Video CGM-Based Roadmaps for Reducing Hospitalizations and CV Mortality in T2DInteractive Case Study: Improving Clinical Outcomes in Vulnerable Persons Play Pause Volume Quality 1080P 720P 576P Fullscreen Captions Transcript Chapters Slides CGM-Based Roadmaps for Reducing Hospitalizations and CV Mortality in T2DInteractive Case Study: Improving Clinical Outcomes in Vulnerable Persons Overview CONTINUE TO TEST Back to Symposium Hello, everyone. Uh My name is Ramsey Ajan. I'm a, a professor of metabolic medicine working in Leeds, UK. And I would like to talk to you today about CGM based road maps for reducing hospitalization and cardiovascular mortality in type two diabetes. This is my disclosure slide and moving on. Now, when you come to HB A one C and vascular outcoming type two diabetes, you know, we've been using HBO one C as a glycemic marker for a long time and we know that higher A one C is associated with increased microvascular disease and increased macrovascular disease. And the UK P DS study has shown that if you look at reducing HB A one C, then any diabetes related endpoint actually improves. And that you can see this in the top of the slide. On the right, you can see the Metformin only therapy and on the left, you can see the other therapies. Now, if you focus on the myocardium function, which is in the middle of the slide, you can see that initially in the study, the difference was not significant. The P value is 0.052. But with a longer follow up, there was definitely a difference uh using intensive control or comparing intensive control with standard therapy. And the difference was bigger in the Metformin group. But you've got to remember that was a relatively small group. And what's really interesting if you look at the bottom of the slide that the earlier you get the glycemia controlled the better. So the green line is glycemia optimized after diagnosis, the blue five years and the red is 10 years after diagnosis. So the uh certainly management of glycemia is really important to reduce both all cause mortality as well as myocardial infarction. And this is where that term comes the um the glycemic long-term effect um or, or glycemic legacy that we often call it. So let's move on to the road map, what is it? So the road map is a strategic plan that defines a goal or designed outcome and includes major steps how to get there. But far more importantly, for me, it serves as a communication tool that helps to articulate strategic thinking as to why we need to do something and how can we get there. So let's start with A Y. Now, you know, a one C will be using this for a long time to measure glycemia. But now it became apparent that on its own is not enough for optimizing glycemic control. Why there are issues with accuracy does not tell you much about hypoglycemic and glycemic variability, which are two important glycemic markers. When it comes to cardiovascular risk, it is slow at addressing response to new therapies. You know, you start a new treatment, you wait 3 to 6 months if you're relying on HBO RC, to know whether it worked or not, that's not good enough. Is it the other thing is that it does not address the effect of daily life activities on glucose levels. My patients tell me that this is very important to them. They want to know that if it, if they do exercise, what happens to the sugar? If they eat a particular food, what happens to the sugar? And of course, the last point is not exactly engaging. You know, you get a number every few months, you look at it, but of the day to day engagement is just not non-existent really. So taking that into account, let me just give you an example about issues with accuracy. You've got a patient who's got type two diabetes, you measure, you measure HB one C and it's 52 millimoles per month. Do you think this is actually not too bad? Maybe we can improve on it a little bit but not far from the target that we were what we want to be. But then you do CGM and shock horror. You can see that the timing range is only 22% and you think, oh my God, what's happening here? Now, some of you may be thinking that this is only two weeks of CGM, maybe things change. But actually, no, it is 90 days of CGM. So it is reflecting HB one C actually, this patient had hemolytic anemia where the HB A one C is completely unreliable. Now you may say, hm, this is an extreme case. Well, not, not that extreme actually. So if you look at studies investigating the relationship between average glucose and HB one C, you can see this great variability in the relationship between individuals and actually that exists at the population level as well because people of black origin have higher HP one C for a given average glucose compared with the white population. But again, as you can see here, each dog represents a person. There's a huge variability in that relationship between average glucose and H A one C. So two people can have identical average glucose and HB one C difference by more than 1% or more than 10 million more per more. So relying on A one C can result in under or over treatment in some individuals. I'm not saying everybody but in some individuals. And actually this may explain why people of black origin have more hospital admissions with hypoglycemia co they HBO C is higher. People think that hm, the control is not that great, let's be more aggressive with the treatment and guess what happens, you precipitate hypoglycemia. And we know that hypoglycemia is really not a good idea. And this uh this is a study that we conducted in our region where we looked at mortality following severe hypoglycemia in the community. And this was hypoglycemia severe enough for the ambulance services to be called out. And what we found that if you exclude people above the age of 75 we've done that to exclude frailty as the cause of mortality. The mortality one year following severe hypoglycemia in type two, diabetes was almost 15% which was identical to mortality. Follow, following my infarction in an aged matched type two diabetes group. So that was actually an eye opener for us. Of course, the question is, can you modify this high mortality? And we did a, a study, it was a local study in a multi center where we had a nurse led intervention which consisted of educating the patients and access of the patient to the nurse for a period of, you know, intensive um access for a period of three months and just a very light touch for one year. And you can see that in the nurse intervention arm, which is the green line, there was higher survivor. I was really surprised at this. And what was even more interesting that it was due to a decrease in cardiovascular mortality. There was a big difference in cardiovascular mortality, comparing the two groups, the standard treatment and the nurse led intervention and this explains the international guidelines um published actually last year that strongly recommend that hypoglycemia should be avoided in people with type two diabetes, particularly in the presence of cardiovascular disease because these people are very susceptible to the adverse effect of hypoglycemia. Now, so we know that hypoglycemia is bad for your blood vessels. I think that's, that's been proven, particularly in the older age group group. What about glycemic variability? And this is a recent study published in a decent number of people with ST elevation myocardial infarction. A quarter had diabetes. You can see the numbers more than 7000. Well, it shows that if you have glycemic variability and the higher tile, then your survival drops. You can see that on the left while your maze major adverse cardiac events increase. So that's your solid black line. So survival is lower and major adverse cardiac events increase in the highest glycemic variability tile. So again, this fluctuation in blood glucose levels is not a good idea. So this was the why we need to get more glycemic markers when we are managing type two diabetes and not rely only on HBO one C. I'm not saying that do not use HB one C. All I'm saying is that supplement that with other glycemic markers. So which groups of individuals with type two diabetes are eligible for CGM? So there are two views here. Really the first view. Oh, let's get everybody uh with type two diabetes on CGM. And I know some of my colleagues would say that the view to the second view, that actually that is not practical and is not cost effective, at least at the moment. And we need to have a more balanced approach. And I must confess, I'm in the second group, I'm very keen on CGM, but I think we need to prioritize it to the right patients. The other thing we, other thing we can do is that in some people with type two diabetes, they'll need CGM all the time in others, maybe intermittent use is enough. And in others, maybe you don't want to use it at all unless there are, there is, there are changes in therapy. So let's review the evidence. So when it comes to multiple daily injection treated, type two diabetes patients, these cars are very similar to the type one. And in my view, they should be having CGM all the time supported by data from the replace trial that show that you get a massive reduction in hypoglycemia. Um in this group using CGM. And other studies showing that you get an improvement in HB A one C using CGM in MD, I treated patients. So you get at the very minimum, you get an improvement in hypoglycemia, but you also get an improvement in HBO one C and other studies. But what's very interesting now, these studies did not have education included in them. But when you have the CGM plus education is where you get the maximum benefit. And this is a study I think he is very clever published recently uh in MD I treated type two diabetes patients and they were divided into um just blood glucose monitoring. It is the blue line. The black line is the um intermittently scanned CGM and the red is intermittently scanned CGM plus education. And you can see that stepwise difference, you get the maximum benefit with the technology plus education. And I always say this do not use technology on its own. Please combine it with education for maximum benefit. And here this clearly shows that you get a very, very good benefit. So that's what that was the MD I. So my view, we should use it CGM in type two diabetes patients or MD I. What about basal insulin, basal insulin? We've got good data as well. So we've got the, the mobile study on the left showing you that if you use CGM, you get the shift to the left in the A one C compared with blood glucose monitoring. So you get an improvement, a significant improvement in HB A one C and on the right, you can see that this improvement is sustained only if you continue to use the CGM. If you discontinue the CGM, which is your blue line, the HB one C goes up again. Whereas the red line, you can see that the um uh the if the improvement is sustained, if you continue on the CGM, and there will be some reward data presented at the meeting that you can see with OO on basal insulin therapy and type two diabetes. Another study, the PDF trial, um, it's a, it's a really very good study that use a combination of basal insulin and oral hypoglycemic agents. Around a third were on insulin. And again, if you look at the red line, you can see that shift to the left in HBO one C indicating improved control. What about people who are not on insulin? And this is where the immediate study comes in. And these were people on Metformin Sulfon, all Urea FGLT two DPP, four inhibitors and G LP one receptor agonist. Um And you can see that with the use of um CGM timing range improved significantly, time above range, reduced significantly and time below range did not increase in anything. There was a decrease, nonsignificant decrease in time below range. So it works in people who are not on insulin as well. The what about using it in the newly diagnosed type two diabetes patients or even people with prediabetes for that matter. Now, remember what I said at the very first slide that the earlier you get the diabetes controlled, the better it gets in terms of all cause mortality as well as cardiovascular risk. So it is quite possible that if you use CGM early on, it would be very informative, but we do not have the studies adequately powered studies to support that. But it does make sense I must confess. Right. You know, newly diagnosed, you give them a sense that they may modify their lifestyle and we see that quite a bit. So to, just to summarize to you in the newly diagnosed, there is, there is a good argument for using CGM. If the patient can afford it or the healthcare system they are in can afford it, but we don't have sort of enough studies to support it. There are some studies when it comes to sort of he that it helps with a healthy lifestyle. But I think perhaps we need, need more studies there, monotherapy. We don't have specific studies in monotherapy, but they, they are part of the noninsulin therapies and they show that you can sort of improve control combined noninsulin therapies. We've got some good studies there. Um uh suggesting or actually indicating that CGM can be helpful when it comes to insulin therapies. I have no doubt in my mind whether people are MD or basal insulin CGM does help that group. Um What about sort of high risk vascular group? We did conduct a study on my inunction patients um with type two diabetes disorder and insulin or feral urea. And the red line is the CGM. Um The blue line is SNP G. You can see that indeed, there was a difference in a one C comparing um the baseline with 90 days, but red reduction in A one C was very similar with CGM and SMBG, you may think, oh, that's disappointing. Not so fast. If you look at the hypoglycemia, there was a massive difference in hypoglycemic exposure with the use of CGM more than one hour a day, regardless whether the patients were on insulin or Suena at Baseline. So what this tells you that following M I, you can reduce the HV one C with the use of CGM safely without increased hypoglycemic exposure, which you really don't want in people who just had an Mr. Finally, you've got some other groups of people who may benefit where studies are really lacking, but it makes perfect sense that they may benefit like presurgical patients. We know that high glucose in these patients is associated with poor outcome. So maybe if we can optimize glycemia before surgery, they may have better outcome, psychiatric disease, obesity, these patients may benefit mental disabilities, cancer, and cancer therapies. You know, there are a lot of steroid therapy with cancer um and, and other glucose modifying agents as well. Uh There are a number of studies that are ongoing including um our own. So we would be able to report on that hospitalized patients. There are some small studies um showing benefit and of course the older age groups. So all these things that we need to keep in mind that people may benefit in these groups. So here is a proposal for you. This is something that we published recently, what we are proposing that in all individuals with type two diabetes CGM may be helpful in diagnosis. Why to establish a baseline glucose profile and guide education in these guys? Remember what the patients are saying? We want to know what daily life activities do to our glucose. It would be very helpful in this regard. Also, if you're starting them on treatment, it helps to evaluate response to glucose management. So that's a diagnosis without a stable disease. It can be helpful to uncover hidden glycemic abnormalities. I can tell you I've seen some very unexpected glucose profiles in my patients and it's very helpful to adjust therapies accordingly for long diabetes duration. It can uncover this glycemia escalation of therapies, de escalation of therapies and health care providers with diabetes management. So there's no any escalation but also deescalating of therapies. And then we propose that we use CGM on a continuous basis in all insulin treated type two diabetes patients because we do have the evidence for that approach to avoid the hypoglycemia, reduce hyperglycemia and limit glucose variability. What about intermittent access to CGM in noninsulin treated type two? Maybe that's the way forward because otherwise it becomes very expensive, it reinforces education monitors the adherence to treatment and it tells you whether a change in therapy had an effect. So whenever you change therapy, CGM can be very helpful. So to conclude, while A one C served us well, we should use additional CGM markers to optimize management in type two diabetes. Remember that by the accuracy, remember about differences between people and and population. We actually have a session on this at the ESD on Friday one hour session. Looking at the um discrepancy between A one C and average glucose, which I encourage you to attend. You'll be surprised by the data. We need to have practical guidance on CGM use in type two diabetes that takes into account local resources and financial burden. And then given the large number of people with type two diabetes, we should prioritize the use of CGM in certain group and need to be innovative in the use of this technology. Now, 10 years ago, I stood at the ESD and I said to optimize glycemic management, we need to lower glucose levels but also avoid hyperglycemia and limit glucose variability. This was sort of a dream of mine and this dream is becoming a reality. We can do this now with all the new CGM devices. So 10 years on dream is getting there slowly but surely. Thank you very much for your attention. I'm going to move now to the clinical cases. So Jes clinical case one is an 81 year old gentleman tattoo Davis for 25 years on insulin for 10 comorbidities, ischemic heart disease um had MRI three years earlier but can walk four miles with no issues. I struggle to do that sometimes and he's got hypertension. He's on mixed insulin also on G LP one receptor agonist and SGLT two inhibitor. And it's nice to see this because he's got vascular protection, you know, had ischemic heart disease and an M I BM I is pretty good at 24 A one C is high. Um, user are normal. Um LDL is pretty well controlled. Um, he does SMBG 2 to 3 times a day and there's a big range 4 to 18 and mostly above 10, he's complaining osmotic symptoms. He's got no clear symptoms of hypoglycemia. Options. Ignore A one C and tell the patient this is great given his age. Well, I'm not so sure because although he's sort of 18, he's in a pretty good nick. If he can do four miles, ask the patient to do eight point SMBG to better assess glycemia. There is certainly a possibility you want to look like you need to understand a little bit more what's happening to his sugars, stop SGLT two inhibitor. It is causing osmotic symptoms. Well, absolutely not. He needs it because he's got ischemic heart disease. So I don't think that's the right approach. Given his asthmatic symptoms, we need to urgently increase his insulin doses. No fear of hype or given the absence of symptoms. Well, um particularly in the olds, the symptoms of hypoglycemia can be minimal and I've seen loads of patients with no proper symptoms other than confusion, for instance, so do not rely on symptoms of hypoglycemia to say that this patient has got hypoglycemia or not, particularly in the older age group. None of the above. And personally, I would go for none of the above because I want to have a proper assessment of his glycemia. And that's exactly what we've done. Um, we had CGM in this gentleman and as you can see it ties in with his osmotic symptoms. His levels are generally high. His timing target is only 31%. And actually that more or less matches his HB A one C. The main issue here is poor diet. Well, somebody who's got a BM I of 24 is unlikely that he's a sort of a very poor diet. Massive glucose variability. I'm not seeing sort of massive glucose variabilities is CV S 31%. I mean, yes, his glucose levels are increasing after the meals, but the variability is not sort of massive, generally high glucose levels with postal peaks. I think I agree with that. These are helpful and confirmed that no treatment changes are necessary. I hope you agree with me that, that's wrong. None of the above. I think I would go with number three. Actually, your best treatment option here is needs to eat less and do more exercise again. I don't think that's a problem in this particular gentleman. Stop SGLT two treatment and increase insulin doses. I certainly wouldn't do that change to basal bolus provided patient can cope. Now, that's an interesting bit. Yes. Can we change to basal bolus if the patient can cope. Certainly, there is an option adding Lisa to his treatment. Option number four, I don't think that will touch anything given he's already on insulin. Do nothing. I think we agree that that's not an option. We've got to do something in this gentleman. So this is what happened. We changed the basal bolus and look at that. His timing range increased from 31 to 70% in a relatively short space of time. Very intelligent gentleman and he could cope with the glucose with the um MD I regime. Very well indeed. And most importantly, he reported feeling fantastic on the Q DS regime so high. He was in all the people who type to diabetes should not be just accepted, particularly when symptomatic technology helps to make safe and effective treatment changes and switching in some regimes should be considered regardless of age. Let's do clinical case two. This is a lady 66 years old type two diabetes for 11 years. Major fear of hypoglycemia particularly because she lives alone. She's really worried about it, which I completely understand. She's got a stable angina well controlled osteoarthritis, affecting her hands. This is her treatment on Metformin, Dapagliflozin and Glargine. She's been intolerant to G LP one receptor agonist. The BM I is on the higher side at 32 A one C is high EGFR with reasonable LDL again, reasonable. Um She's doing SMBG around twice a day. And there's a huge range 5.5 to 21.2. So in this lady, you want to know what's going on, don't you to adjust her treatment? Now, this was her treatment before and after a particular intervention, right? So again, look at the time frame. So this is um fourth of May, the first sensor, fourth to 17th of May and the second sensor is 18th to 31st of May. So there was a an intervention in between and I would like to urge you to look at the second sensor that actually the glucose control improves particularly in the second week of the second sensor. So it becomes absolutely lovely. Uh What was the treatment change? One glargine dose was increased, possible glargine dose was reduced. Is that possible switch to basal bolus? Yeah, maybe clip in added. I don't know whether that would make such a difference or glipiZIDE added again. I'm not so sure. And actually what happened here, which may come as a surprise to you. The dose of glargine was actually reduced. So what was happening that this lady was so worried about hypoglycemic. She was eating all the time to make sure she doesn't get um hypoglycemic. And by having the sensor, she got that, I'm really not worried anymore because I can see my sugar levels at any time. And what we've done, we actually reduced the dose of glaring, we did not increase it. So she was eating a lot less and her control improved. So the sensor is very helpful at deescalating therapy, not only escalating therapies. So CGM in my experience and I think we all agree on this is very useful in people with F of hypos. CGM helps to understand patient habits, which again, helps in the management and improving glycemia is not only about escalating therapies but also deescalating. Now, the last case, this is Hassan a 66 year old man tits for five years. He's got heart failure following his MI-5 years earlier. He's got also Parkinson's disease and hypertension. He's on Metformin, linaGLIPtin, dapagliflozin and glycoside. So he's on four hypoglycemic lesions but not on insulin. This is his weight BMIs on the higher side. Um HBO one C 79 EGFR 58 and LDL is well controlled. So he's got some renal impairment. He's unable to perform SMBG because of his Parkinson's disease. Now, this is his um CGM June to July 2024. And then on the right, you've got it three weeks later. So something happened, some kind of intervention happened on the first of July and you can see that his diabetes control improved because his time in target went from 23 to 50% in a space of three weeks. So what was the treatment change? Was he started on basal insulin, possible sort on, on an insulin pump. I think that would be a bit too much. Probably not. So on G LP one receptor agonist with lin li linaGLIPtin stopped, started on a glinide with a glycoside stopped or Metformin changed to an sr preparation. Actually, what happened here is number three nerd lipin was stopped and he was started on GRP one receptor agonist. So still not on insulin. So the take home message is here that CGM helps the early assessment of response to new therapies. CGM can help type two diabetes, Individuals who are not on insulin and introducing new glycemic therapies. In my view, um needs CGM because you want to know whether that therapy is working or not. You don't want to wait for too long. You want to make sure that the patient is not getting hypoglycemia if they're on agents that can cause hyperglycemia. And remember sometimes when you're introducing new therapy, you may need to stop other therapy because there's not much point in this case for, for instance, in having leptin with a G LP one receptor agonist. So I hope that you find this session helpful and I would like to thank you very much for your attention. Bye bye for now. Published Created by Related Presenters Ramzi Ajjan, MD, FRCP, MMed.Sci, PhD Professor/Consultant in Diabetes and Endocrinology University of Leeds and Leeds Teaching Hospitals Trust United Kingdom
