My name is Vivian Fonseca. I'm from Tulane University in New Orleans, Louisiana and I'd like to welcome you to this symposium at the American Diabetes Association uh scientific sessions in San Diego. This symposium speaks to moving beyond hemoglobin A one C setting new standards and target destinations for optimizing glycaemic control with continuous glucose monitoring. This CME certified symposium is jointly provided by U University of Massachusetts, Jan Medical School and C AC me resources. Commercial support was uh was obtained by an educational grant from have a diabetes scan. This is an interactive symposium and you will be asked to participate in real world case study based discussions by voting through your phones. I'm really delighted today to have uh outstanding co presenters. Eugene Wright is a consulting associate in the Department of Medicine at Duke University in North Carolina. He's the inaugural chair and ad a primary care of the ad, a primary care interest group. He's the medical director for the Charlotte A hack in Charlotte, North Carolina and Eden Miller is the founder of diabetes and obesity care uh in, in, at Saint Charles Hospital in Bend Oregon. So I'm gonna start off by how we can apply some of the new glycemic, uh, metrics, uh, and use them in a, in clinical practice. I wanna start off by talking about a couple of patients. The first is a 63 year old man with type two diabetes for 11 years and he's been on insulin for three years. He has common comorbidities, coronary artery disease, hypothyroidism. Uh, he's still taking hemologic, uh, mix 25 42 units in the morning, 34 units in the evening. He also takes uh uh Metformin twice a day and a GRB one receptor ago. He didn't bring his meter, he didn't bring his log. Uh He says his glucose varies a lot from normal up to about 200 with very rare readings uh in the hypoglycemic rich maybe once a month or so. And his hemoglobin A one C was 7.1%. Now, many people would say that's pretty good and very acceptable, but he then tells you that he gets a little sweaty. Uh Sometimes he thought this may be due to his thyroid medication. Uh Sometimes he forgets them on one day, it takes two or three another day. Uh But it really is not clearly linked with that. And so, uh because of that and to make sure that he's doing all right, I suggested he do continuous glucose monitoring. Initially, we did professional CGM and I subsequently recommended that he use continuous glucose monitoring because I uh uh you know, if somebody taking insulin, having symptoms really should be on this. And here is his continuous glucose uh monitoring uh report uh incidentally he was using a a European uh system. So this has got uh uh millimoles per liter. But you can easily translate that into milligrams or with the conversion factors. And what you can see is that his time and range in the target range that we like to see, which is 80 mg to 100 and 80 mg per deciliter is only about 59%. And ideally, I would like to see that over 70 may be much higher than that. And occasionally, he's getting low. Uh not very often but but occasionally, very low and he's getting high fairly often and he uh and very high occasionally. And you can see that the peaks are occurring mainly after lunch, but sometimes very high after dinner. And he tends to decline during the night. And on some nights, he's getting into the hypoglycaemic range. Sometimes he's in the hypoglycaemic range even in the daytime. So, you know, he obviously needs some changes in his treatment and we will discuss that uh further later on. Uh let me talk about another uh patient, a 59 year old man with a known diagnosis of type two diabetes. Uh He has been admitted with a myocardial infarction his previous m I was four years ago. Uh He says he's generally well, but he gets a history of confusion off and on uh his glucose and his A one C are, are fairly good. Uh uh He has not recorded any hypoglycemia uh uh during any of these confusion episodes. He's taking Glycol twice a day, takes Metformin Cyle. Uh He takes a statin and AAA in A and uh aspirin and here his is his continuous glucose monitoring. Uh This could be done professionally. It could be done by him since he's, you're suspecting hypoglycaemia, he could have it on a regular basis or you could have it. Uh uh And at this meeting, you will hear uh um more presentations about use of CGM in hospital. But this is this particular patient's uh continuous glucose monitoring and it shows a fair degree of low blood sugars. And uh it really is quite worrisome. Is this the reason for his getting confusion off and on? Uh perhaps he, the confusion uh does not lend itself to him doing uh a fingerstick blood glucose. And we miss this kind of information. If you look at his A one C, it's very good and we rely on a one C a lot uh for uh overall measure of glycemia. Why do we do that? Well, there's good long term data that it predicts complications. We know that people with high A ONE C have greater degree of complications and bringing the A one C down has been shown in multiple trials to improve outcomes. It's easier to understand and explain this to people. You say that this uh uh as compared to a fingerstick, which is a snapshot, this gives us a whole picture over a three month period and the clear targets have been set most of the time we are familiar with those targets. Patients are familiar with the targets uh uh through a variety of educational programs and advertising, et cetera. So we use it for glycaemic man measurement, uh a and management. And also, uh, it's approved for the diagnosis of diabetes. However, it has limitations which we will discuss. Um, but it has a number of weaknesses. There's several factors that affect accuracy that we will discuss. Uh, we, it sometimes leads to delay in therapy escalation because it takes time to change. And, uh, you know, today, uh, we have a lot of medications that we start and we don't, uh, we carry on for 3 to 6 months before we see a change or lack of change in A one C and maybe we should have done it earlier and it doesn't address the but daily activity it's, and their impact on blood glucose hypoglycemia following exercise, for example, would not be picked up. In fact, hypoglycemia is never picked up. And glycaemic variability, which actually when patients see, they really get quite upset about it, they know, uh then what raises their glucose and what lowers it. And that uh can, can vary quite a lot in an individual. Several years ago, the American Diabetes Association did a study and they came up with the concept of using the A one C to explain glucose with an estimated average glucose. This was a relatively small study and there were a lot of inaccuracies there. Although the ad a pushed this concept for a while. They, they, it after a while it's not fell out of favor. However, I think the overall concept of time and range and that its relationship uh to a one C what's been called glucose management index is coming back. Uh It's still not perfect because remember a one C tells you what's happening over three months. Your ef continuous glucose monitoring reading is over a, a 10 day to two week period and that, that they cannot be perfectly uh correlated with each other. There are other factors, I'll only touch on some of them. One is the lifespan of the R BC because glycated occurs uh as the red cells are forming. And if you have short lifespan of R BC, you might get a falsely low. Uh A A one C and, and you undertreat your patients long R BC lifespan is less well recognized uh and may lead to uh lead to overtreatment. Uh And this, if you look at the relationship of A R BC lifespan with uh A one C adjustments that are needed. Uh It's a very linear relationship. However, I think there are other, perhaps more important factors. Most people's R BC lifespan is relatively stable, but there are other factors that affect it. Uh Certainly recent hemorrhage pregnancy, high altitude, uh use of erythropoetin can make a difference. Uh hemolysis for any reason. And sometimes hemoglobinopathy that run in families uh lead to low A one C uh in relation to glucose. You can also get falsely high A one CS when you have anemias uh against certain other types of hemoglobin properties, et cetera. And I've been very interested in this uh uh uh concept of hemoglobin glycated. And I'll come to that in a moment. But let me illustrate that with a case. A 45 year old lady uh goes for routine uh checkup with the doctor and the A one C is 6.6%. The doctor wonders whether she has diabetes, but the fast thing glucose is 97. So, uh you know, this is a common clinical scenario. Uh the relationship in general in populations, it is good but in individuals, it may not be. And perhaps this is an indication for a glucose tolerance test. And she did that and on that particular day, her fasting was 94 and a two hour glucose is 1 28. She doesn't have diabetes. Uh just by chance, the doctor decided to do a continuous glucose monitoring and you see that the glucose is almost perfect all the time. Uh They, they clearly this fits with the G TT which is cumbersome to do and we don't do, by the way, I'm not recommending that we routinely use uh uh uh uh CGM to diagnose diabetes. It's currently not uh uh an approved indication, but I I thought this graph, you might be interested in this particular graph and uh we look for an explanation for it and you find that she's a bit anemic, a ferritin is low. So she's obviously got iron deficiency. So she was treated with Ferris sulfate. And that A one C which was falsely high at 6.6 came down to 5.7. So clearly A one C while being very good in many ways is not perfect. Uh As I pointed out, you get delays in escalation, uh oo of therapies and there's another factor. If you have an A one C that's high for a given level of glucose, it might indicate that you're glycated proteins at a faster rate. And if it's on the other hand, low, you're glycated at a lower rate. We have been very interested in this. We call it hemoglobin glycated index and it actually predicts outcomes very well. It did that in the DC CT. Here's data from the court trial that we published with some support from NIH a few years ago. And it showed that people whose A one C was the highest in relation to glucose so-called high ay uh eye people high glycated index who are glycated, their proteins more, had more myocardial infarction, uh, more mace, they had a higher mortality. And interestingly, they had much more hypoglycemia. And the reason for that was we were focused on a target. A one c irrespective of the glucose. So, if you had a falsely high A one C, you'd increase the dose of insulin in the trial and the patient would get hypoglycemia and it's something we want to want to avoid. Let's look at another case. A 67 year old gentleman with type two diabetes. Recent M I is second in five years. Uh, he's on Metformin and glime. Uh, he's a little obese. A one C is very high at the 11.3. He does uh glucose measurements. Occasionally they're all above uh 1 80 but he says he doesn't want to take a higher dose of medication. He gets lightheadedness, he gets sweating before meals clinically. We suspect that he's getting hypoglycemia uh before escalating therapy. And certainly you may want to think twice about insulin in such, in such a patient. And so as he, uh AC GM was done, uh in this particular patient, if he relied on a one C alone, we may, may not uh have no, uh you know, be able to pick up any hypoglycemia he's been having. However, in this particular case, there's no hypoglycemia. This patient is high all the time. He may be getting lightheaded for some other reasons. And you see how high he is and you might be able to persuade him now that he really needs uh some treatment, he perhaps needs a better diet, but he needs additional medication to bring down both his fasting and postprandial hypoglycemia. What about the concept of glycaemic variability and its relationship to hypoglycemia? There are a number of studies showing that hypoglycemia is associated with cardiovascular events. This is data from the leader trial showing that if you had recent hypoglycemia, you had more events, the risk of events was higher. This was true in the court trial as well. And uh the risk of mortality is also increased. In fact, hypoglycemia to me is a very good uh predictive marker of adverse outcomes. And uh it identifies the people who are likely uh to, to have problems. And uh the many of these deaths do not occur during hypoglycaemia just identifies a patient uh who is at risk. And uh this is, has been seen in multiple, multiple studies uh in, in the US and in Europe and uh people who, who get less hypoglycemia do better. In fact, here is uh a, a compilation of, of data showing mortality is higher. Uh in patient is high in patients who have severe hypoglycemia. In fact, it's high in people who, it's almost the same as people who had a prior M I on one year follow up. So it's like, uh you, it's like a cardiovascular risk equivalent. And if you look compare, uh, people with low hypoglycemia with high, uh, uh, uh, high, high, uh, rates of hypoglycaemia. Mortality is much higher in those who, who, who have, uh, that, uh, uh, uh, hypoglycemia despite interventions to correct it. Let's talk about another case. Yasmin is 69 year old lady with type two diabetes for 19 years. Been on insulin for six years. Takes glargine 60 units a day as part, uh, with males, Metformin A as well as some other, uh, usual, uh, diabetes related and comorbid, uh, related medications. Unfortunately, she's unable to tolerate, uh, some of the newer medications that she probably needs, uh, to manage her diabetes better. But she feels great. She has occasional headaches and she feels that this is due to stress. But A one C is very good at 6.5% and she shows you her glucose log, uh, which is, uh, looks very good. However, when you do, uh, a continuous glucose monitoring, you find that she's going hypoglycemia, uh, uh, hypoglycemic at various times, particularly during the night. And she doesn't complain about it at all. She probably has some degree of hypoglycemia unawareness. And this is probably one of the greatest strengths of, uh, uh, continuous glucose monitoring that we came to recognize very, very early that, uh, a we missed a lot of hypoglycemia, particularly in insulin treated patients. But even in, in others, uh, uh, when, when we do only, uh, uh, uh, fingerstick glucose monitoring and uh somebody like this on MD, I really, today should be on CGM. Uh It's very obvious why she's getting these morning, morning headaches. And if we eliminate the hypoglycemia, things might get better. And there's a lot of data. Now, I, I won't go into the details of it that on starting CGM, people get less hypoglycemia. Uh right from the first day of using a sensor, uh uh and uh not just minor hypoglycaemia, but also severe hypoglycemia. In fact, 74% of the reduction is observed in the first two days because people get an alarm and they in they intervene immediately to treat it as the glucose uh is going low. Now, there's a lot of talk of glycaemic variability and one of the problems is that what we don't quite know how to define it, there are multiple measures, major coefficient of variation and values. Uh II I actually find this very, very uh difficult to uh reconcile as to which is the best measure. No one has really come up with a good measure that is linked with outcomes. Whatever it is, you can see variability, some of which may relate to uh emotional or lifestyle factors. There's variability in a one c in fasting glucose uh in postal glucose and so on. Uh The much of the of the variability relates to hypoglycemia and treating it or overtreating it so that there's a big difference between high and a low but even within the normal range, you get some glycaemic variability. However, uh the adverse event effects of that has really not been well quantified. We need more studies to uh demonstrate that even within the normal range fluctuation in glucose is, is bad for you. It would be that as it may, we have metrics of, of variability. It's uh available to you in your CGM report and, and, and you can discuss it with your patient. So A one C is served as well, but it has limitations related to inaccuracies uh uh in different some individuals, it's very slow to change. It doesn't address hypoglycemia variability, uh uh some of which may be related to adverse outcomes. And there are other metrics and you'll hear more about them from the, from my colleagues about time in range, time below range, which is real, essentially hypoglycemia and variability and how we can address them. I think CGM offers an opportunity to personalize a one C uh as a glycemic marker and uh allow us to better control our patients. And I'm, I'm very pleased to now have uh gene, right? Tell us a little bit more about how he uses this in, in clinical practice to improve the care of his patients.