Trisha Williams (Host 1): Hi, guys. Welcome to the Advanced Practice Perspectives. I'm Trisha Williams.

Tobie O'Brien (Host 2): And I'm Tobie O'Brien. This is a podcast created by Advanced Practice Providers for Advanced Practice Providers. Our goal is to provide you with education and inspiration. We will be chatting with pediatric experts on timely key topics and giving you an inside look of the various Advanced Practice Roles at Children's Mercy.

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Now that we have the housekeeping tasks out of the way, it's time to sit back, tune in, and get started.

Host 2: Welcome back to the Advanced Practice Perspectives. Today, we are pleased to have Amanda Williams visiting with us. She is a Family Nurse Practitioner at the University of Kansas Health Systems in the endocrinology department. Today, she is going to visit with us about a practice shift happening with treating Type 1 diabetes in children.

Host 1: Before we meet Amanda, I have a little disclosure statement. Amanda Williams is on the Speaker's Bureau for Sanofi. All relative financial relationships for this individual has been mitigated. No other relevant financial relationships were identified for any member of the committee or Now let's get to the good stuff. Welcome to the podcast.

Amanda Williams, MSN, FNP-BC, CDE: It is so great to be here with you guys this morning. I feel honored and privileged to be speaking with your audience today about Type 1 diabetes and, and our practice shift in how we diagnose and treat Type 1 diabetes.

Host 1: Yeah, we are so excited to hear about this practice shift. How about you start off by just telling our guests a little bit about yourself?

Amanda Williams, MSN, FNP-BC, CDE: Alright, so I've been at the University of Kansas Health System for the last 14 years. I've been in the endocrinology department for 7 years and prior to that was a diabetes educator on the inpatient unit for 3 years. Type 1 diabetes is near and dear to my heart because I live with Type 1 diabetes and so does my My goal is to help educate people on what diabetes is and find ways to improve their quality of life. I live here in the metro with my husband and my seven year old son. We enjoy just spending time together, playing games, building snowmen outside. We love the cold outdoors. And we have a dog and then two cats that we live with.

Host 2: Well, that sounds like a fun family and we have had plenty of snow for you to build your snowmen in.

Amanda Williams, MSN, FNP-BC, CDE: We have.

Host 2: Well, let's get started by covering or reviewing the pathophysiology of Type 1 diabetes and Type 2 diabetes.

Amanda Williams, MSN, FNP-BC, CDE: All right, so just a quick overview, quick pathophysiology. Type 1 diabetes is an autoimmune disease caused by interactions between the immune system, genes, and the environment. Autoantibodies cause the destruction of insulin producing beta cells. Unlike Type 2 diabetes, Type 1 diabetes is not caused by diet or lifestyle choices.

And once a person presents clinically, the result is lifelong need for intense insulin therapy. Type 1 diabetes is caused by the activation of two or more autoantibodies. These include the GAD autoantibodies, insulin autoantibody, or IAA, insulinoma associated type 2 autoantibodies, or IA2A, and a zinc transporter.

In the United States alone, 64,000 people are diagnosed with stage 3 Type 1 diabetes each year. And there are roughly 2 million people in the United States living with Type 1 diabetes. So, I want to ask you guys a question. What percentage of people do you think are diagnosed with Type 1 diabetes over the age of 20?

You think it's like 12%, 23%, 47%, or 59%?

Host 2: I'm going to guess 12%.

Amanda Williams, MSN, FNP-BC, CDE: Trish, what do you think? You think it's like 12, 23?

Host 1: I'm going to think it's higher. I'm going to think 23%. We don't deal with adults very often. So you're us out of our comfort zone here. I'm going to say 23%.

Amanda Williams, MSN, FNP-BC, CDE: The answer is 59% of people are diagnosed over the age of 20 with type 1 diabetes.

Host 1: Wow.

Amanda Williams, MSN, FNP-BC, CDE: And up to 62% of patients are initially diagnosed with a presentation in DKA, or diabetic ketoacidosis.

Host 1: Wow. So talk to us a little bit about the difference of Type 2 diabetes versus Type 1.

Amanda Williams, MSN, FNP-BC, CDE: So, Type 2 diabetes, oftentimes we think of it as being a lifestyle or as a person gains weight, they develop insulin resistance. And so Type 2 diabetes is a combination of insulin resistance and their pancreas not being able to keep up with insulin production.

Host 1: So today we're going to focus on Type 1, and I think that the biggest practice shift is the staging of Type 1 diabetes, which I find absolutely fascinating. So let's dive into that.

Amanda Williams, MSN, FNP-BC, CDE: Okay, so there are three stages of Type 1 diabetes development. Type 1 diabetes is a chronic and progressive disease. You'd have a person who is at a genetic risk, has an immune activation event, such as they had a virus or there's an environmental factor that triggers those autoantibodies. These three stages of development start in stage 1.

And this is referred to the pre symptomatic stage. So in stage one, a person has two autoantibodies and normal blood sugar. This is what makes it so difficult to diagnose is because you see a person sitting in front of you and they have normal blood sugar. You test their A1c and it's under 5. 7. You do a fasting glucose and it's under 100.

And there's no clinical manifestation of this stage one besides those two autoantibodies.

You would see this person in a well child visit. You'd encounter them on the street and they don't know that they have Type 1 diabetes. They probably have never even heard of what Type 1 diabetes is because 90 percent of people who are diagnosed with Stage 3 Type 1 diabetes do not have a first degree relative that has Type 1 diabetes. If we don't detect that they have stage 1 Type 1 diabetes, they progress into stage 2, which is also pre symptomatic, also making it very difficult to diagnose. A person who's in stage 2 Type 1 diabetes has two autoantibodies, but those autoantibodies have started to cause beta cell destruction and they start to develop what we call dysglycemia.

Dysglycemia is defined by a fasting glucose of 100 to 125, a two-hour postprandial glucose during an oral glucose tolerance test between 140 and 199, and an A1c between 5.7 and 6.4. And over time, that beta cell destruction continues and the person develops what we know and have always thought of Type 1 diabetes being stage 3 type 1 diabetes. This is a fasting glucose over 126, two-hour postprandial glucose during an oral glucose tolerance test over 200, and an A1c that creeps up over 6. 5. This is where you start to see that urinary frequency, that increased thirst, weight loss, fatigue. This is where they're at highest risk for developing diabetic ketoacidosis and what we've always thought of being a diagnosis of Type 1 diabetes.

Host 2: So is this typically when kids are diagnosed with diabetes during the stage three?

Amanda Williams, MSN, FNP-BC, CDE: Correct. Yes. So, this is what we were taught in school, that this is what Type 1 diabetes is. The increased thirst, the frequent urination, you check their blood sugar, and it's over 126, oftentimes it's much, much higher than that. In 2015, the ADA changed the definition of the diagnosis of Type 1 diabetes to a person having two autoantibodies.

And that's because if a person has two autoantibodies, and normal blood sugar or dysglycemia, their lifetime risk of progressing to stage 3 Type 1 diabetes is 100%.

So you're sitting in your clinic for your well child visit with a six-year-old and you test those autoantibodies because it is now recommended by the ADA to screen children for Type 1 diabetes because if there are two autoantibodies in that child, they will 100% progress to stage 3 Type 1 diabetes.

And what that means for a person is that they today, they wear a continuous glucose monitor, they take multiple daily injections of insulin, so every time they consume carbohydrates, they need an insulin shot, and you think about how many times you eat a snack during the day, you eat a meal during the day, you're going to need insulin with all of those interactions with food. Even if you decide to eat really super low carb and you go out for barbecue, that fat breaks down and two hours later you're going to need insulin because it raises blood sugar. So this is a huge, huge change for a person in their life and it's a huge impact on their family. The burden to a mom and a dad who have to think about their child's blood sugar 24-hours a day. There's not a break from that.

Host 1: So as we're thinking about this six-year-old and potential for these antibodies and nobody knowing, it appears that there's some screening labs that can be drawn, for us in the primary care setting, to be able to determine this.

So is there screening labs? What do primary care providers order? Kind of talk a little bit about that.

Amanda Williams, MSN, FNP-BC, CDE: When we have children sitting in the office, there are times where we draw annual labs for those children at certain ages, and to screen for Type 1 diabetes, you would order a GAD antibody, IAA, IA2A, and zinc transporter. Here at the University of Kansas Health System we use EPIC and in EPIC you can build a smart order set and so we've labeled it as a Type 1 serum panel and then that Type 1 serum panel just pulls up all four of these autoantibodies. I hear you guys are moving to EPIC and so this will be something that your endocrinology team is already working on.

Host 1: Yeah, we are moving to EPIC. So that's exciting. And I know that, you have shared with me that our endocrinology department and one of our attendings is specifically, spearheading this movement and this change in practice. So this is very exciting.

Amanda Williams, MSN, FNP-BC, CDE: Yes, and so if two of those antibodies show up positive on that screening; the conversation you're going to have with that family is that in your child's screening there were these two antibodies that showed positive and this means that your child is at high risk for developing Type 1 diabetes and I want to send you over to our endocrinology department who is going to take the utmost care of your child so that we can potentially delay the progression of them developing stage 3 Type 1 diabetes.

Host 2: So, Amanda, going back to the ADA recommending doing these sort of screening tests, is there age recommendations or like, is there certain kids that are at risk that should have this testing?

Amanda Williams, MSN, FNP-BC, CDE: The ADA recommends that we screen children at ages 2, 6, 10, and 18 because those autoantibodies go positive at those age ranges, and at age 40. So that's why we end up with all these people who get diagnosed with Type 1 who are over the age of 40, or who screen positive at age 10 or 18 and then those antibodies manifest at stage 3 Type 1 diabetes when they're older, when they're over 20 years old. Higher risk populations are those who have other autoimmune diseases. So people who have celiac or Hashimoto's, Graves disease, rheumatoid arthritis, or Addison's disease. But really the recommendation is that we start screening all people. In 2023, the country of Italy declared that they would screen all people for Type 1 diabetes.

And they don't have a medicine approved in their country to delay progression of Type 1 diabetes. We here in the United States have a new medicine that was approved by the FDA called teplizumab or TZIELD. And what TZIELD does is it is a monoclonal antibody that binds to CD3 destructing antibodies to preserve beta cell function and delay the progression of stage one diabetes by 32 months, or a little over two and a half years.

So if you're having a conversation with a parent, and you can say, well, we can delay this progression for almost two and a half, three years, you give that child an elementary education without Type 1 diabetes. You can get them through middle school. You can get them through puberty.

You can get them through high school. You can get an 18 year old through college without having to do multiple daily injections or wear an insulin pump or wear a continuous glucose monitor all the time.

Host 2: That's incredible. I was thinking about how overwhelming it is for a child to get the diagnosis because typically, like you said, it's in stage three, so it's like, boom, you have to learn everything and basically your life kind of changes overnight and how this will completely shift basically onboarding their education much more slowly so they can kind of get a handle on it as they know it's going to happen, but perhaps they can learn about it a little bit easier just because it's not as overwhelming.

Amanda Williams, MSN, FNP-BC, CDE: Right. So instead of starting four injections of insulin a day, we can just learn about what Type 1 diabetes is and still live an active lifestyle, still live a life without insulin injections. And, after that three years, and if they start to develop dysglycemia, we can introduce one injection of insulin instead of having to do four injections of insulin all up front.

A person who's diagnosed with Type 1 diabetes in diabetic ketoacidosis, they lose brain cells in that episode. And their IQ and their trajectory for life decreases.

Host 1: It's just so fascinating. My research brain is thinking about the longevity, and the studies that can be done looking at outcomes with early intervention like this and the screenings and then, introducing, like you said, one injection a day and lifestyle and what that means later in life for patients that go into stage three after they have delayed the onset of that, kind of what their outcomes are. And, if, their insulin is less, if their quality of life is better, just kind of looking at those things. It's so interesting.

Amanda Williams, MSN, FNP-BC, CDE: If I had been diagnosed with Type 1 diabetes in stage 2, that would have given me the opportunity to go through college without having Type 1. I was diagnosed when I was 18-years-old, after high school. I had enlisted in the Air Force and was two weeks out from going to basic training. I had developed I have a lot of urinary frequency, going to the bathroom 20 times a day, and I decided to go see my primary care doctor to get treated for a UTI before I went off to basic training.

And I listed out all of my symptoms, you know, I'm so thirsty all the time, and I'm peeing all the time, and the wonderful nurse, knew right away, checked my blood sugar, and it was over 300. And so that changed my life dramatically. I didn't go to basic training. I stayed at home and worked for that semester and then in January went off to nursing school. For me, Type 1 diabetes is annoying. I haven't had a lot of complications like other people do. I know a lot of people who have retinopathy or they develop chronic kidney disease.

They've had a loss of a pregnancy because their blood sugars were too high. Three years after my diagnosis, my dad was diagnosed with Type 1 diabetes at the age of 47. And that was really hard for him. When you're 47-years-old, you are set in your ways. You're set in your lifestyle and your food choices.

And without an insulin pump, my dad would not have an A1C under 9%.

Host 1: And to think all of that could have been discovered earlier in life and with these practice changes, the overall quality of life for patients with Type 1 diabetes is going to change. I mean, this is just groundbreaking. It's so exciting.

Amanda Williams, MSN, FNP-BC, CDE: For a hundred years, we've had insulin, which is the life saving medicine that keeps people with Type 1 diabetes alive. We are at the end of that century of only having insulin to treat Type 1 diabetes. This is the start of treating Type 1 diabetes before it manifests in people and requires them to be on insulin.

Host 1: It's just fascinating to me. When we talk about those screening labs, you know, and doing it at that certain pivotal ages, does insurance cover these tests? Because I think that that's a big question that families are going to ask, you know, does insurance cover it? Is it a routine screening lab?

Amanda Williams, MSN, FNP-BC, CDE: Insurance does cover this. If somebody is hit with the cost of this, I think it's under $15 for these labs, but if you code it with screening for Type 1 diabetes, you should be able to have it covered. This is routine screening.

Host 2: So are there any cons to screening, Amanda?

Amanda Williams, MSN, FNP-BC, CDE: Well, if you screen positive for two autoantibodies, that is now a diagnosis of Type 1 diabetes, and that person will have that on their medical record. I mean, it's true. It's not a false statement. I think over time, insurance companies are going to realize that ' ' if we treat stage 2 Type 1 diabetes with teplizumab, that their lifetime cost for insurance is going to be less. The average cost to a person who lives with Type 1 diabetes, or cost to the insurance company is about $500,000 over a lifetime. And that's without a lot of complications. When we start adding in complications of chronic kidney disease, diabetic retinopathy, diabetic wounds and neuropathy, cardiovascular disease, this is what starts adding up those costs even higher.

Host 1: Not to mention just the overall cost of insulin itself, right? So if we could give people time, to settle into their diagnosis, to prolong that stage 3 Type 1 diabetes, I mean that is an overall huge healthcare cost savings.

Amanda Williams, MSN, FNP-BC, CDE: And just overall improved quality of life.

Host 2: What is the typical cost of the medication and is insurance covering it?

Amanda Williams, MSN, FNP-BC, CDE: So, teplizumab's not cheap. It is about $200,000 for an infusion of teplizumab. Teplizumab is approved for people who are 8-years-old and older in stage 2 Type 1 diabetes. They get an infusion every day over about 30 minutes, for two weeks. So 14 consecutive days they get an infusion of teplizumab. That seems like a lot. That seems like a big commitment to families. But the way that I look at this is, this is kind of like chemo for Type 1 diabetes. You know, if you told somebody that their child had cancer, they would drop everything and do whatever treatment was necessary for their cancer and to go into cancer remission.

Cancer we can treat and you can be in remission. Type 1 diabetes, you will have this the rest of your life. And so, if we can delay that progression, as long as possible, this person won't have to be on those multiple daily injections.

Host 2: Right, that makes sense to me. Is it after the two weeks of the infusions, do they have to repeat it like a year later or is there any potential that they could get it again to then again delay it for another 30 months or whatever you had mentioned?

Amanda Williams, MSN, FNP-BC, CDE: We don't know that yet.

Host 2: Okay.

Amanda Williams, MSN, FNP-BC, CDE: For those of us in this field, that's kind of our hope. You know, if we give somebody an infusion of teplizumab, that in three years or four years when they start to develop dysglycemia again, who's to say we can't give them another infusion of teplizumab and then push it out again, another three or four years.

Host 2: Well, it's so exciting.

Amanda Williams, MSN, FNP-BC, CDE: There are also a lot of other medications being studied and developed in this treatment. And so if a patient doesn't want to go through an infusion of teplizumab, there are other choices for them. The Barbara Davis Center is the group that helped develop this medication. And right now they are enrolling people in the PETITE study, and that's for children under the age of 8-years-old.

Host 1: So I kind of want to recap, because the way that my head works, I need to kind of put it step by step. So we have a patient in the primary care and at 2-years-of-age, we do that screening, okay, and they get those islet antibody testing. Those are the islet antibodies.

Amanda Williams, MSN, FNP-BC, CDE: Correct, yes.

Host 1: Okay, so we get those islet antibodies. Is there resources that the primary care provider could look up to say, oh, yes, these two are elevated. This is the normal range. So they know what they're looking for?

Amanda Williams, MSN, FNP-BC, CDE: So they should show that they're abnormally high. And if they are elevated in any way, then you would refer them over to endocrinology.

Host 1: Even at stage one, you would refer them to endocrinology to get that conversation started.

Amanda Williams, MSN, FNP-BC, CDE: Absolutely.

Host 1: Okay. And I like the verbiage that you used earlier in the podcast about how to direct those conversations. So that's fantastic. So, we get those labs, send them to endocrinology, and then the medication infusion can happen when they advance into stage two. Is that what I'm understanding?

Amanda Williams, MSN, FNP-BC, CDE: Yes, and they have to be over the age of 8.

Host 1: Over the age of eight. Okay. So you would just monitor that little tiny two-year-old, with endocrinology and a collaboration until they develop stage two and are over the age of eight.

Amanda Williams, MSN, FNP-BC, CDE: Correct.

Host 1: Okay.

Host 2: And then say they're negative. They could still be screened again at 8 and at 10 and those ages that you said the ADA recommends testing.

Amanda Williams, MSN, FNP-BC, CDE: Right, at ages 2, 6, 10, and 18. So before you send them out to and 40! So before you send them off to college, you know, let's make sure that they don't have Type 1 diabetes.

Host 1: Wow. Yeah, there is a family friend and her daughter got diagnosed, I believe, in her sophomore year of college. She was pretty sick and they couldn't figure out why. So I think it was her freshman or sophomore year in college that she got diagnosed with Type 1 diabetes.

Amanda Williams, MSN, FNP-BC, CDE: If we had screened that individual when she was 18 before she headed off to college, we could have given her that teplizumab infusion. before she went to college and then got her through college without having Type 1 diabetes. What a huge relief.

Host 1: Huge relief without the stress of college and being on your own and managing that all by yourself. You know? Yeah. Amazing. Fascinating.

Host 2: Yeah, this is awesome information. Thank you so much, Amanda, for hanging with us today and, just sharing all of this information. It's really exciting.

Amanda Williams, MSN, FNP-BC, CDE: Thank you guys so much for having me, for thinking of me. It's a privilege to be here with you today.

Host 2: So we end each of our episodes with a question. And so we ask all of our guests the same question, each season. So the question for now is what is filling your cup in the season of your life?

Amanda Williams, MSN, FNP-BC, CDE: I think making people more aware of this is what keeps me going.

Host 1: I love it. Cause it is so innovative and it's, it's like you said, it's a practice change. It's a paradigm shift with Type 1 diabetes and the future's bright and you're part of it. So thank you so much for being here today and sharing your knowledge.

Amanda Williams, MSN, FNP-BC, CDE: Thank you so much for having me.

Host 2: If you have a topic that you would like to hear about or you are interested in being a guest, you can email us at tdobrian@cmh.edu or twilliams@cmh.edu. As a reminder, to complete your evaluation and ensure that you get the credit for listening, visit childrensmercy.org/appeval. That's childrensmercy.org/A-P-P-E-V-A-L. Once again, thanks so much for listening to the Advanced Practice Perspectives podcast.