Tom Rountree DO (00:01.546)
In today's podcast, I wanted to cover type 1 diabetes, the symptoms as well as the current screening recommendations and the current and future treatments. So let's go over the symptoms first. So typically in children, we'll see excessive thirst and this is where they're drinking milk and water or
apple juice throughout the day, they will start to frequently urinate as well. And this occurs mostly at night. You'll see them wetting the bed more often. And parents are like, not sure what's going on, but they just recently started doing this, even though they were maybe potty trained before. And they'll present with unexplained weight loss, meaning they will, on the growth curves, they'll start to go down.
a little bit. And the parents are like, they are still eating normally, but I don't know why they're doing this, right? They'll have fatigue or exhaustion where they just want to sleep more, they don't want to get out of bed. And sometimes they're irritable more because of this. And you'll see just kind of a change in their mood and demeanor. And less likely, they'll get huts and sores that heal kind of slowly. So
It's not the fact that they get these cuts and sores, it's that they're healing slowly and don't heal as fast as they used to. And so why do we want to screen for type 1 diabetes? Why are we doing this? Well, one, it's to prevent all these symptoms that we see that we just talked about. And also, one of the main reasons is to reduce the risk of something called diabetic ketoacidosis.
And what is this, right? Like, what is this weird word? And this word means that it arises when the body doesn't produce enough insulin. And this leads up to this buildup of ketones in the blood, which essentially turns the blood to acid. Okay? And then this leads to multiple other problems. And this is why it's called ketoacidosis.
Tom Rountree DO (02:27.958)
And typically when they would present in the hospital, I would see things like nausea, stomach pain, sometimes vomiting, as well as they'd be super tired, right? They would just not be moving. They would answer me, but they'd be tired. Now, those are usually the more common symptoms. Less commonly, I would see things like confusion as well as rapid breathing.
as as drowsiness. And what's one of the special symptoms of this is fruity smelling breath. And kind of odd, but it's like they've ate a piece of candy or it's still in there, even though they're not eating anything. And you smell their breath and it smells kind of fruity. So it's kind of sweet, almost sometimes sickly sweet. And that is one of the
first presenting symptoms of ketoacidosis as well. And up to 30 % of type 1 diabetic children present with this problem. This is a major problem because they're going to the hospital, right? And eventually, we have to admit them to the ICU. Now, if they are lower socioeconomic status, can present, like 50 % of them can present with this problem.
So the main thing is to prevent this problem from happening, which is why we screen them. In the hospital, their sugars will be above 250 milligrams per deciliter. Their pH of the blood can be below 7.3, and oftentimes I would see ketones in their urine.
And sometimes they can present with a co-infection or an illness along with this problem because if they're ill or they have an infection, it will drive them into this state. So it will cause them to have this diabetic ketoacidosis. And another thing that can cause it is emotional stress. So sometimes we can see this when they
Tom Rountree DO (04:45.902)
you know, are in a stressful problem at school, maybe they're transitioning into kindergarten, and we'll see this start to arise, we'll see it happen, and then they get admitted to the hospital. And in the ICU, they have to go there because they're getting all kinds of things happening, and we're having to check their blood every half hour to an hour, sometimes in the beginning, 15 minutes.
But what we're doing is we're giving them insulin. We're replacing all the fluids they've lost. We're fixing their electrolytes so they don't start to develop heart arrhythmias. And at the same time, we're going to try and treat the underlying infection if they have one. So this is where we have multiple problems going on. And this is why they're being admitted to the ICU. They also have a risk of brain swelling.
So we don't want that to happen. And then there's long-term risk of them even having this diabetic ketoacidosis because the risk to their organs goes up. So their brain, like I just said, their kidneys, their liver, their vascular system, because as they go into this problem, their vascular system has increased risk of blood clots. So there's a long-term risk of diabetic ketoacidosis.
then of course there is this emotional trauma to the patient and the family. So we're trying to really prevent this. And in general, we're also trying to prevent the onset of diabetes as well as keep the sugars controlled because over time as the sugars are out of control, it gets harder and harder to control them. Plus they have impacts to memory, cognition, which affects schooling.
and they have risks for micro, meaning small blood vessels like an eye and macrovascular complications like their leg blood vessels. And so we're trying to prevent these from happening. We're trying to reduce the severe hypoglycemia or the sugars dropping, reduce the risk of eye damage, and improve their hemoglobin A1C, their markers.
Tom Rountree DO (07:10.264)
that show that their diabetes is improving and we're trying to reduce their total daily insulin use. And this comes into play when they have to take insulin or maybe use a continuous glucose monitor that also administers insulin. Now, when we're screening, we ask some questions to increase what's called a pre-test probability. And this means that
When you get these tests, if they are positive, sometimes you need additional information to increase the chance that they are right. Because every test has what's called a false positive, meaning it says you have it, but it's not true. And every test has a false negative, meaning it says it's negative, but it is not true either. Meaning you do have the disease. So we want to...
increase the likelihood or the idea that you have or that the child has type 1 diabetes. Now how do we do this? We say you have a first degree family member that has type 1 diabetes and this means that you may have a 10 to 15 times higher risk for it. And in increasing order, this is the mother, the father,
the non-twin sibling, the dizygotic twin, and then the monozygotic twin. And these are genetic terms that I'm not going to go into right now, but for those who are interested, that's what it is. Now, interestingly, nine out of 10 do not have family history. And so this is why it's important to sometimes screen at multiple years throughout their life.
I'm going to talk about how we screen in just one second. Studies show that when we screen for the antibodies that cause type 1 diabetes, they peak between nine months and two years. But we should continue screening at two, six, and 10 years old because this will provide us with the best sensitivity, meaning that if it's, you know,
Tom Rountree DO (09:35.53)
negative, then we've kind of ruled it out. So how do we screen? There are four main antibodies used in clinical practice to diagnose type 1 diabetes. These are antibodies against insulin called IAA, Irosine Phosphatase antibodies, IA2, Glutamic Acid, Decarboxylase, GAD65, and Zinc Transporter 8 antibodies.
biochemistry, but the point is, is that there's four main ones that we test for. Now, the most highly sensitive one, in specific, is IA2A, which is the marker that determines the higher rate of progression. So we screen for this in the beginning, and then we talk about the different stages. So this test, the four antibodies, can typically be ordered through Quest.
or I think right now it's like $150 or less if you go through what's called a direct primary care practice where I practice them. Meaning we try and get the labs as close to wholesale cost or physician cost as possible.
So the next steps after testing positive, what are you going to do? What are we typically going to do? Well, we're going to talk about symptoms. Because before this, you come in, your child's two years old, and the doc is like, okay, I recommend that we screen for type 1 diabetes. And in a screening, you don't really ask for symptoms all the time. You can, but typically a screening is like,
you have no symptoms. That's where you're getting screened to prevent this from happening, to prevent having to be admitted to the hospital. So after you test positive for either one or two of these antibodies, of the four total, then we can ask in for symptoms of diabetes. We check for the level of sugar in the blood or urine. We check a hemoglobin A1C, which tells me the
Tom Rountree DO (11:52.878)
amount of sugar in the blood across three months. And then we do another test for the antibodies itself because, like I said before, these tests can be wrong. So we check again and see that that test was right if it was positive. So the American Diabetes Association says that even in the absence of high blood sugars,
The diagnosis requires two abnormal test results from the same or separate samples. Meaning, if they can retest again from the same sample, sometimes that's great because that's testing again without having to poke the kiddo two times, right? But oftentimes we're separate samples. So they say in that instance, same thing.
Now, what kind of stages are there in type 1 diabetes? Because there are certain stages and why do we stage things? We stage them because that tells us what to do at that moment. So, at-risk stage is the first one. You're at-risk with one positive antibody. Sugars are normal, but you have one positive antibody.
The five-year risk of progression is 14.5%. So across five years, there's a chance of going to stage one from at risk to stage one, the 14.5%. And so what is stage one? Stage one, no symptoms again, two antibodies. Okay, two antibodies, normal sugar. So we went from one antibody to two antibodies.
This increases our chance to 44 % of going to...
Tom Rountree DO (13:53.016)
stage two, right? And this is...
This is not like they're not, the rest of them are not going to progress, but all of them will progress to clinical disease. And stage two is two antibodies, and then we get into the sugar tests, okay? Where the abnormal glucose, the two-hour tolerance test is between 140 and 199. Fasting glucose is between 100 and 125 milligrams per deciliter. And then...
The hemoglobin A1C is between 5.7 to 6.4. In adults, this is like your pre-diabetes level. So same thing here. But also, we have another criteria that says if the A1C increases by 10%, then this is also part of that criteria for stage two.
And this is categorized, this is called dysglycemia. The sugars are kind of going out of whack, right? This is where you first start seeing a kind of a problem on the labs themselves. And these, stage two has a 75 % progression. So stage three is where we do not want to get to, okay? Stage three is
We don't want to get to stage two or stage three, but stage three is one of the main reasons why we screen also because at this point they have symptoms and they're hurting, right? We don't want our kiddos to hurt, so we created this screening to prevent this. This is where they have symptoms and greater than or equal to one antibody. And the glucose numbers, the sugar numbers are higher than what we stated in stage two.
Tom Rountree DO (15:50.676)
and there may be clinical disease present. They may have problems already that are going on.
And so when they have these problems is when we really start to see something going on. But we want to catch it before this, which is why we screen for it.
Tom Rountree DO (16:16.302)
Sorry, I had to take a drink of coffee because my throat's getting a little dry. Okay, so how are we treating this? What are we doing to delay the onset of stage three? Because we don't want to get there. We screen for it, we've noticed something's wrong, there's an antibody or maybe two, and now we're like, okay, the sugars have gone a little bit out of whack. What are we doing?
we are treating or we can treat with something called Teplyzomab. And Teplyzomab is a monoclonal antibody that's approved to delay the onset of stage 3 type 1 diabetes in children ages 8 years and older. That's what they have to be eligible for. So they have to be 8 years or older with stage 2 type 1 diabetes.
And so what does this look like? This is an IV infusion, meaning they get poked once daily for 14 days. And typically what happens is they get a port, meaning it's a connection to the blood system underneath the skin. So that way they know exactly where to put it. And they put the little needle in there and it pokes through as one little poke and then they don't feel anything.
And so they get that infusion for 14 days. And what is this infusion? This is an anti-CD3 monoclonal antibody and it works by changing the phenotype of activated T cells. And T cells are what's attacking the pancreas, typically islet cells. Okay, this is the pancreas. And they have something called islet cells and these islet cells produce insulin.
So what it's doing is changing that connection of the T cells so that it can't connect on and cause inflammation and destroy these things. There's a study called TN10, TN-10, which showed delayed diagnosis of stage 3 by 24 months. And it's important because now we've reduced the chance of symptoms as well as organ damage.
Tom Rountree DO (18:43.008)
So those are the two main things as well as diabetic ketoacidosis being admitted to the hospital, right? So they usually by 24 months in a follow-up study showed delayed onset by 32 months. And that's really cool, right? Almost up to three years of delayed onset of this disease. And so it's important because like I said,
right, that delays having to do certain things, know, increasing treatment levels, as well as running the risk of the symptoms for almost three years. Now, what do we have to be careful with is one, this is a drug that lowers the immune system. So have to make sure there's no active infections, no bacterial or viral infections that we're going to draw blood.
We're going to draw blood and look for things like Epstein-Barr virus, Cytolomegalovirus, hepatitis C, B, TB, and COVID. So that's what we're going to look for. And then we also have to draw other labs. So we're going to check things for the blood's size, and color with CBC, a CMP, which checks the liver, kidney function, electrolytes, things like this. We want to kind of make sure that they're in...
tip-top condition before we start this treatment so that we know that they can make it through the treatment and delay progression to stage three. Now, side effects include things like lowered blood counts, like lymphopenia and leukopenia, meaning the immune system is slightly lowered. They can get a headache and rash, and sometimes they feel like they have the flu with it.
And also we'll see a little bit increase in the liver enzymes on follow-up testing, which they should be getting done. They should be getting labs drawn while they're getting this infusion or this drug, as well as afterwards. And then sometimes you can get something called a cytokine release syndrome, which I won't get into now. But as always, before you start anything, you should be checking with your doctor to make sure this is the right way.
Tom Rountree DO (21:04.216)
to go with this. Now, recently in the New England Journal of Medicine, there was a small study that they reported on which showed something called Zymoslesyl. So Zymoslesyl is a stem cell derived therapy that can restore islet cell function. Now this is only in phase one or two and there was only 14 participants, right? But this is pretty cool because it essentially means that we can fix this problem.
which is the ultimate goal of medicine, fix the problem.
Now, what happens after we've done the infusion treatment? Okay? Or what happens maybe we're not there yet, we're not, maybe we're not stage two, maybe we're kind of close, we're not too far away, we see certain numbers. What do we need to do in the meantime? Okay? We're going to talk about taking insulin, we're going to talk about counting carbohydrates, fats, and proteins, we're seeing the nutritionist.
We should be getting referred to someone. We're monitoring our blood sugar, right, through either a little poke, the A1C, continuous glucose monitor, and the gold standard, which is the oral glucose tolerance test to see where our sugars are, right? Plus, we're eating healthy foods, we're exercising regularly, and we're keeping this healthy weight. And so,
I want to take a second here that children with type 1 diabetes can lead a completely normal life. I have worked with people in the medical field who have type 1 diabetes and they've learned to manage it. So they can totally, totally have a normal life. And the goal with these interventions is of course to keep the blood sugar level as close to normal as possible.
Tom Rountree DO (23:05.71)
to delay or prevent these complications we talked about. And generally the goal is to keep your daytime blood sugar levels before meals between 80 and 130 and then after meals we keep it below 180. And this is typically two hours after we eat. So that's the goal. Okay. That's the goal is to use these measures that we talked about, the...
insulin, counting carbs, the monitoring blood sugar, right? The whole goal is to keep the blood sugar within these normal physiologic levels that the body can deal with with respect to the other organs and preventing their damage. And so not only should it be following up with a physician who kind of specializes in this, but also a
a nutritionist as well as, and this is a very important part, a counselor. Okay? We should be checking in with a counselor. should also be screening. We should get screened for anxiety and depression, right? Because having a chronic disease can be really taxing on our mind, right? We have enough things to worry about, but on top of this, we have a chronic disease. So this is why your
primary care provider, pediatrician, family doc should be screening for anxiety and depression, especially not only in the child, but also in the parents or the caregivers as well. Very low threshold for referring to counseling for both of them.
That is something to be aware of and watch for at home and just kind of ask how they're doing and tell them, hey, this is a normal response to a chronic disease that we're having to live through. We're having to go through this and it's appropriate to be anxious. It's appropriate to feel down and out, right?
Tom Rountree DO (25:26.092)
but it's also appropriate to get counseling for it. And that is something that should be definitely looked at and discussed with children and their caregivers. So other things, let's talk about resources. Where can you go to find additional help? There's the American Diabetes Association, super helpful. Go check out their website, all kinds of materials on it.
And what's really cool is they have a type 1 diabetes camp. So they have a camp which you can search. put in your, I just did it, put in your zip code and there's one near me in Missouri. Put in a zip code and it shows you. It shows you like, hey look, there's a camp here. Then what you can do is they go to the camp and then you can meet up with parents. They can meet up with kids who also have type 1 diabetes.
share little tips and tricks and just become more aware of how to live a little bit more normally with this problem. And they can see that, hey, other kids have this. I'm not such a weirdo that this is a huge major problem. It's that there are people with this that I can relate to. And of course,
I'll try and have more updates on my podcast, as well as TikTok and Instagram. So if you like this podcast, then feel free to subscribe or send it somebody who might enjoy it or find it helpful as well. And as always, have a healthy and happy day.
