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Foreign.
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Welcome to ACE Podcasts. Thanks for tuning in as we elevate clinical endocrinology by taking deep dives into trends and topics that can help us improve our patient care and global health. Find the latest episodes on aace.com podcasts and now let's meet the endocrine experts who will be talking with us today.
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Hi, and welcome to another Ace podcast. I'm Dr. Lubaina Praswala. I'm a clinical endocrinologist and assistant attending physician at Memorial Sloan Kettering Cancer center and assistant professor of medicine at Weill Cornell Medicine in New York. I am the online resource workgroup leader for the Diabetes Disease State Network at ace. My area of expertise is diabetes management and the use of advanced diabetes technologies in people with cancers. Today, we are discussing a very important and exciting topic, the early detection and monitoring of type 1 diabetes. Before we begin, I'd like to thank our sponsor, Sanofi, for their support in bringing this engaging podcast to our listeners. Joining me today are two leading endocrinologists, Dr. Jeff Unger and Dr. Javier Morales, who bring extensive experience in managing diabetes. Dr. Unger, welcome to our podcast. Please introduce yourself and tell us a little bit about yourself.
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It's great to be here. I'm a family physician as well as a diabetologist, practicing concierge medical care, dealing with intensive diabetes management in Southern California. And I am honored to be here.
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C
Thank you, Dr. Unger. Dr. Morales, please introduce yourself to our listeners.
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Sure.
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My name is Dr. Javier Morales. I also am an internist. I practice out in Long island, but I am a diabetologist. I am associate clinical professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra Northwell, as well as practicing with the Advanced Internal Medicine Group located in East Hills, New York. Thank you for inviting me.
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C
Thank you, Dr. Morales. It's great to be a part of the team here. So let me start by highlighting the significance of type 1 diabetes. There are about 8.4 million individuals worldwide with type 1 diabetes, and there are predictions that this number may even increase to 15 million by the year 2040. Dr. Unger, can you please elaborate on the enormous burden of the disease associated with type 1 diabetes?
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Yeah, it's scary. Every year, we've got 64,000 new Americans that are diagnosed with type 1 diabetes. And the problem here is that it's this very scary disease. Think about it this way. This is a disease that. That never goes away. And it's like being at work 24 hours a day for the rest of your Life. And it's really important for people to be able to identify this disease state early, to be educated on it, and to treat it intensely right from the start.
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I think also really important is the fact that you don't really need to be young in order to have an established diagnosis of type 1 diabetes. In fact, probably about 40% of patients with type 1 diabetes, they're diagnosed about less than age 20, but about 60% of those patients tend to be above age 20. So we shouldn't really let age be a discriminating factor towards that type 1 diabetes diagnosis.
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You know, Javier, that's really a good point. But the way I look at it is, ask anybody that comes into your office what scares you the most about having diabetes. And there are. Their answer is 100%. They know about this disease state, and they say, I don't want to lose my eyes, my kidney, or a leg, and I want to be able to watch my daughter walk down the aisle some days. So they don't want heart disease either. But we know if we could find this disease state early and treat it aggressively and intensely right from the start, then there's very little likelihood they're going to get these complications. So we got to do it. We got to screen these patients early on and do something to minimize the effect of this disease on their bodies.
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Yeah, absolutely. If we can actually delay the progression and delay the need for intensive therapy with multiple injections of insulin, certainly it would be beneficial for the patient as well as the family members. They're very important as well.
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Type 1 diabetes involves something called diabetes distress syndrome. About a third of the patients that have diabetes high here, they are anxious every day. They're worried their blood sugar goes up to 180. What do I do? How do I exercise? What, how do I sleep with this? And then they got their wives behind them yelling, you're doing it all wrong. This is a disease state that really requires a team effort. But again, it goes back to primary care physicians like you and me. We're the ones that find these people that have risk factors and, and we need to screen for them.
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Yeah.
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And the diabetes distress is very real. And it's applicable not just only to the type 1 diabetic, but also the type 2 diabetic. And as you mentioned before, I think it's really important to remember that it's not just about the clinician that's taking care of the patient, but there are many hands that are involved in the care of these patients that include pharmacists, diabetes Educators, and they're also very instrumental in trying to dispel some of this diabetes distress, making the disease more manageable. This way, they could succeed in achieving their goals.
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C
That was very detailed. Thank you. I think it's the early detection that you had mentioned is key. To Summarize this point, Dr. Morales, can you please explain the different stages of type 1 diabetes and the key factors that are present in each of these stages?
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Age.
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I would love to. Well, first and foremost, I'd like to say that, well, maybe we should be screening. And if we are going to be screening for diabetes, then we need to assess certain antibodies in order to detect what the risk actually is to progressing onto type 1 diabetes. We'll talk a little bit about these antibodies shortly. But nonetheless, there are three stages that have been defined. The first one is really with their immune system has started attacking the beta cells, but the blood sugars tend to remain in normal range and there's absolutely no symptoms whatsoever. The second stage of type 1 diabetes, the beta cells continue to be attacked, but we start to see a little bit of dysglycemia, dysregulation of blood glucose. So these blood sugars tend to be outside the established normal range. And again, no symptoms have evolved as of yet. And then we finally get to the third stage of diabetes, which is where significant beta cell destruction has actually occurred, where you've lost the capacity to produce sufficient enough insulin to bring down that blood glucose. Here you start to see hyperglycemia, where blood sugars tend to be a little bit higher than what we normally find in a healthy range. And insulin will be required in order to control these blood glucose ins. Now, some of these symptoms we're very, very familiar with in these patients that have poorly controlled diabetes, and that includes the increased thirst, the frequent urination, the dry mouth, the fatigue, and the unexplained weight loss. All of these can actually suggest significant glucotoxicity, with the end result being the potentially fatal ketoacidosis.
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Fascinating. So, to summarize, I guess we can say that all stages have the presence of insulin. Autoantibod invasiveness of disease with beta cell destruction varies throughout the course, manifesting with specific clinical presentation and biochemical abnormalities in each of these stages.
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I'm going to. I'm going to take a different approach to identifying people with type 1, type 2 diabetes. Javier, how often do we see people that they don't know if they have type one or type two? And if you ask clinicians, a lot of times they get it Wrong. They're treating patients with type 1 diabetes as having type 2.
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Very simple.
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Bonia. Let's say Javier wakes up one day and he tells his lovely wife, I am sick and tired of my pancreas. Wife says, don't worry, Javier, just go down to Walmart. They got a sale on pancreas. And you get a whole pancreas brand new for A$98. Javier likes that because he hates his pancreas. He heads down to the local Walmart, he picks up a new pancreas. He's so excited that he hates his pancreas. He pulls it out, throws away, plugs the new one and pays $98. Everything is really good. And then six months later, just like everything else you buy at Walmart, the warranty runs out. And then the body starts saying, what you do here? This is not my pancreas. And the body develops antibodies against the pancreas. And like Javier mentioned, there's four different antibodies that we can screen for. And when you have those antibodies present, the disease state of type one is diagnosed.
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And, and who should be screened for this? Dr. Unger, would you say we screen.
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Anybody that is at risk? So these are patients that have a family history of an autoimmune disorder, a family of type 1 diabetes people that may have Hashimoto's thyroiditis. If they have celiac disease, vitiligo, other autoimmune disorders, then there's a pretty good chance they may screen positive for at least one autoantibody. If you have a positive one auto antibody, it doesn't mean you're moving towards diabetes. You really have to have two. So we screen children, we screen adults, we screen anybody that has a tendency towards developing these autoantibodies.
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And that is important to remember that certain autoimmune disorders like you mentioned before, celiac disease and thyroiditis in particular, should be screened. There might be some genetic risk factors that do exist, particularly in patients who may have HLA Dr.3 or HLA Dr.4 serotype or genotype type of autoimmune disorders. And even in a patient with a family history of type 1 diabetes, having that one family member increases your risk by 15 times. So it is important to take all of this into consideration when it comes to screening.
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But here's the problem, Javier. We all see this, all of us. We tell family members they need to screen their kids and they put it off. They just, they just don't do it. But as been has been mentioned, if you don't screen, you're missing the opportunity to identify these people early. We have immune modulating drugs now that we could use to delay the need for using insulin in these patients for up to three years, which is a really, really big deal, because if you find a kid age 2 that has autoimmune disorder ongoing, isn't it easier to start insulin at a later age than age two? So we've got to identify these people, and then we've got to push them across the endpoint. We have to say, please do this for your family, screen your kids. And don't just say, I'm going to do it, do it.
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Well, Jeff, you had mentioned before about antibodies and antibodies that we can use for screening these people. And I think it's important that our audience really understands which antibodies to assess. I'm sure, Dr. Preswala, you probably check a lot of these antibodies with a lot of your patients in your clinical practice.
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Absolutely. And a lot of my patients and families are initially even overwhelmed and anxious and postpone the screening. Which really, you know, begs me to ask is what misconceptions about type 1 diabetes might prevent people from screening for autoantibodies? What do you think, Dr. Unger?
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I don't have a really good answer for that because to tell you the truth, I've got type 1 diabetes too, and I have not screened my kids. It's not a topic I don't know. But it's not that we're lazy or just forgetting things. Life gets in the way. I think as a family physician, we just have to encourage people over and over, do it. I sometimes I say to the patients, do it for me. Please get the screening done, because it makes me look good. If something comes up positive and you motivate them. And then here's the big deal. When they do screen, you have them come back even if it's negative, and say, I am so proud of you. You screened, everything's negative. We have to do it again in a year. Good for you. When's the last time we actually praised a patient for doing something right?
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So let's define these antibodies that the audience listening today should be using in order to identify some of these patients that may be at risk for developing type 1 diabetes. And these include insulin antibodies or insulin autoantibodies, so to speak. Glutamic acid decarboxylase, autoantibodies. We have insulinoma associated 2 autoantibody or Ia2a. We have zinc transporter 8 autoantibodies, and we have islet cell antibodies. So there's a total of five antibodies that we really should be screening for. Now, it's a mouthful to remember this if you're going to be ordering all of these things, but some of the commercial laboratories that we utilize actually panels that include these things and Trialnet happens to be one of these reference laboratories that have these panels. And online ordering via finger stick can actually be conducted as particularly for some of the younger population that may need to be screened. Now, again, if more than two autoantibodies are detected, we really need to explain the significance of these results and, and we have to look at the stage of the patient to determine at what level we really should be intervening. If you have one autoantibody that's present or less, then you probably should be screening again in another couple of years or so.
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The question, Javier, is okay, you got two auto antibodies, which by the way, I could never remember these fancy names. I've got them all written down and I just circle them and we send them in to the lab and it's done. But what do you do if you have two positive and their blood sugars seem to be okay? And what I do is I put them on CGM and we monitor intermittently. We don't do it all the time. I don't want to spoof people out. And also remember, some of the CGMs are approved down to age 2, but some are aged down to age 4. But what you do is you look to see the percentage of the time that the glucose level exceeds 140. And it turns out if 5% are above 40, you have like a 30% chance of developing type 1 diabetes, converting to clinical type 1 diabetes in about a year. But if you got 20%, 10% of the numbers that are above 140, you're going to go there. It's coming. And that's why I think, Javier, that CGM is really starting to play a role in this.
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But you know what, Jeff, I can't be more on board with you on this one because I mean, CGM, aside from the type 2 diabetic population, which really influences behavior and eating patterns and so forth, it's really going to be very instrumental in terms of picking up the dysglycemia associated with antibody mediated beta cell destruction. Remember, the key thing is that you have three stages of that type one diabetic and stage two is when you start to exhibit some dysglycemia. Fortunately, we have something that we can do to delay the progression to overt stage 3 type 1 diabetes. And that's an antibody, a simple antibody directed against a CD3 protein that's present on the lymphocytes that's responsible for destroying these beta cells. And this CD3 monoclonal antibody, there's only one that's in the marketplace right now, and that's teclizumab. And it's a very, very interesting agent because it's been shown to delay the progression from stage two hyperglycemia to stage three by as little as two years and sometimes even longer.
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And so I look at it, you got to explain this to patients. So I live in California. A lot of fires happened here recently. There's a fire that breaks out in the hills behind me. What are you going to do? Okay, you're going to put water on that area and it's going to calm it down, it's going to put the fire out. However, fire season here is in September, October. I'm not saying in the future we're not going to have more fires, but at least we can calm it down right now. Then we can take away all the brush, make sure the fire doesn't spread later on. And that's basically what we're doing. We're calming the immune system. Javier and the other problem that we really haven't mentioned is what if we don't screen for this? Well, then there's a really high likelihood that these kids might go into diabetic ketoacidosis, and that's a deadly disease and it's scary.
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Jeff totally acknowledged the fact that diabetic ketoacidosis is extremely dangerous. We know how difficult it is for the patient, their loved ones as well, because it creates a significant amount of anxiety and stress. But also think about the effect that this may have on the healthcare system in general. We know how expensive an ICU admission is for our hospitalized patients and on the healthcare system. So it just makes sense that earlier identification and instituting therapy that could significantly delay the progression of this diabetes makes absolute sense. So fortunately, we have this one agent, this anti CD3 monoclonal antibody. Toplizumab is the name of the agent and the way that we use this is over a 14 day course without patient administration. Now, the dosing is going to be escalated over several days during initiation of therapy. And it's actually quite simple because it is a once daily infusion over 14 days. So I know it's. The availability of finding an infusion center can sometimes be difficult for some of these patients. But what's also very nice is that if you have visiting Nurses that are able to go to the home, then home administration can also be exercised for this toplizumab.
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Looking forward to if you have type 1 diabetes. Here's the thing that I really love about delaying or intensively managing people with diabetes. Javier, do you realize that if you could preserve some beta cell function, some of your own endogenous insulin secretion, you're not going to get severe hypoglycemia moving forward? I mean, I started on a pump really, really quick 30 years ago, but I can exercise down to a glucose level of 40. I feel funny, but I ain't dying. And the other thing is that there are less long term complications if you preserve some endogenous beta cell function. That's why another reason, like Javier said, we've got to screen and we've got to do something to modulate the immune system. So kid live a lot longer and healthier Life.
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C
Thank you, Dr. Unger and Dr. Morales. We will continue our discussion on type 1 diabetes screening as well as monitoring post type 1 diabetes screening. But first we have a brief message from our sponsor, Sanofi. From the very beginning, they mean everything to you and that means you do anything for them, especially if they're at risk. So when it comes to type 1 diabetes, screen it like you mentioned, mean it. Because if just one person in your family has type one, your kids are up to 15 times more likely to get it too. Screen it like you mean it, because one blood test could help you spot type 1 long before they need insulin. The more you know, the more you can do. So screen it like you mean it. And welcome back. Now we're going to discuss monitoring post type 1 diabetes screening. Dr. Morales, you had already alluded to a medication that can be used in patients at stage 2 of type 1 diabetes. How do you use our biochemical markers like a 1C or 75 gram oral glucose tolerance test or other insulin markers? And how do you monitor these patients once they have been screened?
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Well, once they've been screened and a diagnosis has been established, and then initiation of toplizumab is going to end up being really important. Now, unfortunately, there's really no markers that I'm aware of in order to see whether or not there is a beneficial effect or shutting down effect on beta cell destruction, aside from glycemic control. So we could use a CGM to help us along in order to determine what those glycemic excursions are and whether or not they're, I guess, appropriate for the stage at which the patient is diagnosed or maybe even establishing a glucose tolerance test of some sort in order to truly demonstrate need for teplizumab in order to gain the approval for use of this agent. But ultimately, after the 14 days of infusion, then it's just going to be watchful waiting, monitoring our patients. We could check things like C peptide, which winds up being quite fruitful in terms of the production of insulin from those beta cells, which tends to be a little bit of a moving target as well. But nonetheless, as long as they're still C peptide present, that means that the beta cells are still producing insulin. I don't know if there's any additional markers that you would utilize. What do you think, Jeff?
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I, I really just use intermittent cgm. And one of the things that's most important, kids progress faster than adults. So if you got a two year old that you screen and they got antibodies, it's going to happen. So it's a lot faster in kids, which is another reason that we need to jump on any types of autoimmune modulating therapies to delay the onset of these diseases.
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C
Great. Dr. Unger, would aggressive diet and lifestyle changes in the early stages perhaps maybe not for kids, but older young adults and older adults, would that be supportive in prolonging this honeymoon phase or this stages?
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I gotta tell you, I, I, I never discussed, and maybe I'm a maverick here, but there's so many things that people with diabetes have to do. It's, it's, and every day, every minute, they're thinking, even when their CGM is beeping, they're high, they're low, they're all over the place. I'm not really a big fan of lifestyle intervention other than to use CGM and see what certain foods do. For example, if you're eating pizza, your blood sugar is going to go up and it's not going to go up right away, it's going to go up two to three hours down the road because pizza has a lot of fat in it. So in these people, they may have to adjust the way that they give their insulin. Also, exercise lowers glucose levels. And you know what the symptoms of hypoglycemia are? It's the sweating, palpitations, feeling really tired and weak. But you see that with exercise anyway. So if you have a CGM and your glucose level drops below 70, it'll alarm. So I'm all in favor of lifestyle intervention with continuous glucose monitoring. I think that's better than figure out if you could have an extra piece of pizza. I Mean, I've gone out dinner with Dr. Morales and you should see what he eats. I can't believe he's still alive. But let us have, let us have a good life. Let us enjoy our food. But watch what happens with every intake in regards to glucose levels.
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B
CGM is really important because CGM really will help to influence some of those lifestyle changes that one hopes to institute. And also you get to see what the glycemic value is of some of these foods that you're actually eating. But I will tell you that lifestyle intervention is going to be extremely important because not every type 1 diabetic is lean. You know, we have this bias about, you know, the skinny kid who's been diagnosed with type 1 diabetes. But remember, it happens in adulthood as well and some of these people are overweight or obese as well. So lifestyle intervention really goes a long way. So instituting appropriate lifestyle changes will minimize some of the weight gain that one can expect with intensification of glucose control, but also would have a beneficial effect on other parameters. Parameters like, for instance, blood pressure, lipids as well. So, you know, we can't minimize lifestyle intervention. It still is going to be a crucial, crucial part of the journey of our patients with diabetes, regardless of whether they're type two or type one.
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Yeah, I like that. It's during this time where you have this quiescent disease. You know, you move into type one, but there's no elevation in blood sugars. This is the time when you call in your CDEs, your registered dietitians, your exercise people, and you start teaching them the importance of lifestyle intervention. I got no problem with that. And neither do the educators. They love this kind of stuff. But it's better to learn early than to learn when you're just getting in the hospital with dka.
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C
Yes, of course. And it would also allow families a way to cope with the anxiety provoking diagnosis that can come ahead with the different stages of diabetes. Dr. Morales, do you have patients who describe this emotional toll that type 1 diabetes takes on all the time?
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We have so many. And it winds up being a very difficult diagnosis to accept for some patients because they have this perception that the ceiling is going to cave in on them. Remember when that happened to me in Las Vegas, Jeff?
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Yeah. The lights actually came down on him while he was giving and it hit all the people in the room except for me and Javier.
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It was a divine sign because of that reason, because we were spared. Here we are delivering this presentation. But yes, it is very, very distressing for the Patients. And it's very important for us as clinicians to really partner with the patient and walk them through the journey. And again, it's not just about us, but it's also about the certified diabetes educator, the physical therapist, if they're seeking physical therapy for whatever reason, and the clinical pharmacist as well. So there's a lot of hands that are involved in the care of these patients, and all of us together help to alleviate some of that diabetes distress.
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And it's great to have teplizumab now available for use to delay the onset of type 1 diabetes. Dr. Morales, are there any unintended potential side effects that patients or families should be made aware of during that infusion time frame?
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Yeah, of course. I mean, the adverse events may occur for everything. Even crossing the street, you could get hit by a streetcar, whatever. But anyway, I think the more common adverse events that have been reported with a medication like diplizumab, because it is an antibody and it's a pretty big protein, is that you can see lymphopenia at about maybe 73% of those patients that were treated with teplizumab in some of their clinical trials. Rash can develop as well as leukopenia and, you know, nonspecific nasal pharyngitis. Nausea and diarrhea have also been reported at much lower levels. But I think the worrisome adverse events would be the leukopenia, the lymphopenia, and the potentials for the emergence of a rash.
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This has been a truly insightful discussion. Our listeners and I have learned that early detection and monitoring of type 1 diabetes have profound implications for improving patient outcomes and their quality of life. Are there any key takeaways clinicians should know about the early detection and monitoring of type 1 diabetes? Let's start with Dr. Unger.
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Yeah, this is something that should be done within primary care. You don't have to send these people to an endocrinologist to get these tests done. In fact, pediatricians should do the screening as well. So the bottom line is, if you have somebody that has a family history of type 1 diabetes or any other autoimmune disorders, then really consider doing the monitoring at a younger age of life. Now, if the test is positive for two antibodies, then put them on cgm, monitor them up, moving on. If they have one antibody, then you got to retest, like, three months later because there's a chance that, well, it's going to revert back to normal. But let's do what we can to minimize the risk of progression towards clinical type 1 diabetes.
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C
Thank you, Dr. Morales. Any final thoughts? Sure.
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Remember, 15 fold increase in the emergence of type 1 diabetes if you have a family member with type 1 diabetes. If you have some form of autoimmune disorder and you're dysglycemic, you should be checking antibodies. If you suspect that there might be type 1 diabetes just in general, you should be checking with antibodies. Remember, there's 5 of insulin autoantibodies, glutamic acid decarboxylase autoantibodies, insulinoma associated 2 autoantibodies, zinc transporter 8 autoantibodies, and islet cell autoantibodies. Remember, if you're using reference laboratories, they probably have these panels already listed to simplify the screening process for you. So think about it, screen for it, detect early, implement therapies that are going to have a beneficial outcome. Thank you for tuning in.
- [31:54]
C
Thank you. Thank you, Dr. Morales and Dr. Unger. I want to thank our sponsor Sanofi again for their support of this engaging podcast. To our listeners, thank you for tuning in.
- [32:10]
B
Thanks for listening to another great ACE podcast. Join us for another episode@aace.com podcast and help us in our mission to elevate clinical endocrinology. Together we are ACE.