Video Moving Beyond A1c: Establishing a New, Personalized, Precision-Based Standard for Glycemic Management of Persons with Type 2 Diabetes Play Pause Volume Quality 1080P 720P 576P Fullscreen Captions Transcript Chapters Slides Moving Beyond A1c: Establishing a New, Personalized, Precision-Based Standard for Glycemic Management of Persons with Type 2 Diabetes Overview CONTINUE TO TEST Back to Symposium Hello everyone. My name is Ramsey agent. I'm a professor of metabolic medicine at the University of Leeds UK. And today we've got a very exciting webcast for you that involves a number of speakers with the title. Moving beyond HB one C. Now this is a symposium that is certified and is supported by Abbott diabetes care of course. All the material in this symposium has been developed without any input from Abbott. You will have three speakers today. First one is myself and we've got Professor Richard berg install and professor today Battellino. And at the end we will have some cases as well to discuss. So I hope you're going to enjoy this program today. So without wasting any time. I'm going to move straight to the first talk which is entitled moving beyond A one C. Now when you're managing type two diabetes, what do you usually do? Let's just start with a couple of cases just to show you some of the difficulties that you can encounter with these patients. This is a 63 year old gentleman tattoo diabetes for 11 years on insulin for three years scott. So chronic obstructive airway disease and hippo forests. The glycemic management is a mixture of insulin 42 units morning 34 units evening metformin and GLP one receptor agonist of course because his hypothyroidism is also on fire oxen When it comes to glucose control. He's doing capillary glucose testing and if you look at the readings are not bad at all. 4.1 to 11.1 million more per liter doesn't have his meeting. You can't check that you've got rare readings below four, just below four and they occur once a month is not bad at all at 54 million more per more or 717.1%. It feels great. But it seems that I can get sweaty now and then. And he thinks that's due to the fact that he forgets the fire oxen on some days and he takes multiple tablets to three tablets together and he thinks that's why he gets sweaty. So if you look at this picture, this actually doesn't look bad at all and things seem to be well under control. But the moment you do see GM things change. Well actually this is a 63 year old gentleman and if you look closely he's got hypoglycemic exposure at 14% with 5% at very low less than three. So three million more per liter. So actually without a C. G. M, you would have known that this gentleman has significant hypoglycemic exposure and that's something best avoided, particularly given that he's an older gentleman. Let's take another case. We've got a 59 year old man with a non diagnosis of tattoo diabetes was admitted with Mark on in function, had a previous myocardial function four years earlier, There's a history of confusion on and off and family things that could be early dementia, capillary glucose on admission was pretty good at 5.3 million more per liter is very impressive. At 38 million more. You can see the treatment that he's on and please note he is not and I repeat he is not on its own. Now again. You look here you think. Well, yeah, I mean the glucose admission, not bad is very good indeed. Not on insulin. Maybe the risk of hypoglycemia is not that high until you do that C g. M. And you discover that actually this gentleman is having loads of hypoglycemia. Each red dot is hypoglycemia and of course that could be the reason for his on and off confusion. So I'm trying to say here that without the U C G. M, you will not know what the glucose profile is really like and you can miss some very important patterns. So I'll tell you what happened with these patients later on now, when it comes to the glycemic measures, our main glycemic measure has been, we do like it, it predicts complications. It's easy to understand and explain. And there are clear cut targets and we are familiar with it. Both the health care provider and the patients are familiar with it. It's used for glycemic management and also is used for the diagnosis of diabetes and you know, studies have shown that as you have higher hB one c you're at higher risk of both micro vascular or small vessel disease as well as macro vascular or big vessel complications. So we know that high. HB one C is not good for you. However this legitimate measure is not perfect because it has a number of weaknesses. There are several factors that affect accuracy. You know if you're relying on an HBO one C, there may be delays in therapy escalations and it does not address the effect of daily life activities on glucose levels, which can be very important to our patients. Also also, it does not measure hypoglycemia and glycemic variability. I'm going to talk about those in detail. Why are they important? So let's talk about accuracy of HBO once in now, we have known for a while that when you say HB one C is let's say 7%. So they take the third one from top a 7% or 53 million more more. Please look at the average glucose. The average glucose will be 154 mg per deciliter or 8.6 million more. But please look at the distribution could be anything between 123 and 185 mg per deciliter and that's for an H beyonc of 7% which is regarded as good. Now if you have an 8% immediately underneath it you can see the overlap with average glucose. So there could be two people with different HB one C but identical average glucose or very different average glucose and identical. HB one C. So H. B. O. N. C. Can differ from person to person in relation to reflecting average glucose lens And one of the reasons is that HB one C. is a measure of average glucose and also uptake of glucose. Barrett cells and red cell lifespan. So let me just demonstrate to you what that means. If you have an average blood glucose of let's say 100 and 54 mg per deciliter and you've got an average red blood cell lifespan, the rich Beyonce is going to be that yellow dot in the red cell. However, If you had a shorter red blood cell lifespan with similar similar average glucose then your HB one seat is going to be lower. Conversely, if you have a longer red blood cell lifespan for exactly the same average glucose your A one C. Is going to be higher. And the problem here that if your red blood cell lifespan is short you can under treat and that predisposes people to complications. And in contrast when you have a longer red blood cell lifespan, you think the A one C. Is high. But actually you can over treat and precipitate high. Globalized senior, you know, we we published this paper a couple of years ago and we have shown that the differences can be quite staggering in terms of H. B one C, one C can differ up or down 1 to 2% or 10 to 20 million more for more. That's something to be taken into account. And there are a lot of factors that modulate that accuracy of H. B. O. N. C. And I'm not going to go through them all. But these are some of the factors that can affect the accuracy of A. One say. So let's take this clinical scenario. This is a 41 year old lady found to have an A. 1 49 million. But the fasting glucose of 5.4 and referred to me because the primary care physician was a bit puzzled. The fasting glucose is not bad but one sees in the diabetes range and you can see that the C. G. M. Was pretty good actually here nothing really to suggest that there are any major issues with Lycee MIa. And of course we've done an oral glucose tolerance test which was completely normal. As you can see other investigations showed her to have no globe in micro psychosis. So had microscopic anemia with a ferret in that was quite low treated with ferrous sulfate And guess what happened? The H. B. O. N. C. Fell by 10 million more. More and essentially normalized. So this lady never had diabetes and the primary care physician was quite right to refer her because you don't want to label somebody as having diabetes when they don't. So that was the reason for the raised a one c iron deficiency anemia. Now what about delaying therapy escalations when it comes to HBO. So let's take this case. This is a 67 year old gentleman tattoo diabetes 11 years and the recent market in function which is the second in five years on Metformin and glimmer Paride. And the results show that H. B. O. C. Is very high. S. N. B. G. Is infrequently done, but all above 10. However, he says that he can go lightheaded and sweaty before meals start immediately thinking, gosh, is he having hyperglycemia? The thing is if you rely on just a clinical picture and infrequent smb G, you can't tell what's going on. So, and that can cause a delay in escalating therapy and in this particular case you really want to improve that lie Ceemea quickly but also safely. So here you do an smb G. Sorry you're doing a C G. M. And clearly no evidence of hypoglycemia whatsoever. So, you know, I can escalate therapy here pretty quickly and no need to wait. So there's assurance to the healthcare professional as well as the patient that therapy can be escalated relatively quickly. And actually we have done a randomized control trial in people with recent bicarbonate function who were on insulin or some finale Arria. And that included 141 individuals. It was over three months. And what we have shown is this that if you use smb G versus flash glucose monitoring. So Smb G. Is blue flash glucose monitoring is red. You can see that the HB one C falls at three months by seven million per mole. So the drop in H. B. R. C. Was very similar whether using Flash or sMB G. However, however, the hypoglycemic exposure was vastly different. So in the flash glucose monitoring group they had more than an hour difference per day in hypoglycemic exposure. And the pattern was similar whether you were on insulin at baseline or cell phone on urea at base. So it appears that the flash glucose monitoring when you use it for semi it's very effective at reducing hboC but it reduces it safely with minimal hypoglycemic exposure which we know is quite important in these individuals. So let's talk a little bit about hypoglycemia, glycemic variability with which HB one C fails to address. So studies have shown that there's a pretty good relationship between hypoglycemia and adverse clinical outcome. And this study I particularly like that looked at major adverse cardiac events on top and all cause mortality in the bottom and then you've got cardiovascular death and non cv death in between. Just focus on top and bottom and you can see if somebody sustained a severe hypoglycemia requiring third party intervention. Then within the first seven days their risk of mace or cosmo mentality is vastly increased. Not only that the risk is still there up to a year following the event. Okay, it is reduced is not as high as in the first week but it is still there as you can see up to a year and mechanistic lee. You can explain this delayed effect of hypoglycemia because we have looked at blood clot breakdown in people on hypoglycemic versus normal glycemic clamps. So the hypoglycemic clamp is the red line. The u. Glycemic clamp is the blue line and you can see that there's a clear difference in the time it takes to break down the clot between the two arms which is sustained for seven days after the hypoglycemic events. And the more recent study last year showed that actually you get an increase in inflammatory markers that is sustained for up to a week after the hypoglycemic clan. So you get a thrombin attic inflammatory response that lasts for at least a year, at least one week following the severe hypoglycemia. Now one of the question is is this modifiable? Is this outcome modifiable? So this is a study that we conducted in leeds where we looked at mortality following severe hypoglycemia in people with type two diabetes versus mortality following my Katelyn function in the same group, adjusted for age. And you can see actually the one year mortality following severe hypoglycemia or my colleague is almost identical in these groups. And then we conducted a very simple interventional study that was led by a nurse and I'm very grateful to this nurse which was quite intense for the three months and very light touch for up to a year. So every two weeks the nurse will contact the patient in the first three months to adjust therapy and give them education and what we found that with the nurse led intervention you get a reduction in mortality that was may need you to a reduction in cardiovascular mortality. So reducing hypoglycemia actually does work. So one of the issues with hypoglycemia always that we do not always detect it. So this is a lady 69 year old daily type two diabetes for 19 years on insulin for six years. You can see she's on basil towards insulin and cock Tale of cardiac drugs. She feels well the only complaint is headaches in the morning on and off and she thinks that is stress related is brilliant. 48 million per mole for 6.5%. Actually she's religiously doing smb. G. You can see the milligram per deciliter on top and my colleague is also displayed and you look at her numbers and they're brilliant. They're probably better than mine. Right. However, when you do percy gm you can see that she's having pretty significant hypoglycemia. Outside those periods when she was checking the glucose using smb gee. So bipolar senior can be hidden in type two diabetes. And that's an important message. And now of course the reason for the headaches are becoming more obvious. And you've got to remember that when you use C. G. M. And this is a study that we conducted when we use C. G. M. You have the reduction hypoglycemia very early on. So 74% in the reduction hypoglycemia occurs in the first three days of sensor use, which is telling you this is patient related. The patient made some changes, it's not healthcare related patient made changes to reduce hypoglycemia. So CGM is very effective at reducing hypoglycemia. What about variability here? You've got to be really careful because there are many measures of glycemic variability. Of course, coefficient of variation and study deviation was widely used. Easy to understand, easy to calculate as well. But if you look at the studies we've got endless glycemic variability measures major L B G I grade G D p g C f g b i g F I conger J index, you name it really very large number and just to completely it matters even more. G B has been assessed as long term variability they call that the HBO on see variability, fasting glucose variability, which to be honest with you, I'm not sure I fully understand what that means. S MBG variability, which is okay if you have enough sMB G reading or CGM variability, which to me should be the gold standard because you've got enough data to really look at variability properly. Now, one thing again, just to draw your attention to that the glucose variability and hypoglycemia is a strong relationship between the two and sometimes is difficult to disentangle which is causing, which. So just bear that in mind. Now, having said all that, this is a study that I quite like had no input into it. Perhaps that's why it's so good. This this had more than 300 diabetes patients who had an acute coronary syndrome and glucose variability was calculated as SD from sMB G readings. The floor was good 17 months with major, major adverse cardiac event occurring in over a quarter of patients. And they looked at the relationship between mace and glycemic variability and as you can see people with G. V more than 2.7 right, The odds ratio for maize was more than doubled. And in the bottom you can have you can see the different turtles of G. V. 1st, 2nd 3rd. If you're on the highest turtle, then your risk of mace is tripled. Now when it comes to improving accuracy of HB one C, if you think about it, you have an HBO one C of 7% going to touch on this very briefly here. Your average glucose can be anywhere between 135 275 mg. Now, if we can come up with a personalized a one C That can address these differences, we might be doing much better. So the personalized a one C will be person specific. And actually there is an abstract in this particular meeting that I encourage you to look at that. Look at the relationship between time and range and laboratory a one c. And there's a good relationship is not fantastic, is it? You've got an off square of 9.45 and if you do the personalized A one C. That relationship becomes far stronger and proper burger stall is going to talk about this in a bit more detail and you will see full details of this at the abstract in this particular meeting. So I encourage you to attend it. So to conclude it was he served as well that it has limitations related to inaccuracy and reflecting average glucose in some individuals. Slow assessment of response to therapy and inability to address hypoglycemia and glycemic variability. Therefore, we should use additional CGM derived markets to optimize glucose management in all individuals with diabetes. So this should not be limited to type one and these additional markets of timing range, time below range and glycemic variability. And finally personalized A one C. May be a useful future glycemic marker as it helps to account for inter individual variability in average glucose H B O N. C relationship. Thank you very much for your attention and I'm going to hand over to our next speaker, Professor Richard Bergen's store Published February 17, 2023 Created by Related Presenters Ramzi Ajjan, MD, PhD Professor of Metabolic MedicineConsultant in Diabetes and EndocrinologyUniversity of Leeds and Leeds Teaching Hospitals TrustLeeds, United Kingdom
