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Um and please take it away. Wish there's a text message from Julia. Has anyone managed to join successfully? I think she's not able to see. Um I, I can see a few people that joined as anyone else. Should I start? Yes, perfect. Ok. Hi. So, hi everyone. My name is Yvan. I'm one of the um I was a previous registrar and I have just started acting up um at the diabetes and endocrinology department at Roy London. I am going to talk on insulin, feel free to ask a lot of questions and feel free to interrupt in between as well and I will go through the chat messages at the end or as I go along, whichever that works best for you guys really? And I have a few scenarios at the end and I really hope that you guys will learn a lot from this. So moving on. So these are the objectives. So I'm gonna talk on insulin structure and synthesis. I'm gonna talk on insulin secretion mechanism of action, physiological action of the insulin, different types of insulin. And at the end, like I mentioned, we will go through a few scenarios. So that you will have a better understanding of what we do with insulin. So, insulin structure, insulin is a, insulin is a, it's a, it's a peptide hormone. There is a 51 amino acid within, within the insulin. And as we all know, it's synthesized and secreted by the pancreatic beta cells. Insulin has two polypeptide chain, the alpha and the beta chain. And they are as, as we can see from the picture, they are linked by the sulfite bridges and there's two sulfite bridge between A and B chain and they're called the disulfide bridges. And the A and B chain are interconnected by the disulfide bridge. And between the A chain, you can see the third inter chain disulfide bridge. So this is the insulin structure moving on. So I I don't want you to focus on the words, just focus on the uh picture on your right hand side. So from the top, when the insulin is being produced, it's produced as prep pro insulin, which is an inactive insulin. So if you focus on the picture, you can see the, can you see me pointing on the screen or or it on the screen? OK, that's fine. So from the picture on the right at the top that like I said before, the insulin is produced in an inactive form, which is called the prep pro insulin. And you can see the blue bit, you can see the red bit. You can see the green bit and the yellow bit. So remember I mentioned about the alpha and the beta chain and that they are connected by the sulfite bridge. So here you can see the sulfite bridge, the S and in between the alpha and beta chain, that's chain C. This is the protein chain basically. And the blue side is the N terminal. So the prep proinsulin gets broken down into proinsulin when the protein or peptide at the N terminal gets taken away. And then it goes through another final process whereby the endopeptidase enzyme, it cuts off the peptide chain between the that was connecting the A and B chain. So from the third image, right at the bottom, you can appreciate the chain A and chain B are still connected but the through the sulfite bridge, but the connection the CC chain has been taken away and this makes it into an active form of insulin. And this is worth mentioning because the CCH chain, which is the peptide chain, which is the c-peptide chain, it matters because I'm sure you guys would have heard us about talking about c-peptide chain, which comes into account and we will discuss this in the scenarios later. So just remember that C peptide is part of the insulin that gets broken down into the active form, moving on. So moving on to the insulin secretion, when you eat something, your glucose level in your, the fluid rises. And with this, you are going to trigger the insulin release. So this glucose is taken up through to the beta cell in the pan pancreas through the glut two channel. So the glucose enters the pancreas through the glute two channel. And this then causes at P production due to depolarization effect. And this ATP channel, this at P production then creates an increase in the calcium rise from the at P sensitive potassium channel. And this influx of calcium will trigger the release of the insulin from the beta cells in the pancreas. And there are two ways where the two processes when the insulin gets released, one is margination, you can see the picture at the bottom. There are the, the the from the calcium, there is an arrow. The next arrow shows the margination whereby the insulin moves to the surface and exocytosis is when the insulin gets released released from the pancreas. Next light. So, secretion of insulin, there are biphasic s in two phases. One is a pulsatile release when, when we eat something, there are short bursts of insulin that gets released. And then there is a pro protect protracted release where it's constantly there in the system and acts as a basal production of uh insulin whereby your body is constantly producing a low level of insulin. So one is pulsatile and one is a protracted release where it's there being released at a small amount every single hour or every single minute, really next slide. So the way insulin acts. So the muscles, especially the skeletal muscles and the adipose tissue in our body will take up the glucose. And for the glucose to be taken up by the muscle or the adipose tissue. For usage of the glucose, you need to have glute four channel. So this glute helps the the insulin to bind to its receptor and the muscles and the adipose tissue can then use this glucose appropriately. So, without this glute, four insulin becomes useless. So you need this glute four channel for you to be able to use the insulin to take up glucose into the skeletal muscle. So a lot of processes in between worth remembering some of them and some of them will be useful when we whe when when we talk about drugs, especially for type two diabetes. I'm not gonna talk about all of the drugs used in type two diabetes. But the way insulin works and the way um the insulin is released matters for some of the medications that are being used to enable insulin rise in the body physiological action of insulin. I'm going to make it quick because there are a lot of things in it. So I'm gonna make it um slightly brief. So insulin as we know is an anabolic hormone, it's uh it's, it's, it's, it's, it's a building hormone. So it assists with the process that compounds for storage. So it doesn't break down, it helps with the storage So it is called an anabolic hormone. So it helps with glucose, protein and fat metabolism. From the glucose point of view, it inhibits the glycogenolysis and gluconeogenesis. So it stores hormones like what I said, it is a storage hormone. So it helps to build up extra energy in the body instead of instead of the energy being used really. So it increases glucose transport into the fat and skeletal muscle. It increases the glycolysis in fat and muscle so that they can use up. But it and and it also stimulates the glycogen synthesis. So it inhibits the gluconeogenesis because the gluconeogenesis will take up protein fat and carbohydrate to make up this process. So insulin doesn't allow that because insulin is a storage hormone and moving on from the fat metabolism. Point of view, essentially, like I said before, from the gluconeogenesis point of view, fat is also used for gluconeogenesis and inhib and insulin inhibits this process and it also decreases the lipolysis. It just contributes to the fat storage, essentially the next one and the last one protein metabolism. Again, like what I said insulin is a storage hormone. So it doesn't break down any of this and it helps with the protein synthesis. And again, it inhibits the glu gluconeogenesis. That means the protein is not going to be used up for the gluconeogenesis. So again, the overall effect is uh plus plus protein in your body. The reason why it's worth mentioning that insulin is an anabolic hormone is because you might have heard patients talking about weight gain with insulin and a lot of patients are extremely worried when they start them on insulin, especially for those who are very weight conscious. So these are the reason why insulin can contribute to weight gain more than weight loss and other actions that I thought worth mentioning but not, don't pay too much of attention to this. They are also involved in indirectly for steroidogenesis, vascular function, fibrinolysis and growth. But the exact mechanism is not very carefully understood. So I'm not going to go into further detail into it. So adrenaline and noradrenaline inhibits insulin secretion. It makes sense because it's uh with regards to adrenaline and no adrenaline, they are, they are fighting hormones. So you need extra energy whereas insulin is energy conserving. So obviously, in fighting responses, you don't want extra insulin because you want to be able to use up the fat protein and carbohydrate essentially. And the hormones that uses up that that increases the insulin secretion are the G I tract hormones and the acetylcholine. So there are different types of insulin. The first one is the human insulin. Second one, insulin analogs where they do modification to the human insulin. And in the past, there were usage of pork and bovine insulin, but we no longer use this insulin. So the two insulins that we use are the human insulins and the insulin analogs. Next slide. So it's, it's, it's a bit small. Um Essentially, I'm gonna go through one by one. Anyway. Um what I wanted to show is that there are rapid acting insulin, short-acting insulin. And then you will hear about intermediate acting insulin, long-acting insulin and ultra long-acting insulin and mixed insulin. So I just made a, I just took this picture because it summarizes the whole thing, but I am going to go through it one by one hereafter. So first one rapid acting insulin. So the although although the word says rapid acting, it usually takes 10 to 20 minutes for it to take its action. And this with this insulin, patients usually either take immediately or the standard advice that we give is for them to take between 15 to 20 minutes before meal. The onset of action, like I mentioned, they take at least 10 minutes, 10 to 20 minutes and their peak action, as we can see from the graph, they peak between 1 to 3 hours and they can last in the system for at least 2 to 5 hours, usually about four hours really. And the examples of rapid acting insulin. So they are brand names and they are the actual insulin names. We usually go by brand names here. So you guys would have heard about no rapid HumaLOG, Apidra and Fiasp is one of the later ones, which is even more rapid acting than the first three. So with FI A S it's worth mentioning. Like I said, for the other insulin, although they are rapid acting, they, the patients for it to take maximal effect, they should ideally take it at least 15 to 20 minutes before the meal. But for FI A s they can take it 5 to 10 minutes before meals. And it's an even more faster acting insulin compared to the first three, second one is the short-acting insulin. So this works slightly slower than the rapid acting insulin. But they are also mealtime insulins. So this is a human soluble insulin. It takes about 30 minutes. It it, it takes about 30 minutes for it to start working. So the patients have to take this insulin at least 30 minutes before their mealtime. So you can imagine how cumbersome this can be because you need to plan your meal properly. And not only that, you need to plan how much you're eating, how much insulin you need to give. And you need to be able to give that 30 minutes before the meal. It can be very difficult, especially for those who are working because you need to be able to plan everything so carefully and you can't do things. So last minute it starts working in 30 minutes, it peaks in 1 to 5 hours. From the graph. You can see that and the effect can last from 5 to 9 hours, usually around 6 to 6 to 7 hours. And the example of this short-acting insulin, HumuLIN, s insulin, rapid and act rapid. Although act rapid has the word rapid, it's actually a short-acting insulin and it's not a rapid acting insulin, intermediate acting insulin usually taken once or twice a day. So intermediate acting insulins sometimes can be used as a rapid as a, as a mealtime insulin. But most of the time in the majority of cases, they are used as a basal insulin. They work for 8 to 14 hours. Hence why they need to be given either once or twice a day and they start working within 60 minutes to 1.5 hours. And as we can see, there is a peak and it peaks between 4 to 8 hours. The reason why it's important to know how long this insulin acts is because when you decide to give insulin to patients, you need to know how long this insulin is going to be in the system just in case they get high post, then you know that this is the effect from the insulin. And whether you need to reduce that particular insulin, even if they have highs, then you need to know what insulin is affecting this and which is the contribute so that you know which insulin to tackle when you see a patient with highs or lows. Really next one long-acting insulin. And this is the basal insulin. This is also a basal insulin, long-acting insulin, which you would have heard quite a lot and these are usually taken once or twice a day, depending on the duration of some of the long-acting insulins and they start working within two hours and their effect can last up to 18 to 24 hours. Examples, Levemir, Levemir is slightly shorter acting than the other long-acting insulin. It works between 20 to 24 hours. The reason why there is a range is because it, it depends on how fast the insulin gets absorbed. We all know that insulin is given subcutaneously. So once they are given subcutaneously, they get taken up uh through the bloodstream. So this absorption from the subcut into the bloodstream varies from person to person exercise can affect this the way the the the the appropriate method of injection matters and the place you inject matters as well. So that's why there is a big range to all of this insulin and the the time it takes to reach the system as well. So Levemir, like I said, it works between 20 to 24 hours. Glargine usually works for approximately 24 hours. And Toujeo is similar to Lantus, but it is a more concentrated version of Lantus. And this is usually used for patients needing very high amounts of insulin. So instead of giving, giving them the larger, instead of giving them the larger unit of insulin, you give them in a more concentrated manner. So less liquid going into the body, essentially less volume of what you need and Degludec Tresiba is uh ultra rap ultra long-acting insulin and it, it, it has the longest, uh it works the longest, it essentially works for 42 hours in total. So that is the longest acting long-acting insulin essentially that we have. So you would have heard about mixed insulins. So mixed insulin, as the name suggests, they have a short-acting component to it and they also have the longer acting component to it. So they are usually taken twice a day or three times a day, more or twice a day, they work between 15 to 30 minutes. But this depends on which short-acting insulin is going into it. So remember I told you guys about rapid acting and short-acting. If the mixed insulin has a rapid acting component, then it works faster. But if the mixed insulin has a short-acting insulin, then it takes a bit longer to work. So please bear that in mind when you prescribe the mixed insulin as well. So the duration of effect depends on which part of the longacting insulin is incorporated into this mixed insulin example of mixed insulins, you would have heard about novo mix 30. So from the name itself, Novo, that means they are using the novo rapid as the short acting component. That means you can take the insulin 10 to 20 minutes before the meal. And novo mix means that they have, they have modified the short-acting component of the novo rapid to enable the novo rapid to be given as short acting. And the modification has allowed it to work in a longer, longer way to cover the basal part of it as well. Other insulins, other mixed insulin, HumaLOG mix 25 which which uses the HumaLOG short-acting the, the rapid acting insulin HumaLOG. And it also has the basal component of it which takes uh which works between 12 to 16 hours really. And we have Huma HumuLIN M three, which is the human insulin, which uses the HumuLIN I component. And it also has the short acting version at the beginning part. And other names you might have heard insulin comp 25 or insulin pump, insulin pump 50. Don't worry about the names too much because um essentially the diabetes you were prescribed, you just need to know how, how long it will work. So that when you see a patient, like I said, just now, if, if you need to adjust the dose, then you need to know which insulin you need to take uh next dose, next, next slide. So I wanted to put this light here because we mentioned about all of the different types of mix, different types of mixed insulin. So HumuLIN M three has 30% of the short-acting insulin and 70% of the HumuLIN I which is the basal insulin HumaLOG mix. 25. That means the 25 is the shorter acting insulin and the 75% of it is the basal insulin HumaLOG makes 50 50 50 50% of shorter acting insulin and the other 50% has the longer acting component. And then NovoLIN, we don't use it here. Novo makes 30 like I said, 30% of the short acting and 70% of the long-acting. So the number is essentially the shorter acting insulin. Why does it matter? Because you can see that most of them has the 25 or 30 as the lower number and some of them have 50. What? Why why these matters is when you when we think of prescribing insulin to a patient, let's say I have decided that this patient is going to need mixed insulin. I need to consider whether or not this patient is taking a lot of carbohydrate for his breakfast, lunch and dinner. And in that kind of situation, I would go ideally for the 50 50 because I know this patient needs more of the short-acting insulin as compared to the longer acting insulin. So in that kind of situation, the choice of this short-acting and the long-acting matters. And that is why this number is important so that you can gauge which is the better version of the mixed insulin to give to a patient. So there is a question there. Uh can we go to the previous slide uh which does the number after the brand name mean the percentage of rapid acting insulin? Yes, like I said, no one mix 30. That means the 30 is the shortacting insulin, which is the rapid, either rapid or short-acting insulin. Yes, that's, that's correct. Um, next one. So I've put this picture here because this is essentially how our body works when we don't have diabetes. So this is the way our body releases insulin. So the top one, the green is the basal insulin. You can see that there is a small amount of insulin, ignore the glucose levels of 102 100. This is just uh something that has been done in the something that was published in the American paper. So they use different units for their glucose and insulin. So the one the the green figure is the basal level of blood glucose that is being constantly secreted in our body to maintain a normal glycemic level. And then you have the purple graph which is the surges of the insulin when we eat. So these are the prandial insulins. The these are the the purple one is the insulin that gets secreted in a, in a burst associated with the meal. And the green one is the basal level is basal level of insulin that is constantly being secreted every second or every minute essentially by the body. Why it matters is because for patients with type one, you know that there is no reserve in their pancreas to produce more insulin essentially towards the end of their disease. So we need to try as best as we could to mimic this body physiology. So we need to make sure that there is a constant low level of this basal insulin being given like what our body usually produces. And we also need to be able to cover the prandial spikes whenever we eat, our body needs more insulin. So we need to give the boluses together with that for these kind of patients. So type of regimens of insulin. So like I mentioned before, type one diabetes is an autoimmune process and it, it invo it, it, it causes beta cell destruction. So it doesn't get uh destroyed immediately or just one shot, it is a gradual decline. And when they present, essentially, they would have lost at least 80 to 90% of their beta cells. So in this kind of patient, you need to think of something that mimics the exact body physiology, the slides are gone. Which Hello. So I just have, I'm just reloading the slides back up. I think some, some why they've been stopped that there al almost ready to get them back up. It's gonna be Yeah, thank you. So like I mentioned before, type one diabetes, it's an autoimmune process. So it leads to beta cell destruction. And at the time of presentation, usually they would have lost at least 80 to 90% of their beta cells. So in this kind of patients, you need to think of a way to mimic the exact body physiology IE by giving them the basic insulin, the c the graph that I showed in green and you also need to make sure that you cover the prandial spikes. That means whenever you eat, your blood sugar is going to spike and you need appropriate amount of insulin to cover the spikes as well. So when we start a patient, a newly diagnosed type one patients on insulin, the way we calculate is by estimating their insulin requirement. Sorry. Uh you can. So I'm I'm just looking at the chat group. They're asking you can repeat again this slide. Do you want me to which slide is it? I think people may just want you to start from the beginning on the slide if that's all right. OK. The one before the graph. OK. Yeah. So from this graph, what I was trying to explain is this is how um our body produces insulin. And this is in a normal nondiabetic patient whereby the the the top one, the the one in green that is the basal level of insulin. So our body is constantly producing a basal level of insulin every second essentially. And this is to maintain normal glycemia and to avoid hepatic gluconeogenesis. So there is a constant level of glucose at of insulin being produced and and then when you eat, there is a search of glucose. So your body needs to produce extra insulin to cover this search. And this is what we call prandial insulins and you need this whenever you eat. So in, in a normal, in a, in a normal uh person who's non-diabetic. So this happens naturally. So whenever they eat, the, the response happens quickly and the insulin search happens and that brings down the blood glucose nicely. And similarly, the basal level of insulin gets secreted and there is no issue to this. But with a patient who's known to have type one moving on to the next slide. So we know that type one is an autoimmune process. It destroys the beta cell. And at the time of diagnosis, like mentioned before, 80 to 90% of these beta cells are destroyed. So you need a way to mimic the exact way where the body produces a low level of basal insulin. And at the same time, you also need to cover the spikes of glucose. You get to cover the the meal times essentially. So the way we calculate is usually at the start, we take the body weight into account. So the starting dose would be 0.5 times the body weight to estimate the total insulin requirement. So if let's say someone is 60 kg, 0.5 times 60 is 30 units. So you will need roughly 30 units of insulin and this needs to be split into basal and bolus insulin. The way we do it is if let's say your total amount of insulin is 30 units, you need to split it 15 to have, you need to split 50% for the basal and 50% for the short acting, which you give with meals. So if the total amount of insulin you need is 30 15 units will be the basal insulin and the other 15 will be the bolus that you use for breakfast, lunch and dinner. That means 555 makes up 15. Does that make sense? If your requirement is 30 then you need to split 50% for basal and 50% for the bolus. But taking into account that the 50% for the bolus has to be divided to breakfast, lunch and dinner. That's how we start someone with type one roughly because after that, you need to adjust the insulin requirement as per the, as per the carbohydrate intake. So this is just a rough way to estimate the insulin requirement for someone who has a new diagnosis of type one diabetes. And yeah, the slides have gone again. Sorry. We're just having technical difficulties with the slides. Um, might be a good time to just ask a few questions if you have. Yeah, exactly. Why don't, why don't you guys ask me any questions if you have? I can go back to the previous slides if um, there was something that you would like to clarify further. Ok. So, um there is a question on the chat box asking what variety of insulin analog is used for insulin pumps. So for insulin pumps. We only use shortacting, we only use short-acting insulins and we only, in, in our trials, we usually use rapid acting insulins like Novo, rapid HumaLOG and Fiasp if the patients have trouble giving the insulin 10 to 20 minutes before the meals. So most of the time for insulin pumps, um, I, I, I'm not, I, I haven't touched on insulin pump. I, I thought I'll just leave it because there's too much to talk about the insulin pump. But to answer your question, the analogs that are used for pumps are usually free. No rapid or HumaLOG. Ok. So moving on to the next slide, type two diabetes, they are different from type one because type one, there is an autoimmune process which is destroying the beta cells. Whereas in type two, there's a slow progress of the beta cell loss and they will eventually require insulin, but not everyone depending on at what age they were diagnosed really. So the way we use insulin in type two differs from type ones and usually what we do with type two diabetes, we start them on oral agents and we add on a second oral agent. If one does not give the HP one C target that we want. And then we might consider another third option. And if that doesn't work, then we will consider insulin and for type two diabetes because most of them will have some functioning beta cells, they don't have a total destruction of these beta cells like how type ones have. So in that case, because they have ongoing beta cells that are functioning, we just need to top up a little bit more that they are lacking. So we usually start them on a basal insulin and monitoring them from there on. And if that doesn't work, then we will think about mixed insulins. And if that doesn't give the optimal hp A one C, then we move on to basal bolus. It's very, very rare for type two diabetes patients to be on basal bolus unless their control is just horrible. And they've reached a point where even the mixed insulins are not working for them. And the way to estimate the amount of basal insulin is by starting at the lowest level, essentially 0.1 units per kilogram to estimate the amount of basal insulin that they need at the start of the prescription of the insulin. So yeah, the last sentence I've written that in patients whose fasting glucose level becomes well controlled with the basal insulin. So the way we assess the basal insulin, whether or not it's adequate for type two diabetes is by asking the patients to check the fasting capillary blood glucose. If the fast, if the fasting capillary blood glucose is high, that means the basal insulin that we started them on has to be increased further. The reason why we take this fast thing to give a gauge of this basal insulin is because the other glucose levels that you check are affected by meals. Whereas when you wake up in the morning, you are waking up from your sleep. So there's no food for a good 6 to 8 hours. Really? So that is the time you can gauge whether or not this basal insulin is enough because basal insulin is not connected to your mealtime production of the insulin in the body. So basal is the low level of insulin that is constantly being produced in the body. So the best way to assess whether or not a basal insulin is enough is to look at the fasting capillary blood glucose and adjust accordingly from then on. So in type two diabetes, that is the first thing that we do when we start them on insulin on a basal insulin, asking them to keep an eye on this. And once the fasting is good at the level that we want and if they are still having suboptimal HP A one C that will prompt you to think whether or not they are having high glucose levels associated with their meals. That means you need to think of a different type of insulin, either a mixed insulin or a basal bolus insulin later on. And it's, it's, it's this is a bit too small but essentially repeating what I have said like what um the top one initiate basal insulin. So this is once they are the, once the HP A one C or the blood glucose is not in target, then you initiate the basal insulin. And then it says if a one C is not controlled, consider combination injectable therapy. So the first box on the left, they have said that at one rapid acting insulin injection before a large meal. So this is once you have initiated the basal insulin. So in a way, they are suggesting a basal bolus but only to cover one large meal. II, I don't usually tend to do this. So if I start patients on basal, then like I said, the next step would be either a mixed insulin. And if you're thinking about basal and bolus insulin, then I usually cover all three meals, not just one big meal really. So moving on to the next box, they have written that at GLP one analog, this is not an insulin, but essentially it contributes to increased insulin production when we eat something by increasing the in creatinine levels, the gut peptide hormones really. And the third box there they have put that change to premixed insulin twice daily before breakfast and supper. So essentially three options. You can either choose a combination, mixed insulin if that doesn't work. Then like I said, do basal bolus. But this is usually towards the end of the type two diagnosis, di diabetes really. And GLP one analog, I usually put them under oral, not exactly an insulin because they can be used early on instead of waiting for the use of insulin later on. Um, moving on to the next one. just a quick question on the in the chat. Um, just ask about type one diabetes. Is it congenital may also come in older age. So it's not congenital, it doesn't come with when it, it's, it, it's not something that happens when you're not born with it. But there, there is an autoimmune element to it. So there is an antibody and because there is also an environmental factor in addition to this autoimmune, when it happens is unpredictable. So you need to have an environmental stressor to exaggerate this destruction to the beta cells. And then eventually these patients will present with type one diabetes and it can happen in older age, usually type one, we categorize them as type one. It, if it happens in patients less than 40 above 40 years, we usually say it's a latent onset type one diabetes, which is called SLAA. But in general it is more common in Children. Exactly. Yes. Yes, it is more common in Children because like I said, the autoimmune process, they are, they already have that autoimmune element to it and they just need an environmental stressor to accentuate the effect of it. Yes, Children can. Yes, generally in Children. But you can see that a lot in teenagers, twenties and even thirties. So I'm going to move on to the scenarios, but I'm very happy to take questions before I move on to the scenarios. Really? Any other questions? Anything else that need further clarification? Ok. So 1st, 1st case study. So this is a patient. This patient is a 45 year old gentleman. He is known to have type two diabetes for six years and he has been commenced on insulin for the past two years. His current weight is 50 kg and his BM I is about 24. He presented to us with uncontrolled and recently increased blood glucose level and a dramatic increase in insulin dose during the past five months without any apparent cause. He has no, he had no recent history of sepsis. Sorry, I can't, yeah, can't see the slide properly. He had no history of sepsis or extraordinary stresses or steroid use and he has had multiple hospital visits um during the past few months because he's quite concerned that his glycemic control is suboptimal and he just doesn't know why this is happening. So um which has kind of created the poll, what uh I would like you guys to answer the question and see where we get along and then we can discuss this case in further detail hereafter. So a lot of you guys, uh most of you guys have put uh all of the above exactly. So the first thing is you need to see whether the patient is taking the insulin or not, that could contribute to hypoglycemia. If the patient is taking and you can definitely trust the patient that he is taking the insulin. Then the next thing to see is whether the insulin is getting absorbed properly. So you check the injection sites, it is very, very important to check the injection site every time the patient comes uh for their diabetic reviews. Because when there is lipo lipohypertrophy, like the picture I have showed there, the patient basically has evidence of lipohypertrophy. It's a wear and tear process because every time you inject in the same region, the the adipose tissue becomes hypertrophic and it affects the absorption of the insulin. So this can explain the case in this patient because essentially he doesn't know why he's having hypoglycemia. It looks like everything is uh it it doesn't look like he's eating more or he's doing something extraordinary or taking any extra steroids that could contribute to his hypoglycemia. So the ex the possible explanation for this patient is that he's injecting into this lipo hypertrophic region, which is causing a delay in the insulin to get absorbed and essentially making it slightly more ineffective really. So whatever insulin that he's injecting is not getting into the body the right way. So it is very, very important to check the injection technique and also to check whether the sites are. Ok. So the general rule of advice that we give patients is if they are on basal bolus insulin, then the basal insulin should be injected around the same region, ie if they choose to inject their basal insulin on their thigh, they should ideally continue injecting this basal insulin on their thighs. Only because every different aspects of your body, the absorption rate varies slightly. This is to maintain a stable level of insulin as they take for bolus. Similarly, if they are injecting into the abdomen, then they should continue injecting the bolus into their abdomen. They should rotate the site of injection. So the way we teach them is you divide the abdomen into four regions and the first quarter, you divide them again into four. So they have four pores around the quarter side of their abdomen and they need to rotate that and then go to the bottom next side and the other side. So they have various injection sites and they should ideally rotate every single time they inject, this is to prevent the lipohypertrophy. If they have lipohypertrophy. Despite that, then you tell them to avoid that region because you know that the absorption varies and sometimes the insulin doesn't get into your body properly. If you inject into that region, it usually gets better, but it takes time but do not inject into that region until it gets better and use a different side instead. So that is about the injection per se. And there is a question they are asking lipo, it's lipo, it's lipohypertrophy. Basically, it's a wear and tear process whereby when you inject the insulin into the adipose tissue, it gets hypertrophied. It's basically the subcutaneous tissue in your body saying that I've had enough. I'm working so hard. Leave me alone kind of situation. Not everyone gets it because if you rotate the injection sites, the same side doesn't get affected too many times in a day or in a couple of weeks or months next slide. So case 32. So this is a 58 year old gentleman. He's, he works as a lawyer. He's, he's known to have type two diabetes for 10 years. He has systemic hypertension, he has dyslipidemia, his current medications, Metformin one g, twice a day, gliclazide, 1 60 mg twice a day. SITagliptin 50 mg once a day, ramipril and atorvastatin. His HP A one C is 90 he only checks his fasting glucose and is around 12 to 15 on average, which is not great. So HP A one C target as per the nice guideline, we usually ask the patients to aim for. Obviously, the target is different from one patient to another. If it is an elderly patient, then obviously the target shouldn't be that tight because you want to prevent the risk of hypos. But as a general rule of thumb with a nice guideline, they usually advise patients to aim for a target of less than 48 but consider an increment of medication if their HP one C goes above 53. So for this patient, you can see that the HBA one C is way above target. So what is your next step of management? Exactly. Start basal insulin. Excellent. So II I very good. Yeah. So like I said, three oral agents already. So the next step is to think about insulin because clearly the patient is lacking, lacking this. And once we give the insulin, then we need to reassess the fasting C BGS. I'm sure it will get better. And then you see whether or not the HP A one C gets better with that. If it does, then it's good, then you can just continue the basal insulin if it doesn't and if it continues to get worse or if it improves and then continues to get worse after some time, then you need to think about mixed insulin before starting insulin. Obviously, you have to ask the patient what they want because if they work as a taxi driver or lorry driver, there are DVL A rules related to insulin, especially for HGV. Drivers, like bus drivers or lorry drivers, anyone on insulin or Sulfon Uria or any medications that can cause hypo, they need to declare their license and they need to declare their medical conditions. Uh, they need to declare their diabetes status and the medications they're on and get the license renewed yearly. So you can see how tedious this is going to be for them. So some patients may not want the insulin. In which case, you might consider other options like the G LP one analog, which is, which is an injectable technique, but doesn't work the same way of insulin whereby it doesn't cause hypos. So before starting insulin, definitely check with the patient what they want and if they're agreeable to it because there's no, there's, there's no point in uh starting the insulin to help them. But if they don't take, then we are going to be at the losing end. So going through the options, add in pioglitazone, it is a medication that works similarly to Metformin. But again, like I mentioned before, the patient is already on three oral agents. So there's no point in starting another fourth agent which is unlikely to be beneficial. The second option, increasing the dose of Metformin, the maximum dose of Metformin is um 2000 g, which is one g twice a day. So there is no uh that there's no real room to increase the Metformin. Here, you might have seen some GPS using 850 mg of Metformin three times a day. There's no real logic to this. The BNS says 2000 g as the maximum. So one g BD is the correct dose for the Metformin. And again, increasing the dose of gliclazide is not an option because this is the maximum um dose you can use for gliclazide, continue with current management. Absolutely not because the patient's HP one C is suboptimal. So basal insulin, like what we have explained just now next scenario. Mhm. Next one which I think we're having some technical issues again. Let's, let's wait, sorry, connection issues. I'm just going to just give me a couple of seconds to get the slides open. Ok. Ok. Yeah. 3rd, 3rd case. So this is a 32 year old, uh, gentleman. He is, um, doing his phd and he works as a part time. We waiter and his work pattern is quite erratic. It could be day or night depending on his um phd schedule and the available shift. So he's known to have type one diabetes for 10 years. His HP one C is suboptimal. It's 65 milli milli more per more. And his current medications, Levemir 12 units twice a day and Arabi eight units three times a day. So on further questioning, he revealed that he tends to omit his long-acting insulin occasionally and he takes his short-acting insulin, post meals most of the time. So what, what should we do? What, what can we do to help this gentleman here? So we know that he's on Levemir a long acting insulin twice a day, 12 units. We know that he is taking Arabi and eight units three times a day. A rapid is the short-acting insulin as compared to a rapid acting insulin. So the options, please, which can you guys vote or, or does that not come up? Oh, yeah. Ok. It is there now. So perfect. So most all of you have answered switch, uh Levemir to Tresiba. Excellent. So some of you have answered, increase the dose of the Levemir reasonable. So we'll talk through all of the options. Ok. So from the bottom add in Metformin, um, absolutely not because the Metformin is not going to do anything bearing in mind. Yes, we use insulin for all of the type one diabetes, but for patients who have had type one diabetes for quite some time, sometimes they can develop insulin resistance where they will realize that they are needing more and more insulin over time. And you have, and you have um obviously inject uh you have obviously inspected all of the injection regions and everything and they're all fine. So that will make you think whether or not they want, they have uh insulin resistance, meaning that the response to the insulin is not as strong and they will eventually need more insulin to have the same effect. This usually happens when patients have gained weight and have all of the other metabolic syndrome uh gain in their waistline increase in weight inactive lifestyle. And these are the patients who usually have insulin resistance in that kind of situation. You can add on the Metformin to help with the insulin resistance in addition to your insulin in hoping that their insulin requirement will eventually come down. So yes, that that is not an impossible answer but be that in mind for patients who have insulin resistance, switching Arabi to novo rapid. I think, I think that is actually uh AAA potential good answer purely because this patient is taking act rapid. And like I said, act rapid is a short acting insulin. You need to give act rapid at least 30 minutes before the meals. So the patient doesn't have time and the patient is ending up giving the insulin after meal. And what happens when you give the short-acting insulin after meal is that number one, you will have such a rapid glucose surge after you eat. And when you give the insulin later, not only you will get very high levels of glucose in your body, you will also end up having high po low sugar levels at a later time because this insulin is acting later and the effect will go on for a couple of hours when the food is out of the system. So you can see how this can be, this can be disastrous for the patient really if they continue to give the insulin after meals. So in a way, switching the e rapid to no rapid might be useful because nova raid is a rapid acting insulin. It can work faster than the uh than the e rapid. So it is a potential potential option, increasing the frequency of the e rapid. Not really because we usually give boluses with meals. So there's no point in increasing the frequency, increasing the dose of the Levemir. It is it is po uh it is possible but the patient is not giving the sorry, did I switch? So sorry, the the other the option before switching the Levemir to Tresiba and a majority of you guys have answered the majority of majority of you have put this as an option. It, it, it is the correct answer. Basically Tresiba, like what I have said before, it acts for at least 42 hours in to it, it acts for 42 hours in total. Whereas Levemir is in your system from 20 to 24 hours. So Tresiba is there in your body for a longer period. And the reason why we consider Tresiba in patients would be in this kind of scenario is when they tend to omit the long-acting insulin or when they don't take their long-acting insulin on time. In this kind of scenarios, this Tresiba will be very useful because it is there in your body for more than 24 hours. So even if you don't take that on time, the remaining effect of the insulin is still there. And if you skip it, it doesn't usually matter as much as compared to the Levemir. But obviously we advise them to take daily. But assuming that even they skip one day when they take it the next morning, the effect of the Tresiba is still there. So in this kind of patients with erratic lifestyle and those who tend to omit insulins, Tresiba do work better for them and increasing the dose of Levemir. Levemir is potential. But again, she's skipping it so many times. So in a way, you want to minimize the amount of times you want to give the injection. So instead of Levemir twice a day, the Tresiba once a day at night would work better. But obviously the bolus cannot be omitted. So the nova rapid or rapid still needs to be given. But I think the novo rapid would be a better bolus option for her purely because it works faster. Uh Moving on to the next scenario. Uh I think we're having um technical issues. Maybe I can just read out and then um you guys can vote because I have the slide with me anyway. So the next case is a 88 year old lady. She was admitted with dense left hemiparesis. Her last HBA one C was 45 6 months ago, 42 to 48. So 48 HP A one C is used to diagnose diabetes between 42 to 47. You call that as prediabetes. So for this patient, she's 88 she came with dense left hemiparesis. Her last HBA one C six months ago was 45 pre-diabetes and she failed her speech and language therapy, meaning that she's deemed not safe to swallow. So they have recommended feed nasogastric feet for 24 hours. So they are planning to feed her for 24 hours with the NG tube and her C BGS during the feed are between 14 to 18 millime per liter, suboptimal. What would you do? Excellent. So most of you have answered um put on a sliding scale whilst on feet. So yes. So going through the options, one by one, put on sliding scale is the best because you want to know because this patient is not even on any medication because the patient doesn't have a known diagnosis of diabetes. So what's happening here is that the patient is having stress hyperglycemia, the patient has just had stroke. So that itself will cause a glucose rise, especially when someone is already in the pre-diabetic category. Your sugar levels are bound to be high when you have this kind of stress factors. In addition to that, she is being given NG feed, which has very high level of calories, a lot of carbohydrate content and obviously, that's going to cause a further rise in her CB GS. So sliding scale is a good option because you want to know how much of insulin she's needing for 24 hours to estimate your next level of plan. So starting nova mix 30 nova mix 30 is a mixed insulin. So it works for about 12 hours and this patient is getting the feed for approximately 24 hours. So if you want to do that option, we can do, but you need to give it twice a day. And in addition to that, the tricky part is it's very difficult to estimate how much of nova mix to start. So maybe not at this point of time, Lantus is a good option because like I mentioned before, Lantus works for 24 hours and this feed is being used for 24 hours, so it works ok. But you would not know how much to start. But if you absolutely want to avoid the use of sliding scale for reasons like the patient is fluid overloaded and you don't wanna give the additional fluid through the sliding scale, then you can start a safe level of Lantus and increase it as per the CBGS Tresiba. Not really because it works for 42 hours. You don't want to give this Tresiba and end up the patient having hypo just in case the feed is being stopped after the 24 hours. So you don't want to give Tresiba in this situation because you don't know how long the feed is going to continue and the feed is only for 24 hours and the patient can't eat at the moment so it can become dangerous and it's not the most suitable option. Give that dose of norepine. Yes, you're giving a short term solution but not a longterm solution. So not really for that option. Moving on to the next case study. So this is a 20 year old uh gentleman. He is, he works as a painter. He presented with a History of Polyuria polydipsia and weight loss of six kg over three months. And his biochemical evaluation shows a random capillary glucose readings of around 10 to 15 high HP one C 87 high. And his G AC A T antibody is positive. So how would you manage this patient? What does the patient have? Excellent. So it's a new diagnosis of type one. So absolutely, the patient is basal and bolus insulin. So for all of these patients, not only starting them on insulin is important, they need to be in a multidisciplinary, in a in a group of multidisciplinary team, they need to be known to the dietician. They need to see the diabetes specialist nurse because it's a lifelong diagnosis and they need to be under a very good team that has all of this um service provision for them. So the dietitian helps with the carbohydrate counting because although we start them on this approximate level of insulins, they eventually need to learn how much of carbohydrates they are taking and how much of insulin to be given as per their carbohydrate content. So the dietitian role is important there. And the diabetes specialist nurse to keep an eye on their control and to help advise on anything that they have. And they see the diabetes doctors every six months or so to look into everything else as a whole. Also make sure that these patients have regular, make sure that they know that they need their eye screening um, to be done annually if there is no problem and if there is a problem, they get it done every six months or so. And you need to make sure you check their feet when they come to the hospital for all of these diabetes patients because diabetes on its own can cause microvascular issues. And these are the other things that you need to pay attention to other than just the medications alone. So moving on next case case five K six. So this is a Lasix. Hopefully it's no good. Sorry, it's later. Are you guys in a rush though? Because I know I have exceeded the time. So I'm happy to stop if you guys feel that I'm going way over the time. So please feel free to stop me at any point. I have um three more cases. 678, I know I have four more cases. So let me know I'm going to continue, but please feel free to stop me at any point. So next case, 50 year old gentleman, um known type two diabetes or NOVO mix, so mixed insulin and Metformin one g twice a day. He could not tolerate SGLT two. It's and due to recurrent uti S and he does not qualify for G LP one analog. So essentially what I'm trying to say is he doesn't qualify for any other um tablet medication and he checks his C BGS four times a day and these are his readings. So fasting, pre lunch, predinner and bedtime, I've put the, the nice guideline target for patients. Usually we use this target for type one patients, but we cross cover and we use the same target for type twos as well. So you can see that all of them are off target. And what would you do? So all of you have put um switch to Lantus and nova rapid. So yes, but we don't have the HP A one C here. So I think uh what I was trying to get here is that it is suboptimal, the the readings are high and you can see that they are above the target. But I think what we can do here is we can try to adjust the novo mix 30 dose and try to increase it by 10 to 15% and see where we are and continue monitoring. And if that doesn't work because let's say the patient is just on novo mix for the last couple of years, I think it's a bit too soon to go on to basal bolus. Really? Like I said, basal bolus is usually towards the end and you can give a good 5 to 8 years of them being on base uh on mixed insulin before thinking of that option. So, in this patient, I would think the best thing to do would be to increase the novamine by 10 to 15% and seeing the response and taking it from there because it's high across. So increasing both the doses of the nova mix, morning and evening dose would be helpful for this patient. And we usually say 10 to 15% in CRE and the patients actually can do it themselves. If they feel that the CBGS are still high after three days, they can increase the NOVO mix by another 10% themselves. Um, next one, so 46 year old gentleman known type one on Lantus 18 units at night and Novo raid six units three times a day and he checks his CB GS four times a day and these are his readings. As you can see they are all again off target. Um What would you do? So first option control already optimized. No further action needed. Absolutely not increase Lantus um by two units. So reasonable. Uh You can see that the I have told before that you use the fasting cbgs to estimate the long-acting insulin ie the Lantus. So you can see that the fasting is 14, which is high and the target that we usually want is between 5 to 7. So if you increase the Lantus by 10 to 15% it comes to approximately two. Yes, I think that is a good option. Increasing the Lantus increase, Lantus only by eight units is a bit excessive. So you're using almost 50% increase, which we don't usually do and it's not like his fasting glucose is in twenties or something for you to think about something extraordinary. But you don't, you still start small and increase it gradually. So increasing Lantus by two units and novo raid by two units. I think a majority of you guys have voted for that. Excellent because clearly the pre luch predinner uh readings are still off target. So you want to increase all of the basal in the Bolus insulins as well. And similarly, we say 10 to 15% for basal or bolus when the C BGS are suboptimal. So you use the fasting reading to gauge the long acting insulin need. And for pre lunch, basically, you check the pre lunch to know whether or not the breakfast insulin you gave is enough. Hopefully, that makes sense because once you give the breakfast insulin, it takes about 4 to 5 hours to be out of your system. So by the time you check your pre lunch reading, you are getting a rough estimate of whether or not the breakfast bolus that you have given was enough. So the pre luch is usually used to estimate the adequacy of the breakfast bolus that you have given. And the predinner. Similarly, it gives us a rough estimate to see whether or not the lunch dose that you have given for the patient was enough. So in this patient, it's pretty easy in the sense that all of them are high. So you increase both both the basal and the bolus insulin but if in some patients you only see the pre lunches being high, that means you adjust the breakfast bolus insulin that you give. Not everything. I hope that that is clear to you guys because you don't always increase all of the insulin. You need to see which meal is affected and which specific insulin you need to increase. If there are hyper, I have two more cases. I'm really sorry. It's a bit long winded. Um ID. Again, any questions in the meanwhile? No, I have two more, but I wanted the last case especially because I wanted to mention about something so that we can all learn from it. Um Let's see. Oh, sorry, wish, sorry, I've just seen your text. Wish so. Ok, I am. Shall we stop? Wish. Yeah, I think we've, we've um probably gone over the time limit if that's all right. It's um I'm really sorry for everyone for all the tech issues we've had today. Um We will get a clean, clean up recording uploaded onto the system. So we'll have all the slides um and everything there. Um So don't worry about that and we'll make sure we'll send the slides out. Thank you for everyone system and also thank you so much, Ivanna for taking the time to thank you. Um Please do fill in the feedback. Um hopefully next time um on the 22nd of March, we'll be talking about a bit more about diabetes. Um And and we'll also talk about, um, sliding scales, diabetic emergencies and dry sliding scales as well. So we'll really delve into practical management of diabetes and try and tie up all the ex and talks that we've had in the past. Um, and, um, if there are any other sort of topics in endocrine and diabetes that you would want us to cover, please do let us know in the chat. Um, and I look forward to seeing you all for the next session. Thank you so much for persistent with us today. Thank you. Bye bye.