TREATING TYPE 1 DIABETES.....

Hi today we are going to discuss about how to manage type 1 diabetes.

Since type one diabetes is caused by autoimmune destruction of the pancreas, that results in an absolute deficiency of insulin, it makes sense that the treatment of type one diabetes is to give insulin. Now, this is true, but unfortunately it's not quite that simple. So let's talk about treating type one diabetes. And before we get into the specifics of the treatment, let's first briefly review some of the metabolic states in the human body. And there are two general states. You have the absorptive state in which the body takes energy and stores it and you have the post-absorptive state, in which the body takes this stored energy from the absorptive state and utilizes it. Now this absorptive state here is driven by the hormone insulin. Whereas the post-absorptive state is driven by the hormone glucagon. Now throughout the day, the human body will typically fluctuate back and forth between this absorptive state and this post-absorptive state. So to get a better understanding of how this looks, let's draw what I'll calla physiologic timeline. And let's just bring in a graph here to help describe this timeline. Now down here on this x-axis we'll have the time of the day. And right here in the middle we'll have noon, six in the morning, six at night, midnight, and then maybe we'll put three AM, nine AM, three PM, and nine PM. Now as I mentioned before, the body will fluctuate back and forth between this absorptive state and post-absorptive state. So let's see that here. And if you look closely, this fluxuation back and forth makes sense here, and around six AM when you go from this post-absorptive state while you're sleeping, and then you eat breakfast, and then you'll go into an absorptive state because you need to absorb the nutrients from the food in breakfast and then as your morning goes you go back into this post-absorptive state and so on and so forth. Now these changes back and forth between these metabolic states are driven by these hormones insulin and glucagon. So on the y-axis here, let's put in these hormone levels. So in purple here we'll put in insulin, and then in green we'll do glucagon. And what you can see from this is that it's really insulin here that's driving these changes between the post-absorptive state and the absorptive state. and glucagon also plays a role, but its level doesn't vary nearly as much as insulin's level throughout the day. Now since in type one diabetes the body doesn't produce enough of this insulin, it makes sense that the goal of treatment when we're treating type one diabetes, is to give insulin that will try and mimic the body's normal production of insulin. However, when we're treating type one diabetes, just giving insulin may be once or twice a day, as is done with most medication, doesn't really work because the levels are changing so frequently. 

So then how exactly do we manage type one diabetes? To get a better understanding of this, let's erase some of our work. Now fortunately, physicians and pharmacologists have created a very elegant method for treating type one diabetes. And this method is known as the Basal-Bolus Strategy. And in order to understand this concept a little bit better, let's first talk briefly about insulin. Now, insulin is a peptide hormone. And as such, that means when we give it as a medication, it can't be taken in a pill form, because the stomach and digestive system would break down the peptides or the protein of insulin into its component parts before it could be absorbed. And there for insulin must be given as an injection. And there are many different types of insulin that are available for use in the treatment of diabetes and they are classified based on how quickly they take effect, which is know as the onset of action and how long they work for, which is known as the duration of action. So to get a better understanding of this, let's create another graph similar to this one that we'll call the pharmacologic timeline. And on the x-axis here we'll put that duration of action. And this will be an hour, so we'll have maybe three, six, nine, 12, 15, 18 hours here. So one of the three main groups of insulins that can be given when treating type one diabetes are known as the rapid-acting insulins. And their pharmacologic time looks something like this. And these rapid-acting insulins usually take somewhere about 15 minutes to 30 minutes before the start working and their duration of action will last, you can see here, somewhere around four to six hours. 

Now the next major group of insulins are known as intermediate-acting insulins. And these intermediate-acting insulins, you can see by the graph, take a little bit longer before they have an onset of action, about 30 minutes to an hour, and then they last a little bit longer than the rapid-acting insulins, for somewhere between maybe eight to 12 hours, as you can see on the graph here. Now the last major category of insulin are known as the long-acting insulins. And as you can see on this graph, the long-acting insulins take even longer to take action, somewhere in the order of maybe one to four hours, and their peek action is not quite as intense as this rapid or intermediate-acting insulins, and their duration of action is much longer. Depending on the type of long-acting insulin, it can be somewhere between 12 and 24 hours. So now that we have a little bit better understanding of the different types of insulin and why it needs to be injected instead of taken as a pill, let's go back to this physiologic timeline here. And let's specifically look at this insulin level 

Now you notice that the insulin level never goes all the way down to zero. There's always this baseline level here. And we'll call this the basal level. And then intermediately there are these peaks, which we'll call boluses. And these boluses occur after we eat and they're what drive the transition from that post-absorptive state to the absorptive state, about three times a day, depending on how often you eat. Now hopefully what you can see by this is that if we transpose a couple of these graphs from the pharmacologic timeline onto the physiologic timeline, we can use injectable insulin to mimic this physiologic timeline in order to treat type one diabetes. So for these boluses, these kind of rapid peaks, you'll notice that they look somewhat like the rapid-acting insulin here. So let's put that on there. And then this basal level here, this constant level, you can create with a long-acting insulin. So we'll put that on the graph. Now hopefully what you can see by this, and it's starting to geta little crowded here so I'll highlight it, is that by using this Basal-Bolus Strategy someone with type one diabetes can kind of mimic the natural levels of insulin that the pancreas should be producing. And this is why this Basal-Bolus Strategy of treating type one diabetes is very efficient. Because it mimics what the body would do if the pancreas was working properly. So an overview of the Basal-Bolus Strategy is that usually once or twice a day, depending on the type of long-acting insulin, say in the morning and then again at night, someone with type one diabetes will take a dose of insulin, of this long acting insulin that will serve as this basal rate. And then at meal time they'll take an additional dose of the rapid-acting insulin to cover these boluses to help the body transition from the post-absorptive hereto the absorptive state, to absorb the energy in the meal they just ate. Now it's important to know that this graph demonstrates the principle of the Basal-Bolus Strategy, but it is somewhat of an oversimplification and that proper insulin management requires one to be very diligent with their insulin dosing and administration. 

This is especially important in regards to the bolus doses here. And this is because the amount of insulin that someone's gonna need to take with each bolus dose will vary depending on what their blood sugar is at that time as well as on how many carbohydrates they're planning on eating. So in order to properly manage their insulin regiment, individuals with type one diabetes must regularly check their blood sugar levels and adjust their insulin dosing accordingly. Now type one diabetes can be a very serious and potentially even lethal disease. 

However, with diligent adherence to the Basal-Bolus Strategy and regular appointments with one's physician in order to adjust the insulin dosing as well as monitor for complications, someone diagnosed with type one diabetes can still live a very healthy and long life.

If left with any query you can comment in comment section below.

DIABETES MELLITUS AND INSULIN

Hi, today we will be discussing about the relationship between diabetes mellitus and insulin.

We can break down food into many different types of nutrients. One of the most important nutrients our body needs is a sugar called glucose, which is the fuel that powers the cells of our body. Glucose is transported throughout the body by blood and requires careful regulation, since too much glucose in the blood can lead to disastrous consequences, such as diabetes mellitus. Read this article to learn more about the symptoms, cause, and treatment of this disease.

Let’s talk about blood glucose regulation first. The body has many ways to increase or decrease the amount of glucose in the blood. Some ways to increase blood glucose include eating a meal, synthesizing glucose from scratch, or releasing glucose from storage, while some ways to decrease blood glucose are to transport glucose into cells, which either use up glucose for energy or store it. Throughout the day, the body is constantly making slight adjustments to keep blood glucose levels at an optimal range. These slight adjustments are controlled by the hormones insulin and glucagon, but in this article, we’ll focus on insulin. Insulin is released into the bloodstream when blood glucose is high, such as after a meal. It signals to cells to take in glucose for energy or storage. It also prevents more glucose from being synthesized or released from storage. Therefore, the overall effect of insulin is to decrease blood glucose levels. Diabetes mellitus, or simply diabetes, occurs when this insulin signalling pathway is broken. Without proper functioning of insulin, blood glucose levels skyrocket. Despite glucose being a very important source of fuel for the body, too much of it in the blood is extremely damaging. In the short term, high blood glucose leads to the hallmark symptom of diabetes: glucosuria, or glucose in the urine. In fact, the term “mellitus” means “honey” in Latin to reflect this symptom of sweet-tasting urine. How does this occur?

At the kidneys, glucose is filtered out of the blood and into the urine, but is later transported back into the blood since the body does not want to lose this valuable source of fuel. This reabsorption uses proteins which have a maximum rate of transport. When there is too much glucose in the blood, more of it is filtered into the urine. Even at their maximum transport rate, the proteins cannot transport all of the glucose out of the urine, leading to glucosuria. This causes excess urination, since the presence of glucose in the urine draws in more water by osmosis. Excess thirst and dehydration are a consequence of this since more water is lost through urine. In addition, since cells cannot take up glucose for energy without insulin, the body perceives itself to be “starving”, leading to both increased appetite and fatigue. In the long term, high blood glucose damages blood vessels in the eyes and kidneys, which is why diabetes is the leading cause of adult blindness and kidney failure. High blood glucose also damages nerves, leading to loss of sensation in the feet and hands. When those areas get injured, such as from cuts or from blood vessel damage, the person does not notice the injury, leading to infections and necrosis that eventually require amputation. Most importantly, the damage to blood vessels in the heart and brain can lead to high blood pressure, stroke, and heart attacks, which account for most of the deaths in diabetic patients.

Most diabetes cases can be divided into two types based on how the insulin signalling pathway is malfunctioning. Type 1 diabetes accounts for around 10% of diabetes cases, while Type 2 makes up most of the remainder. The last few percentage points are attributed to rarer forms of diabetes that you can check out in the video description. Type 1 diabetes is caused by a lack of insulin production. In the pancreas, there are special clusters of endocrine cells called the islets of Langerhans. One type of endocrine cell in these islets is the beta cell, which produce and release insulin. In Type 1 diabetes, the beta cells are destroyed by the immune system. Therefore, the body can no longer produce insulin and blood glucose levels rise uncontrollably, leading to the symptoms mentioned earlier. Scientists believe both genetic mutations and environmental factors, such as infections, may play a role in triggering this autoimmune attack. An additional symptom of Type 1 diabetes is rapid weight loss, as fat cells, or adipocytes, begin to break down fats into another type of energy molecule known as ketone bodies. Large amounts of these ketone bodies are released into the blood, which can be taken up by other cells as an alternative source of fuel. However, ketone bodies are slightly acidic molecules, so excessive amounts of these molecules can acidify the blood. This is known as diabetic ketoacidosis, which is a life-threatening condition if untreated. However, when most people think of “diabetes”, they are probably imagining the more common Type 2 diabetes associated with obesity, ahigh sugar and fat diet, and a lack of exercise. These three lifestyle factors, as well as genetic factors, dramatically increase the risk of developing Type 2 diabetes. Unlike Type 1 diabetics, Type 2 diabetics continue to produce insulin. However, their cells have become resistant to insulin, meaning that more insulin is required to achieve the same effect of lowering blood glucose. 

To compensate for insulin’s ineffectiveness, beta cells will produce even more insulin. However, when insulin resistance becomes so severe that the insulin required by the body exceeds the maximum amount of insulin produced by beta cells, symptoms of high blood glucose begin to appear. Weight loss and diabetic ketoacidosis from fat breakdown also occur in some cases of Type 2 diabetes. Furthermore, in some cases the continued overproduction takes a toll on the beta cells, which eventually die and causes a lack of insulin production, further worsening the problem. The cause of insulin resistance is still not well understood; however, factors such as high insulin levels from excessive sugar consumption and fat around the liver and pancreas are being investigated as possible causes of insulin resistance. It is important to note that it is very difficult to “cure” diabetes as of now. Doctors are only able to make living with diabetes tolerable, as long as medications are taken and lifestyle changes occur. Current treatment depends on the type of diabetes. Since the high blood glucose of Type 1 diabetes is caused by a lack of insulin, simply administer insulin during periods of high blood glucose, such as after a meal. However, this is easier said than done. Insulin is a protein and will get degraded in the stomach if taken orally. Therefore, Type 1 diabetics must inject insulin directly into the bloodstream, usually just under the skin of their abdomen. The dose is also extremely important – too little and blood glucose levels remain high, but too much insulin will cause blood glucose levels to plummet, leading to coma or even death. On the other hand, decreasing high blood glucose in Type 2 diabetes is much more complicated. Insulin is only effective in around 30% of patients as cells are already insulin resistant, so other methods of decreasing blood glucose are required. Many diabetic drugs have been developed which target the mechanisms of blood glucose regulation mentioned in the beginning of this video. These drugs can decrease glucose absorption in the intestines after a meal, decrease synthesis of new glucose, or increase insulin sensitivity which leads to more glucose uptake by cells. For example, the drug metformin is the first line treatment to Type 2 diabetes because it can activate certain metabolic pathways to both decrease glucose synthesis and increase glucose uptake by cells by increasing insulin sensitivity. However, despite our best efforts, diabetes is the 6th leading cause of death worldwide, with 3 people dying from diabetes complications every minute. Therefore, the best treatment of diabetes is to prevent diabetes from occurring in the first place. Though no prevention method is known for Type1 diabetes, frequent exercise and a healthy diet drastically reduces the risk of the much more common Type 2 diabetes. Currently, it is estimated that 400 million adults, which is around 10% of the worldwide adult population, is living with diabetes, although this number is expected to increase in the future. If more people become aware of and avoid the lifestyle choices associated with diabetes, we can slow down or even reverse this trend. 

Furthermore, Type 2 diabetes in particular develops slowly and silently over time, leading scientists to suspect that almost half of the worldwide diabetic population is undiagnosed, which is why it is so important to educate the public about the causes and symptoms of this disease. It is also important to note that diabetes is an extremely complex and not fully understood disease that scientists are still finding new information about everyday. So if you want to learn more about diabetes, like new treatments and research, check out the links in the description below.

Thanks for reading.