dear colleagues and friends, thank you very much for joining us. And this foundational approach to optimizing health metrics and cast across the entire spectrum of diabetes care symposium at E. S. D. This is a C. M. E certified symposium jointly provided by the University of Massachusetts Medical School and the CME Educational Resources and was kindly supported by an educational grant from Abbott diabetes care. We have a very distinguished faculty whom you may well know. Professor Ramsey a john professor of metabolic medicine from the University of Leeds and from leeds teaching Hospital trust in the United Kingdom. Professor Park, the car consultant in diabetes and endocrinology in Portsmouth Hospital and also at NHS Trust and a well known proponent of the use of technology in diabetes. And I'm today Battellino, a professor of pediatrics from the department of entrepreneur ology, diabetes and metabolism from the university Medical center bibiana in Slovenia? Please allow me to start with some ideas on the mainstreaming CGM across the spectrum of diabetes care and perhaps discuss a possible road map to clinical success and satisfaction of individuals with diabetes. Those are my disclosures for you to review and allow me to propose the following agenda for today. A little bit of a background. Why something doesn't go well, why we believe we have to move forward a little bit about GM in this year, what groups could benefit most and perhaps a suggestion of a roadmap to clinical success and satisfaction of individuals with diabetes. So something doesn't go well. This is a very interesting report from a UK bio bank. The good 3rd of a million of individuals from European ancestry without diabetes completely healthy in this regard, linear and nonlinear Mandela and randomization analysis was used To associate like calculated Hemoglobin predicted by 40 genetic variants with incidents coronary heart disease. And these jeans were related to the coronary heart disease. It was demonstrated that each minimal promote increase in genetically proximate A one C. was associated with an 11% higher risk in coronary heart disease. And also those responsive curve increased at all levels of dedicated hemoglobin. Individuals without diabetes lowering average blood glucose. Actually it's to better outcomes. Please note on the left hand side, it's a linear analysis and here we see the group with a located hemoglobin of 4.9 perfectly normal. And the other one of 5.8 also perfectly normal. But the risk difference in between these two is threefold and this almost exactly holds for the pollen normal analysis on your right hand side, the nonlinear Mandelli in Random ization. So within the normal range of located hemoglobin between 4.9 and 5.8 in genetically proximate individuals, there is a threefold risk in the coronary heart disease. And if we look at the brain, this is a beautiful study from direct net in the United States. A longitudinal follow up for 12 years and they realized that the full scale I. Q. Was diminished in young individuals with diabetes as well as the total brain volume. Very interestingly. This was only related to percentage of glucose above 180 mg per deciliter or an A. One C area under the curve above 6%. So high glucose and hyperglycemia is associated with cognitive impairment and brain damage. Also this cohort from the Swedish registry when they used 8400 individuals with childhood cancer type one diabetes and matched with 84,000 Kelty individual controls. They clearly showed that the higher a. one c. was related with the worst outcome in neurocognitive development. So please allow me to conclude for the first part that it's hyperglycemia time above range that is associated with severe damage to the brain and to the cardiovascular system. It's the burden of diabetes perhaps that's the problem. And also on the site on the healthcare professionals. This is a Medscape analysis that clearly showed that there is a burn out present because of the increasing burden of this very important chronic disease. You all know this report from the Taiwan Exchange Cohort and then the huge cohort from California demonstrating a deterioration in the United States in metabolic control over the last 10 years. Despite the use of technology, this was actually not replicated in the sweet analysis here. A similar comparison 2000 and 8, 2000 and 10 versus 2016 and 2000 and 18. So a 10 year difference here we see an improvement a decrease in like oscillated hemoglobin in all pediatric age groups. And this importantly was in all centers that participated All together as you see was 13,000 individuals in the end. And the technology increased preceded the improvement in located hemoglobin. And this recent report gives another extremely important angle. The original orders of the CCT jOHn Larkin and David Nathan report the attic follow up the 1st 10 years of metabolic control seem to be more important than the 2nd 10 years of metabolic control. And if you have both 1st and 2nd, 10 years better, You really have a reduction of 50% in the cardiovascular outcome. And in this analysis a Almost 73 improvement in the arenal outcome. So the initial metabolic control is of extreme importance and we have no time to waste. When we start our therapies, we have several challenges as we discussed and perhaps we need the new philosophy that would probably have to address the burden of the disease, the use of technology and the artificial intelligence. So how is C. G. M. In this year? Importantly, this sweet report published recently in diabetes care included 25,000 individuals and they divided them about no technology, just injections, injections plus sensor pump without a sensor and finally pump and sensor. As you can see here, the more technology is used the batteries, the outcome when you look at the A one C with different co variance, controlled decay or severe hypoglycemia which groups would benefit most well, I think all of them will. There is perhaps a focus on Children. This is also a very recent report coming from Australia and they showed when they started to use the intermittently scan C G. M. And C G. M. In this pediatric population there was a prompt reduction in located hemoglobin as well as the trend of changes of increase of located hemoglobin diminished immediately after the use of C. G. M. And also in this important report coming from stanford, they demonstrated when they use the C. G. M. Air disease onset, they can considerably improve time in range without any increase in hypoglycemia. And they even proposed in a threshold alarm of 65 mg per deciliter may actually be enough to reduce hypoglycemia without risk of reducing time in range or increasing hyperglycemia. Finally, this important study, published in Jama this year, there was a first release in june during the 80 td online form demonstrated that in people who use basal insulin only with type two diabetes There is a very significant improvement in located hemoglobin and more importantly, the timing range is considerably higher here. You see 114 individuals were included and this is actually the timing range initially and then increase is very significantly as you can see after eight months of use with a C. G. M. Here. Almost 60% of time in range importantly. Also the time below range was improved with the use of course of C. G. M. And this is an analysis from the Kaiser permanent insurance system in California published in the same issue of the Jama Journal. And they showed separately Type one and type two diabetes. But if we focus on type two diabetes, see GM decreased emergency department visits or hospitalization for hypoglycemia. In addition to significantly lowering located hemoglobin and increasing the timing range. So very important. Additional outcome from this insurance focused report that admission to emergency department decreased for acute complications with the use of C. G. M. Most recently results of these relief study from France were published and this is a total of 74,000 individuals with type two diabetes and the freestyle library use was identified from the national french claims database. And interestingly for the beginning of this story, deliberate was used in more than 98% at the end of the first year. So a very high persistence with the use of this intermittently scanned C. G. M. System And to sum up the diabetes related acute events were in type one diabetes reduced by almost 50% by almost a half with the use of liberal And in type two diabetes by almost 40% with the use of liberal If we want to further investigate the percentage of individuals. Hospitalist with acute diabetes complication. There was a 52% reduction in type one diabetes and a 50% reduction in type two diabetes. So most pronounced benefit in those who didn't measure and a little bit intriguingly in those who measured more than five times a day but obviously a very significant improvement and particularly a half reduction by half in acute admissions. With the use of intermittently scan C. G. M. So how could we imagine a simple roadmap to clinical success and satisfaction? Well first we have to acknowledge that like a dead hemoglobin alone is not enough anymore. They studied the dialect to cohort divided people into three groups with increasing located hemoglobin and what they showed is is that there was of course a no difference in glucose variability and of course a very important difference in time and range. But interestingly no difference in time below range. And the important message is that when you increase located hemoglobin, you did not prevent hypoglycemia. So the hypoglycemia the time below range remain the same. And this of course is a very good message to all those that try to prevent hypoglycemia with increasing glucose levels. It doesn't work. And of course this mastering study analysis that was published recently here they checked whether proxies of long term cardiovascular outcomes were influenced by C. G. M. Metrics and they clearly showed that karate femoral pulse wave velocity. So the stiffness was associated with glucose variability and lower timing range. So the greater glucose variability and the lower time in range the more the vessels were affected. And this was also true when the model was controlled for all known. Co very it's like smoking totally LDL HDL antihypertensive and lipid modifying drugs so with all controlled for discovery as it was still significantly related to the karate funeral pulse wave velocity. And in this interesting study performed in china they initially measured with the C. G. M. Time in range and they followed up these people over 12 years and they clearly demonstrated that the higher the timing range, the lower was the all cause mortality and the cardiovascular mortality in this cohort. So obviously timing range seems to be related to important long term endpoints including mortality. The most important advancement in C. G. M. In the intermittently scan. C G. M. Is the Advent of the Liberal three System. The new freestyle inbred three has received approval in the European Union. It provides all benefits from deliberate too 14 day accuracy and optional glucose alarms. But it adds a continuous real time glucose reading delivered on a smartphone every minute. And in addition uses the smallest sensor so far in deliberate system available here you have an approximation of its size. The Freestyle three has a mean absolute relative difference mark That is below 10. So it's around 9.2 for adults and this of course is within the target. More stringent target that was currently agreed it has been designed to be more environmentally sustainable with reduced volume and reduction in plastic and cartoon paper and most importantly, perhaps for many users in public systems, the freestyle liberate three will be priced at the same as previous generations which is about depends on the system that we live in but always considerably cheaper than current other systems. We believe that all these C. G. M. Should be part of a digital virtual environment of a connected care environment. We published this year a consensus that addressed opportunities and obstacles in this connected care that we believe will look like a cloud that will include people with diabetes engagement with all their technology. They're using a population management that includes insurance system and governmental bodies that would analyze the data and then the care management with electronic medical records and the hospital systems and of course the health care practitioners us it will try to use all this data with the help of perhaps automatic analyzers and decision support systems with artificial intelligence with some of them being already ce approved and FDA approved. Please allow me to propose a couple of conclusions to you. Hyperglycemia seems to be the primary cause of short and long term diabetes complications. C. G. M. Brings individuals closer to time in range and time below range targets Like a did hemoglobin. A one C is simply not enough anymore. Evidence is mounting in support of the time in range centered diabetes management a perspective way of looking at it. Every person has if the timing range is not satisfactory at noon, every person still has half a day time to improve and to really become closer to the target. And we hope that with this day to day management, with time in range, long term outcomes and particularly reduced burden are seen with the use of C g. M. You are warmly invited to the at D. The 15 meeting of ATD. That will be in Florence March 23 to 26 next year. Hopefully face to face many new things will be presented buy from the medicines and of course technology in diabetes. And with this, I would like to thank you very much for your attention. This is my team that does all the difficult and important work and I will be very happy to reply to any questions you may have in our discussion panel. Thank you very much again for your attention.
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