Blood Glucose after Transplant: Why It Matters

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Blood Glucose after Transplant: Why It Matters 

Monday, May 1, 2023 

Presenter: Emily Gallagher MD, Ph.D., MRCPI, Mount Sinai Hospital 

The presentation is 35 minutes long, followed by 15 minutes of Q&A 

Summary: This video discusses what normal blood glucose levels are, what the health consequences are of having blood glucose levels that are either too high or too low, how a stem cell transplant can affect blood glucose levels, and steps stem cell transplant recipients and their healthcare providers can take to detect and manage blood glucose levels. 

Highlights: 

• High blood glucose can lead to short-term health consequences such as frequent urination, dehydration, increased appetite, weight, blurry vision, tiredness, and confusion. If left untreated, it can result in serious long-term health problems. 

• Several factors associated with a stem cell transplant can increase the risk of high glucose levels in patients. These include the chemotherapy and/or radiation given prior to transplant; graft-versus-host disease; drugs used to control graft-versus-host disease; infection; intravenous feeding; and the stress of transplant. 

• Low blood glucose can also be a problem after a stem cell transplant causing increased hunger; feeling pale, sweaty, cold and clammy; irritability; heart racing; and/or weakness or tingling. 

Key Points: 

(01:31): Glucose is a type of sugar that is commonly found in food. Glucose provides energy to our organs, such as our brain, for thinking and our muscles, so that we can do activities.  

(02:51): The body regulates blood glucose levels through insulin. When we eat, our blood glucose levels increase, and our pancreas produces insulin. The insulin helps transport glucose from the bloodstream into muscles and fat for energy, then lowers the blood glucose levels back to normal. 

(03:24): High blood sugar is caused by insufficient insulin production in the pancreas or the body's inability to respond normally to the insulin produced. This condition is commonly known as diabetes. Certain medications may also affect insulin production, leading to high blood glucose levels. 

(07:09): If the blood sugar is very high for a long period of time, people can get very dehydrated, which can cause changes in some of the salts and the electrolytes in the bloodstream and can eventually affect the brain, kidneys, heart and/or nerves.  

(07:43): Diabetes can have long-term consequences, including changes to the back of the eye that can cause vision loss, kidney damage leading to failure, and nerve damage which high blood sugar levels can worsen. It is one of the most common causes of vision loss and kidney failure. After a bone marrow transplant, chemotherapy can also cause nerve damage that can be worsened by diabetes. 

(17:27): While body mass index (BMI) is a risk factor for diabetes, it is not the only factor. Many people with normal BMI can still have high glucose levels. And even people with high BMI can have normal glucose levels, especially after stem cell transplants. 

(25:24): People can develop low blood glucose levels after a stem cell transplant if they have been taking glucocorticoids or corticosteroids for an extended period of time. When the steroids are stopped, the body may not produce enough cortisol, which can lead to low glucose levels. 

(27:35): To treat high blood glucose levels after a stem cell transplant, it is important to inform your doctor about all your medications. Some of the medications used after stem cell transplant may contribute to high blood glucose levels, and there is also the potential for drug interactions. Your doctor can choose the right medication to treat high blood glucose levels. 

(34:23): High blood glucose after transplantation can lead to short-term and long-term health problems. Knowing the symptoms and talking to your doctor about treatment to reduce your risk is important. 

(32:39): Be cautious about taking supplements or herbs to control glucose levels after transplant. They may interact with other medications you are taking. 

Transcript of Presentation: 

(00:01): [Marla O’Keefe]: Good afternoon. Welcome to the workshop, Blood Glucose after Transplant: Why It Matters. My name is Marla, and I will be your moderator for this workshop. 

(00:11): Introduction of Speaker. I am pleased to introduce today's speaker, Dr. Emily Gallagher. Dr. Gallagher is a board-certified physician in internal medicine and endocrinology, diabetes, and metabolism at Mount Sinai Hospital in New York. In her clinical practice, she sees firsthand how diabetes may contribute to specific symptoms and illnesses in people who have received a stem cell transplant or CAR-T cell therapy. She also treats patients with no history of diabetes but who develop high glucose levels when diagnosed with graft-versus-host disease. Please join me in welcoming [Dr. Emily Gallagher]. 

(00:51): [Dr. Emily Gallagher]: Thank you, Marla. And thank you, BMT InfoNet, for inviting me to present today. I'm going to present on blood glucose after transplant and why it matters. 

(01:05): The learning objectives from today's presentation are to hopefully help you understand what normal blood glucose levels are, what the health consequences are of having blood glucose levels that are either too high or too low, how a stem cell transplant can affect blood glucose levels, and then steps stem cell transplant recipients and their healthcare providers can take to detect and manage blood glucose levels. 

(01:31): First of all, what is glucose? Glucose is a type of sugar that is commonly found in food. Our bodies make glucose from carbohydrates. So, if you look at the nutritional label here, as an example, that you can frequently find on many food items, you can see that the main food categories are total carbohydrates, which is here, which is the glucose or sugar in your food. It can also be made up partly of dietary fiber. And then the other two major constituents of nutrition and food are fat and then also protein. 

(02:11): Why do we need glucose? When we eat food that contains carbohydrates, our body breaks it down to form glucose, or what we often call sugar. This causes the glucose levels in our bloodstream to increase, which is shown in the schematic here. And this is important because it provides energy to our organs, such as our brain for thinking and our muscles, so that we can do activities. 

(02:35): We also store this glucose in our liver. So when you're fasting, you don't want your blood sugar to drop too low. And so when you're fasting, your liver puts out a little bit of glucose to keep your blood glucose levels normal. 

(02:51): How do we keep our blood glucose levels normal? As I said, when we eat, our blood glucose levels increase, which is regulated by our pancreas, which makes insulin. Insulin helps our bodies take the glucose from our bloodstream into our muscles and our fat so that we can use the glucose for energy. And then, the blood glucose levels will come back down again and return to normal, as the insulin from our pancreas causes the glucose to go into these tissues, such as muscle and fat. 

(03:24): What makes blood sugar go too high is if we do not make enough insulin. Some people's pancreas doesn't work properly and can't make enough insulin to bring down blood glucose. Or, they can produce insulin, but for some reasons, such as sometimes certain medications, we can be making insulin. Still, our body doesn't respond normally to the insulin that we make. And so our blood glucose levels don't decrease when we make insulin. And this is what causes blood glucose levels to be high. And this is what we commonly refer to as diabetes. 

(03:53): How common is having high blood glucose or diabetes? This is a picture of the world from the International Diabetes Federation 2021 Diabetes Atlas, showing the rates of diabetes across different countries. So you can see some countries with the darkest colors, where more than 12% of the population have diabetes. If you think about it another way, this is one in every eight people or so has diabetes. And then in other countries, like the pink ones, it's closer to one in every ten people. So diabetes is a very common disease affecting one in 10 or more people in different populations. 

(04:45): Diabetes also becomes more common as we get older. In this picture, you can see the rates of diabetes as people age. On the left-hand side is people aged 20 to 24 years of age. And then on the right-hand side, it's age 75 to 79. As you can see, in high-income countries, middle-income countries, and low-income countries, the prevalence of diabetes goes up as we get older. 

(05:14): What happens if blood glucose levels go too high? If your blood glucose is too high, you can get short-term and long-term consequences. 

(05:24): Symptoms of high blood sugar. A symptom of having high blood sugar, in the short term, is that it tends to cause people to urinate more frequently. And this is because if your blood glucose is too high, the only way your body can get rid of that glucose is in the urine. And this causes people to become dehydrated as they urinate more to get rid of the glucose from their bodies. This draws out the water as well. And this can cause people to become dehydrated or feel thirsty. And so, there's an increase in thirst. 

(05:49): Surprisingly, people can have an increase in appetite when their blood glucose is too high. And this is because the glucose should go into this muscle to give you energy. Still, your body can't get the glucose where it should be. And so even though your blood glucose is high, people frequently feel hungry and crave sugary food, sometimes because their bodies think they don't have enough glucose. And so sometimes you can get an increase in appetite. 

(06:14): People often lose weight. And so, this is a problem that we frequently see when people have high blood sugar, in that they're eating, they're taking in calories, but the glucose is getting wasted in the urine. So, they're losing all those calories in their urine. When the blood glucose is high, they can lose weight, and it can be very difficult for people to regain weight when they have very high blood sugar because they're losing the calories that they're taking in. 

(06:36): Another thing that can happen is that people can get blurry vision. This needs to be more recognized. People don't realize their vision is blurry because their blood sugar is high. This is because the lens in the eye can get dehydrated. It can change the vision. When the blood sugar returns to normal again, people's vision returns to what it was after a few weeks. 

(06:57): People can feel tired. And this is because the glucose you're taking in your diet is in the blood, and it's not getting into the muscles and the tissues that it's supposed to be going to. This can cause people to feel very tired and lack energy. 

(07:09): Eventually, if the blood sugar is very high for a period of time, people can get very dehydrated, which can cause changes in some of the salts and the electrolytes in the bloodstream. And this can eventually affect the brain, and people can become confused. People can become comatose because of high blood sugar in its most serious form.  

(07:31): So, all of the symptoms, usually the urination and the thirst, come first, and the weight loss is after that. And if it goes on for a very long time, the people develop confusion and a coma. 

(07:43): Long-term diabetes can have other consequences. So, if somebody has had diabetes for 10 or 20 years, if it's uncontrolled, they can end up with changes to the back of the eye, which can cause loss of vision. Diabetes is one of the most common causes of vision loss. 

(08:00): It can also damage the kidneys. So again, when the blood sugar is high, over time, the glucose can cause damage to the kidneys, and this is a common cause of people ending up with kidney failure. 

(08:12): It can also damage the nerves. Specifically, after a bone marrow transplant, many people have had chemotherapy which can cause damage to the nerves. And if people also have high blood sugar or diabetes, this can worsen. 

(08:25): Numbness in the feet can be a problem with longstanding diabetes. It's important because when people have numbness in their feet if they get an infection or an ingrown toenail, they sometimes don't feel any pain from the infection in the foot, which can lead it to become uncontrolled. And then the infection can sometimes get quite deep. Then people can end up with serious infections in the bones of their feet on occasion or non-healing ulcers in the feet. 

(08:49): In the long term, we also can get circulation problems related to high blood sugar, which can affect the heart. So, people can end up with a narrowing of the arteries in their heart. 

(08:58): It can affect the brain. People can sometimes have a stroke from longstanding diabetes. 

(09:02): The circulation to the legs can be affected by diabetes, which can cause pain or cramps in the legs when people try to exercise or walk. And they can also end up with poor circulation. So poor healing in the feet if somebody was to get an infection. 

(09:17): Consequences of high blood sugar for transplant recipients. Specifically in stem cell transplant recipients, there are other consequences of high blood sugar. Sometimes high blood sugar can cause somebody to stay in the hospital for a more extended period of time, and this is because the glucose needs to be under control for the person to be discharged home. 

(09:33): It can also lead to an increase in graft-versus-host disease. Some studies show that people with high blood sugar or diabetes are more likely to get graft-versus-host disease. 

(09:43): As I mentioned, diabetes can cause some kidney damage, partly related to dehydration from diabetes and also related to high blood sugar. 

(09:50): People are more likely to get infections with uncontrolled high blood glucose levels. Along with all the complications that people can get from diabetes and high blood glucose, especially in the setting of stem cell transplants, it can reduce life expectancy. It can reduce the quality of life-related to some of the complications. 

(10:11): So, I'm not going to get into great detail about the long-term risks of heart disease. Essentially, there are many individual factors, such as the person's age, sex, race and ethnicity, and family history of cardiovascular disease, that can increase their risk. And diabetes plays into all of these factors that can lead to accelerated heart disease. 

(10:37): So, the treatment factors related to the stem cell transplant include chemotherapy, and sometimes radiation can increase the risk of developing cardiovascular disease. The stem cell transplant itself and the conditioning treatment for the stem cell transplant can also increase the risk. And then graft-versus-host disease, a type of inflammation, can also increase heart disease. And diabetes, on top of all these factors, can also increase the risk of developing cardiovascular disease. 

(11:09): There is another myth that's out there. People think that glucose [sugar], itself, can cause cancer. So why is this propagated, and why do people believe this? 

(11:19): Some cancer cells take up glucose. If you ever go for a PET or a PET CT scan, the injection they give is a type of glucose, which tends to go to very metabolically active cells. And the metabolically active cells take up glucose, some of which are cancer cells. 

(11:38): But as we know, we also have to use glucose for our skeletal muscles to get energy. And so when people go for this test, they fast specifically so that the glucose doesn't go to their muscles and instead can be taken up by the tumor cells. 

(11:53): The second thing is that people with diabetes have a higher risk of developing certain types of cancer. So, for example, with multiple myeloma, some studies show that people with diabetes have a greater risk of developing these cancers. However, there's no evidence that the glucose in our diet causes these cancers. And so, this is a very different thing. We must have a certain amount of carbohydrates or glucose in our diet to give our bodies the energy they need. And so, a lot of confusion happens here, basically, related to the links between glucose and cancer. Still, it's important that we don't starve ourselves of glucose because we need nutrition, especially to recover from stem cell transplants. 

(12:36): How can the stem cell transplant increase blood glucose levels? The conditioning treatment before stem cell transplant has been associated with increased blood glucose levels. The stress of the stem cell transplant itself can increase glucose levels. Sometimes after stem cell transplants, people can't eat or take nutrition. Sometimes if people have complications from the transplant, they require intravenous nutrition, which tends to contain lipids or fat, protein, and carbohydrates. And sometimes, the glucose of the carbohydrate in the parenteral [intravenous] nutrition can increase glucose levels. And so often, people will end up with insulin in the parenteral nutrition, as well, to control their blood glucose levels. 

(13:21): The immunosuppressive treatments after a stem cell transplant include glucocorticoids or steroids. Immunosuppressives such as tacrolimus, cyclosporine, and sirolimus can increase glucose levels. 

(13:35): Graft-versus-host disease can cause glucose levels to increase. And then the inflammation after the stem cell transplant. Inflammation can come in a variety of ways. One can be infection, sometimes increasing and decreasing blood glucose levels. Graft-versus-host disease is a type of inflammation in the body that can cause glucose levels to go up. And then again, the steroids used to treat these conditions can also increase glucose levels. These factors can either reduce insulin production - so as I mentioned in the earlier slide, the way that our bodies usually control glucose is to increase insulin production from the pancreas. But if we cannot increase the insulin production from our pancreas, or if one of these treatments affects insulin secretion, then glucose levels will increase. 

(14:18): The second way they can affect blood glucose levels is to reduce our body's response to insulin. We can't reduce the glucose levels as usual because these medications, or these treatments, can sometimes interfere with how our body responds to insulin. And so both of these things can then increase blood glucose levels. 

(14:39): Age is another factor that increases the risk of developing high glucose levels. So, as I showed you in the earlier slide, the older we are, the more likely we are to develop diabetes if we have a family history of diabetes. So, if we have mainly a first-degree relative, such as a parent or sister or brother, with diabetes, then that increases our risk of developing diabetes. 

(15:00): Certain racial and ethnic groups are at higher risk of diabetes. And then being overweight or obese, as measured by body mass index, can increase the risk of developing diabetes. 

(15:10): People with certain health histories have a higher risk of developing diabetes. If you ever had diabetes during pregnancy, it increases the risk of developing diabetes down the road. People with a history of polycystic ovarian syndrome can also have a higher risk of developing diabetes. 

(15:21): People who have HIV or medical treatments for HIV also increase the risk of developing metabolic diseases such as diabetes. And physical inactivity can also increase the risk of developing high glucose because normally when we're active, we use the glucose in our muscles, whether walking around or doing the more rigorous activity. And therefore, if we're not active and not moving around, then we're not using up as much glucose, which can increase the glucose levels. 

(15:50): What is body mass index? I mentioned body mass index or BMI, so what is that exactly? When we see patients, we measure their body mass index, which gives us an idea of whether they're a healthy weight or overweight or underweight. And so, what we do is we measure somebody's height, and we measure their weight. And then, there are online calculators that we use or that you can use to calculate your body mass index. 

(16:22): What is the body mass index, and what do the numbers mean? If the body mass index is calculated as less than 18.5, we're underweight. A typical weight body mass index is considered between 18.5 and 24.9. It's considered overweight if the body mass index is between 25 and 29.9. And obesity is a body mass index of 30 or greater. 

(16:48): A body mass index in the overweight or obese range increases our risk of certain conditions, including diabetes. There are some very important caveats to body mass index. It's not a perfect measure. The BMI ranges are different in different racial and ethnic groups. 

(17:08): For example, in Asian Pacific regions, the numbers are different. This is because people can develop metabolic diseases at lower BMI levels. And so here, overweight is considered 23 to 24.9, and obesity has a body mass index of greater or equal to 25. 

(17:27): There are also some other important caveats. You can have a higher risk of developing diabetes with a higher BMI. Still, many people have typical body mass indexes and can also have high glucose levels. And so, although it does increase the risk of having an overweight or obese body mass index, there are plenty of people, especially after stem cell transplants, that, due to other reasons, can have high glucose levels, even if their body weight is normal. 

(17:52): The waist circumference is a different measure. Suppose you think about somebody's body mass index. In that case, you can have two people with the same body mass index, but their weight distribution is very different. So, some people can have weight around their thighs and hips, which is considered more metabolically healthy than somebody with the same weight. Still, the weight is distributed more around their stomach. So, the body mass index cutoffs may be imperfect in certain racial-ethnic groups, in people getting treated with stem cell transplants, and in people with different body weight distributions. 

(18:32): How can we tell if we have high glucose levels? I always tell people about the symptoms of high glucose levels. This is important to recognize because often, people don't realize why they're losing weight, they don't realize why their vision's blurry, and they don't know why they're always thirsty. And so, recognizing the symptoms of high glucose is one very important thing. 

(18:53): The second thing is that you can get blood tests to check your glucose level. And, if you regularly get blood tests done, you may not realize the glucose is done in almost all routine lab tests. 

(19:06): What are normal and high blood glucose levels? There are different criteria used to define high glucose. This is from the American Diabetes Association 2023 Guidelines. Depending on which country you're in, the measures are slightly different. 

(19:21): So in the US, milligrams per deciliter, which is the top row here, is the typical measure. In Europe and Canada, and other countries, millimoles per liter are typically used. The numbers look quite different, depending on which measurements you're using. 

(19:36): So, to focus on the US ones, normal is considered less than a hundred milligrams per deciliter, and this is fasting glucose for at least eight hours. A borderline or prediabetes glucose level is between 100 and 125 milligrams per deciliter. And then greater than or equal to 126 is considered high glucose or diabetes. And this is again fasting. 

(19:57): Often, people aren't fasting when they come in for blood tests, and they just get blood tests done as part of their random routine measurements. And so, in that situation, the glucose levels will be different. 

(20:09): One test that we do sometimes is a two-hour glucose tolerance test. This is where somebody comes in fasting, and we give them 75 grams of glucose to drink and then measure the blood glucose for two hours after the test. If the two-hour level is less than 140, it's considered normal. The Borderline is between 140 and 199, with a high glucose level greater than 200. 

(20:34): We can also define diabetes based on hemoglobin A1C, which I'll explain in more detail on the next slide. But a hemoglobin A1C of less than 5.7 in the US is considered normal. 5.7 to 6.4 is what's considered prediabetes or borderline diabetes. And high glucose or diabetes is considered an A1C greater than or equal to 6.5. In Europe, the measurements are slightly different. They're measured in millimoles per mole for the A1C. And here on the bottom are different cutoffs. 

(21:09): Now, as I said, some people don't come in fasting for tests and don't have a glucose tolerance test, but we can still define high glucose. And this is where somebody comes in with random glucose, meaning it's any time of day greater than or equal to 200 milligrams per deciliter. Suppose they also have symptoms such as thirst, increased urination, and weight loss associated with high glucose levels. In that case, you don't necessarily have to have the glucose tolerance test or fasting blood glucose to define diabetes. 

(21:36): Hemoglobin A1C, why is it important? What is the hemoglobin A1C? Some people find this confusing because, if you look at your blood tests and you're used to thinking about the bone marrow and your cells, people often confuse hemoglobin A1C with their hemoglobin level. 

(21:54): So what exactly is hemoglobin A1C? Your red blood cells are made in the bone marrow and released into the circulation [bloodstream]. And the red blood cells live in the circulation [bloodstream] as long as nothing is happening to them for approximately 120 days, which is three months. 

(22:16): Your red blood cells contain hemoglobin, a molecule that carries oxygen around in the blood. If you get your complete blood count done frequently, we will get the result of the hemoglobin level. If it's low, this is a sign of anemia. Essentially, this is a measure of red blood cells in the circulation. [bloodstream]. 

(22:38): So, the hemoglobin carries around oxygen. If you're anemic, your red blood cells are low, or the hemoglobin level is low. One major symptom people often get is fatigue because they have a decreased ability to carry oxygen around in their blood. 

(22:50): However, the hemoglobin also binds to glucose. So, when you have high glucose in your blood, this glucose also binds to the hemoglobin. We use this as an indirect measure of glucose levels over the past three months because that's how long the red blood cells, or the hemoglobin, survive in the circulation [bloodstream]. So as the red blood cells go around in the circulation [bloodstream] over the course of those three months, they have the ability to bind to whatever glucose is in the circulation [bloodstream]. Then we use this hemoglobin A1C measure to measure the blood glucose level. 

(23:23): So a caveat to this: In people who've had a stem cell transplant, is that if somebody gets a blood transfusion and the red blood cells in their circulation are not theirs, then for the period of time that those red blood cells from a blood transfusion survive, the hemoglobin A1C is going to be inaccurate because the red blood cells haven't come from their glucose being bound. So in that situation, you can't rely on the hemoglobin A1C, and we typically will measure the blood glucose levels instead. 

(23:53): The second thing is if somebody is bleeding, so if they lose blood for some reason or are not making red blood cells properly from their bone marrow, the hemoglobin A1C measure can also be inaccurate. 

(24:06): What happens if blood glucose levels are too low? So, we focus mostly on high blood glucose levels, but people can also have low blood glucose levels after stem cell transplants. The symptoms of low glucose levels are often that people feel hungrier, and this is because they're missing the nutrients that they need. They often feel pale and sweaty and cold and clammy. This is a common symptom of low blood glucose levels. 

(24:32): They can often be anxious or irritable, so not acting like themselves because the glucose levels in their brain are decreased. You can feel like your heart is racing, and people can feel a weakness or a tingling. If it's a severely low glucose level, people can become confused and blackout and have seizures and coma. This is a very severe situation if this occurs. 

(24:55): So how do you know if your symptoms are from low glucose? Sometimes these symptoms can be confusing because people can feel anxious and irritable for other reasons, and sometimes anxiety can cause the heart to race. It may not be from blood glucose. So, the main way to check the glucose levels, if somebody's getting these symptoms, is to check it with a finger stick glucose meter. And if the level is less than 70 milligrams per deciliter, this is considered low glucose. 

(25:24): If somebody's been on steroids for an extended period, then the steroids they take as pills cause their cortisol levels to decrease. How can people develop low blood glucose levels after a stem cell transplant? So, this is typically seen in a few different situations. One is that often, after a stem cell transplant, people can have been treated with glucocorticoids or corticosteroids for a period of time. If somebody's been on steroids for an extended period, then the steroids they take as pills cause their cortisol levels to decrease. So, because you're getting the cortisol in from the pills, your body doesn't have to make cortisol. And so, over time, this can cause somebody's cortisol levels to become very low, which can lead to adrenal insufficiency or low cortisol levels when the pills get stopped. And one of the symptoms of low cortisol levels is low glucose levels. And so, this is a very common thing that we see. It's very important to recognize that when somebody stops steroids after having been on them for a very long period, they are at risk of having low cortisol levels. 

(26:26): Sometimes, when people are on steroids and other medications that increase their glucose levels, doctors prescribe them a lot of glucose-lowering medicine. And so it's important then if the steroids and the other transplant-related medications are getting reduced or stopped over time, that somebody's looking at those medications that are being prescribed to lower the blood glucose as well because they would also need to be decreased or stopped at the same time. 

(26:50): When somebody has a loss of appetite or is fastening and also taking blood glucose-lowering medications for diabetes, then this can also contribute to low glucose levels. So some of the medications to treat diabetes are pills that increase the amount of insulin that we make in our bodies. And, if you're not eating and you're making too much insulin, this can drop the glucose levels to become too low. So it's important again if you're not eating, to talk to your doctor about whether you should be taking your diabetes medication or not. 

(27:19): Certain infections can sometimes lead to low glucose levels. So bacteria occasionally like to take up glucose, which can reduce the glucose levels in the circulation and blood and be a sign of somebody potentially having an infection. 

(27:35): Then how do we treat high blood glucose levels? The doctor treating you for your blood glucose must know that you had a stem cell transplant because some of the medications you're taking after the stem cell transplant may be contributing to the blood glucose levels. There's also the potential for drug interactions related to stem cell transplant and glucose-lowering medication. And so, it's very important that your doctor knows all of the medications that you're taking so that they can choose the right path for you or the right medication to treat the glucose levels. 

(28:11): Also, tell the doctor helping you take care of your blood glucose about your symptoms. So if you're experiencing a lot of weight loss or have lost a lot of weight, diabetes medication may not be the right choice. And so, it's essential to talk to your doctor about all the symptoms you're getting and all the treatments you're getting to make the right decision. 

(28:28): It's also ideal if your oncology or your stem cell transplant doctor can communicate with your diabetes doctor so that if one person is changing a medication, the other person is aware of it in case you develop a side effect or that the medications can be changed together. If you're reducing medications, like steroids, make sure that the diabetes doctor is aware that this is happening so they can also reduce your diabetes medication. 

(28:54): What are the main things we do to treat high blood glucose levels? One thing is lifestyle changes - nutrition and physical activity; I won't get into great detail about nutrition. There is a talk by Michelle Myers on Thursday about nutrition after a stem cell transplant. Still, one of the simplest things to do is avoid concentrated sweets and sugars and have a balanced food intake. Sometimes all you need is to reduce a lot of sweets and sugars in the diet, which can help with glucose control. Sometimes people can do this and not even need extra medications or pills to regulate their glucose levels. 

(29:38): Physical activity. Suppose somebody's able to do some physical activity, even if it's a small amount of activity. In that case, it will also help to decrease glucose levels. 

(29:47): Then diabetes medications. There are several diabetes medications that we have. As I mentioned, it's important that your diabetes doctor knows what medication you're getting after the stem cell transplant, if any, because some of these medications haven't been studied in people who previously had a stem cell transplant. Sometimes they can interact with stem cell transplant therapies. And so, it's important to weigh the risks and benefits and for your doctor to be aware of everything going on after the stem cell transplant. 

(30:15): Sometimes, we treat people with insulin if their blood glucose levels are very high. This is because it can be easily adjusted. As long as you understand and your doctor has explained how insulin works, you can often more rapidly control the blood glucose levels with insulin. You can also reduce the doses quickly if somebody needs to reduce the insulin doses. 

(30:36): It also doesn't typically cause other side effects, so it doesn't cause issues like diarrhea or stomach upset. The disadvantage to insulin is that it's an injection, so people often don't like taking the extra injection to lower their glucose level. 

(30:53): Another important thing about insulin is that insulin. At the same time, controlling glucose levels can be very helpful; it can work a little too well. It can lower your blood glucose levels a little too much. There are different types of insulin. There are long-acting insulins and short-acting insulins. And so it's helpful if you understand the type of insulin you might be taking so that you can work with your doctor to adjust it to control the blood glucose levels as much as possible. 

(31:18): And it can be dangerous if, for some reason, you have been started on insulin and you were also, for example, on steroids, and then the steroids got reduced, and you're still taking the insulin. This can cause your blood glucose to drop too low, which can be dangerous, and you can develop the symptoms that I mentioned before at low glucose levels. So your doctor must be aware of what other medications are being changed so that you can also adjust the insulin. 

(31:45): So, how do you monitor your blood glucose? There are a few ways that you can monitor your glucose. One, the most traditional way, is by finger stick monitoring. In people with neuropathy, like numbness of their fingers or painful neuropathy after previous cancer treatments, this can sometimes be problematic because you have to prick your finger with finger stick monitoring. 

(32:06): Similarly, if people have graft-versus-host disease that affects the skin and have dry or cracked skin on their hands, this may not be a practical way of doing it. 

(32:15): So, fortunately, we do now have what is called continuous glucose monitors or fingerstick-free glucose monitors that people can wear either on their stomach or the back of their arm, and it allows you to check your blood sugar without actually sticking your finger. And this has been very helpful for people with peripheral neuropathy who find it painful or have difficulty checking their finger sticks after stem cell transplants. 

(32:39): Be cautious about taking supplements or herbs to control glucose levels after transplant. Finally, the last thing I will discuss is supplements and herbs to treat blood glucose levels. So many people ask me if they can take certain herbs to reduce their blood glucose levels. I would be cautious with this in people after stem cell transplants. 

(32:56): It is true that many of our currently prescribed medications originally came from natural sources such as herbs, animals, and flowers. Metformin, which is a commonly used diabetes medication actually, was originally derived from the plant French Lilac. 

(33:11): Other diabetes medications, you might be surprised to know, were discovered in a reptile's saliva and obviously were modified and made into pharmaceutical products. This is how the chemical was initially discovered. 

(33:26): Cyclosporine was originally discovered in a fungus, and tacrolimus originally came from bacteria. So, we prescribe many natural sources of the current medications. 

(33:36): However, it's very important to notice that FDA-approved medications are regulated regarding their dose consistency and quality, while herbal medications and supplements are not. So it's not guaranteed that the actual dose you think you're taking is the actual dose. They're not regulated in the same way as prescribed medications. 

(33:54): We have a lot to learn about medicines, but always talk to your doctor about the safety of any herbs [you are taking] because you can be surprised that they can sometimes interact. They may have medicinal qualities, but they can interact with some of the other therapies you're taking, including herbal teas or supplements you're considering. So, I always ask people before taking anything to check in, so we can always make sure that it's a safe supplement for you to take. 

(34:23): High blood glucose levels can cause short-term and long-term issues after transplantation. It's important that you know the symptoms of high blood glucose and low glucose levels and ask your doctor about the right treatment for you to reduce your risk of short-term and long-term complications related to high blood glucose. 

(34:40): Thank you very much for your time, and I will be very happy to take any questions. 

Question and Answer Session: 

(34:48): [Marla O’Keefe]: Thank you, Dr. Gallagher, for this excellent presentation. We have a few questions, so we'll start with them now. Is it true that some patients are no longer diabetic after their transplant? 

(35:04): [Dr. Emily Gallagher]: It can be true, depending on the circumstance. Sometimes people have high glucose levels, and the glucose is related to inflammation or the medication prescribed. And so, if those medications get reduced or discontinued, their blood glucose levels can always return to normal. 

(35:25): I usually tell people that if their glucose returns to normal, they may not need to take any diabetes medication anymore. They may not need to check their blood glucose levels because everything has resolved. But it is important to remember that they had a reaction to whatever treatment that they had in the past that caused their glucose levels to go up so that if they ever go on that medication again in the future, they'll know that they are at risk of developing high glucose levels. They can either monitor for it or tell their doctors so that they can put a precaution in place to stop the glucose levels from going high again. 

(35:57):  [Marla O’Keefe]:  Thank you—next question. "My non-fasting glucose typically exceeds 100, but my A1c level is usually in the low fives. Do I need to be concerned?" 

(36:11): [Dr. Emily Gallagher]: So that question would be person-dependent. It would help to understand why the A1C level is slightly lower, and the non-fasting glucose level is high. In theory, a non-fasting glucose of over a hundred can be normal. We get concerned about the fasting glucose level greater than a hundred. A non-fasting glucose level exceeding a hundred could be normal; therefore, an A1C in the fives might be okay. In that situation, I would get a fasting blood glucose on somebody or do a glucose tolerance test to check if the glucose levels appear high. And then with the A1C, if for some reason the A1C didn't make sense, it could be a specific issue related to the stem cell transplant, like higher turnover of the red blood cells, that's causing the A1c to be a little bit lower. 

(37:03): So, I would investigate a bit more, with the fasting glucose and a glucose tolerance test, if I thought that the glucose levels didn't match up with the A1C. 

(37:16): [Marla O’Keefe]: Thank you. This person wants to know if they put honey in their morning coffee, will that affect their blood glucose? 

(37:25): [Dr. Emily Gallagher]: It can. Obviously, there's some sugar in honey so that it can increase blood glucose levels. If you're concerned about it or think you have high glucose levels. You feel the honey is affecting it; one thing to do is check the blood glucose on a day when you don't put honey in the tea and another day when you do. Then you can see how much it has affected the blood glucose levels. It's not going to put everybody's blood glucose up, but if you have a tendency to high glucose, it can increase it a bit. 

(37:56): [Marla O’Keefe]: Thank you. She'll have to do a little taste test there. Does the glucose level or diabetes in the donor affect the recipient? 

(38:05): [Dr. Emily Gallagher]: That's an excellent question. It shouldn't. Yeah, it shouldn't affect the glucose levels in the recipients. It's usually how the glucose levels are regulated, not directly by the stem cells. Usually, it's you making insulin yourself and how much your body responds to the insulin you make. So sometimes there's inflammation and stress related to the stem cell transplant that can sometimes increase the levels, but it's usually not directly... It shouldn't be directly related to a stem cell transplant donor having high glucose levels. So, it's an interesting question, but it shouldn't cause a problem.(38:58): [Marla O’Keefe]: Thank you. The next question is, this person tends to have high blood glucose, which is always measured after eating breakfast. So, should this glucose be interpreted the same as if I was fasting? 

(39:15): [Dr. Emily Gallagher]: No. If you check the blood glucose after you eat, it will always be higher than if you are fasting. So it depends on how long after you eat that you measure your blood glucose levels, but everybody's glucose is going to increase within an hour after they eat their breakfast in the morning. If we're considering diagnosing high glucose levels, that is considered random glucose if measuring it when you're not fasting. So if you wanted to know if the glucose level was high, you would need to do it first, like fasting after an eight-hour fast in the morning before eating breakfast. 

(39:56): [Marla O’Keefe]: Thank you. Next question, do you have any statistics for post-CAR-T therapy outcomes with people with diabetes? 

(40:06): [Dr. Emily Gallagher]: I do not have outcome data post-CAR-T with people with diabetes. I don't know that anybody has that data. It's also a very good question, though. CAR-T, if you have what's called a cytokine response or an inflammatory response, can increase the glucose level, and people who've been treated for multiple myeloma with steroids tend to have higher glucose levels sometimes. With multiple myeloma, some studies have looked at outcomes in people who have diabetes but are not specifically related to CAR-T. Still, it's a very good question that we should look into. 

 (40:59): [Marla O’Keefe]: We'll say more to come on that one. Does tacrolimus increase blood glucose? 

(41:09): [Dr. Emily Gallagher]: Yes. Typically, the one that causes the glucose levels to go up mostly is steroids. Still, tacrolimus can increase glucose levels a bit, along with increased lipid levels. So it does contribute. It's usually not a severe hyperglycemia, but it can cause a mild increase in glucose levels. 

(41:31):  [Marla O’Keefe]: Thank you. This person said that for 10 years, they had successfully maintained prediabetes via diet. They are finishing R‐CHOP chemo for follicular lymphoma, and the glucose has spiked. They're now in CAR-T therapy, and their blood glucose is higher. Have they lost their battle with diabetes? 

(41:54): [Dr. Emily Gallagher]: No. This is probably a typical situation a lot of people run into. It's a battle, but people can maintain their glucose in a prediabetes range for a number of years. Typically, as people get older, they might have had prediabetes. As time goes on, the glucose in the hemoglobin, A1C, creeps up, and people transition into diabetes. But some people are able to maintain themselves in a prediabetes state for a number of years. 

(42:30): With the R‐CHOP, the thing is the prednisone in the R‐CHOP, the dose of the prednisone, which is a type of steroid, tends to be high. And so if somebody has prediabetes and goes on this high dose of prednisone with R-CHOP, their glucose can go up. 

(42:44): When the R-CHOP is finished, and the prednisone gets tapered off, the glucose levels can come back down again. It can take some time, and it often depends, with the steroids, on the duration, somebody's been on steroids because steroids also have other side effects. They can cause people to gain weight and eat more and things like that. So, sometimes if somebody has prediabetes, the longer-term effect of the steroids can make it harder for the glucose to return to normal. 

(43:11): There's no great data on CAR-T and its effect on diabetes or the effect of diabetes on responses to CAR-T. But it can cause an inflammatory response that also can increase glucose levels. 

(43:26): So, I would not say this person has lost their battle with diabetes. They will probably need to control it in the short term, potentially with medication. And then, as time goes on, I would follow up and see if we could taper off. We don't want the glucose to be uncontrolled, so that you may need medication in the short term. But then I would say follow up with a diabetes doctor because sometimes, when people go on medication for diabetes, people are reluctant to taper it off again. But I would follow up with somebody to see, long-term if those medications are still needed while the glucose levels come back down again. 

(44:07): [Marla O’Keefe]: Great, thank you for that. The next question is they want to know about low glucose upon waking up in the morning. 

 (44:17): : [Dr. Emily Gallagher] Okay, so this depends on the situation. So say somebody's on no medication, wakes up fasting in the morning, and their blood sugar is low; sometimes, it can be normal. So it's surprising. It depends on somebody's age and many other things, but what keeps our blood glucose normal when we're fasting is that our liver puts out some glucose stored to keep it up. And also, our kidneys, up to a point, can control the glucose levels as well. 

(44:52): So sometimes people who don't have diabetes can have low glucose levels if they have any liver or kidney issues. Also, people who are quite thin can have surprisingly low glucose levels. Younger women can have surprisingly low glucose levels fasting in the morning, and it's actually a normal glucose level. So it depends on if somebody's getting it. If somebody has no symptoms and their glucose number is just low, then it often doesn't mean anything. 

(45:21): The other thing is if somebody's in the hospital, we frequently get low fasting morning blood sugars, and that's just a technical thing related to the blood sample that gets drawn and how long it takes for it to get from the patient's bedside to the lab to be analyzed. Sometimes the glucose levels can decrease while it's waiting to get transferred to the lab. 

(45:40): If somebody has low glucose levels in the morning and they're actually on diabetes medications, then that actually is a different issue. So if somebody wakes up with low glucose levels in the morning and they're on a pill that makes them make more insulin, or if they're on insulin injections, we get more concerned about the fasting blood glucose in the morning. And so in that situation, you would want to reevaluate the medication that somebody's getting and see if they actually need to have their diabetes medications adjusted so they're not getting low fasting glucose levels in the morning. 

(46:13): Sometimes, people, if they have low glucose levels in the morning, are afraid to take their diabetes pills. In that situation, it can cause the glucose levels to go higher later in the day. So that one would be dependent on what the person's situation is, whether they have diabetes or not, or whether they're getting symptoms or not with low glucose, and whether they're on diabetes or glucose-lowering medication or not. 

(46:37): [Marla O’Keefe]: Thank you for that. And this looks like it's our last question. This person writes, "After being treated with a lot of steroids, I'm nervous about getting diabetes. My cardiologist suggested I take in very low amounts of carbohydrates, less than 50 grams daily, with normal protein intake. Have you heard of this?" is the first part. "His concern is not only elevated sugar levels but the amount of insulin I might produce, thus having insulin-resistant cells." 

(47:08): [Dr. Emily Gallagher]: Okay, that's another interesting question. So there is a lot of. It will be interesting to hear what Michelle Myers, the nutritionist, will comment on this. Still, a low carbohydrate diet of less than 50 grams daily falls into the ketogenic diet. And there's a lot out there on people using ketogenic diets. There's a whole collection of people discussing this in the setting of cancers, weight loss, and things like that. A very low carbohydrate diet can sometimes control the glucose levels to a point, and it can reduce the amount of insulin your body needs to make to control your glucose levels. So the theory behind it is that taking in the same calories but having them in fat and protein rather than carbohydrates help reduce glucose levels. That is true. 

(48:07): The main issue with ketogenic diets, there's a few, so one is when you take away the carbohydrates, which is often fiber, in your diet, then people can get gastrointestinal side effects, most commonly like constipation. It's also hard for people to maintain, at least in my experience, hard for people to maintain ketogenic diets for longer than a couple of months at best. I would say three months, and this is just anecdotal. If it's a massive change to your typical diet and routine, people tend to only be able to sustain it for a short period of time. 

(48:49): So with the amount of insulin you might be producing, that's a little bit more complicated. If you reduce the carbohydrate levels, you basically reduce the amount of insulin you need. You can measure that in a blood test if somebody wants to, and you can see that somebody can be less insulin resistant. My concern with it is that it's not a long-term solution to anything. And so in that situation, I would have people meet with our nutritionist and evaluate exactly what is typical for you to eat, what's your typical diet; depending on where they're from, a normal diet for them can be quite different. 

(49:35): Usually, our nutritionist will work with somebody to develop a suitable meal plan. And sometimes it's just a case of replacing one item, like a snack or something, with something else. So you can do things like that. I tend not to recommend those very low carbohydrate diets for practical reasons. Plus, it depends on what you're trying to achieve. Suppose somebody's lost a lot of weight. In that case, I recommend replacing certain carbohydrates with healthy fats if their blood glucose is high. But long term, it's more important to have something that's going to be a sustainable diet long-term for an individual rather than something that's going to be a short-term, very restricted diet that's going to be very hard to maintain. 

 (50:26): [Marla O’Keefe]: Thank you for that. That was our last question. So on behalf of BMT InfoNet and our partners, I'd like to thank Dr. Gallagher for a very helpful presentation and thank you, the audience, for your excellent questions.