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Diabetes Core Update
Special Edition - Early Identification and Delay of Type 1 Diabetes April 2025
00:26:33
In this special episode on Early Identification and Delay of Type 1 Diabetes, Dr. Neil Skolnik this emerging area with Dr. Jay Shubrook. This special episode is supported by an independent educational grant from Sanofi. Presented by: Neil Skolnik,...
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- [00:02]
A
Welcome to this special series of Diabetes Core Update where we will discuss a topic that has become important over the last few years and that is early identification and delay of type 1 diabetes. We know that family members of people with type 1 diabetes are at increased risk of developing type 1 diabetes. In fact, though that risk is higher than is often appreciated, it is a 15 fold increase in risk. That risk used to be a statistic that we knew maybe we'd repeat on rounds when we wanted to look really smart. But now it's of practical importance since therapies have been developed and are now FDA approved that can delay the onset of type 1 diabetes in people at stage 2. Type 1 diabetes. Yes, I said stage 2 type 1 diabetes. And we'll explain in a little bit about the pre clinical phases of type 1 diabetes that many people are not yet familiar with but important to know. Today we're going to be discussing how to differentiate between type 1 and type 2 diabetes. A small but important percentage of people who are assumed to have type 2 diabetes actually have type 1. We're going to talk about screening for the detection of preclinical type 1 diabetes. We'll talk about who should be screened, who might be screened in the future, and we're going to talk about some practical aspects of carrying out that screening. I'm your host, Dr. Neal Skolnick, professor of Family and Community Medicine at the Sidney Kimmel Medical College of Thomas Jefferson University. This series is being sponsored by sanofi. Joining us today to help us accomplish these goals is Dr. Jay Shubrook. Dr. Shubrook is a family physician and fellowship trained diabetologist and a professor and director of Diabetes services at Touro University. He is also a past chair of the American Diabetes Association's Primary Care Advisory Group, an associate editor for clinical diabetes, he is the past chair of the American College of Diabetology. You get the sense Dr. Shubrook is very busy and very devoted to diabetes. Welcome, Jay.
- [02:38]
B
Good morning. Welcome. So glad to be here, Neil. Thank you.
- [02:41]
A
Jay. I want to start with our conclusion. Can you fill in a few more details about why our listeners should care about early identification of people at risk of progressive to type 1 diabetes?
- [02:56]
B
Yeah, I think this is really an emerging and an important topic. We know that currently those people who are diagnosed with type 1 diabetes often find out when they're in DKA. This is a traumatic crash landing into type 1 diabetes and can be very upsetting and actually a heavy lift to start doing self care. We now, after decades of research, are aware that we can identify people before they become clinically hyperglycemic and before they become sick. This is not only important for their immediate prevention, but also could change the course of their diabetes from screening and intervention so that we have an opportunity to change the lived experience with people who are going to get type 1 diabetes in the future.
- [03:43]
A
Yeah, and this is a big deal. We had on our sister podcast Diabetes Day by Day, a colleague of ours who has type 1 diabetes, and this is a physician, and his daughter developed dka. They were on a trip, going on vacation. She wasn't feeling well. And just to say how subtly this can present, this is a family of physicians, mom and dad both. And the daughter was feeling worse and worse. They stopped at a rest stop. She was vomiting, and they said, you know what? Let's check her blood sugar. And oh, my gosh, it was very high. And she was very sick and in dka. So the opportunity to know this might be coming and to avoid that level of illness and as we'll talk about more, perhaps delay onset is critically important and is very real. Jay, let's now go back to basics, and we'll quickly ramp up. What's the fundamental difference between type 1 and type 2 diabetes?
- [04:50]
B
Yeah, so this is really important, particularly for people who are newly diagnosed. Type 1 diabetes is an autoimmune disease. It's not something that's caused by your diet. It's not something caused by your lifestyle. Your body attacks the beta cell of the pancreas, so it's autoimmune. Type 2 diabetes is a metabolic condition. It takes years to develop, and while there's also a genetic component to it, it is largely influenced by the environment, our diet, and our activity. So it's really important to separate those out that are related to our lifestyle versus not related to our lifestyle. And of course, type 1 diabetes has to be treated with insulin. Type 2 diabetes has a plethora of treatments available.
- [05:30]
A
That's so helpful. Now, we know that for young people presenting, as we described acutely, that is almost always type one. We also, though, take care of a lot of people who are 20 years of age and older who are diagnosed with type 2 diabetes. When should we try to differentiate whether or not they have type one and how should we go about doing that?
- [05:53]
B
So age is no longer a predictive component of knowing what type of diabetes there is. As we start to have more and more people who are overweight or obese, we actually are seeing more and more children being diagnosed with type 2 diabetes. Now, I'll say most of the time that occurs at age 10 or puberty is when we start to really see a ramping up of type 2. But we also know that there's more adults being diagnosed with type 1 diabetes every year than there are children. And so I think the key thing that I want to take from that is while we used to call type 1 diabetes juvenile diabetes, we know that's no longer the case. We have those that develop more slowly, progressive type one. And while type two used to occur in middle aged adults, we are now seeing more and more younger people. So I think you should have a healthy index of suspicion, regardless of the age for type 1 diabetes.
- [06:45]
A
And that's critically important. And briefly, how do we distinguish that?
- [06:51]
B
First of all, I think that you mentioned something earlier. Type 1 diabetes, if it goes to the point where they're severely hyperglycemic, they're going to present with the polys, polyuria, polydipsia, polyphagia and weight loss. Eating a lot, drinking a lot, peeing a lot and weight loss. That's the classic syndrome of insulin deficiency. We're trying to prevent that. Those with type 2 are most commonly found with labs. They just have screening labs done or they have non specific symptoms. The key difference when we're identifying the two is really looking at autoantibody testing, which is a key marker of type 1 diabetes, not so much type 2. And we'll talk about when to do that.
- [07:30]
A
Jay, let's now focus on type 1 diabetes. We talked about different presentations of type 1 and type 2, but a lot of people don't appreciate that with type 1 diabetes, it is not always clinically manifest that there are actually preclinical stages. Can you go over what those stages are?
- [07:53]
B
Sure. So now we know confidently that there are preclinical stages of type 1, just like there's preclinical stages of type 2. So you can identify people who have measures of autoimmunity but have completely normal glucose, even upon oral glucose tolerance testing. So stage one means you have markers of autoimmunity and normal glucose. Stage two, you have markers of autoimmunity, but you have glucose readings in the pre diabetes range, much like we think about pre diabetes for type 2. And then stage 3 is what we call, typically call clinical type 1 diabetes, where your glucose readings are in the diabetes mellitus diagnostic range. And often those patients have symptoms. So what's key there is that you're going to have a period of time where this glucose is normal. And this could be up to years. But where we know the type 1 diabetes is going to manifest. So we want to find those patients before they become hyperglycemic and certainly before they go into dka.
- [08:56]
A
And that begs the question, of course, about screening. Who should be screened with autoantibodies in order to detect disease early?
- [09:05]
B
Yeah, and I'm going to take that question even one step back when we think about screening for diabetes. When we now screen for type 1 diabetes, we screen with antibodies, not glucose. All other forms of diabetes we screen with glucose, but this form we screen with antibodies. And you had mentioned earlier that a family history is a predictor of being at higher risk for type 1 diabetes. Who do we screen? If you have a first degree family member who has type 1 diabetes, you are at a much higher risk for Type one. You should consider being screened. Those who have a personal or family history of autoimmune disease are also at higher risk. And they would be another high risk population worth being screened for Type one diabetes.
- [09:47]
A
Now, Jay, let's say we have a patient with type 1 diabetes, we screen their family members and the autoantibodies are negative in that eight year old brother. Are we done with screening forever or should we screen again at some point because that individual might develop autoantibodies later?
- [10:13]
B
This is a really important question, and it's one that's still evolving a little bit. We know that your likelihood of having autoantibodies is highest during childhood. If you're going to repeat screening and you describe someone that's at high risk, the times that we might consider it are age 2, 6 and 10. If we're thinking an age based screening. If you get to age 15 and you don't have autoantibodies, the likelihood of you developing autoantibodies de novo is quite low. So I think the timing of the first screen will determine if you do it again. But I would say someone with a first degree family member who is still a child probably is going to be rescreened. And quite honestly, the families are demanding it.
- [10:57]
A
You actually anticipated my next question, which is when we talk about family members, let's say a 30 year old is diagnosed with type one. We're only talking about first degree family members or a broader set of family members.
- [11:12]
B
I think the data is most solid for first degree family members. Autoimmunity is still being evaluated. And so certainly now that we're offering wider screening, other people could be screened. But I think if you're new to this science, I would start with first degree family members where you're going to have the highest yield for pickup. And I do think it's important that you said something up front. The risk is quite a bit higher than we anticipated scientifically. But most people with type 1 diabetes overestimate the risk that their family members will have Type one. And so there is an educational component so that we really have solid numbers to give our patients and families what is their actual risk.
- [11:53]
A
Jay, that's so important because one of the dangers of screening, of course, is creating anxiety. And it sounds like at the same time that we should be screening in order to detect disease early, we can also be reassuring, particularly when there is a negative test, that we're not talking about an overwhelming likelihood of developing type 1. Again, particularly with a negative test, that risk would be relatively small. Is that a correct understanding of what you said?
- [12:29]
B
Absolutely. And we could put some numbers behind it. If you were doing population based screening, your risk of developing type 1 diabetes is somewhere between 0.3 and 0.4%. If you have a father with type 1 diabetes, your risk is 7%. If you have a mother with type 1 diabetes, it's one and a half to 3%. And if you have a sibling, it's 6 to 7%. So that percentage is quite a bit higher of the 0.4. But lots of times people will think, oh, my baby's definitely going to have diabetes because I have diabetes. So it's not, it's still a small percentage, but much higher than the general.
- [13:04]
A
Population to say it a different way. While screening is clearly relevant, we can reassure our patient there's a better than 90% chance that their family member isn't going to develop type one. So we can at the same time do responsible screening and responsible allaying of anxiety, which is understandable when we screen. Is that screening usually paid for by insurance?
- [13:32]
B
So this is a really great question. So we have not had any trouble getting this screening covered, but there's actually multiple ways you can do this today. So if you have an insurance that challenges it, you can actually screen high risk people through Trial Net, which is a network of trials around the country. As well as breakthrough, Type 1D is also offering free screening to anyone who wants it. If a person wants it. Yes, I have had success getting insurance cover it, but you can also get it done outside of insurance for free. Really open to anybody.
- [14:06]
A
Critically important to know. So when we think about it, screening is not that difficult. Can you tell us what autoantibodies should we order? How do we go about doing that?
- [14:17]
B
Yeah, so there is very good agreement that the four auto antibody Panel is the best way to screen. If you're looking at the test, it is GAD65 antibodies, zinc transporter, insulin autoantibodies and IAA2 antibodies. We used to use islet cell antibodies, but we no longer use them. We keep them in the research space and many of my clinical labs have that as a panel. I just order type 1 diabetes panel and they come as a panel.
- [14:46]
A
Very helpful, clear, not difficult to do. Then next step, what do we do if our screen comes back positive?
- [14:54]
B
Yeah. So first of all, I think if you're going to be screening patients, it's really worthwhile to give them those very specific numbers and let them know that we're screening for a condition that will blossom later. Letting them know what it is that they're being screened for and what we're going to do with the results, I think is very important. So let's say that we do that education and they do screening. The screening will come back anywhere from one to four weeks later, depending upon the method that you do it. And I have a face to face appointment with them and I say, let's talk about this. If they have zero antibodies, odds are they're not going to move forward. And depending upon their age, I may or may not re screen. If they have one autoantibody, it's the hardest because it's not definitive. They're at risk, but we can't diagnose diabetes. And if they have two or more autoantibodies, I say this is a high risk test and I will always repeat that one more time, separated by time, so that I can say that you have persistently positive autoantibodies. And I think that's really important that people know that you want to show two positive tests with two antibodies to confirm the diagnosis and then what happens? Then the next step is, of course, if they have two autoantibodies, I need to determine what stage they're in. So now I'm going to do a glucose tolerance test. And I really want to highlight that while this is not a fun test for people to do, it will give you the best information about where you are on the diabetes spectrum. But I'll start with saying that you have two positive persistent antibodies, you have type 1 diabetes. Now I will do the glucose tolerance test to say what stage you're in. If your glucose is normal, you have stage one. If your glucose is in the pre diabetes range, you have stage two. And if your glucose meets diabetes diagnostic criteria, you have stage three.
- [16:46]
A
And that's helpful. And while Many of us in primary care, once we have those autoantibodies, we will refer on to a diabetes specialist. I think it's important that we have that sense of what's done. So at that point they're going to get their glucose tolerance test, we're going to stage their diabetes. What happens if they have stage two? So their glucose is elevated either at fasting or post prandtl, but not to the level of diabetes. So what happens if they have stage 2 type 1 diabetes at that point?
- [17:19]
B
Yeah. So any of the stages need immediate attention and stage one, I know you asked about stage two. Stage one, we have clinical trials they could consider or we'll start the education process because we want them to be well informed. Stage two moves along quite a bit further and so the risk of becoming hyperglycemic in the next five years is quite a bit higher. We are definitely going to start diabetes education, healthy coping, training them, but we also can offer them a clinical trial or an FDA approved treatment called toplizumab. And so now a patient has a choice and the only reason they have a choice is because you took the time to screen them and find them before they had clinical type 1 diabetes, which I think is really great.
- [18:04]
A
And then give us a sense of the benefit of toplizumab.
- [18:10]
B
There has been autoimmune regulatory medicines being studied for a long time. Teplizumab is the first to have really significant benefit. And essentially this is a 14 day infusion of an immune regulatory agent that's given to the person that has been shown to delay the progression to type 1 diabetes by two years in a five year measurement and almost three years at a six year measurement. No one is saying that this is curing type 1 diabetes, but what we're saying is it's longer before you develop clinical type 1. And quite honestly, I believe this to be the first step into a multiple immune modulatory treatment that might really impact the progression to Type one in the future.
- [18:53]
A
This is a pretty exciting cutting edge area which is really changing our approach to early identification of type 1. Now it's clear that we haven't at this point routinely incorporated screening of family members to identify high risk family members who might be eligible for treatment that can delay the onset. One approach to screening we know is that for us as clinicians to understand the importance and to remember to screen, that's how we typically approach a lot of screening that we do in primary care. That's dependent upon us as individual physicians and currently the state of the Art, are there any other approaches to screening that are being looked at? Population based screening, for instance?
- [19:45]
B
Sure. First, I think I want to just highlight that again, when we're doing screening for conditions, primary care is the place to do it, because we have that insight. We know the family histories and we want to be doing anticipatory surveillance to prevent things from happening. So, absolutely. I want to highlight that there have been some more population based screenings. These have been largely done in studies, and sure enough, some of them have actually found that when you screen all newborns, the rate of type 1 diabetes is actually higher than we anticipated. So that's actually important that we know that this is still in the research space. It's not currently recommended to do population screening, but we are actually doing it at our center as well, doing a community based population screen in our outreach van. So anybody who comes to us who wants to be Screened for type 1 diabetes, we do that education process, but we offer that as well because we know that awareness is quite low and we want people to know that they do have a choice and they can be screened. Now, that's balancing the risk and benefit of screening. When you take it beyond the highest.
- [20:55]
A
Risk group, that makes sense. And are there any other novel approaches using EHR data to identify type 1s rather than waiting for them to come in?
- [21:04]
B
Yeah, I think there are things in process and I do think we could leverage technology to help us. Right. It would be very easy to put a tickler in your chart to say, anyone with a family history of type 1 diabetes or autoimmune, highlight in that chart that they should be screened. I've not seen that done at the population level yet. I certainly have seen some early indicators in research and I do think that can be positive. But it has to be coupled with good clinician knowledge about how to communicate with the patients about to be screened. Because if we don't have solid data to share with our patients who are screening, there could be confusion.
- [21:40]
A
I think that's so important, Jay, and I so agree with you. There's this opportunity that we now have with large amounts of EHR data. Our institution, for instance, identifies individuals who are the appropriate age and who have had colonoscopy in the past 10 years. And they get a portal message sent out saying, please get in touch. Talk to your doctor about colonoscopy. Makes so much sense because not everyone thinks to come into the office. And even when they come in, often they have a list of agenda, none of which has to do with screening or all of which we, as primary care physicians, need to prioritize the patient's concern. One could imagine a time when, through population data, individuals with type 1 get sent a message that you might consider screening your family members. And I think your point here is so important, and please talk to your doctor about this. That meshes the promise of population management with what we have to offer that's so important as primary care clinicians.
- [22:56]
B
Exactly. Yeah. And I think this is important, and it requires work on the patient side, but also work on the clinician side to be knowledgeable, how to communicate it, and then decide who your team is. If you're not going to test, there's certainly people out there that can help you do the testing and interpretation. But the first step is knowledge of the availability and the benefit.
- [23:16]
A
Oh, I think you're right. And we're getting toward the end of our podcast today. What do you see as the biggest challenges to implementation of screening and treatment to delay type 1 diabetes?
- [23:29]
B
Yeah, so I think there are a few. I think awareness, of course, is the biggest one. And again, getting this message out is important. I think really having a clean understanding about what contributes to type 1 diabetes, both for the patient and the clinicians. I think there's still a lot of myths out there that make it more complicated. And then having the comfort to have that discussion in a more population health preventive mode to say, this is your actual risk. Is this something you want to do? And then be comfortable with that shared decision making. Because I have many patients who say, yes, I want to be screened or I want my family screened, but some say no. And I think we have to respect that. This is, again, sharing information and letting a person make that decision, what's going to be best for them. And I think those are things that do add time to our visits, and I think we'll have to somehow fold that into our equation. But I think that it's doing the right thing for the families, and I think getting the awareness out is that first step.
- [24:28]
A
Thank you so much for going over all of this. Any last thoughts that you have?
- [24:34]
B
I want to thank everyone who's listening today. That means you're interested in this topic and you want to know more. We are doing some exciting things with the American Diabetes association. So if you'd like to hear more, we'll be doing a webinar with an expert panel on April 28 at 10 to 11am Eastern called early Detection Saves Lives. And then there is a work group at the ADA called the Type 1 Diabetes Screening and Advisory group trying to get these workflows in place. And so the ADA is working on behalf of you and patients who are at risk for Type one or have Type one so that we can get this information out in a way that makes sense. And you are supported.
- [25:13]
A
Dr. Jay Shubrick, thanks so much for joining us.
- [25:17]
B
My pleasure. You have a great day.
- [25:19]
A
And most of all, thanks to our listeners. Thank you for joining us on this important discussion that about identifying people with type 1 diabetes and delaying the onset of type 1 diabetes. This is a topic that I think is new for many of us. It is, as Jay said, an emerging area that we are just now at the beginning of. And there's going to be a lot more going on in this area over the next few years. Stay tuned. This special edition of Diabetes Core Update is sponsored by Sanofi. We thank you for listening and for the American diabetes association, I'm Dr. Neal Skalnick. Till next time, stay safe and keep learning.
- [26:21]
B
Sam.