I'm Dr. Mitchell Geffner from Children's Hospital in Los Angeles, and I am co-hosting this with myself Apparently and Someone else was going to pitch in but couldn't do it at the last minute And then just so you know you're in the right place here if I don't get buzzed here So we're gonna have our symposium today on racial and ethnic disparities in adolescent health care It's gonna spill into young adults a little bit And This is at least the I think it's the fourth session on this general topic at this meeting Implying Or more than implying but showing that how important this topic is and and if this is your fourth session On it that you've attended you're taking this really seriously as you should Even though the room is maybe not the most well attended I'm hoping the bigger virtual room has about a thousand people that are are watching us, so So the the order that we're going in is Might be different than what you see in your agenda for no apparent reason But we are going to cover three important areas related to food diabetes And cardiovascular disease not necessarily in that order and perhaps with a little bit of overlap, but all of those in the context of Racial disparity so our our first speaker standing right behind me pacing making me nervous Stuart Shalhoub who is from Louisiana State University correct and is a Long-term friend and an expert in type 1 diabetes and the racial disparities As they relate to that topic so I'm not going to say much more Not take his time before he comes up here We're gonna the way we're gonna do this is we're gonna Have the speaker finish their talk hopefully in 25 minutes And then have five minutes for questions either from the room and or from the other world that's watching us so on that note Thank you, dr. Geffner, thank you for attending. Thank you for inviting me I have one disclosure I'm periodically serve as a member of the Medtronic health care disparities advisory board And I guess I just go push this and get it to go forward all right the That's probably you all know type 1 diabetes is the most common and curable endocrine disease and possibly the most common Chronic and curable disease of childhood this shows type 1 diabetes in relationship to other chronic disease You can see it outpaces all the cancers And it's not good to have type 1 diabetes as you can see I don't know I have a cursor here Am I supposed to use this? Okay, cursor you see mortality rate much higher in type 1 patients than the match control group Today's challenge Is management can improve outcome in type 1 diabetes we know yet our african-american Patients also often have suboptimal health outcomes and Today, I'm not going to focus on the totality of disparity and underserved populations I'm going to focus particularly on the relationship between a1c is a glycemic marker I'm going to talk about biologic factors that may influence a1c independently of glucose also going to discuss management patient support factors that may help improve the outcome of some patients, and I'm also going to talk about the room for us to grow and develop and along these lines So let me give you some background We'll hearken back to the DCCT which is the diabetes control and complications trial seminal study Where the normalization of blood glucose levels in patients with type dumb type 1 diabetes was found to prevent? Complications and this was a phenomenal trial you can see That you can see that the Well going The here we go here's the pointer in the DCCT the investigators were able to maintain this type of mean blood glucose during the average day between Patients only got a couple of shots of insulin versus What was called the intensive control then which was MDI or pumps? And we would call this standard therapy nowadays, and you can see over the 10 years of the trial there was about a 2% difference between the intensively treated group and the conventional group and There was a success there were decreases in Retinopathy neuropathy and nephropathy in the group that had the lower a1c's this led to the rationale for guidelines and goals and glycemic control that were All referring to and using and it also enshrined hemoglobin a1c is a metric for management and a predictor of complications But One thing should be pointed out many of you have probably seen this this was circulated by the ADA where Source says that a1c is a surrogate for mean blood glucose, and they distributed these and when you would get a An a1c you could tell the patient about what their a1 what their mean blood glucose is by looking at this table or Reading off of the regression line from a1c on to mean blood glucose So there was sort of the idea that mean blood glucose and a1c are the same thing But I want to give you evidence that There are other factors besides mean blood glucose that also influence a1c that's referred to As biological variation and here's here's all the data points or data pairs between a1c and mean blood glucose And the DCCT there's about thirty three thousand pairs but if you choose to Pick out Individuals whereas this and you know there may be one individual here at the same mean blood glucose will have an a1c of five and yet one up here who has a A1c at the same glucose of ten when you start picking out the individuals You can see that they're individuals that are always above always below and that their data points Don't necessarily overlap with the data points of other patients who you select out this is referred to as biologic variation in other words that the repeated measures analysis that the Variation in Inter-individual variation of a1c is less than the between patient variation in a1c and you can see this in many other analytes It's just not a phenomenon of a1c We came up with a gimmick to kind of quantitate this which we call the hemoglobin glycation index Very simple minded type of metric kind of thought of it looking at Z scores, it's kind of like a modified Z score like you'd look out for a height differences And we took the observed a1c And subtract it from the regression line or predicted a1c and patients that tended to be above average had a positive score and those who were below average had a negative score and The important question from that even though it's a it's a nice gimmick to kind of Quantify this doesn't really mean anything To calculate this HDI and I would say yes, and the reason I say yes Is here where dr. McCarter? Took the DCCT data and he Grouped patients by Thirds by turtles as to what their HDI was now by doing this each group has the same mean blood glucose Okay, so the higher turtle here has three times the risk of retinopathy as the lowest turtle and If you look at nephropathy the highest turtle has six times the risk for retinopathy For nephropathy rather over the course of the DCCT Well Is there evidence for racial disparity and outcomes and Can this be attributed to factors other than glucose? So here's data from New Orleans From our hospital shortly after the DCCT. You probably could find many other studies which were looking into what? Disparities and differences between groups and a1c and turned out that race was a disparity and of course at that time we assumed that the difference here was because Many of our patients weren't getting adequately controlled and their glucoses were not controlled and unfortunately, if you look at Epidemiologic data from that time you can see that African-american population associated with higher a1c is also had higher mortality Now it's been 30 years since the DCCT. We have A1c treatment goals we have reasons now to use Standard of care which used to be intensive insulin management. We have designer instance. We have better toys We are aware of psychosocial factors, which may impact Compliance and nutritional needs and yet and Yet there still is a racial disparity in a1c. This is from the type 1 diabetes exchange and you can see African-americans and black columns have higher a1c than the white or hispanic patients and Here's more recent data from a search study over three different time periods and you can see that the furthest away from the y-axis are African-americans and you can see they still have a higher a1c than the non-hispanic whites or the hispanic patients in the study and Unfortunately mortality is nearly twice as high in african-american patients with type 1 diabetes So is part of this Due just to management and We did a study dr. Camps published this Where at the bottom in the block was where you do a multiple very varied? Analysis and you adjust for a1c and we did a couple other adjustments and you can see even after adjustment for the mean blood glucose the a1c and the HGI are higher and african-americans by Not only a statistically significant amount but by a Clinically significant amount that's about 0.8 a1c and I think that would be actionable and in your clinic a type of difference like that and Here's just a a graphic view of what I'm talking about There are two things going on in this way of presenting the data one as you can see the typical Increase of a1c with increasing mean blood glucose But the other thing is that the regression line the top one is For african-americans the bottom for whites and you can see at any given level of mean blood glucose African-americans in general have higher a1c s. So it's a non. It's a glucose independent difference and And here's a more recent where this this was done by CGM and the axis are switched you notice that the Mean blood glucose is on the left but if you if you look and you take say at 200 level you can see that African-americans at any given level blood glucose tend to have higher a1c. So the regression lines Are you know beyond? here, too So do these differences in the glucose independent component of a1c between ethnic groups make a difference and I'll cite data from dr. Phillips group who are here in in Atlanta They looked at a large sample of veterans and I think the title just summarizes what I've been said Retinopathy develops at similar glucose levels, but higher a1c levels and people with black African ancestry and now there have been a number of studies looking in individuals with type 1 and other Types of this glycemia is using HDI and HDI has been a predictor and other studies of complications so The other thing I'd like to talk about here is hypoglycemia the type 1 diabetes exchange noted that blacks Who were surveyed in that study had a much higher? reported frequency of hypoglycemia than whites and Hispanics and paradoxically, they noted this was despite higher a1c's and If you've been wondering what to do with GMI I'm sure you're all familiar now with CGM and you get this GMI GMI is just a predicted a1c so you can now calculate HDI at home by taking the patient's actual a1c and Subtracting the GMI and you'll have HDI and a recent paper by dr. Toshi in Boston kind of did that with data they had from continuous glucose monitoring and they found that the As you can see on the left the two groups of non-white patients if their HDI was greater than 0.5 had a greater percent statistically significant percent of Time below range if their HDI was greater than 0.5 So, where where are we now at this this point? HDI mean blog, I'm sorry a1c is a combination of Mean blow glucose plus individual factors and probably some measuring error Complications are can be attributable not only to what the mean blow glucose does but to these other factors a1c certainly overates overestimates mean blow glucose and African heritage patients HDI can be calculated as I said before by a1c minus the GMI and this metric may confer extra risk or may suggest Extra risk of Hypoglycemia, but I'm going to make an editorial point here. I think that this is from people Treating to a1c goals not to glucose goals if you treat looking at Glucose in your clinic. I think you'll avoid the a1 the Extra hypoglycemia that's been reported. What's the mechanism of this difference? I don't know Don't know yet, so they don't really have a method of interfering with this but certainly Treat treatment with more insulin is not doesn't appear to be the answer at this point So, how about management support issues and about how much time do I have left I'm not seeing the Ten minutes ten hours ten minutes. Okay good. All right So how about management support? Let's go back to the DCCT DCCT lasted about ten years then well at the end of the ten years you can see that The study was stopped And everyone had the choice of doing the treatment that they wanted so if you were in the conventional group, you could now use MDI or a pump and you can see that That led to a decrease in a1c and I'm going to call this the tech effect But you can see that in the formerly well-controlled group when they stopped the DCCT They went up and they met in the middle around eight and I'm gonna call this the support effect And if you ask anyone who is an investigator in the DCCT, they will basically tell you for the intensively treated patients They basically live with them. They got all sorts of support. There was one nurse for maybe about 20 patients and You could possibly call all the patients once a week make sure they were in line so to speak so what type of support is lacking here and Some people have suggested it's the lack of access to tech and Unfortunately, you can see here the white column is pump therapy the black is MDI and At the bottom I've kind of emphasized the the grouping that the white patients in every category are far and above have much more utilization of pumps than the black colleagues Across the board here But if that were the only Difference I would expect that if you group the patients by Insulin delivery system the a1cs should be equal and unfortunately Here again the type 1 diabetes exchange. You can see it every Slice at every gradation African-americans have higher a1cs Compared to white and non-hispanic whites in the Hispanic population regardless of age Well, can we can we improve things by Access to hybrid closed-loop pumps. This is some data. We presented last week at the ADA these children that you're gonna see were Chose to use the tandem control IQ System which came out in January of 2020 The patients were had to have use for over four months. The average duration of use was about 200 days they were self-identified as either white or african-american and They were all trained by the company representative and after about a week Their follow-up was through general general clinic general diabetes clinic so here's here's the response and unfortunately, you can see that even though there was a A very good response and improvement in the white group our african-american patients had no change in a1c over this period of time and the salient feature that we found in this was that the African-american patients were unable to keep the pump in auto mode You can see significantly less most of the white patients and and the lines here medians in the middle of that box is median that the median for the white patients with time in auto mode is probably about 80, 85%, and for the African heritage patients, about 60%. So it could be, if there were a way to give more support for this technology and figure out why they're not able to keep the pump in auto mode, we may be able to get much better response in this population. But this is something we're working on. And to go back to the question of hypoglycemia, the African American patients had, it wasn't statistically significant, but quantitatively less occurrence of hypoglycemia than the white group. And this is why I emphasize it's to prevent hypoglycemia, I think you treat to glucose targets rather than A1C target. So let me give you some parting thoughts here. African American patients still have worse outcomes than whites. Access to tech alone I don't feel is sufficient to overcome these differences. It's important to address these differences in childhood because we're aware of a legacy effect of poor control that would contribute to a greater proclivity to complications as these children get older, even if they decide as adults to get into excellent control. I recommend treating to glucose targets rather than to A1C target. And I think we'll be able to identify various ways to intervene with our clinical support for the new technology that's coming down the line. I want to recognize our patients, they didn't deserve or desire to have this disease and I admire their grit and it inspires us to figure out ways to improve their health and survival. Here are some of my colleagues that have added, contributed to the ideas I've presented to you. And of course it helps to have a little bit of money to do this. And here's a Mardi Gras Indian, I want to bring you a little piece of New Orleans. So thank you. Thank you very much for sticking to the time limit, that's beautiful. As usual, I learned a lot. This is the time for questions, and one of our speakers, Dr. Pereira, is going to ... She'll get her time later. You'll get back at her. Go ahead, Ro. Feel free to come to the mic. Oh, there we go. Ro Pereira, Denver, and I'm going to speak in a little bit, but great talk, very interesting. I was wondering if you have any information about the use of continuous glucose monitoring in this population. I know you mentioned that insulin pumps, you don't think, make a difference, but I'm wondering if you know anything about continuous glucose monitors. I have to say, I was just at the ADA, and I think you probably find that it's catching up. I think tech is catching up, but as you're aware, a lot of kids will use continuous monitoring but not stick with it, and this could be a problem, and we're going to look here to figure out whether that's a problem. For some reason, they need more support to stick with it, because otherwise they're not going to get the time and range or effectiveness of these new technologies that are coming. Thank you. Thank you. Great talk, a lot of good information. I was just wondering, I feel like in clinic control IQ works great for people who are savvy enough to have great insurance and keep all the supplies they need to keep this going, both from the CGM side and the pump side. I'm just wondering, in the study you did, were you supplying all of these, or were you... They had to get it through their primary source of care, so as you're hinting, are these people necessarily adept at contacting the office, getting the supplies, calling the rep if there's a problem, calling us if there's a problem. There are other differences that we're going to try to cone down in when we continue our intervention. By the way, we used a different pump, and we had a little bit more support, and we didn't see a difference with that one either, but we didn't give any intensive care after, say, the first month. I think the cost would be astronomical, but if we could get industry support to actually mail everything reliably to people on time, I think that would be a study that would address that issue a lot better. Yeah, I think you're right. Yeah, that might be why they're not... If you don't get the supplies on time, you're not going to be in control or in automatic mode. Stuart, let me ask a question, as other people may be thinking of theirs. Obviously, your talk was based on racial disparities between blacks and whites. Do you have information, if not your own, others, on Hispanic versus white? We're obviously focused in New Orleans a little bit more, since we have a larger experience with African heritage patients there. I think if you look at other sources of disadvantaged populations, I think Hispanics, even though you can see from the Type 1 Diabetes Exchange, didn't have the degree of A1C disparity as obviously the African Americans have. I can't completely address that, but I think in certain areas, and that might be more addressed by the other speakers about Hispanic populations. Sure. Dan? Yeah, Stuart, Dan Domesic, UCLA. Thank you so much for the speakers for doing this for us today. I was just curious, I'm not in this field, but are there any ethnic or racial differences in glucose effectiveness? If you do an IVGTT and you're looking at this insulin-independent movement of glucose into the cell or interstitium, is that potentially determined by race or ethnicity? I'll have to punt on that. I don't know at this point. I thought you would say, is there a difference? It's interesting, I'm not answering your question, but A1C in the red cell gets through the barrier through GLUT1 transporter, and endothelial cells have GLUT1 transporters, which I don't believe is insulin-mediated. So it may be that some of the differences and complications may be that the effect of a non-insulin-sensitive transporter on the glucose response. But I don't know. There probably are some differences, but I can't quote you chapter and verse, particularly in kids. Oh, no, that's great. I think there may be some data that the other speakers might have to be able to address glucose effectiveness, since you guys are using clamps and things and different. Yeah, the next speaker may have a better answer for you. Thank you, Stuart. Hi, I'm Catherine from Duke Pete's Endo. I have a question about blood glucose variability. Is there any data on whether the variability of the blood glucose differs between different races and whether that might relate to the HGI differences or the higher complications of the same blood sugar? As you're assuming aware that there's some idea that glucose variability may contribute to complications, unfortunately, one of the reasons A1C was so liked is that was much easier to get in the past than glucose variability. So the glucose variability isn't picked up very well by A1C and in at least the, we looked at the DCCT data and the best we had was the standard deviation of those mean blood glucose profile sets. That really didn't weigh in. But I think now that we have continuous glucose monitoring, we're going to find that there will, I saw the ADA, they're already looking back at some of the other data and trying to calculate that and then going forward there may be answer to your question with the glucose variability. Awesome. Thank you. All right. I have one more question from the distant audience that reads as follows. What may be the difference in clinical support that would be needed, that would need to be optimized to, I guess, narrow the disparity? That's a wonderful question. Yeah. And who will pay for it, I guess, is the other. I think the DCCT is intriguing because that was an example where I think psychological and behavioral support had a very strong influence on the outcomes. We're planning a study to have a nurse sort of provide supplies as was recommended here. Basically hold hands with the patients as they need it, whatever they need. Use now all the virtual technologies that we have to communicate with patients and see if that will make a difference. We're hoping that that may be the secret sauce to this as technology is improving. As heard in the TODAY trial in the early phase when there was a whole support staff that held the hand of the patients with type 2 diabetes and adolescence, sort of a similar phenomenon. It makes a difference. It does make a difference. All right. All right. Well, thank you. Thank you for your attention and your questions. Appreciate it. Thanks so much. Okay. Okay. We're doing great here. So our next speaker wants some water is Fida Baca whose title, it's not up there so I'll read it to you here, is Prevention of Cardiovascular Disease Among Young Adults. For those of you who don't know Fida, she comes from Texas, probably not originally but most recently, and is now the Director of the Metabolic Research Unit and the Energy Metabolism Unit at the Children's Nutrition Research Center, which is part of Texas Children's Hospital and Baylor, and Fida and I are co-workers on the TODAY trial and perhaps what you'll hear today has something to do with what she learned in that trial or not, but it'll be very informative either way. Thank you for the introduction. I thank the organizers for the invitation. I thank the audience for staying here on Monday afternoon and to our virtual audience as well. So I was asked to talk about prevention of cardiovascular disease among young adults, I would say adolescents slash young adults, with the focus also to highlight some of the racial ethnic disparities that we see in this context. So I will talk on the trends cardiovascular has in the U.S. and the fact that racial disparities persist. Talk about young adulthood and what's different about this period and the increased vulnerability to cardiovascular disease in adolescents and young adults. Summon the cardiovascular disease pathogenesis and remind everyone that it does start in childhood, particularly looking at risk factors and how they relate to cardiovascular events in adults and diabetes as well as a major risk factor for cardiovascular disease. And then end with some thoughts on whether we can prevent cardiovascular disease in young adulthood. These are data from the American Heart Association statistics. By 2035, more than 130 million adults or 45.1% of the U.S. population will have some form of cardiovascular disease. This is not surprising if you look at other statistics such as that 46% of U.S. adults are estimated to have hypertension. And only one in five adults or 22.5% meet physical activity guidelines. The cardiovascular health in the U.S. continues to decline, unfortunately, and we see trends in racial ethnic disparities in these cardiovascular health outcomes and metrics. And as you can appreciate on this slide, we see some of the declines happening particularly in this young adult group of 25 to 44 year olds. And although we see some narrowing in the race ethnic disparities, this is due to loss of cardiovascular health in whites rather than gains in minority population. The life course health development is proposed to be a good model because it studies health as a trajectory in which early events and influences shape health throughout the life course. And so these developmental trajectories are determined by interaction between biological and environmental factors. Within this context, adolescent and young adulthood are important transition periods that are critical because these trajectories are especially sensitive to conceptual influences during this period. And so within this framework, we can understand the importance of environmental influences, but also behavioral risk factors of inactivity, diet, psychosocial stressors, social determinants of health that impact racial ethnic disparities, and how these factors interact with some genetic predisposition to influence the risk factors of obesity, diabetes, hypertension, and eventually result in cardiovascular events. Of course, this is complicated by factors such as access to healthcare and adequacy of medical care received. So in young adulthood, we see this greater risk and worse outcome than adolescence. For example, a nationally-launched study of adolescent health called ADD Health. For about two-thirds of health indicators, health risks increased and access to healthcare decreased from the teen into the adult years. Diet, inactivity, obesity, healthcare access, substance use, reproductive health worsened with increasing age, and particularly in this transition, and the relative rankings varied by sex and race ethnicities, but these trends varied over time. And if we look at the cardiovascular health metrics that were proposed by American Heart Association, which involve Life's Simple 7, that consist of health behaviors and health factors that are most linked to eventual cardiovascular disease, we can see that if we look at these, we can evaluate ideal cardiovascular health by having these health behaviors of good physical activity, diet, and no smoking, and maintaining normal cholesterol, BMI, blood pressure, and blood glucose. So looking at these health metrics, we can see that adolescents, age group 12 to 19, continues to fare better with respect to these health metrics compared to adults greater than age 20. But when we look closer, the major losses in these health metrics happens in the early adult years, age 20 to 39, where you go from somewhat better prevalence of these health metrics in adolescence, despite what you think of adolescence, to these poor health outcomes in the older adults, particularly if we look at hypertension, glycemia, smoking, and then in particular obesity, where about only 40% or so of young adults are able to maintain a BMI less than 25 in this transition from adolescence to adulthood. Who are these young adults? They are young people who are different from groups of cohorts of young adults studied in previous epidemiologic studies. They live in an environment undergoing substantial economic, social, technological transformations, and a lot of them are disconnected from the healthcare system, may not prioritize long-term health. And although some increase to electronic media use can engage them more in recruitment into programs, unfortunately, we find that increased electronic media use is associated with insufficient sleep, physical inactivity, increased caloric intake, and elevated BMI. So in general, this is a group at higher risk that we need to understand better. And in this group also, young females are of reproductive age, and a lot of them are becoming parents for the first time, and it's concerning that we see major racial ethnic disparities in cardiovascular health among females in this age group. After adjusting for potential confounders, non-Hispanic black women continue to be less likely to have these ideal cardiovascular health metrics compared to non-Hispanic whites, and significantly lower odds of having adequate BMI, blood pressure, blood glucose, and physical activity. And the disparities are somewhat less between non-Hispanic whites and Hispanics, but there are still some disparities in that category as well. So can we prevent cardiovascular disease in young adults? First, we have to understand who's most at risk, when does the risk develop, and what are potential underlying mechanisms. And again, if we think about it from this perspective, we can think that it depends on the degree of risk that we have genetically, but also intrauterine factors, social determinants such as neighborhood and demographic factors, exposure to stress and trauma, and we know all these issues are more prevalent among racial ethnic minorities. And so dependent on these factors, and adoption of risky behaviors, we can see a shift to having these cardiovascular risk biomarkers of hypertension, dyslipidemia, and diabetes occurring earlier and earlier in life, and lasting for a longer period of time, and thus impacting overall quality of life and well-being for these individuals. And in terms of mechanisms, there are several factors that occur in the development of atherosclerosis and cardiovascular disease that are often comorbid, right? Obesity, insulin resistance, hypertension, dyslipidemia, hyperglycemia, they often occur together. And I would propose that insulin resistance and hyperglycemia are the two major drivers of cardiovascular disease. Insulin resistance promotes macrovascular abnormalities through formation of plaque, there's a dysfunction, ventricle hypertrophy, and hyperglycemia, again, promotes atherosclerosis. And we have this issue of advanced glycation end products and oxidative stress, among other factors. So all these genetic lifestyle factors, obesity, nutrition, et cetera, drive insulin resistance, then links to other components of what's called metabolic syndrome, and eventually that lead to cardiovascular disease. And I don't have to convince this audience that cardiovascular disease starts in childhood. Atherosclerosis is a lifelong process that begins early in life. This has been proven based on autopsy studies, like the pathobiological PDA study, or the Bagalvuza heart studies, that linked the presence of plaque to risk factors starting early in life. When we looked at this through evaluation of subclinical atherosclerosis in youth, we found that in children, you should not, despite the fact that you do not expect to find coronary artery calcifications, which are linked to future cardiovascular events, we found that those with higher BMI index and higher visceral and subcutaneous adipose tissue had already presence of some coronary artery calcifications, which is concerning for high-risk disease in the future. And different aspects of the vascular function are affected by different mechanisms, it seems. So what we also found that intima-media thickness, which is thickening of the inner lining of the arteries, was more related to hyperglycemia exposure with some race-ethnicity differences with blacks having higher IMT. And pulse-wave velocity was more determined by insulin sensitivity here, measured by the hyperinsulinemic euglycemic clamp. Furthermore, we showed that endothelial dysfunction starts very early on in childhood, also majorly determined by insulin sensitivity, or reduction of insulin sensitivity. And several epidemiologic studies have linked cardiovascular risk factors and carotid changes to events. But these risk factors in childhood were related to subclinical atherosclerosis measures in early adulthood. Bougalow's heart study, if you look at LDL quartiles, were related to intima-media thickness measured in middle adulthood. And the Youngfin studies, the risk factor of smoking, BMI, systolic blood pressure, and LDL were related to intima-media thickness measured 21 years later in young adulthood. And furthermore, we can see similar findings with blood pressure and dyslipidemia affecting coronary artery calcification in adulthood nearly three decades later. And more recently, this publication from New England Journal of Medicine looked at cumulative risk of cardiovascular events in adulthood in relationship to risk factors measured in childhood, in children between the age of three to 19. And in this study, the investigators used the International Childhood Cardiovascular Cohort, and they divided these scores for each risk factor, and then looked at the cumulative risk score in relation, at this time, to events. And both for fatal cardiovascular event and non-fatal cardiovascular event, we see this graded relationship between risk factors in childhood and having cardiovascular events in adulthood. So it's not just subclinical atherosclerosis anymore. Now we have evidence that what's happening in childhood is influencing cardiovascular events in adulthood. And I wanna turn to youth-onset diabetes because it's a major cause of cardiovascular disease, and it's influenced by race-ethnic disparities. Both type I and type II diabetes have increased in children. Dr. Shalhoub spoke about the racial-ethnic disparities in type I. In type II diabetes, there's even more racial-ethnic disparity in that this is a disease that affects racial-ethnic minorities more than non-Hispanic whites. And we see that even early on in life, children with type II diabetes have, or children and young adults with type II diabetes have greater risk for several microvascular conditions compared with those with type I diabetes, despite similar A1c and shorter duration of disease. So the today's study was a study that recruited equal number of children from different racial-ethnic groups who were diagnosed with type II diabetes at younger than age 18. And today's study showed how type II diabetes is rapidly progressive in youth, and about 50% failed the randomized treatment arm of today, which were either Metformin or Metformin Plus lifestyle or Metformin Plus rosiglitazone. There were some race-ethnicity differences in response to therapy. African-American responded less to Metformin, for example. And what we learned from the today's study is that these children are very high risk, and may be related to the fact that youth have more insulin resistance than adults, about they are 50% more insulin resistant than adults, and also have more rapid deterioration of their beta cell function. But look at this high prevalence and rapid progression of cardiovascular morbidities in youth onset type II. Over 3.9 years of follow-up in today, hypertension rates tripled, microalbuminuria increased about three-folds. Dyslipidemia doubled despite treatment of these comorbidities according to protocol in the today's study. And by the end of the today's study, we started seeing granulopathy. And today was followed by the today two, which was an observational trial. And by the end of today two, these young individuals were in their early 20s. And by that time, this is a busy slide, so I will just draw your attention to the prevalence of microvascular disease on the right-hand side. Over a follow-up years, by nine years of the disease, 50% had evidence of one microvascular disease. And by 15 years of diabetes, 80% had at least one microvascular condition. And the factors associated with development of microvascular complications included race, ethnicity, hemoglobin A1c, lower insulin sensitivity, hypertension, dyslipidemia. And these models were adjusted for sex, race, and age at randomization. Moreover, there's evidence of macrovascular disease. And when we look at vascular stiffness in these young individuals compared to the normal weight in blue or those with obesity in red, we see that youth with type two diabetes have worse vascular stiffness at various sites. And not only that, but when you follow them over time, again, and today with repeat measures, arterial stiffness worsened and was related to glycemia and hypertension. And also, the vascular stiffness was related to left ventricular diastolic dysfunction obtained in echo towards the end of the study, suggesting that really heart failure has its origin in early in the childhood years in these youth. Hemoglobin A1c control and glycemic control are really important for macrovascular and microvascular complications. So when we see these children with really higher hemoglobin A1c long-term, we are really concerned about future outcomes. And if you look at type two diabetes that is diagnosed early in life versus later in life, we can, this is data from Health Maintenance Organization, and for type two diabetes diagnosed early in life is associated with eight-fold higher risk of macrovascular complications and 14-fold higher risk of MI compared to type two diabetes diagnosed later in life in comparison to the control population. And with that, also we see that having type two diabetes early in life is associated with increased cardiovascular mortality. And the younger the diagnosis, the more exposure to these risk factors that then the wider the gap in mortality. So is prevention possible? Lifestyle partially attenuates genetic risk, and these are the cohorts, three different cohorts. We are looking at high genetic risk for cardiovascular disease and having a different lifestyle. And you see that with unfavorable lifestyle, there's significantly higher risk of coronary event rates, and that risk declines with better lifestyles. This is encouraging. Do improvement in lifestyle translate to changes in risk? And this is, again, taken from a study in Cardia where the young adults, 18 to 30, were evaluated, and 20 years later, they had assessments. And looking at healthy lifestyle factors of smoking, physical activity, BMI, alcohol intake, and healthy diet. And 20-year change in healthy lifestyle attenuated the incidence of coronary artery calcium at year 20. So this is encouraging, and similar trends were found for intima-media thickening in this cohort. Lifestyle changes can reduce the need for drug therapy in those with impaired glucose tolerance. And again, we can see here with lifestyle in adults, being able to reduce weight more than 7%, and maintaining physical activity was associated with less requirement for blood pressure medicine and lipid-lowering agents compared to the drug treatment alone or placebo. And controlling cardiovascular disease risk factor other than hyperglycemia can also have significant impact on reduction of cardiovascular events, and even more powerful than just the glycemic control. So in thinking about approach to prevention, we have to pay attention to all these very connected issues, lifestyle, lipid and blood pressure lowering, weight reduction, glycemic control, to achieve optimal cardiovascular disruption regardless of race, ethnicity, but we know that all these factors are affecting, in a negative way, race, ethnic minorities more significantly. And of course, I don't wanna overstress the importance of glycemic control, and now we have newer agents that could help us to achieve these goals, individualize and treat the different cardiovascular disease comorbidities, and individualize therapy. So in summary, young adults are vulnerable to decline in cardiovascular health, and the steepest decline begin at 17 to 18 years of age, and this emphasize importance of transition programs. We have to improve lifestyle, and behavioral and lifestyle improvement can lead to improvement in cardiovascular disease. While treatment lowers risk, it cannot completely remove the risk once disease is established, so prevention is really important, and we need to emphasize the social determinants of health to decrease racial ethnic disparities. So we have to change our style and think about the individual within the context of the community, the family, and all the different factors that are influencing disease risk in order to achieve our goals of decreasing racial ethnic disparity in cardiovascular disease risk. And some prevention strategies can be increasing healthcare engagement of the young adults, community-based, but also more population-wide intervention, and more behavioral research that is potent, efficient, and scalable. And so thank you for your attention. I'm gonna conclude at this point. I acknowledge collaborators, funding, and our research participants. Thank you. All right. Anybody in the audience with a question, come forward and say who you are. Okay, here we go. Pınar Gümüş Balıkçıoğlu from Duke University. Dr. Bahat Başa, thank you so much for the beautiful presentation. The differences you showed in insulin resistance youth versus adults. I mean it's obvious that youth are more insulin resistant, have got decreased hepatic insulin sensitivity from the clamp studies you showed. What are the biological reasons or what is driving that difference? Why are the kids or youth are more insulin resistant? There are several things of course you can consider, but what would you say? Well, thank you for this question. It's really important, yes. We see 50% lower insulin sensitivity in youth compared to adults despite similar body composition in terms of percent body fat. And the thoughts are is that pubertal insulin resistance, it's a physiologic state where you get three times higher growth hormone levels mainly during puberty that affect insulin resistance. And it's physiologic because insulin is needed to build muscle, to grow, etc. But in this critical period of adolescence, if you add on top of it the obesity factor, you get this marked reduction in insulin sensitivity, which we think is a major driver of worse diabetes, but also cardiovascular disease risk. Let me ask you a question about insulin. Obviously the resistance to insulin that occurs in these settings is to the metabolic actions of insulin. But we also blame insulin for doing certain things such as you pointed out, maybe left ventricular hypertrophy. So insulin is able to work in certain tissues when not doing its metabolic thing. And this has been discussed for umpteen years, but nobody I think knows exactly how that happens. We see insulin, for example, causing increased hepatic lipogenesis. And yet we have less response in terms of glucose metabolism to decrease hepatic glucose production. And we see effects on the ovary and we see effects on where it needs to be effective in terms of growth, etc. But yet resistance to its effect on adipose tissue and muscle and liver. So yeah, it's a conundrum and depends on the pathway that is involved. Okay, well, I guess we'll be back here another 30 years not knowing the answer to that one. Thank you. All right. I don't see any questions. Well, don't leave. Well, you can leave because I don't see any other questions coming from the outside world here. So thank you so much, Fida. This is great. All right. We're getting into the home stretch here. Ro, come on up. And our last speaker is Rocio Pereira, who I've met for the first time today, actually. And who is the only non-pediatrician in the group. So she's brave to join us young folks here. I'm not speaking for myself. And Rocio comes from us from the Denver area where she's the chief of endocrinology at the Safety Net Hospital System, Denver Health. And is also an associate professor of medicine at the University of Colorado. And division chief and extremely active here in the endocrine society. And I encourage you to read an article that she co-wrote that appeared in JCNM in May. It's entitled, Eradicating Racism in Endocrine Society Policy Perspective. It's beautifully written. And really sort of nails the head on so many of the different areas where the disparity exists that I didn't actually necessarily think about. So thank you for putting that together. And her title today is Sociodemographic Factors in Eating Habits. Can we improve healthy eating? So the answer is yes. And you're done. Thank you. Well, thank you. Thank you so much for that kind introduction. And thank you for inviting me to speak to you today about this topic. So I am going to we started off with type 1 diabetes. We then moved to youth at risk for cardiovascular disease. I'm going to widen the lens way out here to all youth and talk about disparities in diet in youth. I do not have any financial disclosures. I do have non-financial disclosures. One is, as you heard, I am not a pediatrician. I'm an adult endocrinologist. The other is I have two youth at home. I have a 12-year-old and a 16-year-old. I don't have the magic pill of getting them to eat the best diet. So those are my two disclosures. Okay. So I think you can use this QR code to later do an evaluation. I'm not quite sure how this all works. Oh, sorry. Did you want to do that? Okay. I don't have any surveys or any questions or anything for this one. Okay. So why is this important? We know this is important. we just heard about cardiovascular disease risk factors for our youth, and diet clearly is important for that reason. Diet in our kids predicts overweight. During childhood, it predicts overweight in adulthood. And often, the diets that they're eating as kids is going to persist as adults. So this is an important time to intervene, if we can. So, the other thing we know is that diet quality among youth is pretty awful, unfortunately. So this is diet information that we're able to obtain from the NHANES surveys. This is a study that looked at NHANES diet data from 2009 through 2014. They used the Healthy Eating Index from 2015. It's just a score that tells us how healthy or not a diet is, based on guidelines. The maximum score is 100, and our youth, on average, scored 54.9. Terrible. And you can see that by age, there is a little bit of difference, so our younger kids are eating a better diet, slightly better diet, than our six to 11-year-olds. And then, it continues to go down in quality for our 12 to 18-year-olds. You can see, also, that there are some race, ethnicity differences, but really, they're small. They're very small. All our kids are, unfortunately, not eating a very good diet, a very healthy diet. This study looked at trends in diet quality among our youth, and found that the quality of our youth's diet has improved over time, so they looked from 1999 through 2016. There was some improvement, but as of 2016, still more than half of our youth were eating poor diets, and you can see the breakdowns there by age group, with 67% of our older youth eating poor diets. We also know that youth that come from a household with lower income, with lower education, or with food insecurity, are more likely to have those poor quality diets. It's important to know where the food is coming from, the food sources from our youth, so that we can try to intervene somewhere, right? This study looked at the food sources for our youth, and it actually looked at trends in food sources as well. The first pie chart tells us the food sources for our youth from 2003, 2004, and the other one from more recently, 2017, 2018. You can see that most of the food that our youth are eating is coming from grocery stores. The next large category there is restaurants. The smaller one in the earlier years is this other category, and then there's another sliver, which is food from schools. And that other source comes from sporting events, food trucks, so everything else you can think of is sort of thrown into that other bucket. But you can see that over time, that amount of food that our youth are getting from groceries has been decreasing, so groceries and schools decreasing, and the restaurant and other source has been increasing. And this is important because those food sources are not equally nutritious. And so the diet quality for food that our youth get from schools and groceries is much better than the diet quality that they get from restaurants or this other source. Also, we have seen very large improvements in the diet quality of the school food, some modest improvement in grocery store food, but we have not seen very much improvement. Small improvements in the restaurant and the food from other sources has actually decreased in quality. So these lower quality food sources are increasing and the other ones are decreasing. We also know that even though kids may be, kids from minority communities are getting food from mostly also from the grocery stores, that the grocery stores in high income communities are not the same as the grocery stores in the lower income communities. And so when we're talking about grocery stores, we're fitting everything together, but in the lower income communities, we have more fast food type of stores and we have more fast food type of restaurants as well. And so the quality of that food, despite the fact that it's in that same category, is not the same for all kids. So we do see those disparities. And we also see that although the quality of food in those different areas has been improving for our high income white youth, it has not been improving for our lower income and minority youth. So the disparities are increasing. We see some disparities also in snacking habits of our youth. So lower income youth are eating more calories, they're getting more beverages, more carbohydrates, more added sugars, less milk, less protein, et cetera. So these are differences that are seen. Sugar sweetened beverage is a particular problem for youth. This has improved over time, but sugar sweetened beverage intake continues to be very high. And the mean intake is 150 to 200 calories per day for on average for youth. And those who have heavy intake, so at 90th percentile, are getting 250 to 300 calories extra per day. So, and we obviously know what that means in terms of their BMIs and their health. There has been a decrease intake in sugar sweetened beverages for high income white youth, but not for high income black or Mexican American youth. So that continues to be a disparity as well. So I talked a little bit about supermarkets and the differences between a grocery store and a convenience store in terms of availability. And so we know that a better access to supermarkets and limited access to the convenience stores is a healthier option and leads to a healthier diet overall. We know that low income minorities, as I said, have poor access to those supermarkets and have health and healthy foods and greater access to those fast food restaurants and high calorie foods. This study looked at four cities in the US, Birmingham, Chicago, Minneapolis, Oakland. They looked at neighborhood income in the early years, 1980s, 1993. And then they looked at the density of these different types of grocery stores, grocery options and restaurants. And they found that the low income neighborhoods that had lower percentage of white populations, in 2011, so fast forward, had a higher density of fast food restaurants. And they saw also that at all income levels, the lower percentage of white population neighborhoods had a higher density of small grocery stores. So there's a difference in which type of business is coming into different neighborhoods. And we see this happens also with soda advertising. So low income non-white teens whose parents have not had a college degree are 54% more likely to see regular soda ads, 44% more likely to see diet soda ads, 56% more likely to see energy drink ads than high income white teens whose parents had college degrees. So this is unequal treatment for these communities. On the brighter side, there are some interventions that may be promising in these areas. So this is a study that looked at 58 different studies. It's a meta-analysis, over a million participants. Follow-up was about 10 months. And they found moderate certainty evidence for some interventions in terms of reducing sugar-sweetened beverage intake for our youth. So decreasing, they found decreased sales with traffic light labeling. So labeling the good ones green and the not so good ones yellow and the really bad ones red. With price increases, with in-store promotion of healthier beverages in supermarkets, with community campaigns focused on sugar-sweetened beverages. They also found decreased intake with government food programs that restricted sugar-sweetened beverage, improved availability of low-calorie beverages in the home. So those were found to be moderately successful. I mentioned before that the quality of food had improved in schools. This is because of the Healthy Hunger-Free Kids Act that was enacted in 2010. So a couple years after that, when these changes were implemented, this led to a number of changes in the school lunch program and the school breakfast program that our kids use. And so this changed the food and nutrient content of the school meals, the type of foods that were included in these federally reimbursed meals, the pricing for full price meals, and it also changed the foods and beverages that were allowed to be sold outside of the food service. So these competing is what they call competitive foods. And because of those changes, the quality of the food served in schools greatly improved. Other strategies to improve, well, these are strategies to improve or increase the amount of school food that our kids are eating or get more kids to be eating that school food because as you saw from that initial pie graph, our kids are not getting much of their food from the schools, even though this is the healthiest option for them. So some promising options in terms of increasing that is offering more menu choices, adapting recipes to be more culturally appropriate for our kids, pre-sliced fruits, presumably for our younger kids, rewarding them to try different fruits and vegetables, giving them enough time to eat in school is really important, recess before lunch and not after lunch because they rush to eat before so they can go out and play. And then limiting these competitive foods was found to be really, really important in this regard. So I've talked a little bit about different strategies and just a reminder here about interventions and what kind of impact they have. Most of us here are clinical endocrinologists. We see patients one-on-one, particularly those of us who are adult endocrinologists, we see just our adult patient. Those of you who are pediatricians work more also with the family. So you're moving to that interpersonal intervention level. But the higher you go in this socioeconomic model, the higher the impact you can have in terms of changing behavior. And so we start from the bottom where if you're working one-on-one with an individual, you can improve their knowledge of good nutrition, encourage and support them to eat healthy foods. In terms of the interpersonal, encouraging the family to have healthy foods at home is very important. Moving on to the organizational piece, school food policies, innovative engagement strategies. I didn't mention this. There was a study where the kids were taught about how food types are related to the environment. And so because they were very interested in that topic, they learned also a lot about nutrition. And then these kids had improved nutrition because of this engagement. Communities, so community organizations can have a lot of impact, and particularly for our more vulnerable communities and our minority communities. And then on a societal level, thinking about what kind of policies, what kind of regulations, what kind of laws can encourage our communities to eat healthier diets and particularly for our youth. And I don't, yeah. And so inclusion, diet quality has improved over time for our youth, but we know that our youth still have very unhealthy diets across the board, more so for those who are of lower socioeconomic status. And we do know that there are potential for interventions to improve the situation over time, but we have to make the effort to implement them. And I will stop there, and thank you. Thank you. Thank you. Anybody have a question, come on up now. I think you'd be happy to know that, at least in my hospital and in Children's Hospital of Philadelphia, we no longer have McDonald's in the lobby. Yeah, it took a while for that to happen, I must say. You used to walk into these facilities, and the first thing you noticed was the aroma of the hamburger or whatever you were cooking. We had McDonald's at Denver Health on the first floor and on the second floor, cardiology. I'm not sure that was because of a lack of our knowledge, or it was due to contractual relationships to build Ronald McDonald houses, as it turned out. But anyway, oh, great. Please tell us who you are. Kristin Dulitz from Ascendis Pharma. No questions related to Ascendis Pharma, but I'm really curious, just because I'm like you, I have several kids, and COVID changed our food intake in our house. Obviously, there were less people going to restaurants, we were cooking a lot more, and I was just curious what your thoughts might be on how COVID has possibly changed some of this paradigm. Yeah, there's good evidence showing that COVID increased obesity, overweight and obesity among children. I'm hearing diabetes as well, which I'm not surprised. So clearly, there were many changes that were made during COVID, not just for diet, but also for activity. So yes, absolutely. I think we need to continue to remember to prioritize that for ourselves and for our kids. Particularly for our older kids, it's difficult because they, as you know, choose their own food is the problem. You can't just, they will find ways to get the food that they wanna eat. And so the best you can do, I think, is when they're younger, get them used to eating that healthier food so that they're more likely to think about that when they're older and choosing their own food. But as I said, I don't have the magic pill, and I have two young ones at home, that I'm always fighting with. So thank you. Ro, thank you. I was curious about your thoughts. We've been studying, oh, maybe about 10, 11, 12 years now, fat metabolism in young, healthy, normal weight PCOS women who are hyperandrogenic, and we've looked at their stem cells of their subcutaneous fat. And if you culture them in vitro, they have this very large enhancement to lipid accumulation. The chromatin's abnormal. It's open around AP1 signaling, so we think it's driving fat accretion. So we think these young women, and they're basically UCLA students that we've recruited to study compared to normals, we think that they're predisposed to fat accumulation essentially against their will. This is gonna happen as an evolutionary metabolic adaptation. Now, we don't know that for sure because we have no longitudinal data, but do you feel, or have you seen individuals in the community, maybe adolescents, maybe not, that are predisposed to weight gain despite normal, healthy habits? In other words, this is gonna happen whether they like it or not. Yeah, it's a difficult question to answer. Because you can't measure what they're eating all the time, what people eat all the time. But I think we know that metabolism is variable. And we know that there's so many other things that go into metabolism other than what we put in our mouths, what we eat, all this variability with microbiome and the effect of microbiome. So I'm certain there's variability. I can't tell you for sure what that is or what's causing that, but there definitely is variability. Well, it would be nice to identify those people young, at a young age and do something about it as best as we could. Yeah, yeah. Thank you. There's also people out there that have healthy obesity. Not that I'm a proponent of that, but it's sort of the converse. Yes, right, yeah. Yeah, the metabolism is not always tied to the, yeah. Do we have any more questions for Dr. Pereira? Once, twice, sold. All right. Thank you all. Thanks to all the speakers. I think it was a great session. Intimate and informative. And I wish you all the best the rest of your time here in Atlanta.

racial and ethnic disparities

adolescent healthcare

diet

cardiovascular health

type 1 diabetes

health outcomes

biologic factors

glycemic markers

management

patient support

young adults

socioeconomic factors