest of their life, if you will. Another finding that we, that we found that I, I think I say this every show I'm on, so forgive me, that's okay. But probiotics in the first month of life, we were not expecting this. The nice thing about being in four different countries is that there are different recommendations for, you know, for introduction of, you know, of foods and, you know, medications and probiotics in the first month of life, actually we saw a difference in autoimmunity. These children had a lower incidence of autoimmunity than those that didn't. And I love probiotics it's like no toxicity. It's just generally good for you.
- [26:38]
Dr. Steve Edelman
Anyway, the probiotics in the, in the milk or how do you give the kid that? Can't chew, obviously no teeth.
- [26:47]
Michael Killiam
Right, right.
- [26:47]
Dr. Steve Edelman
So.
- [26:48]
Michael Killiam
So they have a liquid formula that they would put in, in the, in the bottle. And so you can mix it either with breast milk or with, with the regular cow's milk formula.
- [26:58]
Dr. Steve Edelman
Wow. Well, the other issue that you touched on is celiac and autoimmune thyroid disease, and that's Graves and Hashimoto's. Yes. As I understand it, those folks have a much higher risk of developing type 1 diabetes after developing one of those autoimmune conditions. And would you put them on the same level of risk as a first degree relative with Type one and those individuals? My impression is they should be the highest level of screening along with family members.
- [27:33]
Michael Killiam
I don't know that we necessarily put them on the same risk level. Celiac disease, it does increase your risk. The problem is that, take coexities, for example. It's like you could be at risk for celiac, but then have one copy of the gene that's pretty protective against type one. It's not going to protect you against celiac disease, but it would be more protective against type one. And so their risk may not be as high. But I do agree with you completely that these people have some of the genes that would increase their risk. And so it is absolutely worth screening them and worth looking at. We know, and we've seen over and over, not just in Teddy, but in other studies, that the earlier you catch it, the better the outcomes. And those outcomes, those improved outcomes last for years after diagnosis. And so it's not just avoiding hospital stays and time in the icu. It's better glucose control for years to come.
- [28:40]
Dr. Steve Edelman
Yep. And I'm glad you mentioned that because one of the benefits of screening in a study like Teddy or any study for type 1 in the early stages is that everyone gets educated on the signs and symptoms of when diabetes starts to kick in. And you could avoid, like you said, intensive care unit visit, a really dramatic presentation where the whole family's disrupted. So I think even knowing that you have risk is important and that has long term benefits because you can have better control from the very beginning. Well, Michael, in 2025, where do we stand with screening for type one? And if, if your centers are still looking for individuals for future studies, it's probably good to let us know how to get more information.
- [29:28]
Michael Killiam
So I will say in 2025 it is very exciting for screening. And, and part of that really is with the first approval of an FDA drug prior to diagnosis. I think that's going to be one of many that are in the, that come out. But, you know, it's very exciting. There are programs all over the world that are coming up. We actually collaborate with quite a few of them providing, you know, genetic and antibody work for them. So, you know, it's an exciting time. But at the same time, there's still so much to do because so many providers don't know who should be tested and don't necessarily have the information. And so that's still very much a part that we and others are working on because it's like you don't necessarily expect the general population to know, but certainly when they're seeing their provider, they should be able to make those recommendations. And those are changing. Cascade right now is just screening newborns up to nine months born in Washington state. And the reason why we're choosing, the reason why we're using that group is that we want this project will end with an application to the Board of Health to add Type 1 screening to the newborn panel. And so we're working with the newborn screening program so that we are using the exact same samples that they collect. We're not collecting anything more, but to demonstrate that those samples work and it's sufficient and it can be done without by their current system.
- [31:12]
Dr. Steve Edelman
And just to reiterate, that's all babies, not babies with a family history or any risk factors. So I think that'd be cost effective as well. I think we wanna change someone's life for the better. But if it's cost effective, it's a win win.
- [31:28]
Michael Killiam
Well, and unfortunately, I mean, it really does have to be cost effective because I mentioned earlier, it's like we only have so many health care dollars and you know, and trying to look at, you know, how that gets spent effectively. And we have an economist that's working with us that it will help us with this final application to look at, you know, okay, if we look at screening everyone and then the children that need to have antibody follow up, you know, what does that look like compared to we don't do anything and then the children in the hospital and ICU stay for a long time. It's been like, okay, the math doesn't add up. It cost way more to screen. But I think that we are, if not there, we are really, really close.
- [32:15]
Dr. Steve Edelman
Yeah. Well, thank you for that. Well, in closing, I want to make sure all of our viewers and listeners know that any first degree relative of someone with type 1 and or with other autoimmune conditions really should be screened and it's very easy to get screened these days. Information for screening is on our website@tcoid.org and if you want more information about Michael and all the studies are doing specifically the Teddy and Cascade I would say pnri.org would that be the best website?
- [32:50]
Michael Killiam
Absolutely and you know we have in the past kind of done we don't necessarily have a general population project right now but it is something that we're hoping to get kind of up and going again and so you know our website would be a great place to kind of get that information as those things evolve.
- [33:08]
Dr. Steve Edelman
Well thank you so much Michael. It's been an ultimate pleasure of mine to get to talk to you about this such an important study that's been going on for so long on a very complicated condition such as the cause of type 1 diabetes.
- [33:26]
Michael Killiam
Thank you so much for your time Sat.