Okay, so what is the objectives of today? We really want to introduce you to the new definition of obesity. So we are very privileged, you know, to be part of the Lancet Commission on Clinical Obesity. This will be the new redefining obesity. So how we're really now tackling obesity today is not with a clear definition. This will be published in January. I can't reveal much about it, but it's a huge group that we're about 57, you know, global leaders among the world. And that's with a lot of representations from all areas from the world to really commission the new Lancet obesity rate definition. And this got a lot of endorsements from ADA, ACE, obesity societies, and many of the regional ones as well. So this is the full list of the commissioners, myself, Dr. Noor, and Dr. Nasreen from the MENA region, but, you know, with a lot of the global leaders among the world. So these are the representations of the 57, you know, global countries that are part of the redefining of the clinical obesity that will be published in the Lancet, you know, in January. So look forward to it. And what is the real aim behind, you know, the redefinition of the clinical obesity is what is the objective criteria for the diagnosis? I think a lot of us nowadays, we're still using the staging, the comorbidities, but we're trying to move away from both BMIs and, you know, and the staging and really defining it in a much easier criteria. And how we look at it is very similar to how we diagnose other, you know, medical criterias. So really, you know, inform the decision makers and health strategies. So if we look today for diagnosis of, you know, similar diseases, like if you have lupus today, you would say, what are the ACR criterias? And you say, if you have four or more of these, then you'll be diagnosed with a confirmation of diagnosis. If we look at something like a depression, again, we have the DSM-5 criteria. And then we say, you know, you need to have five or more criteria to be present for a confirmation of diagnosis. And that's what we have been trying to move and to redefine the obesity in the new Lancet commission. That is the limitation. We understand there is a limitation of the BMI based on obesity. And we know that excess adiposity impairs health. But what if we say someone has excess adiposity with illness versus excess adiposity, but still with the preserved health and no ongoing illness? So the good news is really, it's not really necessary to achieve a normal body weight to achieve health benefits. And that is really very true when it comes to, you know, diabetes per se. We know that the ectopic fat and visceral fat impairs your health. And so, but any modest or moderate weight loss makes a huge difference. And if we look at the, you know, the ADA ESD guidelines, you'd see now, things has really changed in the cycle where the weight management became a big center, you know, part of it. And then we have the cardiovascular, the cardio renal, and the glycemia. So it's no longer about just blood glucose centric. And you see that the patient is the center of the whole criteria. And then moving into many new areas that we really need to look at, whereas, you know, the shared decision, language matters, and, you know, social determinants. So we really want to focus on the weight management part when it comes to the type 2 diabetes. And we know that type 2 diabetes and obesity are very much interlinked. And in all corner stores, you see the lifestyle is a major, you know, part of it. And again, you know, when we look at the diabetes point of view, we know that, you know, lifestyle, medications, and surgeries, and with any movement in the obesity world has always centered in diabetes, then things has expanded over the years to include, you know, the diabetes. So from the DPP trial, we know that the impact of weight loss and the lower risk of diabetes, and, you know, we need a very small weight change, and that will lead to improvements of diabetes. We know also from the lifestyle that Dr. Noor will cover a whole topic on it tomorrow with the diabetes and the remission criteria. So today, I just want to focus on the GLP-1s and how things has really moved, you know, over the years. The GLP-1 has been there for a long time. Many people would question their safety. It's been around since 2005, since they have been approved initially for diabetes. It took almost 10 years to be approved for obesity, but, you know, when we had the first approval for diabetes, it's more than almost 10 years, and then we saw how things has moved over the years, you know, when it becomes not only about the diabetes, but it's about the cardiovascular protection, cardiorenal protection, and more so. And that's how we should practice. And these are the GLP-1 receptors, you know, that are today available for diabetes and for obesity. So you would all remember we had exenatide as the first molecule that was available, and we've moved over the years to some short-acting, long-acting. Some would have, you know, cardiovascular benefits, while others might not have any benefits. And it's really good that when the FDA has mandated that all diabetes medications must have, you know, a cardiovascular benefit. And this has changed the science and really mandated the pharmaceutical companies to move forward and provide us with a much more, you know, data to protect and see where is the beneficial effect. So when we look at the GLP-1s today, you know, you see that not all of them are equal when it comes to cardiovascular benefits. Some would have neutral benefits, while others, you know, that would have cardiovascular benefits, you know, with the Rewind Study, Sustain, and Leader. None of the DPP inhibitors have shown any cardiovascular benefits. So again, when I'm using these agents in our people with diabetes, you really need to think of what I'm controlling. Is it a weight loss? Is it, you know, cardiovascular benefits? And if we look today at the GLP-1, you know, pleiotrophic effect, just think of your patients with type 2 diabetes. So we know people with type 2 diabetes have increased hypercoagulability, and the GLP-1 would decrease your coagulation. We know our people with type 2 diabetes and obesity have dyslipidemia, you know, and then they do have also increased inflammation. Most of them are overweight or obese. They have hypertension, and they have cardiovascular problems. And if we look at what we're trying to do with these agents, we really want to address every part of it. And how can I address it in my, you know, diabetes clinics? We saw the FLOW trial, and that was, you know, in semaglutide use in people with type 2 diabetes. That was halted before and did not continue because we have seen a 24% risk reduction in our people with type 2 diabetes. So again, you know, we really need to implement these guidelines, the ADA guidelines, the ESD guidelines, when we practice in our people with type 2 diabetes. And how can we really, you know, integrate all of the factors within it? You know, the guidelines have advocated for the use of combination therapy even prior to had any evidence of the combination therapy until recently where we have started to get some evidence. This really moves us to, you know, what about type 1 diabetes and obesity? And this is what we have really been, you know, pioneering in Kuwait. We were probably the first group among others in the world looking at this for many years, and not until last year where, you know, the big, you know, conferences like ADA and ACE started to have, you know, the type 1 diabetes and obesity as, you know, a main area. Many of us think of type 1 diabetes are thin people, lean people, young and children. Well, we know this is not the case. We know now we're seeing new phases of type 1 diabetes where we're seeing, you know, the type 1 diabetes happening 50% in adult life and they're overweight or obese. So, we have, you know, taken this work forward with the European Commission and SOFIA. We have, you know, we've really the main, you know, leaders with this and we have published our data in the Lancet looking at, you know, the adjusted prevalence of obesity in type 1 diabetes and you'd find that among at least 23% to 15% people with type 1 diabetes compared to the adult population have obesity. If we take both overweight and obesity, we're reaching almost 35% to 40%, really mirroring the same adult population within your country. So, it is real, it's happening, and it's there. And that has led us to put, you know, the review first in obesity in people living with type 1 diabetes in the Lancet back in 2021, looking at the major drivers of obesity in type 1 diabetes. Sadly, none of the current guidelines when it comes to obesity with many plethora of the guidelines address, you know, obesity in type 1 diabetes. Most of the pharmaceutical companies today and most of what we see for the GLP-1 therapies, that they are initially insulin manufacturer pharmaceutical companies excluding people with type 1 diabetes from any of the, you know, international trials. So, this has really led us to take this work and we published our data looking at both the use of the GLP-1 and SGTL-2 in people with type 1 diabetes, you know, to an overweight and obesity. And we have showed that this data are very similar to people without diabetes. As we know, obese people without diabetes lose more weight compared to obese people with type 2 diabetes. And the beauty of the type 1 diabetes is really mirroring what we see. This has led us to continue this and taking it into a randomized control trial, looking at the effect of, you know, putting an RCT, randomizing people to five groups, to lifestyle alone, to, you know, GLP-1 alone, SGTL-2 alone, a combination of GLP-1, SGTL-2, or, you know, GLP-1, SGTL-2, and, you know, a lifestyle. This we have had an oral presentation at the ESD and the results are, you know, currently under review. And our key questions in a randomized control trial in people with type 1 diabetes and obesity, is it safe? And would it provide any additive effect? And can we improve outcomes? We're really looking beyond, you know, just, you know, weight loss here. We have selected, even here, people with microalbuminuria. As I've shown you in the flow trial, this was done in type 2 diabetes, and we know our type 1 diabetes even have a higher risk of, you know, cardiovascular disease and renal disease, but they've always been, you know, excluded from these trials as well. And this is, you know, what we have shown, that, you know, the percentage weight change per six months, you know, both in the intention to treat and the intention protocols was almost 12.5%, you know, for weight loss, and we were able to reverse the microalbuminuria in these patients. Probably many of you have seen this, that, you know, the major breakthrough that we had this year in 2023 was the, you know, the select. But here, what we're trying to make sure, can we have a major breakthrough in the type 1 diabetes, where, you know, we're actually providing a treatment for them that causes weight gain, and then how we're going to take this factor into account. We cannot really advise with the type 1 diabetes lifestyle measures, because it's almost impossible that, you know, you exercise and then you would have a higher risk of hypoglycemia. You'll have the defensive stacking because of hypoglycemia. We know from the DCCT trial that people have gained at least five to seven kilograms with the intensifications of, you know, treatments. So, we have double burden. It's the type 1 diabetes are, you know, mirroring the adult population of being overweight and obese, and we are adding also factors that make their, you know, weight is even higher. So, we really need to think how we're going to move the science of what we have today, of advent today, of pharmacotherapy that is available in, you know, in the world of obesity, and how can we change outcomes for people with type 1 diabetes. And I believe that, you know, what we have today from both the GLP-1 of semaglutide and triseptide are just the beginning of a very bright road that we're seeing to change the practice in people with type 2 diabetes and also mirroring it in type 1 diabetes. And you'll soon be hearing the results of, you know, triseptide in type 1 diabetes as we have won a grant from the JDRF to continue this work. And there is much more coming when it comes to the obesity medicine in the field of phase 3, you know, in both, you know, an obesity world, but many also happening in the type 1 and the type 2 diabetes. And, you know, we're trying to bid for European Commission for the use of these also for the type 1 diabetes. Dr. Tariq has really showed us today that, you know, with any, you know, any treatment that we use, you know, we're going to lose both the lean mass and the fat mass with the weight loss. And it's even worse because we have published our data, you know, that people in Kuwait compared to the U.K. biobank have at least 15 to 20 years difference, you know, with obesity and type 2 diabetes and with type 1 diabetes. So, a 45 years old in Kuwait is equating, you know, about 60 years in the U.K. And not to state that the U.K. already have a low muscle strength and low muscle mass. So, it's not a good population to compare. They're already bad in their terms and we're even far worse when it comes to type 2 diabetes and obesity. So, we're running now a randomized control trial to see if we can improve the muscle weakness in our people with type 2 diabetes and obesity. So, how we're going to take this further and how will it have, you know, a long-term productivity on your people, you know, in the future. What is really important, whatever we do, is we have to think of, you know, safety in people with diabetes. Patients would lose, you know, at least 3 to 5 kilograms in the first week and, you know, this will exceed your energy deficits. We know that the glycogen depletion causes water loss because we know each molecule of glycogen is stored with two molecules of water. So, you know, with the weight loss, liver glycogen is depleted and this would lead to think of, you'd need to reduce your insulins in, you know, people with type 2 diabetes or sulfonylureas because of danger of hypoglycemia. But when it comes to type 1 diabetes, you have to really follow a very strict protocol because what you're worried about is the increased risk of DKA and increased risk of hypoglycemia and hence we have, you know, now specific protocols that we use when we use these agents in people with, you know, type 1 diabetes as well. Do please remember that, you know, with the depletion of glycogen storage, you have a risk of hypertension. So, you have to really monitor your hypertension medications. Probably you would know that in remission, you know, both direct diadem and in Kuwait when we have piloted in the type 2 diabetes, you really need to stop these medications and have their antihypertensive medications or stop them completely right from the beginning because of the acute effect of, you know, the weight loss that we will see. And of course, you know, these people would have constipation and already people with, you know, diabetes are a higher risk of constipation. So, these are all areas that we have to think of when we're treating people with obesity and, you know, diabetes with the pharmacotherapy agents. But I think there is, you know, a very bright future that is coming across and there are many, you know, things that is moving in the world of diabetes. So, this is now currently under trial for people with type 2 diabetes. It's a gene therapy and that is already recruiting. It is once a year you would need to do this and, you know, this would advocate that, you know, where they will inject, you know, low doses of viral vectors. Two companies are already now in the trials of doing this and then you'll have the double alterations of the metabolic hormones. I have not touched today about endoscopic treatments or, you know, bariatric surgeries, but what we can see from the development is beyond imaginations using, you know, magnetics to really staple the stomach nowadays. So, mimicking your bariatric surgery with using endoscopic magnetics that would, you know, come out by its system. But what we really need today is, you know, how we're going to have many unanswered questions. So, we have these weapons. We see the developments and we see the bright future. But honestly, without a proper training and educated workforce in how to deal with obesity in people with diabetes is highly needed. So, I would really advocate for all people practicing, you know, diabetes is to really, you know, become certified in obesity as well. I think it just came, you know, across and then endocrinologists thought by default, this is how we're going to take it. We're very easy in using the GLP-1 medications, but not thinking of how I'm going to tackle obesity and diabetes. And I would advocate for, you know, certifications in scope of all your members of the team, whether it's the dietician, the psychologist, the doctors, the primary care physicians, the endocrinologists, so you all will be speaking the same language together. It's very easy for us to write the prescription, but it's much beyond writing the prescription and that's what we really want to take into, you know, into the future. And what are the downsides of the use of these medications? Are these medications have class effect when it comes to protections? Do we need to continue them for life? Do we need to use the intermittent use? Do we use the lower dose? These are many questions that we need still answers and that's what we need to advocate for. You'll be glad to know that many of the new GLP-1 therapies are today, you know, combining, you know, actin and myosin activators to activate the muscle growth as well. Would these have benefits? Would they have extra side effects? These are things for us to look for the future. I think today we're very lucky that in the diabetes world, we have a lot of changes. We had, you know, a magnificent journey when we had nothing to offer to our people apart from sulfonylureas and insulins. We really had a better understanding with the advent of the bariatric surgery was a real opening of how we redefined diabetes and how we became to the idea that diabetes can lead to remission. Something that we were always taught in the medical school, once you had diabetes, you had a pancreatic beta cell failure, it's the end of it. Until, you know, bariatric surgery, then the lifestyles, remission studies, and today with GLP-1s. And it's our duty today, how we're going to utilize every single tool that we have, you know, on the toolbox, whether it's a lifestyle, a medications or bariatric surgery that we can offer best to our patients. And please do not forget our people with type 1 diabetes that do suffer from obesity and how we're going to, you know, safely tackle obesity in type 1 diabetes and not exclude them from future trials. So it's important for us to have, you know, people living longer, but we want them with better physical function and less comorbidity. We want to increase productivity and prevention and treatment is what we really aim for people with both obesity and diabetes. Probably many of you, you know, have heard the word diabetes. I think it's a bad term because it has reduced from both diseases, diabetes and obesity. And we really need to highlight what is coming up next. So I would, you know, ask you all to point through the January new, you know, Lancet Commission on Clinical Obesity, how we're redefining the clinical obesity and diagnostic criteria that will be launched in mid of January. And we will have launching, you know, sites for each country as well. With this, I would really like to thank, you know, the Dasman Diabetes Institute and the team that I work with, you know, with a lot of funding. As you know, Daphne has been running in Kuwait for more than 16 years. And we have been running a lot of the type 1 diabetes literature and obesity since then. And we have been partnered with SOFIA and European Commission with a lot of funding from Minister of Health and Kuwait Foundation of Advancement of Science. We came through a very long way. It's a very bright way. And we're here really to close the circle of diabetes and obesity with a very bright future. Thank you.

obesity redefinition

BMI metrics

GLP-1 therapies

type 2 diabetes

cardiovascular benefits

healthcare certification