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Endocrinology - Type 2 diabetes update - tips and pitfalls

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Summary

This on-demand teaching session will cover the progression of type 2 diabetes, the evidence that supports treatment, the UKPDS study, the legacy effect of glycemic control, and clinical inertia and how it can be avoided. Medical professionals will be presented with informative insights and gain messages to use in exams and clinical assessments. They will learn how a proactive approach to treating Type 2 diabetes can lead to fewer hypoglycemia cases and fewer microvascular complications and save lives. This session will also discuss the importance of controlling cholesterol and BP in patients with diabetes.

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Learning objectives

Learning Objectives:

  1. Identify the risk factors and biological changes of Type 2 Diabetes
  2. Explain how effective glycemic control can reduce risk of microvascular and macrovascular complications
  3. Outline the Legacy effect of effective glycemic control
  4. Describe the clinical importance and implications of HbA1c
  5. Understand the need for aggressive interventions early in the course of Type 2 Diabetes to reduce risk of complications and mortality.
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The following transcript was generated automatically from the content and has not been checked or corrected manually.

I do a bit of an over bending and being recorded. I have time to diabetes. So changed. So what I'll do is I'll. I'll go through it relatively fast, become a bit of pathaphysiology and some evidence for treatment, know just kind of agents, but actually timing for treatment. And I'm going to giving you a few messages in the ship tapes that you can use both in your exams but also in your kind of clinical assessments and placed on the European calling practice. We'll talk a bit about HPV one C, which is the goal standard tool in assessing placing control. And we're going to talk a bit about drugs, which and a lot of the questions that you had last time related to. And then if you have time, we can do some clinical case. These passions. If no, they hurt section on those so change like please. So the fact the first thing that I want to kind of reiterate with you is that time two is actually a progressive disease on, but it is a progressive disease. You know much of what we do so us, most of you will know in touch people have got a degree of injury and resistance. But what happens with time? People start losing the function of the beta cells so they actually start losing their ability to produce adequate insulin to control Blucas levels. And we have studies now that tell us that even in people that are normal glycemia and will stay normal life stomach, it will never develop diabetes in life, even in those glucose levels at tend to go up with time. And, of course, one of the one or two of the main reasons for that is that as we grow older with, um to, uh, gain weight, so that's a natural progress in life. And also we have four more more changes. So women go from a very estrogen estrogen, a rich condition premenopausal, menstruating into menopause. So it's estrogen poor, and the saucer levels in men tend to go down with time. So that's the kind of confusion, logical reasons why chains like now, I think is a is a very important message. The UKPDS is a is a study of quite a few 1000 people dating back in the 19 nineties, and it has given us the loss of the evidence that we currently still practice and still very very condoms. What this light shows is that in the different groups off people that were underlies the different types of treatment. So we have people that were being treated for type two diabetes with diet on and and exercise alone. So no medication have people taking sulfonylureas. We have people taking that forming, and we have people taking the insulin therapy regardless off what we do. And, um, I've, um, to on how intensively we treated them. So the intensity arm of the study, which was randomized, wants to treat to any. It will still be low 7.5%. And regardless, whether belonged, they all progressively lost a degree off better self unction and progressively with time over the years of the study, the 10 10 years of the study they're HBA one C, uh, escalated, and you can almost see a part of it is a big part of little to each other amongst the different treatments. And this gives us that the chemical translation of what I said in the perfectly slides change slide now and the other thing to bear in mind that very frequently and and depending really where people lives. For example, in the UK, once you hear the age of 40 and sometimes now area you get invited to have a routine blood test to see whether you have diabetes with develop diabetes, they are you on and, uh, symptomatically, but in other countries that that is not the case. So still for a big part of the world where people develop time to their business by the time somebody presents and says, I need you have symptoms and I needed to check what is going on and they get a diagnose, effective diabetes. They've lost the function of about 50% of the beta cells. So they went they actually present. They are under producing already to a level insulin. And I'm not saying here that about about going is a reversible. I'm just saying that the disease has already progressed. Change slide. Now the thing. Another study that you may have come across a during your your previous lectures and your your readings. But you will definitely come across it a lot in your clinical practice is that this isn't a so this 30 days back in the early 19 nineties is actually a study that took glycemia and a risk of complications and people with type one diabetes. So people treated with interferon for specifically for type one diabetes, and he gave us a very important message again. That's completely translated into what we do for a conference off patients with Type two diabetes. And it has told us that the higher your HB a one c the higher risk off microvascular complications if we bring the HBA one c done with decrease your risk of microvascular complications. So I disease, kidney disease and nerve damage in Europe. Uh, next comes the you JPs UKPDS. As we said, it's a randomized control start e in type two diabetes, now whereby we've treated with random list of some 4000 people into being treated it intensively with a target age where one C off under 7.5% and the less intensive group where people hard in HB a one C of 7.9% or above. And what the studies told us is that by decreasing people's HBA one C or controlling your other people's HBA one c what street Lee, we protect them for both from microvascular complications, but also for microvascular disease or heart attacks and strokes. And very interesting me. When somebody presents with an HB a one c o Vexo. Why, when everyone's on 1% at that point, you decrease the risk of developing I kidney and nerve damage by 37%. You decrease the chance of dying by 20%. And that's so just just a simple example. 8% age he was 7%. That's about 10 million, most from also, this is a new unit. So you go from, um, you go from 70 Family, Most promoter, 60 female, most remote. Uh, you didn't this they're all cause mortality by 14%. And you did, with the risk off having either fatal or non fatal heart attack by only 15%. So it is really worth paying attention to HBA one c next slide. There's another thing that has it's actually we've known about it, probably since I was a police. The junior doctor, I would say, which was a bit of time ago. But it is something that has impacted on our practice, I would say probably the last 15 years in clinical medicine and There's something. There's something we call the legacy effect off area glycemia control. Um, again, what? What? We did, uh, were saying the UKPDS. We took a group of people who said age We want to very tightly controlled HB one c not too tightly controlled. And we did that for a period of 10 years. And that is what gave us a data on on HB A one C in relation to microvascular and microvascular complications Risk. What we did after that is we left those people to go out in the community, back to the GP surgeries. They're specialists, the local hospitals. They went back to normal life essentially outside the limits of this time. And And what? What we did is we group of people another 10 years later and we looked at where they way with the guards to like cynical in troll and where they were in crimes off complications. And what we found is that the HBA one C of one group in the other group 10 years after the study ended was very, very, very similar. So you realize if you realise circumstances but the risk of complications and actually it was the instance, and prevalence of complication in the groups was still much lower in the group of people that had initially been treated intensively with an HBA one C that was very tightly controlled and blood hence the term legacy effects. So it's almost a safe. The body remembers at cellular level how it has been treated in terms of sugar control at the very beginning, off the diagnosis and those first years of diagnosis tell us and large and counter large. So that brings us to the next light. Where was what I'm showing you on the on the left. Inside there on the bill and red blood red graph is what we tend to do. Generally speaking of a skin issue is this is what people are used to doing. Somebody presents with diabetes. We give them an initial treatment, let them go away. Then they come back. A few years later, they gained a bit of weights. Lifestyle has changed. Order has no it intensified in the beginning and then kind of going off the bed and then you see a trip. It has gone up. You give them something else. HBA one c improves. Then you let them know, go for another few years. And exactly what happened with UKPDS happens, you let people go back to normality, normal kind of community to normal life. And they kind of lose good habits. They lose the music at the back, um, intensification, and we tend to intervene time points where people have truly gone off. We don't tend to intervene when the H one C is a bit on the rise. We always give people that benefit of the doubt away to a bit of exercise. That was a bit of ways. Cook a bit more at home, avoid alcohol, avoid carbohydrates and come back. And every time they come back, actually, to come back a bit worse off and eventually way make the interventions. What I've shown you in the previous slice, uh, concerns us us as a big argument for us to intervene. They really alien practice is on a limb proactive approach can prevent people from the becoming hypoglycemic over a long period of time and, uh, and can present in every present are also least cramping mark of aspirin and microvascular complications later in life. So we have to give up on this kind of, uh, what we call clinical inertia. Don't be afraid to propose drug treatments aggressively in earlier, and that leads us to the next slides. Where I hope, uh, given the color of the first message off what I wanted to put a cross, which is that we need to advocate fairly an aggressive treatment in time to diabetes because we're going to save people's people's lives. We're going to look a quality of life at free of complications. Forest Longest possible Next life, please. Now people with diabetes Obviously we the major thing that we tend to talk about in constraint on his his age, be a one C's a black see me, and on occasion, people tend to forget cholesterol and BP people, people that are not very good and not forgetting attacks. Actually, medical students, because you get asked about this so much in your exams about kind of kind of vascular risk factors. That's always part of the history that you take in the history that you give your condition called Lidex. So cholesterol and BP, um, our come actually we can argue that they're actually even more important than glycemia controlling people with diabetes. As we said by decreasing, some is actually want to buy 1%. You decrease the chances of having cardiovascular death by about 20%. So here you can see that if you treat 119 people to decrease of atrial one C 5.9% you will actually save one life. And that is also an inconsiderate inconsiderable a number. Now, if you drop somebody's cholesterol by one minimal, minimal pre later. And so if you take 44 people and you drop the cholesterol by one minimum later, you will actually save one life from a cardiovascular death. And if you drop the BP off 34 people by 10/5 millimeters of mercury, so you go from 150 over 9240 over 85 you will save another life. So these are risk factors that we really need to pay attention to change my please again. I've got coming back to the UKPDS for anyone who's interested in diabetes, read Um UKPDS and your diabetes will be part of your clinical life if you choose a career in diabetes and endocrinology, the UK periods told us exactly that way. If we lower people's look that systolic BP in the context of that base by 10 millimeters of mercury, we decrease the risk of having a heart attack by mouth. We did is the risk of developing heart failure by 15% with decrease the risk of having a stroke by almost 20%. And we decrease their risk off dying off anything related to diabetes by 17%. So BP major importance change slight. Interestingly, we're not doing as well in the clinical world when it comes down to, uh, cholesterol and BP control. It would even HBA one C. So about a third of our patients with Type two diabetes, at least in the UK, do not reach the target of HPI. Once feels, UH, 7.57 point 5% around about I don't do it. It's probably after about 15% now. This is a bit slightly older slide achieve goals that are community so a multi factorial BP cholesterol and HBA one C and the upper up to half of our patients that take at medications for all three aspects of care, and they still failed to meet the target so they're under treated. You have to bear in mind that, uh, people's weight is going up and it's going up at a population level. So the national average national wasting for this country was about 3.7 kg. So that's population level, and that's average. So you can imagine what the standard deviation would be. And the prevalence of obesity is increasing and probably I see here, um, about over 45% are obese. That probably has also gone up since I have used the slide previously. A Z. Many as 80% of our people with time to Debbie's have got hypertension. 40% of them actually failed to reach the mild attire 140 over 80. So that's in the absence of my classes are complications, and about 60% of the patients also got high bility demon. So important response is to look for and to treat for, so you have to diagnose them, will have to treat the change slide, please. So the second message is exactly that BP controlling diabetes, lipid control in diabetes uh, next light. So this this, um, this backs another question. He's glucose control only about every one C. So he is able to the only thing that we need to, uh, look at and it is a message that have just given to you that the lower the HBA one c the better is that are treated fox or not. So I'm going to leave that there is a question and we'll try and answer that, Uh, in the next line. I just want you to see to look at this is a very practical point, er, to get you thinking under certain circumstances. So what that shows is that, um if people who may present with an HB a one C that is exactly identical, but they may have very different license growth files in type two diabetes. Specifically, we have very good data, uh, at the cellular level. Now, actually, we haven't say 11 vitro and we will start ease. But we know that at 7 11 or body does not like life, Simic variability. So the picture that you see on your fire right on the slides where HBA one c 7% but you have the line of glucose control within the range of relative normal. It's normal glucose levels or acceptable good glucose levels. That is what our body likes. When we walked to the left, where our sugar level goes up and down from low blood glucose level too high blood glucose, never something that the cells, in addition, do know like they start becoming inflamed. They start becoming tired, they start becoming ill. So you may have an individual that falls on the left and that individual that falls on the right. They both have an HBA one c of 7% but the right one is free of complications. And the left one is the read a lot with him. So you always need to think is my patient at risk of having like Simic variability and many, many Alaska? I'll ask you guys, if you want to put some hands up, when would you be worry about twice a week variability? Where would you worry that a patient of yours may have any frequency that's not cruelly a representative off off their overall glycemia control? Can you think of any cases any circumstances? Return yourself you're doing on so you can just drop it in the chart box below. Yeah, I can read the, uh uh, books is Well, so I got to send him to Yes. Yeah, I can see a doctor that says a West Wing symptoms of your patient. Your patient presents that may be may be having asthmatic symptoms and they have an injury. One since then. Percent, that doesn't fit. But why would that be, though? What? I want you to think about it. Why would somebody have guy Simic variability? What treatment? Maybe if they are on, like, high high pressure medication. Pretension medication, have it. How would hypertension medication interfere with this? Do you think Don't Actually I got to go. You've ever done has said inappropriate, interesting regimen. So actually in itself has its moments can precipitate a profile that looks a bit worn, like the kind available profile on the left rather than the nice Professor. If you have somebody presenting newly and early given the metformin and the have in HB a one c of 77% you can trust that the sugar levels are going to be based able, but somebody who is on on insulin might be having a lot of hypoglycemia in and a lot of hypoglycemia as a result, or a lot of hypoglycemia, that ball losing a lot of insulin, causing hypoglycemia So they go up in time like you or and generally speaking, drugs that are what we called injuring secretagogue cause more insulin production or cause more interesting to circulate countries carving the type of variability. For example, so far, your areas and they may be like a close eye. So whenever your patient is at a risk of having hypoglycemia, they would be at risk of having a bit more variability. And it's very much worth thinking about now over the next life. So the next the next practical point, er, which is that about of food thinking about something, you know, this kind of up and down, which we can meet again by the way we could mitigated, for example, with technology, we now have excrement. Liberate technology, continues glucose monitoring technology. Uh huh. It's people controls the self morning toward. This is something that we use very much in pregnancy, self monitoring, off locus levels in the business and much better understanding off what lose control. It's light and makes the HBA one C. We're not accurate. This takes it about out of the equation. The second point they're here I want to make is that atrial? Once you might actually be misleading in certain circumstances. So in in conditions that is a condition that you know. Second stance is when you have your pregnant. If you're on the making, you have a human blow on the senior. For example, if for whatever you have an increased chance Ultram over, you got plenty disease. Which, of course, is mycological condition. If you are a patient that has chronic renal, stay or or even end stage renal failure, Diane's their own deficiency. Or, if you have liver failure, liver cirrhosis. Uh, whether that is from the alcohol excess or any other reason. 80. Once it becomes very be seating and why? Because under those circumstances they're other proteins that also get glycated, and it's no, just the hemoglobin. The hemoglobin was very immensely so if you have anemia and your hemoglobin is 80 your HBA one c underestimates. There's less off it around in order to get like ages and give you the results so you can basically underestimate the control off these patients. We can monitor other other albumin's and you know globulin. Sometimes we use for those, um, but also continues glucose monitoring in those circumstances, maybe a value this again to think about it when you're looking. Um, but your patients that I seem to control changes like, please, um now was where the the other thing that I wanted you to kind of realize the bed is that we clearly have a very, very, very good evidence for hb one C control and decrease off. Um, I seem to control the better your glycemia control. We tell people, the less likely you are to develop complications and half Myklebust, you don't cardiovascular disease. What we now also know, though, and this is only one of a few started. So this is a primary care study off 30,000 and so individuals. We have other studies, especially in people over the age of 50. A thousands and thousands of participants that tell us that these, um that is a really strange relationship between pretty much around comes in glucose control. So if you see, you can see gonna be a u shape in in these graphs. And what that tells us is that as your HBA one C increases clearly you're you're risk or off dying. Um, dying overall in your risk of suffering, kind of, uh, slow death increases. But when you come down to the HPI one c towards your left, uh, as you drop down 81 c to well below 77 6.5% and the bit further down, that tells us that your risk starts to increase again. So the changes lives. The same thing also applies to people that have chronic kidney disease, especially people that have CKD stage four and five or are dialysis. When your injury one c drops below 6% and believe you don't know, we see that a lot in patients that are on dialysis. Frequently, people on dialysis end up end up even coming off the majority of the medications by the time they well establishing in dialysis and when your your your age. But once it drops below 6% then your risk of death increases just like getting places when you're angry, one C is high. Um, if you change the slides, we have even more recent evidence that I have been It's been this evidence that have been more more relevant to what's been going on the last couple of years that it comes from from the UK group, probably still on some diabetes, Probably. I think it's about seven months into the corporate pandemic in the UK, and I've circled the bit that you're interested in is that the the five sacks cycled. It shows exactly in turn for people that were admitted to the hospital with diabetes and go bid. This is admission because of called it into hospital whether HBA one C was hugely strictly controlled the risk of death Waas was much higher and high enough as those that had poorly controlled diabetes. So this liters of the Fed message from the stock so far Next light there is what we call a year shaped relationship between HB a one c in mortality to yes, we want to control it Be one scene, but out to a point. And after that point, we need to be exceptionally curved. Careful on how we monitor peoples medications and how we support thumb. Um change slide, please. Now we've talked quite a bit about essentially when we talk about James of slide along, please, When we talk about HPV one C Essentially, we're talking about, uh, lessening control, um, hyperglycemia. And there's the other side of the coin, which is high blood glycemia. And this, instead of this is a study in people. It's called a Gleason Aging study. They very interestingly, it's It's includes people over the age off 50 so it's not that much aging, but it goes up to above 80 and it works. There were a few aspects in the study, but essentially we ask people to tell us about whether they have they. They suffered with hypoglycemia, and actually more than one in 10 people told us to have hypoglycemia if they were taking insurance and no, no, not known injuring agents after 20% of them said yes, I suffered with hypoglycemia and and regardless off where patients where in terms of the glycemia control it to be one c wise Uh huh. Listening, gentle people call heart severe hypoglycemia, particularly in ensuring, even if overall control was very good, for even if control was very, very, very poor. And the how how old people wear how long the heart diabetes or what treatment they took, or I'll have a glass in the Cajuns noninsulin injectables or insulins that did not affect other the relationship with HBA one c. But what you can see here circled is that the rescope severe, high off hypoglycemic severe hypoglycemia was actually much more likely tok in those that were either, um, control to a near normal glucose level. So just below the diabetes kind of capsules or those that hot, very poor glycemia control. Overall, that's a very interesting thing to see. But I also have a dressing thing to bear in mind when we're treating patients next light. Now, why do we care about hypoglycemia? We care about hypoglycemia in our patients. Will was asked about it because it causes a lot off processes against sending her level. It causes in on inflammatory process. It causes a simple for renal response. It effects and in pairs and the feel of function in blood vessels, and it also can cause abnormalities and blood's blood clotting. And if you change the slide, what we see US conditions now not on a central number exclamations Well, you can see in people that have either recurrent hypoglycemia or severe hypoglycemia or hypoglycemia where symptoms very evident. You've had so much of a little bit of time that they don't get the symptoms over. You start seeing a cardiac electrical cardiogram is easy. GI changes, and the risk is the risk of people dying in the hospital because of severe hypoglycemia and know. Inconsiderate. That is one hospital with obsessive about preventing hypoglycemia. Hypoglycemia. Husband's One of the heart is that with named here in the UK that we tried to bottle again. So you got your cardiovascular and physiology can change for the worse. When you have a blessing, it change a slightly so hypoglycemia. This is 1/4 message. Hypoglycemia can cause morbidity and mortality to our patients. Something to bear in mind. Now if you change the slides, how do we treat? This was a question. I think quite a few of your colleagues us last time when we were doing the previous session. There are a lot of ways of treating heart of listening. We know that that the major organs involved in time to diabetes or the muscle reliever and are better cells is what we call kind of that that they're trying virus A sweet call you, but far cells Articles, article cites play a part there is increased, like polices and touch the diabetes. They just read the spinal tract. Place of parts were talking about incretins syncretic deficiency resistance. Entire Bt's we care about the pancreatic out for cells haven't produced glucagon. We care about the kidneys because glucose reabsorption happens in the kidneys and we care about the brain hard to diabetes. Because, um, there's newer transmitters from, uh from into the brain that essentially gives us that that sense of supply itty when we eat. So these are all potential sides where we can tackle the disease. It's not just the muscle, the liver and the better cells, which is what we've traditionally known for years and years. And in the next line, you'll see that up to is seven, which is actually when I entered University. That was my first year of university. These were our drop choices floor for the treatment of time to diabetes. And if you fast forward to the next life to 2000 and 19, these are the ages rehung on. These are all the combination tension combination, so massive boom in what we've known about talk to that isn't how to intervene and obviously always as you're seeing the next light. There's all these kind of the guidance that's coming out of Nice or, uh, the American Diabetes Association, with all the flow charts that you're very welcome to look up that tell us you know what comes first. We'll come second, really look closely into those, and I'm not sure whether you can see them very closely. But if you were to start it, he's closely. You will find out that the amount of the way that we have to treat people, that entire two diabetes is immense, and the sequence of drugs and the combination of drugs that we can use can be completely different in 10 people presented at the same time the same numbers that have different profiles, lot of a lot of leeway to essentially do watch a message. Five. The provider Patients with work Michael personalized. Yet that's when we are currently time to diabetes. If you change the slide Ellum, um, and change one more slide there. So how do we best personal lives treatment in people with time to diabetes? Well, we have all this massive, massive diabetes knowledge, and we combined them with all the new evidence that's coming out at a huge speeds, and we take into consideration on patients profiles, the patient's profile, their gender there be in mind the waist circumference. They're ethnicity. A pre existence of cardiovascular disease or not, family history, a cardiologist, restful actors, levels of activity. This this huge amount of factors around the patient we can take into consideration. Now, in this case, it's like, Please, my next message is actually what we do first in in type two diabetes. And I have I call this, um, see no line treatments. So even in the older days, he would go to your J bigger diagnosed. With that you you would be sent away with their diet sheet and, um and you know, activity sheet. We will do that, by the way. We would people through programs to reverse their diabetes, and that is always a little calorie restriction or carbohydrate restriction and activity. But when when you start considering treatment for somebody that has to be a really owners, we said before metformin, he is the first line treatment, unless contraindicated, it's the all this drug with having diabetes. Metformin is a mention sensitizer. It tells your tissues like muscle and liver and adipose tissue to open up the gates. A PSA response to ensuring that the pancreas is producing to let Lucas in. And that's how it lowers glucose levels, and it should it it is the all this treatment with the most evidence behind it now in the next lives off course. When we think about first line treatment and second line treatment, we need to start filtering for different things. For example, you want to you want to think about contraindications. So what type of diabetes special patient have? For example, does your patient have that one diabetes truly ordered, Like to have the destroyer? Is there a chance to Miami Type one? Is it time free diabetes that may come from destruction of pancreatic cells? And is it a woman that has just patient with diabetes that gets in pregnancy in pregnancy? We don't use anything else, are common forming an insurance, so it's easy for us to use other oral hypoglycemic agents. Doesn't nation have morning maturity onset diabetes of the young? But it looks like somebody school type two diabetes, a patient actually respond really well to lifelong sulfonylurea. So that's something to consider. You want to consider your patient's kidney function for example, even metformin. If your Egypt five below 30 that's a contraindications. But this contraindications kidney functions kidney function for other medication. Does your patient have heart failure? So, for example, in heart failure wouldn't consider giving somebody cletus those. Are you having any side effects from existing medications? War is the age being one C. They have any cardiovascular risk. Is a patient on elderly woman who lives by herself? Uh, who is at risk of having hypoglycemia and fall and break her hip? So from various is not a good a good decision for that. If you change the slide, well, I've got and I want I want to speak to that too much. But I don't know. I don't know whether you can tell, um, maybe chilly trying to copy Paste this in the chart books for people on. I need to send me one little try and do that's related, or only if we reach clinical case is otherwise, I'll send you. I'll send you this to have to use when we're talking about clinical case later on. But you can see here that according to your patient profile of the indications contraindications, you can easily decide what you should or should not go for next. Now, if you change the slides, just a couple of highlights that are important to know in terms of the drug drug groups. So performing very good evidence with regards to cardiovascular movie pill reduction vanquish evidence with regards to stroke prevention. So for Algeria's they UKPDS told us, the Children hungry is due date, Chris. The risk of cardiovascular complications. So if you if you have somebody who picks the profile, you're thinking about the creasing risk of microvascular complications, you can use that. The delete is, um's been some evidence there for a reduction of cardiovascular. So cardio convert ask you a risk cane slide. GLP agonists. So the injectable drugs, like Leonardo tied and some are blue tide that we're using currently, some evidence there for induction off your vascular end points. Change the slides maybe before inhibitors being neutral that drugs without much cardiovascular endpoint very neutral and the slightly newer kids on the block their scale to two inhibitors strong, strong developing cardiovascular end points and also three million points for microalbuminuria. But also untainted, actually, renal function. And I shelter two inhibitors that are even used in people with heart failure and diabetes, but also in people with heart failure that don't have diabetes. It's a therapeutic option, even in the absence of diabetes. Um, change slide, please. Uh, this is still still indicate that when we treat people who just SGLT two inhibitors, which which easily they are the newer medications essentially a sheltie two inhibitors prevents reabsorption of glucose through the kidney and make people pee out sugar. And they take this glucose level at the same time, make you pee out calories so people can also lose weight. But it has multiple effects because it causes BP reduction. But that happens only in people with black, which is actually high normal people who are normal cancer. As I said, he page lose weight. You can have a diuretic effect, so people that have heart failure can really well in combination with other medications and obviously on like semi control and is this place chropic effect and we don't know exactly why they work so well. Why the work the way the work? But there's a lot of studies underway. Middle of interest change, slide, please. And actually, if you go to the next slide and, um, just we can pass that one. The final thing with the dust treatments for diabetes is that we're very frequently go through, um, a local of lifestyle and medications base. And we forget about basically surgery business surgeries, a very formal treatment intervention for people that have time to diabetes. Um, obesity and obesity surgery. Actually, when it goes well and it does go very well in hands, especially centers, which is how we deliver that ugly here in the UK Obviously, the surgery decreases cardiovascular mortality for people that are on the goal. The treatment more than any other treatment we have available for time to diabetes. So cardio was looking, and that is an important message to put out there. If you have a 25 year old with a beer mine or 40 that's person's cardiovascular risk, Easy men's and considering obesity surgery that l e. On at the time of the diagnosis and your in the journey comprehension be absolutely the right thing to do for them. And in the next light, uh, the the message about bariatric surgeries. That's 10 years after people have hunt century. There is a multitude of benefits they have. You can see on the top right there how much they they retain, the exact low risk of microvascular complications. And that's 10 years after after surgery. So the metabolic effects and a off, off, off, basically century are can potentially be emancipate. Use our patients, prop you so my neck, my message from all of that the next. That's night is that we we Dent and we want to try and use drugs and interventions that have proven cardiovascular benefits for the right people. So drugs like metformin as GLT to him, just like empagliflozin and comedy flaws in, um GLP Ana looks like likely I blue tide some regular tide. We're getting more and more evidence for it. We use a widely and obviously body out trick century, and, um, in the next light, how about I might I might use this L0 l a would tell me, um, I use this is the last year slides message wise, and we might have to postpone our case is how about all the others? So what? This light shows? Um, it's not historical life expectancy is this is actually life expectancy that you realistically expect if you take account the medical advances. So if you reach the edge off 17 as a woman, you should expect to live for another 18 years. Is the money should expect to live another 16 years or something? Something like that. If you actually reach the age of 90 in the UK um, you should expect the for another five years as a mom was a woman in this country. So this is something to bear in mind if you have somebody reaching on on aged, you know how much longer you expect them to leave. So, like some control becomes important if we bear in mind that that after 50% of people may end up on insulin out of those with types of that the school being mind that they cut off for developing microvascular complications in life is it only takes five years of threat to their babies. For somebody to develop, there was a medications. If you bear that in mind, you look at life expectancy that helps you think about what to do for your patients, that you're older course So next light, the standard to to study has told us that when you have all their adults, obviously again, it's not that old. Here it's 55 minutes or 55 plus minus happen, but it's they're not. You told us that in older adults middle aged bottles If you, um if you manage your cardiovascular risk factors and HBA one c, you know that you're going to decrease microvascular complications so that the message that we've had I already the next life, um, tells us that if we control people's HB a one c an irrespective of duration of diabetes, we're going to decrease their cardiovascular events and mortality. And that's again in older adult. So this is a slightly older age group, 65 74. So those who slice not tell us, but it even all the others we still care about HBA. One C was still care about my semi control of one point in life. The next line tells us that's when it comes to do your A shin diabetes and HBA one c HBA one c becomes completely irrelevant only when your patients functional status is low. So when your patient is becoming frail and they are 80 or they are 19 HB one c is not. Management is not going to impact their outcomes. It might impact the quality of life. You have somebody who is 85 years of age with an HBA one C of 10%. You don't want it to 10% because that individually you're frail and dependent. They will start having, for example, functional incontinence the osmotic they're becoming that will impair the quality of life. If you're incontinent as a a frail adult, you're you're prone to developing urine. I start planning to sepsis and you can die. So you want older their outcomes. So you did. No, No care about bringing HBA one c done aggressive. You care about treating them to an HBA one C that will, ah maintain quality of life In the context of frailty. Extremity is the predicts, or here predictor of death amount Come. And that is what your curve next. The next line tells us when we're treating l. Older individuals always always always assign the frailty scored to them is a failed. The score is high. We need to rethink about how we approach glycemia HBA one C Naturally, with felt goes down because food intake goes down, their argument levels go down. They're not as well nourished. Their cholesterol will go down again. It's It's mostly about activity, low dietary intake, dependence, a chatter, chatter and master laws. Um, they lose, they lose muscle and Mardi prostate issues simultaneously. So that is kind of the reverse metabolism when people become frail. So this message, what this tells us is the message is that older adults come benefit from HBA one C control in the next slide alum. But frailty predicts mortality with HBA one c having very little impact in that context. Um, And I think what I might do is I will probably stop there because with just the rich one of looking, I think Is there another lecture? Ellum? Sorry. I was meeting, you know, So the next session will be our five o'clock doctor. So if you do want to Okay, Do people want to want me to call you about the slice that I've got? I mean, I got a lot of slides, actually. Yes, he can continue. Okay. Lovely. Lovely. Okay, so So, um, we can go. We can go over and let me do a couple of slides down. You'll see Case case 31 and we can make this a bit interactive if you guys want to. So comments, hands, whatever you want. So this is it's it's gonna do about 69 year old mine his heart up to diabetes. Um, you will be for the last 13 years, Uh, when he was aged 53. He actually somebody who doesn't really attend his appointments. So you haven't developed a relationship with him and his age. We will see how it's funny. Lot of range. 83 229 million Most remote 10 to 14% he's being mine is elevated, but he's kissing the overweight range, and he takes Mph engines for humility. Night long acting, long acting, insurance, up bag, bedtime. And he takes short acting, intrigued with his meals, and you don't know how much he's taking that. So he's concordant without is a bit variable. So he's on Baylor basal bolus injections, basically 33 shots with each one each of the meals, with short with each of the meals and nine time insurance. He has already proliferative retinopathy. He's got, um E Jafar of 30. So ckd stage five. And he has neuropathy, but he doesn't have any lesions in his feet. And he also tells you, uh, he actually came to clinic to see he would have story because he has erectile dysfunction. So what I want you to before before we go to the next lines, I want you to tell me a few things that that are important here because you need to decide what you're going to do with him. His own insulin. He's kind of this for a long time. He said my capacity complications. He comes to see it was called Benicar dysfunction. I want you to tell me the things that you're going to try to think about with this guy and think also about war medications, mice. End of being, um, used about it for you on I'm gonna, um You you, um just to start with. Obviously, he's he's got CKD so we can think about metformin in this case. Um, and it started. Looks like he's starting to get some microvascular complications because he's got the retinopathy and he's starting to get the erectile dysfunction. No. Yeah. Yeah. So they very good metformin is probably not one of the drugs that we can use. Very good. Um, he's got microvascular complications. So you want to think about something that will potentially slow down those a basic. He's got an E Jafar of 30 already and what you want to try and prevent years. He's got established disease. But it would be good if we could prevent this guy from losing more kidney function and potentially going on dialysis. They may be a good points anyone else. And when I was getting other foot, feel free to meet yourself. Um, Sierra, I'm going to meet you. Well, his hate to be a one c is quite high. So it seems like he's not going to look at insulin. And because he doesn't know how much he's probably injecting at mealtime and everything is probably having adverse effect on his cells within this point is, Well, yeah, very good. And actually, with those comments that's serious made, you can go to the next lights. L um you made 22 points there, Number one. You made the point of concordance compliance compliance. I think people like like the world concordant bit more. It's been more politically correct for for patients that so you raised nation concordant. So he's, um, insure him. Does he take it as you know, if you could get dozens so we can even think about it, That type of injury he's taking for his supposedly taking four injections a day? You know, there's no point in giving somebody for injections today if they're not going to take them. We make ourselves feel better about you know, the choice of regimen being perhaps the ideal one. But if your vision is not going to take that, you're not really serving them. The second thing that you said is he doesn't know when he's injecting what he's injecting. Absolutely So it is an opportunity to review his knowledge on carbohydrate counting and injecting insurance. Because if you can count carbohydrates and march that with your insulin administration, then you can reach much better than I see me control. So so very, very, very, very good points. And will you go to the X Slide Ellum so specifically now, specifically now on this on this case, um, with me. Okay. Is it easy on this case? What? You what you see here is essentially some very fancy chance that tell us that, um, very in men that have diabetes and established erectile dysfunction, you can feel confident that they probably have either established coronary artery disease or cardiovascular large vessel disease, or that they have a very high risk off developing into a sooner rather than later. So what this tells you here? And actually, I think if you pick again there, if you're other slides that that tell us a bit about, um let me just see. Yeah. So So what? This immediately tells you this guy has presented with erectile dysfunction in immediate tells you that you really you need to be very strict with your targets. You may not achieve them on the targets have to be very strict age. But once you, of course, really ideally needs to be under 7%. We may or may not reach that. Want his not a cholesterol below for in his LDL below two and one. His BP under 1 30/75. So we want to think again. Multi risk factor. Um, and you can click again and probably get us fine. Yeah, and yeah, this is a kind of reiterating that erectile dysfunction in men with type two diabetes is reflective off their small vessel and large large vessels. Now, if you change the slides, yeah, If it changed in slide, we seem to have lost it on my computer. Um, yes. So if your HBA one c is 7% that I think he may still develop, but it is much, much slower to develop that if your HBA one C is 9% if your age we want to fight to 7% you have about 75% less progression after two years compared to somebody with an HBA one C of 9%. So that's a bit a bit of an idea to give you here. So this guy has a proliferative retinopathy. You can still progress progress. From that point onwards, he's not being blind. So you're going by controlling agents, you're going to prevent him from going on dialysis. You're gonna prevent him from having a lier rather than later heart attacks. And you're going to prevent him from going blind from the establish residency opathy eso far can slightly. Um, actually, I haven't spoken. Actually, before we go into the second case, I can you tell me, considering he's, um he's gonna be a bite of 28. He's gonna need your father of 30. And he doesn't like taking his same surely out something. The kind of drugs that we mentioned earlier on. Would you have any thoughts on what you might try without guy from my first case, what would you guys attempt? It's a difficult question, By the way, you need to know a lot about the drugs. But if anyone has any, any ideas, I'm very happy to hear them. The light. So I tell you what I would do. Yeah, I think that would be great, Doctor. Yeah. So? So I would probably go with this guy. I e I think you would probably benefit from an SGLT two inhibitor. I would probably give him some empathy. Flows him his age. Fr is not a contraindications. He's very hypoglycemic, so he will probably start losing some. You need to have a degree of kidney function to lose some some glucose. You won't lose a lot, but he will lose. Some may drop a bit of Wales and his atrial to might come a bit further down, That'll long can give people a bit of motivation to comply with insurance. The other thing is that I would probably change his interesting regimen. I will change his interesting regimen to two injections a day and give him a bit of a breather. Doesn't mean that if he needs baseball's, you can't go back to it. Of course you can't, but he take away the load of the four injections. There is no, because there's a compatible data When you're 15 years into your diagnosis. Doesn't matter when you switch people from one to another regimen. It's the same what I wouldn't give him. And I would love to be able to assist in jail. Panel looks, some argue tied or the lab you tired, which works fantastically. He would drop ways he potentially reverse. Is diabetes because it's contraindicated in people with retinopathy police. It probably is a contraindications to inject injectable jail pee on. Those are just not so let you look. So this is a question in terms of you're going to decrease the insulin regimen, so it's gonna be two injections. Would you actually put the person on the long acting insulin and or would you still keep it to the short acting, you know, So actually, I would take away both times. I will put him on mix in showing so insulin that has probably about 70% of it is long acting and 30% of it is short acting. And I will give it to him twice a day with his breakfast and his dinner. Something like Humulin, um three or something like Humalog mix 50. That's got a 50 50. And what that does is when When you eat. Actually, if you want to come back and talk emotional resonance, I couldn't do that. Azzam, I know what you guys want to hear about. I can prepare something for next time, but it was mixed. Insulin does is it gives you bit of short acting to cover your meals. But then he gives you a bit of long acting as well to last you until the next meal is actually covered quite nicely, right? Well, despite the streets like you've made, so makes insulin neither long nor nor short acting, but a combo. Um now shall we haven't looked at this case, and then we might have to call it a day. Um, so this is a 51 year old guy. He was diagnosed with type two diabetes six months ago on, and at the time he was diagnosed, having presented acutely with acute cholecystitis, his HBA one c was 9.4% or 79 millimeters promote. So that's at the time of presentation with his colon societies. And because she was going into surgery, we gave him in trouble Central. So in, um, intravenous variable rate insurance. And then we switched the multi after his operation toe a mixed type of victory. Humulin n feel we should take twice a day. You take it with breakfast, you take it with dinner. Usually we give it to people that no, no off females a day, relatively similar hours and have it relatively stable, stable lifestyle he's just been diagnosed with. It doesn't have any evidence schools, microvascular disease, feet, eyes and kidneys. Okay, and he's been my eyes. Now 28 when he presented six months ago, she's been my was 34. His age we want C has come down to 6.8% 51 million most remote, and he's taken up exercise. So he exercises regularly. What would thinks? What things that you're going to consider with this going now very different scenario to the previous one. You see him in your clinic? So he's improved since you've lost. Seen him? Yeah. Absolutely. Um were happier with his His HBA one c yes, we're we're very happy with the therapy. Won't see. Are we completely happy with his age? He was saying that if you if you think about about what he's on and his everyone seen We're delighted by the way at this point. But if you think about the combination of his everyone zero what he's on, what is question that you will ask yourself about the treatment and your patient? Would you ask about whether the incident that he's on the regimen is actually effective for this patient? So you may have to change it because the HB a one c is still not within range that we want it to be in. Actually, it is considered for one c not within range. We want it to be Oh, yeah, was 51. I was reading the first one. That's right. Is there? Ah, I mean, this patient seems like They're quite concordant and they're dropping the B M I themselves. Is there a a regimen that's more, you know, that's that's more appropriate for those concordant patients. Their effect. Perfect. So what happened here If you can go to the next line? L um So what's happened here is you have a middle aged man that presented acutely. He probably had hard diabetes for a while, and, you know, he didn't have any symptoms, which happens to a lot of people, So we just we picked Occupy. Abate is probably by coincidence when he presented Unwell and Santic with his cholecystitis. And what happens is when you present with an actually one c that is relatively high. And this is not the highest age, but once you have seen. But it was a bit elevated. He was on insurance. Sometimes it's a bit of the reflex in the hospital. You go from a naive insulin regimen to stop card because, you know, that's kind of what we do, and we let people go home. But also, when you are symptomatic for a while and your cumulate time with diabetes, it it kind of broke or toxic so you can also become a big intrigue and efficient at presentation. So many drugs might not work very well. It's also not unusual to give ensuring in in the beginning off the journey if they present with high hide, really high glucose levels. But now this guy has taken his medications. He's exercising his bm my husband, he's HBA one c has dropped, and now we start. We should start getting warded with that HB one scene, The Diagnostic HB a one C for Type two diabetes diabetes is 48. This guy's only at 51. Is his near it near normal age where one C. So you start to worry about whether he's having hypoglycemia and obviously, what What did we talk about? The first use lies about age here. Once a day. He's his. Is his sugar level. Going like this Hand's giving you a nice age we won't see or she's sugar level going like this, giving you an HBA one C of 6.8%. So here you're interested to look also on his glucose book and and see because his monitoring for stating interesting he should be monitoring, and that gives you more of an idea off how much time he spending in range and whether he's got a license variability. Whether he's having hypoglycemia. Also his his his managed to lose weight on insulin. Insulin is another bullet hormone. It causes you to put on weight normally, but he's losing weight, which is fantastic, is making fantastic. Careful what? That that that makes a question she actually needing treated. Can we just take you off it? Why not? He's doing so well, and I would take this guy completely off insulin. At this point, there's no sign here that indicates that he needs to continue with insulin what he needs to do. He needs to maintain his atrial one c. And the only way to do that is by losing weight. So I would concentrate on giving him a drug that will help him. Main thing was levels way whilst he loses weight and he goes into the normal being my range, and that the drugs that do that are primarily SGLT two inhibitors. And actually I said that it will sensitize is SGLT two inhibitors and GLP analog. So this guy would it would benefit potentially from a jail panel, local or SGLT. two inhibitor and metformin. Metformin was had his zero steps I'm informing here is another sort of mask for this guy because it's going to protect his, uh, vascular system in there in the absolute long term. And if he comes back on metformin and, uh, next year old to inhibit of metformin and the gel, the arm a log in probably a year even do from now, he may still have the same age. Be one c. So you're you're buying him years in? I'm absence of complications. So, um uh, can I can I ask you guys, if you have any questions, I think I will stop here. Um, yes. Thank you so much. Took some, um, detract we to have a couple of questions, if that is okay. Yeah. Um, some He's asking What is the correct dose off my for me? For a patient with glassy to him. A global level 6.7. Okay, fantastic. So it metformin. There's no kind of right and wrong dose. And the actually metformin therapy should be irrespective of your HBA one scene. Um, this is like, you know, the HB a one c was 6.7, so the patient. It depends if your patient here is has already been on treatment or they present very early or the starting dose of metformin is 500 mg twice a day. And ideally, you want to maintain someone who who potentially hasn't reverses diabetes completely. You want to maintain people on the what we call the maximum, tolerated those so you can increase that to 850 mg twice a day and then go up to 1000 mg twice a day. If you're just starting this personally on metformin, 500 mg twice a day is probably enough. And I would revisit and see what is their HB a one C in three months and what is their every one c six months after that and see whether there is any change or large. And do I need to increase the metformin they met? The metformin can have a G I effects. If you're patient, has got normal renal function against no no contraindications and metformin is contraindicated in with energy, fatherless at 30 of any dose. It's not those dependent contraindications. Not that you give somebody low dose, but you wouldn't give them ha don't either couldn't give it on. Cannot give it's does not answer your question. So me? Yes, doctor. It's not that I'm so grateful. Of course. Thank you. Some results. Um, another question. How can clinicians the friendship between type one diabetes from time to when a patient is in front of the commission for assessment? Okay, very good question, because these days it's becoming a bit more difficult to do. So now, in absolute people, on absolute but in theory and in practice a lot. But in theory, your patient type one diabetes tends to be younger. So you've got actually a paint the picture for you. Type one type two type one 21 year old presents with a B M I of 21. They have actually lost a bit of weight unintentionally, uh, and then they also have another autoimmune condition. So that may have also Vitti. I go Ah, type two, 53 years old being my of 32. Um and um and they have a bit of polyuria bit of politics here, and actually the reading and lost their the drinking a lot of water, but they're eating a lot and the putting on way This is your typical kind of female time when you see a person with diabetes, but you can't have side to die. One. Diabetes us someone who is, um, older and more more than normal being my and it's it's for example, if you're Asian, you can have time to diabetes and have a BM Mine's 23. You have a normal being mine and tell you concern initially when they present. If you're Caucasian and thing, why don't think more likely to have Type one type two. But now we also have, um, people presenting with a later, later on settle immune diabetes. So type one diabetes. So a 35 year old who is again usually will be off normal. Being mine are particularly white. You have to think called this big type type one Diabetes is not. It makes it a martyr's. For example, you have a BM i of 23 your chorea. You have a BM I was 21 your Korea or Japanese Korean Japanese ethnicities far more likely to be insulin deficient, rather insulin resistant. But you have most likely got type two and we'll go attention in very quickly, so again. I don't know whether that answers your question. The the typical phenotype is what I described before. But there's a lot of mixed now with more and more and more things that we know to thank you, Doctor, um, blesses asking how this the gestational diabetes go away? What is thebe assess? Okay, so it's essentially the biggest, by the way, the diabetes never goes away, even in people that present and let's say, looked up to date. And I wonder if this doesn't go away after about S O in type two diabetes. In my presents, go on a diet and exercise build muscle. Having normal, completely normal age feels completely normal Glucose levels. We still consider, you know, have a bit more risk in somebody who has never had diabetes. So you're type two. Diabetes don't go, always goes in remission. It's like cancer. You go into remission. You never know. Have diabetes. You You have had diabetes in remission in just a shin diabetes. So that's that develop in pregnancy without pre existing diabetes. So they haven't had type one or type two and then went on to become pregnant. They have not had diabetes get pregnant and then get diagnosed with diabetes in pregnancy. And that's because again in season, naturally entry in resistance states Essential Woman put on weight around the abdomen, and there's a lot of part because they eat what they should be eating for one. But it will say that for too. So just a little diabetes doesn't go away. It gets treated during pregnancy and we treat it. It were very successful in treating it with diet so, carbohydrate restriction or calorie restriction. But carbohydrate control can reverse glucose level spot to normality. We use metformin and lows and we Escalade to ensure very, very quickly if we need to, because glucose controlling the mother impacts the outcomes of the baby, whether the baby is going to be born or nose and whether they're going to be born healthy or not. And what happens once if you if you if you have 100 stational Diabetes is the majority of women. They give birth. Obviously they lose a lot of water little ways immediately, and then they start breastfeeding. Breastfeeding is a very calorie burning exercise, huge amounts of calories out, and that's why we typically see women's weight go back down and back to the pre pregnancy weight, and then we check them a few weeks later. About six. If I remember correct about six weeks after delivery, we would check their numbers. The majority of them will no longer have diabetes because I've lost the weight. The pregnancy essentially, is a state of phone off metabolic stress. If you develop hypertension or the diabetes in pregnancy, we know that later in your adult life you're more prone to develop Type two diabetes, um, hypertension in life. So it's almost kind of alarm bell that you need to retain the lifestyle your lifestyle measures, retain your weight's abnormal levels and maintain activity. And what your diet in later life Because you may develop diabetes later on. Does that answer your question? Think someone took them? I think it does so well. So here he's asking, Is it true that DPP four I increases the risk of cancer? So it is not really true. The evidence for the US is very, very, very, very, very soft, as we call it, and we actually do use that before inhibitors in large. Um, well, we use them a lot. We no longer use them as much because there are actually not effective medications. So they've been your HBA one c down by a maximal marks in 10.6%. So, you know, if you're really trying to talk a little bit, want to do it before? Well, not doing much better drugs. The evidence for that is very, very, very soft. However you know, with nothing is risk free. The same applies, for example, to jail Panalog something. If you have a jail, be on a low key might be quote to the slightly increased risk of developing pancreatitis or cancer. That risk is tiny compared to the intended benefits. But the for debate before anybody, specifically the evidence. Slightly soft super pinky doctor. Um, one last question. Sierras asking. So because PCOS is insulin resistance, will that increase the risk of developing gestational diabetes? Yes, absolutely. In fact, when you enter pregnancy with a pre existing diagnosis, be so as you immediately get filed. Asshole, I risk for gestation diabetes, and we don't let you go to the 28 weeks where we normally would do an oral glucose tolerance. That's for erectile women. So it was pregnant will down any existing conditions. You do your OGTT 28 weeks. They have a problem or know if you're a one With PCOS, you start monitoring your levels at home much earlier in the pregnancy. It's kind of a suicide. You end to the second trimester about week 13, and so you start morning touring to see whether you're developing high, because semen, because you may develop just sexual that it's much air in here. Absolutely. Thank you so much, Doctor. Is there any other questions that anyone's to ask? Then feel free to give me your cell. Yeah, I just wanted to know, You know, with in terms of concordance, if the patient is an UN compliant, what are the options? How do you use Ah, um, insulin pump? So definitely not insulin Pump is an absolute contraindication in somebody who's not concordant because interesting Pound needs. It depends on people being concordant and self managing in order to work to their benefits. Absolute contraindication business. My uncle quarter, I. I'd say it's a bit of kind of start psychology here. You need to find out why they're non concurrence, and this is a lot of reasons. The commonest reason you'll find Phenocal. Gordon's is that people make bad decisions. And I think as clinicians, we have to be able to just accept that people are free to make bad decisions. That's their their choice. But you have to sit down and give people time to explore why they're not taking medications. Is it because they don't have access to them at the right time? Because they're embarrassed, especially with actually, If somebody, for example, is on High Flying executive, it's out all the time. Doesn't want their colleagues know the whole diabetes that the mind and I'm not taking their insulin up of their meal times easy because it's a young mother that looks after five kids at home who hasn't time for herself. Is it somebody who's got a cognitive impairment or memory loss and forgets to, you know, fully against the medication itself? There's a lot of reasons for non concordant somebody might be in denial of the diagnosis. There are people that have a strong um, either cultural or religious views that you can do nothing about. It is completely their choice with regards to that, but you have to spend time with people that are known according You have to explore What is the life like what other their beliefs like, What is their knowledge? Like what they're understanding? What are the essentially the factors that prevent them from from being concordant? Thank you so much dot Okay, No, I have a question least in regulating off diabetes or sugar level we combined. Can any a that drives you combine with metformin may for for the treatment? Yes, So metformin I think I can see there a question about is metformin the best with gold before he is the best we've got because it's the oldest is the oldest thing with course, with whatever I tell people, no matter what do you use, use metformin with it. But they're drugs that are much better than metformin in helping people's glucose levels come down and the weight to come down, which is what you want to do in time to diabetes and namely, the ones that I use a lot is SGLT two inhibitors and jail panel looks. If you don't have contraindications to those drugs in your patients, these are fantastic agents to use with metformin, riven all three together and to achieve good life senior and to lower people's weight because if you lower the waves, that is what gives them the chance of sustaining the good control. If you keep giving the medications that coupon, it's given more and more and more and more, and eventually you have to give the mention it. And I might have to stop here because I had another meeting about five minutes ago now in the bottom of their happiest come back and do more sessions if I know what guys, What if they want to go through cases more? If the house specific questions, I can put things together. That's perfectly fine, thank you. Some respect the Plavix for the exception and in the obsession on type two diabetes with regards to the pitfalls and tips. Now, in the light of the grafts and illustrations, I think it does. And it has actually solidified our understanding regarding to type two diabetes. Thank you so much for taking the time and having us over and teaching us for dissection. We were really, really delighted for having you Him. Now on next session will be a five o'clock with Dr TT and she will be going over infectious disease, Israel. So what I'll do is I'll keep the chart open for a couple of minutes, just in case. And people still haven't received thief feedback form on. I will then see you about five o'clock. Take care, everyone.