Good morning everybody. So thank you for having me and today is my birthday so I am very honored to be here on my birthday too on the podium. Thank you so much all the you know interest for from the ACE. So um do you okay I'm trying to be sure. Okay so these are my conflict of interest slides. Today we'll be talking about the typhoid diabetes management in the world. So I will start first with the typhoid diabetes prevalence and incidence. So as you see that typhoid diabetes has been increasing across the world and you we all know that typhoid diabetes is a far more common disease in the northern European and in people in lives in northern Europe or in the people in the U.S. or in the North America from the northern European ancestry and also from the Middle East actually it's interestingly. But if you look at the typhoid diabetes prevalence across the world and the estimations in 2040. So you can see the highest increased estimations are from sub-saharan Africa and the MENA region. And then you see that there will be a third the Middle East and North Africa region will be typhoid diabetes prevalence. And if you look at that in the following the prevalence is the incidence is just the third also. The incidence actually we have always been taught that typhoid diabetes is a disease for kids and for adolescents and you can see that we see the typhoid diabetes all across the ages and especially even for the older adults that we see the people are you know sometimes misdiagnosed with type 2 diabetes and then we do antibodies and we see them is that they have typhoid diabetes. Sometimes we see them the oral antibiotics are not working then we start insulin and somebody's doing the antibodies. And if you see that the incidence is also increasing and also the Middle East is the third. And if you look at a little bit more closely the stages of typhoid diabetes and we have the four stages of typhoid diabetes. So first of all you should have an immune background and sorry in the genetic background and some environmental risk that triggers that you know immunology. And you see that in the stage one there is a normal blood glucose and they have some antibodies are already attacking the beta cells. And then in stage two you have some impaired blood glucose and you have two antibodies or more. And the progressive loss of the beta cell mass and the insulin production and causes the stage three which is a clinical typhoid diabetes which you have all the classical symptoms of typhoid diabetes the poliuria, polydipsia and polyphagia and weight loss. And then in the stage four is the then people are insulin dependent and using insulin and their c-peptide is very low and lost almost all of the beta cells. So how can we tackle this one? And in the last 30 years there have been so many studies are we have been working on to slow down this progress and also prevent typhoid diabetes or have a cure. But none of them has been successful until the recently we are getting a little bit better for the prevention. So this is the most recent guidelines for the antibody screening and the pre-stage three typhoid diabetes and who should be screening first and who should be screening. The people are have a first degree relatives of the typhoid diabetes people with typhoid diabetes are the people that most likely develop typhoid diabetes and we also do some mass population-based screenings at schools or in the primary care in the pediatricians. And if somebody has more than two antibodies for typhoid diabetes almost 100 percent is the risk of developing typhoid diabetes in their lifetime. So why do we screen people with for typhoid diabetes? Because if we can catch that typhoid diabetes is coming up we can prevent the diabetic ketoacidosis sometimes can be a life-threatening and debilitating problem and we can start insulin earlier and we can involve in these people to clinical trials for the prevention and possible cure. And also we have some medications right now there is an FDA approved medication that can delay the typhoid diabetes up to two years and we will definitely I will be mentioning that. So what we do is we do screening and if the person is antibody positive and if it's one antibody we do follow-up. If that person is more than two antibodies are follow-up and then we assess the the glycemic load and with an OGTT and other things and then based on that if you know we just assess the person if this is a candidate for a teplizumab treatment or not. And so what is the teplizumab? Teplizumab is an anti-CD3 antibody so it's in a clinical trial its efficacy has been assessed and 76 people with typhoid diabetes more than two antibodies and at risk to develop typhoid diabetes have been chosen and it's in a placebo-controlled clinical trial and it's a 14-day infusion and it's mostly well tolerated and it causes transient lymphopenia some rash and some a little mild fever and 43 percent of the people received the the teplizumab developed typhoid diabetes and versus 72 percent of the people developed typhoid diabetes in the placebo group. So the delay in typhoid diabetes was up to two years. So this was the one of the fascinating study the results that caused the FDA approval for teplizumab in the delay of typhoid diabetes up to two years and it was the only one that worked actually in the field. So if you look at that if the teplizumab is working for everybody the answer is actually no and then it works for some people a little bit better some people a little bit less. If you look at that the teplizumab is more effective in the HLA-DR4 positive and HLA-DR3 negative people and from the antibody device the anti-zinc transporter and ICA negative people a little bit more better. So as you know that typhoid diabetes and the people are sharing the same genetic background up to 90 percent is the HLA-DR3 and DR4 most of the HLA-DR4. So if you look at the typhoid diabetes management in the U.S. so we have typhoid exchange. Typhoid exchange is the largest collaboration right now. It's up to 62 centers that are sending the data for typhoid diabetes and more than 100,000 patients as of today and that's a study compared to typhoid diabetes people with typhoid diabetes data in the typhoid exchange from 2010-2022 to 2016-2018 and you can see that we still have the highest hemoglobin A1c in the adolescent ages and only 21 percent of the people are achieving the ADA goals of less than the seven percent and you see that despite all advances in the diabetes technologies and the new insulin and new medications we are still struggling to have a control in typhoid diabetes and if you look at that is actually 2010-2016 and we were doing actually a little worse unfortunately in 2016 compared to 2010 and then after the 2017 and then there's another study that we compare 2016-2022 you see this decreased for the first time in the U.S. population which is can be contributed to diabetes technology use and you can see we still have disparities unfortunately and in terms of ethnicity and then and races in terms of using the diabetes technology and there is a good association in for the hemoglobin A1c decrease in the diabetes technology use and you see that the people are achieving hemoglobin A1c less than seven is it has been increasing in the recent years and I was at the Typhoon Exchange annual meeting last week in Chicago so I got this slide from there so this is right now we have 114,000 patients with typhoid diabetes from 62 centers in the U.S. and you can see that all ages these are the mean and the median A1c's and the CGM uses 84 percent so and then that's getting higher and higher in the U.S. population and in parallel we have been doing so much better so if you look at that the early initiation of diabetes technologies are the key into getting a better success so this is a study that we did and the early initiation of the CGM in the first month and if you see that the people are we looked at for following them for seven years this is a retrospective study and design but it was looked at the for seven years and how it works in the you know the CGM the people are getting at their first visit versus not getting and you can see this in the seven years the the difference in the hemoglobin A1c and you can see this from the metabolic memory we see from the dissociative clinical trials and how you start you just continue and if some of these people already starting the diabetes technologies especially CGM at some point and you can see that they're also doing better but they were never able to achieve the same glycemic control unfortunately and the people like the people are already initiated from the day one and if you see that in the first six months all both groups have been decreasing their A1c because of the honeymoon period then you see the gap is has been increasing so it shows the early initiation of the CGM is the key in success in glycemic control so the diabetes technologies and the mean A1c and we have a strong association and you can see that the people are when we look at this people are using AID versus CGM or not using any of this and then you can see the difference in the more than 3,000 patients in this study and then you can see that is a difference in this mean hemoglobin A1c are the difference in the people are using AID then the CGM then the people are not using the diabetes technologies at all so which one is first the AID pump CGM or and you know or a insulin pen or with the CGM so there are so many studies show that actually the CGM is the game changer and you can see from here that in the groups in all ages and you can see the people have the highest A1c for the no pump no CGM and followed by the pump and followed by the CGM and then the people are doing if they are using AID and they have the lowest A1c compared in the old age group so the in here if you are not connecting your CGM to your pump actually your pump is not helping much compared to an multiple daily injections if you are not using the CGM so the differences are minimum so if you look at that the people are losing their excess in us you know they or they are gaining excess and temporarily so really we also looked at the people are how they are doing from 2016 to 2020 for the same patients that changed from pump to hybrid closed loop or pump CGM to pump and finger sticks BGM or the pump CGM to an hybrid closed loop and you can see the people are changing from pump and you know self-monitoring blood glucose with a glucometer to changing the hybrid closed loop they are doing so much better and the in parallel the people are losing their excess to sometimes health care or their insurance and then the people are going back to the finger stick they are unfortunately increasing the A1c and even temporarily you can see in your clinical practice and the people are doing pump and CGM not integrated and then changing to an hybrid closed loop which is integrated and you can see that they are doing so much better so the how the insulin pump use recommendations change by the years and we have the ACE consensus and from 2014 and these are all copy-pasted from this consensus and you can see that when we were suggesting people in 2014 you should be motivated to you know do achieve blood glucose control and you should be using typhoid diabetes you should have typhoid diabetes or MDI or type 2 you should be doing finger sticks more than four times of the day and or doing four injections per day and willing and able to carry out tasks and doing this and that and then how things are changing in the first time in the 2021 is you know guidelines I mean the consensus and the same authors are actually this is a one single simple sentence which is the AID systems are strongly recommended for all persons with type 1 diabetes actually at that time obviously in 2014 there have been no AID system so the recommendations are not anymore insulin pumps recommendations are based on the AID systems so you can see that things are changing a lot and then in the ADA follow the same pathway of the ACE and there is a strong recommendation or AID system should be offered in diabetes management to everybody with type 1 diabetes it says here is the youth and adults because there are different sections for the piece and older adults so you don't think that they are not suggesting for the piece or older adults so you can see that you only need a motivation a follow-up plan and then an education to start an AID so we don't have any all the other old criteria that we have been doing 10 years ago that somebody should be checking their blood glucose somebody doing the carb counting somebody should be doing the you know the doing this doing that obviously when somebody's doing the carb counting is they should be doing so much better somebody is you know is know what they are doing and so much better but now we have systems that can also be used is even if you are not you know following the traditional pathway so these are the FDA approved diabetes technologies in the US in anywhere else in the world is a little bit different you know we have some of them are in the European Union approp some of them are in the Middle East I you know discussed some of you yesterday and then which systems are available in this region also and you can see the up I put the CGMs and down I put the hybrid close-up systems and their FDA approval years and you can see that there is a there are a lot of CGMs a lot of AI systems and all of them are actually working in a different way some of them you can just change one setting and when you do the same thing in a different pump it's not going to do anything so there's a lot of education and follow-up and things are changing a lot in our field and there are like so many different things that you know and needs to be achieved from the both side providers and from the patient side so if you look at the typhoid diabetes management a little bit more closely in Europe so I again looked in the registries because they are you know in the registries they are putting the patients and following for a long time and they are have a large amount of data and you can see this is a DPVs registry from the central Europe mostly the Austria and Germany is doing that and you can see that they looked at their sensor augmented pump in the AID changes from 2018 to 2021 and then you can see that the AID use has been increasing and since the introduction of the first AID systems and it's getting more common in the hemoglobin A1Cs are also in all ages are getting better too but if you see that there are some still you know discrepancies in the results that you know some for some ages and some A1C numbers are not doing very well and even though we have been using a little bit more AID systems and it should tell us that yes the diabetes technology is helping a lot but it's not the the only answer here that we need more than that if you look at this is like an incredible you know study this year published from Norway and you will see the success of the northern European countries in the typhoid diabetes management if you see this this is a pediatric cohort from the Norway the how things changed from 2013 to 2022 they decreased their mean hemoglobin A1C significantly and achieved more people achieved significantly in the ADA and ACE goals and you can see that insulin pump use and CGM use increased incredibly in the in a pediatric cohort because they are trying to put everybody in a registry in the country and they are just following you know so many other things other than diabetes technology which I will be coming to this at the end of my talk so you can see that there is an incredible success compared to the US actually or the central Europe and this is a very recently published also study if there's the same thing they similarly dated in the Swedish type 1 diabetes registry which I also mentioned that in type 1 diabetes is far more common in Sweden and Norway compared to other parts of the world and you can see that the numbers are very similar they are achieving incredible numbers for time and range and you know time in tight range more people are achieving less than 7 A1C goals and the CGM and the pump use are you know getting more than almost 90% right now if you look at the differences between 2000 to 2023 it's an incredible results that you see that the people are achieving less than 6.5 or 7% A1C are actually right now almost half of the people are doing that and compared to 20 years ago and we are doing so much better in the type 1 diabetes management so if we compare the US data to Europe and for the central Europe and as always unfortunately in the US we have higher A1Cs compared to Europe and you know there are so many different reasons can be you know you know we can talk about that and in all age groups actually and also all groups like a pump CGM MDI CGM pump and MDI patients you know type 1 they exchange higher A1Cs compared to DPV registry which traditionally DPV registry have significantly higher hemoglobin A1C levels compared to northern European registries so if you compare the northern European registry to US the difference will be actually so much bigger if you look at the Australia and Asia and the different registries and from the Europe they compare and then you can see that the hemoglobin A1Cs and in this particular study they look at the severe hypoglycemia rates which is the dotted line is the hemoglobin A1C other line is the continuous line is the severe hypoglycemia and then you can see that and then we are doing so much better and then in the last 20 years things are going down but there are still people are having the severe hypoglycemia despite the all this you know hybrid closed-loop systems and advancements and the glucagon use that you know we have the nasal glucagon we have the injectable ones so you don't need to mix the forms and other things so and so things are doing better so we still need some improvement to do so if you look at the all comparison in the same study and then you know from a different perspective and the same you know registries in the US Central Europe and Australasian and you see that the people are achieving the hemoglobin A1C less than seven actually in doing so much better in the Europe compared to US and compared to Australia and in Asia and if you look at the diabetes technology use in parallel they have in higher diabetes technology use but still unfortunately fewer than half of the children here met international targets of hemoglobin A1C target less than seven percent so you see that it's still that we for example in the AID use in US you know higher than some of the regions but it doesn't reflect to do you know hemoglobin A1C as much as that we want so if you look at the management in the world and a little bit more comparing to the all regions together this is from the SWEET registry which actually have so many countries are contributing to that including the Middle East and Africa and Northern South and Europe and Asia and Australia and Oceania and you can see that I just want to highlight a couple things and the highest the you know hemoglobin A1Cs are still coming from the actually the well-developed countries and the presentation of the DKA actually coming to less developed countries and most of them are in the in the you know in that SWEET registry. And the hemoglobin A1Cs, and despite the highest use of the pump and CGM use, and still from the North America. And unfortunately that there is a huge, the equity problem also to accessing to diabetes technologies, and you can see some regions are using more than 50% and 60% in the pump and CGM, and some regions are using actually less than 5% in the accessing the diabetes technologies. And if you look at the suite registry, and in a different study that is updated, and you can see the hemoglobin A1C is the best in Europe, and is actually in the worst in the MENA region, and it's very close to the North America, actually 8.7 and 8.9 A1C. But the people are achieving the, the less than 7.5 hemoglobin A1C, you can see that the only 18% of in this region in the MENA people are achieving compared to 46%. If you compare the MENA to the US, and you can see that it's not very different, actually 18.1 to 18.8% the people are achieving, despite the huge differences of the diabetes technology use, which is 80% in the US, and versus 11% in this region. And if you can compare the South America, unfortunately it's only 4%. So there are a lot of inequities in the diabetes care, as I showed that, and if you look at a little bit more in detail that in the diabetes technology use, especially in the US, and you can see this if you compare the people are using the diabetes technologies, the insulin pump and the CGM, the non-Hispanic whites, and Hispanic and non-Hispanic black people, and in the adjusted for their use and the age and other co-founders, you can see that 61% of in this study, the people of the white people with typhoid diabetes were using the insulin pump, versus 49% in the Hispanics, and 20% in the non-Hispanic black people. In the CGM use, and you can see that the 53% of the non-Hispanic white, and 58% of the Hispanic people, and 31% is the non-Hispanic black people. So there is a lot of inequities in the diabetes technology use. If you look at that all together on the minorities from the type on the exchange, and if you see that the differences are actually larger, the people are achieving hemoglobin A1C less than seven, which is the goal, and 19% versus 24%, and their A1Cs are also different, 9.2 to 8.4. And if you look at that from the publicly insured versus privately insured, and as I can explain that the people may not know what is a publicly and privately insured. Publicly insured people are mostly Medicaid in the US, so if you should be making less than a certain amount of money to be qualifying for Medicaid in the US, so privately insured actually is a reflection of how much the people are social economically are doing better than the other people. And you can see the differences are achieving 19% to 32% in the hemoglobin A1C. So the discrepancies are not stopping there. So there is contributors to inequitable outcomes, and it's far more complex than actually we think. So there is a systemically institutional, operational, and individual levels. If you think about this is like a Swiss cheese, and there are so many things, systemic level, and structural racism, and neighborhood factors in the healthcare, and we have some language barriers, and then insurance, and clinical staffing. We have so many patients. And education level, patient-provider relationships, and then we have to see a lot of people, especially in the private hospitals and clinics, to reach some RV goals and other things. And individual-based family support, and provide an implicit bias, and other things. And we see so many people are getting, the healthcare system is so complicated, and you can see that the people are not achieving the getting the diabetes technologies. They get denials for their insurance, and every year insurance is changing. And getting a struggle to use the same device or the same medications for a long time. And a follow-up in education is also another big problem on that. So if you look at the six pillars to achieve optimal glycemic control in typhoid diabetes, and this is kind of finalizing the success, and summarizing the success of the northern European countries actually. And as I mentioned that in the US, we use the as high as in some parts of the US actually for as high as the Sweden and Norway, but we are far more behind in this success because they start the diabetes education, and in the earlier stages of typhoid diabetes in a very structural programs. And they have the nutrition counseling, and carbohydrate counting from day one. And especially for the newborn sets, they have a very structured program in this registered in Norway and Sweden. And they are starting the diabetes technologies as I explained that the early initiation of the diabetes technologies are the key. And they are starting the diabetes technologies, especially CGM, also the AIC systems as soon as possible when they were diagnosed. And the quality improvement projects, that's something actually we are ignoring most of the time. And then they are also trying to improve themselves as centers. And they are doing meetings, for example, in the Norway, they are doing twice a year. And all the physicians are taking care of the people for type one diabetes. And independently from the diabetes and endocrinology meetings, they meet twice a year and to talk about how can we improve the care for the type one diabetes. And they do quality improvement projects, and they compare their results to each other. And why one center is behind, and why one center is heading. So they are trying to look at their system. And they have the universal healthcare, so everything is registered in one time. And then they don't have any qualification criteria and other things, we are trying to implement that. As I understand, they are smaller countries compared to some of the larger countries. We may have some more problems related to that. But definitely there are a lot of things we can learn based on that. And a follow-up, they have a regular follow-up system, they have a lot of reminders, they have a huge collaboration between the primary care, primary care adults, Peds, and also endocrinologists, diabetes specialists, and they are just all working together and for the follow-up of the patients so nothing gets lost. And for the screening for complications, and they got a lot of reminders, and people are getting very regularly for their diabetic eye exam, so diabetic nephropathy screening, and neuropathy, and all other complications. They are educating the patients and also screening, and they are comparing from the day one. And what's going on there also, their implementation for the preventive medications, whenever they need, it's so much earlier than what we do. If I summarize, the typhoid diabetes management varies across the world, and diabetes technologies are helping a lot and making a huge difference in the last, especially, seven years. But unfortunately, you see that the diabetes technologies alone are not enough to achieve the optimal glycemic control. Access to diabetes care and technologies is a universal right for people for typhoid diabetes, and disparities in access in diabetes care and technologies, and unfortunately, in other parts of the world, and some parts, you know, getting more easily, some parts don't. Even in the same country, some people cannot get that. Some people can get a little bit easier. So, that's the end of my talk. So, I just would like to thank to all the staff at the Barbara Davis Center, and for my lab members. Thank you very much. I'll be happy to answer your questions. Thank you so much for this elegant talk. Any questions? We'll take the microphone, and introduce yourself. Hisham Abu Saud, endocrinology, NMC Royal Hospital, Khalifa City, Abu Dhabi. Thank you for the nice, informative lecture. For those type 1 diabetics who are already diagnosed and with positive antibodies, and then after diagnosis, we find that their insulin requirements started to decrease, decrease, decrease, until almost we cannot give them insulin, because we'll have hypoglycemia, what's called honeymoon period. And those patients, can you give us how we will follow them, and how frequent, and by which tools you prefer? So, the question is, regarding the honeymoon phase, the people are decreasing their insulin requirement, how should we follow them? So, it's individualizing, I think the things we should do. It's not everybody is the same for the honeymoon period, it's mostly done at six months in most of the people. We see about 100 people every year, as anyone said, in our clinic for adults, and all total in a year. And then, so what we do is just, you know, following a little bit more closely, and we have a structured plan in the first week, and then, you know, two weeks, and one month, and then another month, another month, then it goes to three months, but we can just change this for the people. So, what we do is, we just start insulin, and we just follow them with a phone, and then we go to the hospital, and we start insulin, and we just follow them with a phone in the three days. And then, they come in person for seven days, if they live far away, we just follow them for a phone. But we have access to their CGM data, so that's the key, because as I said, in the first visit, we connect them to a CGM, so we have the remote control all the time. If they call, hey, my blood sugars are going down, or it's going up the opposite way, and then we are trying to individualize things. And starting the AID systems, I think there can be different opinions here. We tend to do a little bit wait, and then just get this honeymoon phase a little bit over to start AIDs. Our pediatric clinic is a little bit more aggressive, and they are starting a little bit earlier, and I think it should be also individual decision. And then, we just follow that, and then if somebody is going down and down for their blood sugar, we just decrease their insulin. And then, whenever they need again, then you will see that it's already going up, and we just give a little bit more. And most people end up, the insulin level that they start, and then between the top and between the lowest one, between something in between. So I think it's a close monitoring, but the remote monitoring is the key answer here, looking at their CGM. Any rule for the medicine you have mentioned earlier to delay or extend the honeymoon? So, teplizumab, and then there are studies, there's another study published, so I didn't put that. It's also for the stage three, and this is for the stage two typhoid diabetes, which they haven't developed typhoid diabetes yet. Current FDA approval for teplizumab is for people developing before typhoid diabetes. There is a study, again, it's published, and that shows that, again, in the New England Journal of Medicine, it delays and extends the honeymoon, but we don't have approval for the FDA approval to use the teplizumab yet. Thank you. Thank you, very informative and illustrative talk. I'm Farid Fawzi from Egypt. I have two questions. First one regarding also teplizumab. After two years, 40 plus percent of those using teplizumab developed diabetes, against 70 plus in the other group. This was after two years. What is the situation later, now after five years, for example? This is one question. The second one, you demonstrated male predominance in the well-developed areas in North America, Europe, and Australia, and the female predominance in the less developed areas. Do you have an explanation? So the first question is about teplizumab. What happens five years later? So we don't know yet, because we have not been using teplizumab five years, you know, enough. So teplizumab has been FDA approved, I think it's two years or so, if I'm not, you know, maximum two and a half years. So, and we don't know yet. So, and then I think the time will show. We have about 40 people receive teplizumab in our center, for example, because it's very expensive. And then, so it's kind of, there is a certain criteria that insurance covers only, and then people should be meeting all this criteria, and it's an infusion for two weeks. And then I think we will see how things go in, you know, five years, 10 years, what happens to these people. Also, I'm also personally very curious about how their diabetes will be. You know, is it like a mild diabetes? It will be a little bit easier to control, or it's going to be the same? Are we only delaying, or are we also making things a little bit easier for these people? I think a lot of unknowns, yeah, so far. So coming to your second question, if I am wrong, just correct me for the male and female differences that have the right for the type 1 diabetes. So the registries can be a little bit different, and because this is volunteer-based, and some countries, like in US, and in the northern European countries, a little bit more like a government-based, they are putting everybody to registries. So traditionally, in the US, registries are more the female dominance. It may not reflect the male or female in relation to type 1 diabetes. As far as I know, as far as I follow, I don't see a difference in type 1 diabetes in terms of the gender. Thank you very much, Asmadib Abu Dhabi. It's very interesting what you said about the diversity of type 1 diabetes around the world. UAE, for example, is the first country to have tublizumab outside USA. The CGM is a standard of care here in most of the centers in UAE, and we have AID at our easy access. Yet, the data that you showed from Sweet Registry is from the Middle East is actually, with no pride here, is from our center. 8.9 was our average A1C in pediatrics many years ago. So what I'm trying to say is access, health economics, provision, insurance is not all what it takes to manage the challenging type 1 diabetes. Behavior, human factor, we're still really struggling to manage type 1 diabetes in the young, and we are far from achieving the recommended guidelines for the diabetes control, despite all the provisions we have, unfortunately. Thank you. I think that's a great point, and if you can have a look at the registries, even if it says study published in 2022, there's always two years behind. I think that's a good point, and also not every country is counted on there. So I just wanted to compare the registries because it's a fair way of doing that, and other than some retrospective studies, and only a couple hundred of people, versus the registries, at least four, five, 10,000 people are at least in the studies. And that's a good point, the AID system, CGMs, obviously makes a big difference, that there is a behavioral component. You know, as I mentioned, the people are counting carbs, or people are just following, or not following, and there is always a human factor in that the technology used, that makes a big difference, too. And there are some cultural differences, too. And in every country, even in the same country, I see people are from everywhere in the U.S., from all different ethnic backgrounds, and I can see that the difference, but that's a good point to know that you use the Prisma panels of AIDs and CGMs. That's great. Thank you. Yeah, very good presentation. Thank you so much. I'm Dossie Trentz, University of Washington. I have two questions. First of all, the diagnosis of type 1 diabetes, as you have mentioned, is heavily dependent on antibody presence. So we check for antibodies, but we know in diabetes centers that we see individuals, typically they're not pediatric, but they are type 1, without question, and yet their antibodies are totally negative. You can check them again, and again, and again, and they're negative. Are we missing an unknown antibody? Is there something else going on in these individuals? I would be interested in your opinion. And secondarily, obviously technology is great, but it's expensive. It is obviously something that, for many people, will probably never be within their reach. So futuristically, do you think that the once-weekly insulin might make this diabetes a bit easier to handle, given that the emphasis has to be on postprandial hyperglycemia control rather than basal insulin? Yeah, so I think I can start from the first question, is that the antibodies screening, I think it depends on something is looking and finding. If you don't look, you don't find. So we do four antibodies in our center, for example, but sometimes, obviously, 10% of the type 1 diabetes people are antibody negative. And in these people, I think the time shows everything. So when I see people are antibody negative, and we just say, wait, and we just follow them a little bit more with the C-peptide by the time. And some people, C-peptide is going up and up and up. And by the years, the antibody is negative. And obviously, these people, they don't have type 1 diabetes. But obviously, when we say that we looked at antibodies, we don't know. There may be so many other antibodies that we are not aware of it, but we just covered most of them. But I just want to be, the people are aware of that when we say that checking antibodies is not only GOT65 or GATA antibodies. A lot of people are only, for adults, they look at GOT65, and say, oh, it's negative. And when we look at other antibodies that can be positive. In different age groups, for the adults, GOT65 for the pediatric is more zinc transporter, can be a little bit more common. And then, so I think it's kind of depends on the, especially in the US, I can answer if it's covered or not. So the antibodies, and I think it should be a common practice to not assume this people, everybody has type 2 diabetes at least once, checking their antibodies, and then going from there. Because there are so many people that are misdiagnosed with type 2 diabetes, and then failure, failure, failure to treatment, then you are just too late. Complications develop and you realize that you have to start insulin. And especially we have some great medications right now for type 2 diabetes, they also work in type 1 diabetes too, you know, of labels, so you know, sometimes people are using that. So sometimes it can be a little bit deceiving. And coming to your second question. Once weekly insulin. Yes, thank you. So once weekly insulin, you know, some people may be using once weekly insulin, and some inhaled insulin maybe, they were just going to skip all injections, they will be using the once a week. So I think that's the first thing is the CGM, as I showed in the previous studies, with the CGM and AID differences are small. If somebody is a once a week insulin, you know, it's a possibility. But as you know that it's not approved by FDA in the US because of the higher rate of hypoglycemia. And then I think it's going to take some time in my opinion and projection for at least the US. I think in Europe, it will be a little bit easier, maybe other parts will be a little bit easier. I am a huge believer of giving more options to people. And I think we shouldn't mandate that people are using this and that. And the good part of the AI systems are people don't need to do much anymore. That is definitely a human factor there. But for the injections or inhaled insulin or other things, they should be more, you know, doing things on time. But I think weekly insulin, if we can figure it out the loading doses and other things and figure out this hypoglycemia risk, especially for type one, I think things will be so much easier. Definitely, I think it will be a great choice for the people. Thank you. Yeah. In view of time please, short question, short answer. Okay. Great. Regarding the Teplizumab, you mentioned there is some people are better responder than others. Is that something that for the insurance coverage is needed or not? That's a good question. No, insurance coverage is not depend on how things are in the FDA approval. And it's a complex answer. And I can just, you know, only speculate why it was in FDA approved and some of the things that I don't want to tell here. So, and but the, based on this one study, obviously we don't have too many things based on the 76 people. They showed that, you know, some of them are responding well other than the others. The problem is you may not show that which one has responded anymore in real life because you don't know when your typhoid diabetes has been starting. But that's a good point. In my opinion, it should be looked at from that way and it should be explained all pros and cons to the people. And not everybody is the same. But current FDA approval is based on the stage two typhoid diabetes. If you have antibody, two antibody positive and you have risk and you can receive that as long as your insurance covers. Thank you.

type 1 diabetes

global prevalence

Sub-Saharan Africa

MENA region

antibody screening

Teplizumab

diabetes technology

equitable access