108 Pediatric Diabetes: Are We Closer To a Cure , Dr. Kimber Simmons MD, MS

Dr. Kimber Simmons (MD, MS) is an Assistant Professor of Pediatrics at the Barbara Davis Center for Diabetes in Aurora, CO. She cares for children with Type 1 diabetes (T1D) and other endocrinologic disorders. She is passionate about educating families and the community about T1D. As a child, she prayed every night for a cure for T1D, and now she spends much of her time conducting research to contribute to the prevention of and, ultimately, a cure for T1D! She is involved in efforts to identify children who have T1D early, before they develop symptoms, and is an active investigator in many prevention trials, including those run by TrialNet. As a collegiate athlete who loves hiking, running, and spending time outdoors with her husband and two young children, she is sympathetic to the blood sugar roller coaster. She enjoys helping young athletes learn to manage their blood sugars better. She is honored to be part of such a dedicated and innovative group of individuals committed to making positive changes for people at risk for and living with T1D!

Ask the Experts: https://www.asktheexperts.org/

Enable:  https://type1testing.enablebiosciences.com/

Ask: https://www.askhealth.org/childhood-diabetes

ADA Article on Population Screening https://diabetesjournals.org/diabetes/article/71/4/610/144874/Screening-for-Type-1-Diabetes-in-the-General

Transcript

IDDM Are We Closer to A Cure 

[00:00:00] Hey, George. Good morning. It's another Tuesday morning. How are you today? I'm 

[00:00:03] Dr. Rogu: doing pretty well. Today, we have another fascinating guest, Dr. Kimber Simmons. And her topic today is going to be pediatric diabetes. Are we closer 

[00:00:13] to a cure? 

[00:00:15] Dr. Simmons, welcome to the podcast. Thank you for making time for us out there from Aurora, Denver.

[00:00:22] Dr. Kimber Simmons MD, MS: Of course. Thanks for having 

[00:00:23] Dr. Bravo: me. How are you today? I'm well, thanks. We always start the show by asking people why they became a pediatrician. In particular, why did you choose this subspecialty of pediatric endocrine? 

[00:00:35] Dr. Kimber Simmons MD, MS: That's a great question. And it's become easy to answer over time. When I decided to do medicine, I didn't quite know why; I just liked it.

[00:00:43] But in retrospect, and precisely why I'm in pediatric endocrinology is from my own experience of being diagnosed with type one diabetes when I was eight years old. And I think that from the time I was little, I had hoped that there would be people working hard within the field to make lives for [00:01:00] people with type one diabetes better. And I am thrilled to be part of that now. 

[00:01:04] Dr. Bravo: Thank you. What was it like? From the perspective of an eight-year-old, it's even hard to digest what that diagnosis means. It is hard 

[00:01:15] Dr. Kimber Simmons MD, MS: To think about what that means long term, you don't, you think about at that moment what's happening to you, and really what I remember was just being scared of needles and feeling like I was being forced to have IVs placed and people standing around me and doing things to me that were new and uncomfortable and I didn't understand why, but I had no idea at the age of eight what that would mean for it.

[00:01:39] the rest of my life regarding the daily burden of chronic management. 

[00:01:44] Dr. Bravo: I think because the kids are so resilient, but the most challenging thing that makes me cry is how do I help these parents? Because we all, as parents, want our children to have what we consider an everyday, healthy life. And anything [00:02:00] that's not quote-unquote normal is such a shock to the parents.

[00:02:05] And all these new things that they have to learn and eventually within, I think, about 18 months, they know more about the management of diabetes than I could ever know. But the parents are so complex, such a difficult journey for the parents. 

[00:02:20] Dr. Kimber Simmons MD, MS: It is an arduous journey, and I think that's one of the things that's special about what we do is you have to take care of the whole family because the family is impacted in different ways, but just as much as the child.

[00:02:32] And so it's an exceptional opportunity to be a part of that whole family's life and helping them deal with type of 

[00:02:38] Dr. Bravo: diabetes. Yeah. In the past, we used to say insulin-dependent diabetes and non-insulin-dependent diabetes. And nomenclature has all changed, and now we talk more about insulin resistance versus.

[00:02:55] Type 1 juvenile diabetes. What is insulin [00:03:00] resistance? And how does that lead to what we commonly refer to as Type 2 diabetes that keeps crawling into our exam rooms today with the adolescents and the preteens? 

[00:03:11] Dr. Kimber Simmons MD, MS: Sure. Insulin resistance is when people make insulin, but their bodies don't use it the same way as someone who is not resistant.

[00:03:22] So how I usually describe it to families is I talk about how insulin is a bridge that builds and less sugar. Go from your bloodstream into all of your cells for energy. So your brain and your heart and your muscles. And in people who have insulin resistance, that bridge becomes narrow. And so the sugar can't get into the body very quickly.

[00:03:44] To make that bridge bigger, you must find ways to decrease the insulin resistance and open it up wider. You can exercise more, eat a better diet, lose weight, and potentially use pills. So that is common. Type two [00:04:00] diabetes, what we talk about. And I think one of the essential things to think about is it's not that everybody gets type two diabetes because they don't have a healthy diet or they don't exercise. Still, there's a strong genetic predisposition to having insulin resistance.

[00:04:16] You have people genetically predestined to have insulin resistance, and all those lifestyle factors just become significant to controlling glucose and ensuring that the insulin can get into the body for energy. 

[00:04:29] Dr. Bravo: That's a beautiful explanation. I listened to three-quarters of an episode of Peter Atteal, and he had a researcher on insulin resistance.

[00:04:39] They started talking about something called mTOR, and I had no idea what it is, but it's some enzyme near the mitochondria. That is very much related to your muscles, insulin resistance or not. They turn my world upside down because you can be an average BMI 20-year-old college [00:05:00] student with a normal hemoglobin AC1. If you become nonactive, they can start measuring your insulin resistance. At the same time, the next person has the same parameters: Not any more active than you are not in insulin resistance. The second takeaway from that, which was fascinating, is that most of the insulin resistance happens in two organs of your body.

[00:05:27] I'm right, but I was just what I took away from it: your liver, and the other, which is much more important, is your skeletal muscle. You are in big trouble if you can't inject insulin into your lean muscle. And that's where not exercising is hurtful because you need to build that muscle, which is tons larger than your liver.

[00:05:53] But it was a fascinating conversation. I didn't know any of these concepts, and I still need to understand what mTOR is. 

[00:05:59] Dr. Kimber Simmons MD, MS: [00:06:00] Yeah. No, many experts deal with insulin resistance at the muscle and liver level and fat all the time. And I also need to be educated in that. Still, I do know that clinically, even our kids with type one diabetes, when they get to a certain age, if they have a strong family history of insulin resistance or type two diabetes, they also will have insulin resistance.

[00:06:21] So it's something that we see in anybody with diabetes that we have to. Think about. 

[00:06:26] Dr. Bravo: Oh, wow. I didn't know that. So, you have to increase their insulin doses or get them to exercise more. What do you do with those kids? 

[00:06:37] Dr. Kimber Simmons MD, MS: Yeah. Their total daily doses of insulin are typically much higher.

[00:06:40] Their carbohydrate ratios and correction factors are much more aggressive. Sometimes, we consider using adjunctive therapies, although the data in pediatrics isn't apparent as to the benefit of 

[00:06:53] Dr. Bravo: that. Yeah. Yeah. What are isolate cell antibodies, and what role do they [00:07:00] play? I'm that's what I remember from medical school. So what are they, and how do they play a role in this insulin-dependent disease? Sure. 

[00:07:09] Dr. Kimber Simmons MD, MS: So people who develop type one diabetes have that process start years before they know that they have diabetes and have the symptoms of drinking too much and urinating too much and potentially losing weight and being hungry.

[00:07:24] But what happens years prior often is that the immune system makes a mistake, and The T cells start fighting off pieces of the beta cell that make insulin when they shouldn't. And when that starts happening, so that autoimmune process starts happening, the B cells produce autoantibodies in response to that, showing that process is happening.

[00:07:48] There are four primary biochemical antibodies, which are immune markers against proteins of the beta cells. That makes insulin. So there's [00:08:00] glutamic decarboxylase or GAD. There's insulinoma, insulinoma antigen two or IA2, zinc transporter eight, or ZNT eight. And then there's also an antibody to insulin.

[00:08:11] Those are important biomarkers because that's the one thing we can measure right now to know that someone is on the path to developing type one diabetes. 

[00:08:22] Dr. Bravo: If I'm correct, there are three stages. I guess I will call it juvenile-onset diabetes to diabetes, right?

[00:08:29] You can have the positive serology for the out of antibodies and your glucose, your hemoglobin AC 1, and your glucose tolerance test is negative. That's great. Then you can have the 2nd type or subtype where. You're still, your daily glucose is average, and your hemoglobin AC1 is normal. Your antibodies are positive, but now you have an abnormal glucose tolerance test.

[00:08:57] Dr. Kimber Simmons MD, MS: Pretty close. I think it's important to realize that [00:09:00] these stages initially when they were designed for clinical trials. And so it was because you want it to take less than 20 years to answer a question in a clinical trial. And so you tried to identify people who were at the highest risk for progression to clinical diabetes to see if the medication that's being studied has an impact.

[00:09:20] Those clinical trials were meant to try to. Differentiate who's at the least risk for progression and who's at the higher risk for progression. And then, over time, it's become part of the American Association, diabetes standards of care where diabetes is now staged. And so that stage two that you were talking about, that second stage per the ADA, isn't just an abnormal two-hour oral glucose tolerance test; it could also be a slightly elevated hemoglobin a one c between 5. 7 and 6. 4 or fasting glucose between 100 and 1 26. So it's showing signs that [00:10:00] blood sugars are beginning. They have abnormal values but are not hyperglycemic yet causing symptoms. 

[00:10:07] Dr. Bravo: Does measuring fasting insulin help you in that decision tree? Are they producing more insulin because the isolate cells are not good, but is the body trying to make more insulin and still keeping up or not at that stage?

[00:10:22] Dr. Kimber Simmons MD, MS: Over the stages, what's happening is that you're losing beta cell volume and also some beta cell function over time. So, if you were to measure beta self, a measure of beta cell function by doing like a stimulated. C peptide, which is a measure of endogenous insulin production, you would see that over time that's decreasing.

[00:10:43] As you move through the stages, your C peptide or your endogenous insulin production decreases. 

[00:10:50] Dr. Bravo: Okay, and then type 3 within the juvenile onset is what we clinically recognize. Yes, so [00:11:00] stage 3. Glucose, what you said, polydipsia, polyuria, weight loss, ketoacidosis. That's stage three.

[00:11:07] That's 

[00:11:07] Dr. Kimber Simmons MD, MS: right. Yeah, it's still all type 1 diabetes, but now there are stages 1 and 2, before Clinical onset, and then stage 3, which is what we've all thought about type 1 diabetes being for a very long time. 

[00:11:19] Dr. Bravo: You know, in today's world, and please feel free to interject and correct me, I'm just what I see in the clinic and what I've seen in the last 30 years most children are in an insulin pump and That's how we try to manage their I will, I'll say it's a hormonal imbalance, they don't have enough insulin.

[00:11:39] We try adding exogenous insulin to manage your glucose. And that's the standard of care. 

[00:11:48] Dr. Kimber Simmons MD, MS: we would all like for patients to utilize technology because it improves glycemic control. And we also know that some of the newer technology [00:12:00] can decrease the burden, which is.

[00:12:02] Even though that might be the standard of care, there's still a lot of work to ensure everyone has access to that technology and that it's equitable. Our clinic has high technology adoption rates, but we have differences based on race and ethnicity; for example, we need to figure out how to ensure everyone can be on those.

[00:12:24] Those fantastic pieces of technology. 

[00:12:26] Dr. Bravo: Unfortunately, education plays a significant role. I have one patient that I diagnosed way, way back. And the mother's a type A; she's just on top of everything. She's just this personality. And she was one of the early adopters. This is over ten years since we diagnosed them.

[00:12:43] She would get text messages on her iPhone when her son's glucose was over 250. In school, she would text the teacher; you have to lay off a little bit; the glucose will go up. Occasionally. You [00:13:00] cannot measure it every minute of your day.

[00:13:02] You cannot be obsessed. But the more educated you are, the more involved you are and the more resources you have. And, sometimes, you become hyper-vigilant, and you don't let the kids have. They will be kids; once in a while, they will eat ice cream, increasing their glucose.

[00:13:17] If hemoglobin AC1 is steady, and they're otherwise doing well and compliant, you have to look the other way. You can't expect perfection out of any human being. 

[00:13:27] Dr. Rogu: Dr. Simmons, why do you think some kids will use a pump and others won't? Yeah, that's a great question. Because you're in the United States, there's mail, and the insurance is everywhere, their access to a pump is not the issue.

[00:13:42] Because you could be in the middle of the United States somewhere, and UnitedHealthcare is your carrier, they'll ship it to your house as long as they approve it. Is it really 

[00:13:52] Dr. Bravo: equity? Insurance is insurance. 

[00:13:55] Dr. Kimber Simmons MD, MS: It is to some degree, although, in Colorado here, [00:14:00] probably our government insurance covers that technology better than any other commercial insurance.

[00:14:05] But as you're mentioning, we have trouble having people adopt that. And those Come down to some barriers related to all the training it takes to be on a pump and feel comfortable. And so there might be some language barriers or trouble attending training, or we have people do virtual activities at home, and they'll try to do them on their phone, and maybe they could be more effective.

[00:14:26] There's still much to be learned about those barriers and how we can work to overcome them. You're right. It's not that for patients who do not have government insurance. It's covered very well. It's just having the tools to be able to see that. 

[00:14:40] Dr. Bravo: Yeah, I've seen 

[00:14:42] Dr. Rogu: one.

[00:14:42] I've seen one endocrine clinic where everybody was on sliding scales. And the chief physician was older than dr Bravo. If he didn't quite understand it, how does he recommend something he doesn't quite understand? 

[00:14:59] Dr. Bravo: Also these things [00:15:00] are all, what is it that they call it in the tech world, the power of everything or the connected of everything, something like that, where your refrigerator, your oven are connected to the internet.

[00:15:09] I don't know what for, and many of these things need the internet. That's how they can; when the glucose is off on me, and it pings my mother on her cell phone, I need an internet connection, although it's not. That is understandable for us. There are many communities, urban communities, where the internet is not available to poor people, and there are many rural communities, they call it the last mile, where the cable will come to the main road, but once you go off, the next mile.

[00:15:46] To where the houses are. No one wants to invest to put the cable down because it's too expensive, and they'll never recover the infrastructure cost. And if you can't connect to the internet, you can't update the devices, you can't communicate with your [00:16:00] doctor. , it becomes challenging.

[00:16:02] And that's what we sometimes miss. Because we all live in our bubble, I can't walk through steps without my iPhone pinging me that I left my cell phone behind me at the house. But everybody needs to have that level of connectivity. That is a barrier that has been well shown for some people.

[00:16:19] Age is also a barrier, and education is another barrier. Some people don't take diabetes seriously, no matter what you tell them. They, they just don't think it's that serious. I've read that we should be doing population screening and antibodies. How does that? What is the thought process behind that? Sure, 

[00:16:44] Dr. Kimber Simmons MD, MS: so I think so for several years since 2014, it's been recommended that family members of people with type 1 diabetes are screened for type 1 diabetes by measuring those autoantibodies that we talked about. And recently, in the last [00:17:00] statement from the ADA, they said that anyone should be considered for ILA autoantibody screening in a clinical research study setting.

[00:17:08] That statement was made before there was... anything available that you could do medically before somebody is diagnosed. Let me back up. Nine out of ten people who develop type 1 diabetes do not have a family history. We know that people with a family history are at the highest risk.

[00:17:28] Their risk is 15 to 20 times higher than if they didn't have a family member. But we also know that if we only focus on family members, we'll miss most kids who end up developing type one diabetes. And that's where the push comes for general population screening to identify all kids in the clinic who have type one diabetes before their symptoms develop.

[00:17:50] The reason for doing that has been because the rate of diabetic ketoacidosis at new-onset is extremely [00:18:00] high in the United States. In Colorado, over 50 percent of our newly diagnosed kids end up in DKA when they come in. But we know that DKA is less than 5% if we identify someone. That's important because not having DKA at diagnosis; data is showing, sets you up even metabolically for success later in life. And if you're starting with an excellent metabolic footprint, that's important. The other reason that I believe Screening, in general, is becoming more important and talked about a lot more is because, in November of last year, there was a medication approved that can be given to people ages eight and older that can delay the onset of type one diabetes by about three years on average.

[00:18:48] So we now have the first intervention we can use to change the natural history of the disease. 

[00:18:58] Dr. Bravo: The [00:19:00] recommendations have been to screen at 2, 6 and 9. As a general pediatrician, I'm curious from an implementation point of view. If I did it at 1, 5, and 10, you would make it easier on me because that's fine.

[00:19:14] Okay, that works better in my workflow. Because everybody else is there if I want, and they get their lead test and their hemoglobin. I could screen them then, and at 5, before they go to school, I could filter them then. And the ten-year physical is essential.

[00:19:30] I could get their lipids, and I could get these antibodies. And see where they're at. And so that would be fine. It's just it was just a number for the studies. Yeah, 

[00:19:38] Dr. Kimber Simmons MD, MS: I think, well, when you look at the data, there's there are several studies that have taken high-risk individuals at birth because they either have a family history of type one diabetes, or they have a particular HLA gene, which is just a gene that is involved in how the immune system presents. So both high-risk [00:20:00] factors, babies that have those were followed over the years. And so from those various studies in the United States and Europe, all that data was collated and said at what ages, if we screamed, would we have the highest chance of catching everyone who develops diabetes?

[00:20:15] And those ages are two and six. But I think practically like you're saying, it makes a lot more sense to have buckets like one and two, four to six, nine to 11, really what when I think of it, the one to two-year-old timeframe, you would probably catch more if you did it at two. Still, that timeframe is to see kids who will develop diabetes as toddlers or preschoolers before school age.

[00:20:38] When you're doing that school-age screening, that will catch most kids who develop diabetes before puberty. And then when you're doing that preteen screening, so ages 10, for example, that's when you're going to catch people who develop diabetes through the age of 18.

[00:20:53] And people who develop diabetes as adults don't entirely develop diabetes by the age of 18. So those are [00:21:00] the time points that won't catch everyone but will catch many people who will develop type 1 diabetes. 

[00:21:05] Dr. Rogu: No, if you think about it to six and nine logistically, it's not a bad idea because people usually go to the physician's office, pediatrician's office to get vaccines at those particular visits to six and nine, which are visits that historically are missed. They don't go because they know you don't have to get any shots. So why should I go to a doctor now if there's something to do? They may go to the doctor. 

[00:21:31] Dr. Kimber Simmons MD, MS: That'd be great. If that's 

[00:21:33] Dr. Rogu: a good thing because you're not getting any shots, and then you also have the idea that I gave a picture, and then your diabetes screen was positive. Did the image cause your diabetes to trigger? 

[00:21:42] Dr. Bravo: I don't know. But what we have seen with school mandates is that. Because in Virginia, daycare mandates that people come in to get their physical because they can't put the kid in daycare, and I need something people come in before they go to a kinder because they [00:22:00] can't get into school, but the six-year-old already had his kindergarten form filled out.

[00:22:05] They don't have to come in once you get to those ten- and 12-year-olds- and 14-year-olds. Man, they're healthy. They don't need to come in, and they feel like they're invincible. They only want to come in for a reason if they want to cheer or play basketball and are mandated to get a sports physical.

[00:22:25] Other than that, you have to go with an ice cream truck through the neighborhoods and pull them out of the houses to get them to do their physicals. So that's why I'm saying that, at one and five and 10, it would be they're already there. It's like what I tell parents: don't wait till it gets too old to give them the vaccines.

[00:22:44] I would give them all the vaccines in two months if I could. They can't run or fight me, and I would just be done with it, and they won't remember it. But that's not what we get. 

[00:22:54] Dr. Kimber Simmons MD, MS: Yeah, I think you'll lose a minor sensitivity, but I think the point is just to be screening a few times [00:23:00] during childhood, in the way that I described, and that will be helpful.

[00:23:04] Dr. Bravo: Okay, and the screening is pretty simple, right? It's not a full-blood draw. It's a finger stick, and then they do it off of a card, and that's it. It can be 

[00:23:15] Dr. Kimber Simmons MD, MS: done. So, the antibodies are in the serum. And so you can get serum from a capillary stick with a finger poke or from a venous blood draw either way. So it depends on the family's preference.

[00:23:27] Sometimes, getting a venous blood draw is better than squeezing a finger for a long time. But depending on the clinic and what's available, either way is acceptable. With the finger poke, some people have dried blood spots. Yeah. Others do like capillary tubes, so small lines where the blood would go in, and then the venous blood draw is a vacutainer, 

[00:23:49] Dr. Bravo: Okay. I think most clinics do mostly finger pricks. They need more time to be doing venous sticks. 

[00:23:56] Dr. Kimber Simmons MD, MS: Yeah, so capillary the capillary blood tubes, the results [00:24:00] are the same as if you did a venipuncture, 

[00:24:02] Dr. Bravo: okay. And then this is where I get all confused, and I get all confused with Bayford is, and I get all confused with this new drug.

[00:24:10] So we now have the ability, which is a miracle, to create monoclonal antibodies that target a specific protein of a virus or a cell in the body and prevent disease. So, these monoclonal antibodies in diabetes. What are they targeting? Are they covering the B cell antigen that's producing the autoimmune response? Or are they protecting the T cell? Where are they being affected? 

[00:24:43] Dr. Kimber Simmons MD, MS: So these monoclonal antibodies to Zeld are binding to T cells, to the CD3 part of the T cell receptor on T cells, and when they bind, the T cell receptor internalizes, and from animal [00:25:00] studies, it looks like those T cells go out of the circulation, and then they start to come back into the circulation rather quickly, but when they come back, they're a Exhausted.

[00:25:10] They have what we call an exhausted phenotype. So they aren't activated against the proteins that they were previously fighting. For example, they can still respond to viruses but can't answer. They don't respond as much to beta-cell proteins. 

[00:25:25] Dr. Bravo: Okay. So, it's at and fluctuating at the T cell level.

[00:25:29] That's right. Okay, very interesting. I like the term exhausted. Maybe somebody threw some monoclonal antibodies at me because I feel exhausted some days. And then, and I, I know this is an unfair question, but I was just thinking as I was reading last night, preparing for your conversation with us, Bayford is, they were able to take a monoclonal antibody, and I don't, I've been able to figure out Where this B40 goes, does it go to the T cells, does it go to the RSV virus, where does it have [00:26:00] its effect?

[00:26:01] But then they naturalized it, and through a process, they make it hang out in your bloodstream for 150 days. And I was thinking, is that the future of prevention of diabetes? If we can make this autoimmune antibody hang out for six months? When we have these markers, we get two shots a year, which would keep delaying the onset.

[00:26:26] Dr. Kimber Simmons MD, MS: That's interesting. I haven't thought about it that way. If you could keep monoclonal antibodies like this one around for longer, what would that do? I don't know the response to that because we don't even know; other autoimmune diseases often require multiple infusions.

[00:26:43] It's not that you get one, and that's it. Still, we haven't Figured out type one diabetes if we also need repeated infusions or if you need to come at the immune system from another direction and use another medication in [00:27:00] addition to the monoclonal antibody.

[00:27:01] So those clinical trials are being put together and ongoing. There's a lot to figure out about the best way to treat type one diabetes or hopefully prevent it in the future. But I do think. Even though this is just the beginning, it is like you mentioned earlier.

[00:27:18] It's incredible that the door has been opened and that something is available now that can alter the natural history of an autoimmune disease. And as far as I'm aware, it's the first therapy in any autoimmune disease, not just type one diabetes, that you can change the course of the disease.

[00:27:37] Dr. Bravo: Yeah. It's fascinating. What monoclonal antibody for RSV? You have to give a shot every month during the RSV season, and then they figured out to put it through some bath or something, and now it stays in the kid's bloodstream for six months, and they can get one shot, and that's it.

[00:27:55] So it's incredible if that was a path that we could, [00:28:00] it would be like, hey, we don't cure your disease. We keep you at a level where you never need to shoot yourself with insulin. That would be huge. 

[00:28:10] Now, what is this medication? It's a monoclonal antibody for T cells and is commercially available now. That's right. And as I understand it, it's an hour-long infusion for 14 days in a row? 

[00:28:24] Dr. Kimber Simmons MD, MS: It's a half-hour infusion. The rate can be slowed down if the patient is having any... Side effects during the injection, but in all the patients that we've infused, we've been able to do it over a half hour, 

[00:28:37] Dr. Bravo: Children’s hospitals with an extensive endocrine department and infusion center generally do these.

[00:28:45] Yes. 

[00:28:45] Dr. Kimber Simmons MD, MS: So it's still being nationally put together because having an infusion of something 14 days in a row isn't something that happens in even oncology. And so weekend coverage [00:29:00] and figuring that out, even within large children's hospitals, requires some work.

[00:29:04] Bye. Our feelings, people who have worked with this drug and talked with people who administer immunotherapies and other areas, is that this medication should be administered somewhere where there's expertise and pediatric-trained people, for example, not that there's a high risk of side effects. Still, you want everybody to get this in the safest environment possible.

[00:29:26] An infusion center, an office-based infusion center, or a hospital's infusion center are probably the safest places. 

[00:29:35] Dr. Rogu: But doing this will be almost like a bit of hospital admission. 

[00:29:41] Yeah, you keep those people in 

[00:29:43] Dr. Kimber Simmons MD, MS: there. Yeah. I'm just advocating for I don't want my patients to get it at home where they may have something happen and can't get to a hospital. But You know that the chances of something happening where they would need advanced life support are meager.

[00:29:59] The [00:30:00] thing we worry about most with the medication is cytokine release syndrome over activating the immune system and causing inflammation. And we administer it for us in our office-based infusion center. And we know that if a patient was. To have symptoms, we would need to evaluate them further and send them to the hospital if we were concerned.

[00:30:21] So, you have to plan how they could get the care they need if they need it. But our nurses administering the drug, for example, are all trained in that so that they would know the signs and symptoms of when care needs to be escalated. 

[00:30:36] Dr. Bravo: You could in a healthy run pediatric urgent care. Led by pediatricians with infusion nurses who are trained or PAL certified, it would also be a viable in-your-neighborhood option because we have to remember that the children's hospitals are understaffed, overburdened, and underpaid. And so we cannot [00:31:00] continue to excuse my language, dump everything on the endocrinologist or the children's hospital.

[00:31:07] We have to do our share so they can be available for the more complicated patients we need the most help with. So a well-run urgent care could adopt something like this so it's available everywhere, not just... In extensive metro areas. Because we need to remember many people don't live near a metro area or a children's hospital.

[00:31:30] Now, what is this skinny on the study? I read it, and I got all confused. I don't do data analysis very well, but it seemed like it took the highest risk kids and siblings of people already diagnosed with diabetes. They gave him this infusion for 14 days, and they were in a large part of the kids able to delay the onset of type one diabetes by something like two years [00:32:00] or more.

[00:32:01] But then there was what I think I understood, which I like more because I'm a Pollyanna kind of person, is that there is a subset that Didn't seem to develop diabetes after this infusion. So, what are the numbers from somebody who does this research? 

[00:32:20] Dr. Kimber Simmons MD, MS: So when you're, when you were looking at this group, and you had all the general details right about this study, so 44 people received the active drug, and when you're looking, you don't expect, you don't know if someone did not get the drug when they would develop diabetes.

[00:32:39] So you have to look at the difference in time to developing clinical diabetes between the group that received the drug and the group that received the placebo. And so in the follow-up study done after the initial study showed that the difference in time to diagnosis was 32 and a half months, almost close to three years.[00:33:00] 

[00:33:00] And that's on average when you're looking at that. Still, what's important to note is that not everyone responds to this drug; just like with every immunotherapy or every treatment, not everyone will have an excellent response. Not having a superb answer means you have a little bit of an improved response, meaning a little more delay or nothing.

[00:33:20] That's hard to tease out because we don't know, again, when they would have developed diabetes. But we know that the people who respond well go longer than 32 and a half months from developing diabetes. So, almost three years is the average of people who develop diabetes at a standard rate and have a good response and delay.

[00:33:40] Dr. Bravo: It gave me the hope that we're getting close to a long-term management that doesn't involve insulin and pumps and daily shots. Thank you to us doses. And, as Dr off often says, the tyranny of small numbers. So when dealing with tiny numbers, you're [00:34:00] limited to the power of prediction.

[00:34:02] And anticipating unknowns, you only see that when you've started using it, the population in general 

[00:34:08] Here's where I have some concerns, and it's not. It's more about how we finance health care in America because this infusion costs almost 180,000. That's the medicine cost that doesn't include the infusion center, the doctors, and the chronologist.

[00:34:28] That's a hefty price tag. If you're looking at it from a societal point of view, I'm not; of course, if it were my son, my grandson, my niece, I'd be like, who cares? Spend the 200 000 give her three years without giving herself insulin shots. But from a societal point of view, that is a tremendous amount of money to spend on one intervention.

[00:34:51] I'll make the same criticism of Bayford; it's a miracle drug. Could we stop the little three-month-old from [00:35:00] getting RSV and ending up in the ICU? It's worth 500 bucks. In aggregate, if we give this product to every newborn at risk, It's 2 billion spent. Again, I'll make this point: our children's hospitals are understaffed, overburdened, and underpaid, and I can't reconcile, and I like Sanofi.

[00:35:28] I'm not hitting on Sanofi in particular. I need help reconciling taking 2 billion and moving it from. Supporting children's hospitals, pulmonary specialists, ICU specialists, hospitalists, and ERs, accepting that 2 billion and giving it to pharma. And then, when I do need that... Inpatient, but it's not there because they don't have enough money to sustain it, which we're seeing at the community level.

[00:35:57] And for the life of me, I haven't [00:36:00] been able to come up with a solution of how do we bring about the finance of these Madison, which I think at the end of the day is going to be the federal government. Nobody has big enough pockets to take these hits, not even United Healthcare. And you can't do it at the Medicaid level.

[00:36:15] Some states have more money than others. And some can’t; they can't afford it. And so these will have to be funded by the federal government, and we will have to set a tariff for a percentage that gets fed back into primary care and the Children's Hospital. To maintain infrastructure because I need an endocrinologist, maybe I only need them once a year. Still, I need them, and I need a pediatric ICU bed when somebody is in a car accident, and I can't vaccinate against car accidents. Unfortunately, Someone will get cancer. I need a new good neurosurgeon for that [00:37:00] baby, and I think we haven't had the conversation, and it worries me because, yeah.

[00:37:06] It's time to have them because we will have more miracle drugs and need to keep the infrastructure. We need the endocrinologist. We need the Children's Hospital. We need to continue the research shift from one bucket to another and remember the community's needs.

[00:37:27] But that's just me thinking out loud about how you will finance this. Which 

[00:37:33] Dr. Rogu: I always ask the drug reps. Why are these medications so darn expensive? Why should it have a ticket of 185,000? That's all your research and development; how many things do they bring out that don't go to market and they lose on, but still 185,000 for one patient?

[00:37:51] It seems like a lot. 

[00:37:52] Dr. Kimber Simmons MD, MS: It does seem like a lot. We're in the realm right now of a rare population because there aren't many kids screened. So I [00:38:00] hope that will change over time if there's approval outside the United States. States that will also drive a difference in the cost here.

[00:38:06] But yeah, I agree with you. Our healthcare system is broken, and in working with this and developing our infusion and immunotherapy programs here, I've learned even more about how broken it is. And it makes me very sad. Some things need to be changed so that Our patients can be taken care of in the way that we know they need to be taken care of.

[00:38:28] Dr. Bravo: We've done this in the past, so this will get resolved, right? If you go back to the 1980s, I remember this because my younger sister is younger than me. She couldn't get vaccinated, and it was all because the pharmaceutical company said, enough, we're getting sued right and left with DPT, and we're not going to take that burden anymore.

[00:38:49] And they stopped providing vaccines. And so, Congress moved to create the Vaccine Compensation Act. And now they have a tariff per toxoid, so [00:39:00] 75 cents per toxoid. And you can't sue outside this vaccine compensation system. So you can't sue the pediatrician; you can't sue the pharmaceutical house. And they started manufacturing creating better vaccines, and life went on.

[00:39:17] And then we got to the point where If you are not insured or if you're commercially insured, some people didn't have preventive medicine. Child exams weren't paid for. Vaccines weren't produced for—only sick visits. And so we came up with a vaccine for children program. And now your pediatrician could give you the vaccines if you were not insured, you're underinsured, or in the old days, your health plan did not cover vaccines, just like everybody else.

[00:39:49] And we got, we did it. We did it, and we found a way. So we just haven't had the conversation about these miracle drugs. How do we finance it? [00:40:00] So it's equitable, and how do we set up? I call it, I'm a great fan of Dr. Offit, and I call it the farmer mentality. When racing corn, you take the best corn and set it aside for the forest for seed for the next season.

[00:40:18] When we think about these miraculous interventions, we must take some of that best corn and plow it back into the infrastructure our communities and our children need, but we will get there. It's just we still need to work it out. And even more optimistic. I know we don't have the answers, but this opens the door to many ways of thinking about how we may be very close to a cure for diabetes.

[00:40:48] Thank you. What are your thoughts about where the future research will concentrate?

[00:40:54] Dr. Kimber Simmons MD, MS: I think the research will have to adjust. We have a standard of care because there is [00:41:00] something clinically available now instead of trying therapies with the placebo group. Some more people will be treated in trials, eventually, because everyone will receive something.

[00:41:12] But we have to adjust when we're doing research and accounting for that, which within the research community takes some adjusting and some time. But, so other immunotherapies against, compared with teplizumab or TZLD, is one way that, or one place where there will be focus.

[00:41:29] There's also much research focused on beta cell regeneration and stem cell transplant. I always feel like maybe in the future, for people with diabetes, if you can put cells back. You still don't know how to turn off the autoimmune process, but instead of doing immunosuppressants, you can give an immune-modulating drug that might be a path forward for people with diabetes, which I think is very exciting.

[00:41:57] Dr. Bravo: I love how you think about that [00:42:00] because these immunosuppressive drugs are not very good. But you could give someone an infusion with the insulin-producing cells, and they can migrate to your pancreas and give him a monoclonal antibody to shut down the immune attack of these cells. In that case, you might start producing endogenous insulin again.

[00:42:21] Dr. Kimber Simmons MD, MS: Yeah, it's exciting to think about all of those things, and within the next five to 10 years, there'll be more than one thing clinically available. And that, once items become available, then that pushes for more things to become available.

[00:42:33] So we're just seeing the ball rolling. I always think akin to the first cell phone, which looks back, and we're like, that wasn't very good, but at the time, it was great. And this field will hopefully evolve quickly over the next few decades. 

[00:42:47] Dr. Bravo: And what will you do for a job when diabetes is all gone?

[00:42:51] Yeah, 

[00:42:52] Dr. Kimber Simmons MD, MS: I wish in my lifetime I could not have to take care of people with type 1 diabetes; that would be a dream come true. Unfortunately, there'll be a need for me, [00:43:00]. 

[00:43:01] Dr. Bravo: There are many endocrine diseases out there that are sometimes too complex to manage. What have I not asked you that you think is essential for the audience to hear the message of whatever you want to discuss regarding diabetes in the future?

[00:43:20] Sure. 

[00:43:21] Dr. Kimber Simmons MD, MS: I think one of the things you were saying earlier about how, their people, not everybody has access to a big hospital setting, for example, and I think because this is also new, there's a lot of questions and a lot of good questions about not only what does it look like, to screening mean?

[00:43:41] How do I care for patients after they are screened? What, how, what about this medication? But also feasibility and implementation and all these things. And we established a program a few years ago called Ask the Expert. And I know that looks generic but ask the experts. Org and [00:44:00] we actually, our goal is to work with pediatricians to work with primary healthcare providers that screened their patient and don't know what to do next, or want to screen their patient and don't know how to do that, or have questions about medication.

[00:44:15] And what we try to do then is train. Someone within their practice or someone locally so that they have the knowledge they need to take things on. And then if their approach doesn't allow for the for, extra whatever the items are if they can't see patients and can't prescribe like a CGM because that's too much in their clinical workflow, we can support remotely.

[00:44:41] We want to partner with primary care providers, support them to do as much as they want, and keep them in what they feel they can't feasibly do so that we can take care of this early-stage T1D population. 

[00:44:54] Dr. Bravo: Wow. That's a phenomenal program, and this is funded through grants.

[00:44:59] Dr. Kimber Simmons MD, MS: It [00:45:00] was funded through the Helmsley Charitable Trust, which is a trust that gives a lot of money to type one diabetes research. 

[00:45:07] Dr. Bravo: Are you limited as to who you can help because of licensing? If a practice in Virginia wants to ask the experts, can you still help? Or do you, are you limited to the state of Colorado?

[00:45:20] Dr. Kimber Simmons MD, MS: Nope, we can help nationally. We've talked with everyone and have all of our ducks in a row regarding what we can and can't do under a medical license. We can't manage someone and tell them what to do, but we can advise about what we think would be best for them to do. 

[00:45:35] Dr. Bravo: And this ask the expert is in particular for the screening when they turn positive, or is that the focus?

[00:45:45] Dr. Kimber Simmons MD, MS: The program was developed specifically for when people screen positive. And have yet to learn what to do, or their healthcare providers don't know we work on that. But what we have gotten inquiries about ranges from how do I [00:46:00] screen to, how do I treat with TZL, for example.

[00:46:03] We are open to questions and triaging the appropriate resources. But our primary focus, if we're talking about how the program was developed, is to help ensure a good care plan for patients who screen positive. We spoke 

[00:46:19] Dr. Rogu: I need clarification about many things and how to screen for our general pediatricians.

[00:46:25] How do you screen? What do you do? How do you order something? Is it an office test? Is it a mail-away test? Can you send them to LabCorp? 

[00:46:34] Dr. Kimber Simmons MD, MS: Yeah. So, all four antibodies are available commercially. So you can order them commercially. You could get into the weeds a little bit about the differences between results, depending on where you send the test and what's the gold standard versus not the gold standard.

[00:46:51] But the critical part is getting someone screened right now. And if it comes back positive, and [00:47:00] it may be a false positive, then we like that ask the experts program I was talking about, we can work with you to get a confirmation test for free. The Barbara Davis Center, for example, is the lab that did all the antibody testing and all these research studies presented.

[00:47:16] So I think whatever is accessible where you would typically send labs is where you should probably do your primary screen. But then, if something becomes positive, we Can help support confirmation testing, or you could repeat testing at your commercial lab because that increases your positive predictive value if you do it twice.

[00:47:35] So 

[00:47:35] Dr. Bravo: what is the test 

[00:47:36] Dr. Rogu called a diabetes screen like a sickle screen. Yeah, 

[00:47:40] Dr. Bravo: that'd be something else. 

[00:47:42] Dr. Kimber Simmons MD, MS: It's those four antibodies for antibodies. Some labs, like I call it a diabetes antibody panel, and they put them together, but when you're. Ordering it would be asking for each antibody to ensure you get all of them.

[00:47:57] Dr. Bravo: Okay. And like we said [00:48:00] before you can get it from a capillary, and they put it on the card, and you send it out to quest a lab corp, and they'll run it from there. 

[00:48:07] Dr. Kimber Simmons MD, MS: The card is not done by commercial labs. So, for commercial capillary

[00:48:12] Or vacutator. So, it needs to be not on a filter paper card. Currently, the company that does a filter paper card is only doing clinic-based screening. So they're called enable, and you would have clinic kits in your office, kits in your office, but then you would send them to them.

[00:48:27] And then the asking program in Colorado, where we do general population screening, also for interested pediatricians, we can have kits. as well. And their finger poke kits that use capillary tubes. So, if you want to avoid doing it commercially, there are other options outside of commercial enable, which is a self-pay situation.

[00:48:50] Their price is 85 for all four antibodies, but I don't know. And then ask is through research, so it's free, but it's through, they would have to [00:49:00] sign a consent, an electronic consent. 

[00:49:02] Dr. Bravo: Okay. And then I will put your, the ask, ask the expert do.org on the show notes for people to link it back if they want to go there.

[00:49:10] Is it just ask the experts.org? Is that the website? It is, yes. Okay. Alright, so we'll put that on the show notes. And then, the self-pay card is enabled, 

[00:49:22] Dr. Kimber Simmons MD, MS: Yes. Enable and. That is one thing that has to be: the kit has to be in a clinic like patients can't order it on their own. 

[00:49:30] Dr. Bravo: Okay. But that would be very simple to put into the clinic process because the kid's getting their hemoglobin, their lead level, they're already getting stuck, and then you put it in the car, and you send it, and you get the results.

[00:49:43] Dr. Kimber Simmons MD, MS: The ask capillary kits that are researched would be the same. You could just do, I think, with the finger poke, fill up the tube and send it. 

[00:49:51] Dr. Bravo: Okay, I'll Google that and put the links for that for people who want to implement this. George, do you have any questions? This is a fascinating topic and a [00:50:00] fascinating guest today.

[00:50:00] Dr. Rogu: Very interesting. It's probably the future of General Peeds. We always have to have something to do. Two, six, and nine is a time to do something. But if you're going to do it at the other visits to four, you're already doing a million pokes and jabs, and it's a very noisy visit, but two, six, and nine are not so loud.

[00:50:20] You might get them in. Then, the problem is if you have a false positive. Then, the drama associated with a false positive because I had seen that personally, when they came out with the sickle screen and the newborn screen, not the sickle screen up cystic fibrosis screen, like every other kid was coming back positive for cystic fibrosis mutations.

[00:50:40] And parents were getting all nervous. Oh my God. Oh my God. By the time they got to see the specialist, it took 15 phone calls to the pediatrician until they saw the specialist. I tell them I don't worry about it. Yeah, 

[00:50:52] Dr. Bravo: just a test. So 

[00:50:54] Dr. Rogu: what tests it takes to adjust it? It's 

[00:50:59] Dr. Kimber Simmons MD, MS: always complex with [00:51:00] tests because you either make it so that you catch everyone and you're going to get some false positives, or you're going to miss people and not get as many false positives.

[00:51:07] You will have some false positives, especially with commercial labs. Still, again, we can have ways of supporting and confirming as specialists that hopefully can put patients’ minds at ease. 

[00:51:20] Dr. Bravo: Yeah, I find that a fascinating program. I love the idea of that program. Thank you so much for your time today.

[00:51:28] Yep. I hope you're enjoying the fantastic weather out there in Denver. 

[00:51:32] Dr. Kimber Simmons MD, MS: It's beautiful. 

[00:51:34] Dr. Bravo: Yeah. Yeah. Yeah. Denver seems always to have good weather in the morning, and then it snows in the 

[00:51:39] Dr. Kimber Simmons MD, MS: afternoon. I don't know about it constantly, but I'll take it today. It's a nice day today.

[00:51:44] Dr. Bravo: Thank you so much for your time. We enjoyed meeting you. We'll have an opportunity to have you back on the podcast to talk about insulin resistance, which always complicates my life regarding what I need to do and how to diagnose it. 

[00:51:59] Dr. Kimber Simmons MD, MS: I'd love [00:52:00] to. And yes, I hope we stay in touch.