Welcome to today's webinar. I am Dr. Sarah Thomas, and on behalf of the Nutritional Science and Metabolism Interest Group Leadership Team, we are excited to welcome our expert presenters to Keto Diet Applications for People with Diabetes. And I am Gautam Annarapur, the Communication Director for Nutritional Science and Metabolism Interest Group Leadership Team. Here's a glance at today's agenda. We will provide a few announcements, and we will introduce our experts in a few moments. They will each present lectures and will be followed by a panel discussion. The presenters will be taking questions from the audience at the end of the event. Please don't wait until the end of the session to send in your questions. Instead, go ahead and type it into the Q&A box in your control panel. Please be sure to use the Q&A box and not the chat function for questions. We will be using the chat box to send you important links during this announcement segment. I'm Communication Director for the Nutritional Science and Metabolism Interest Group Leadership Team, the team who coordinated this webinar. I wanted to take a moment to thank all the members of the leadership team for their work throughout the year to provide the opportunities to the interest group members. To learn more about the ADA interest group, there is a link in the chat. And please remember, ADA professional members can join three interest groups, including Nutritional Science and Metabolism Interest Group, as well as enjoy members' exclusive webinars and webinar recordings. Additionally, recognition opportunities and volunteer leadership positions are available. Use the link in the chat to learn more about the ADA membership. Another benefit of ADA membership is connecting with the members of the interest group on the Diabetes Pro member forum. See the link in the chat now. For those of you attending the upcoming 84th Annual Scientific Sessions, here is some information about the session we are hosting. If you haven't yet registered for this amazing conference, please consider. The ADA Scientific Sessions hosts thousands of annual attendees as a premier diabetes conference, providing a platform to delve into the latest advancements in diabetes research, prevention, and care. Highlighting cutting-edge research and innovative treatment and care practices, the groundbreaking educational content is beneficial for both seasoned and early career professionals. Looking for nutrition resources and patient education materials? Check out the materials in the SHOP Diabetes site to see the link in the chat. Now we would like to introduce our today's presenters. Dr. Nia is Michelle, she is an Associate Professor of Medicine and Weight Management Specialist at Duke University. She will be discussing the effects of the keto diet for type 2 diabetes from clinical experience. And then we'll have Dr. Andrew Kutnick, he is a Research Scientist at Sansum Diabetes Research Institute. He will be sharing evidence and research on the impact of the keto diet for type 1 diabetes. And then we have Dr. Elisabetta Politi, she is a Certified Diabetes Educator and a Dietitian at Duke Lifestyle and Weight Management Center. She will be offering insights and tips for counseling patients on keto diet. As a reminder, please drop your questions in the Q&A box, and Gautam and I will ask these questions of our panelists at the end of all the presentations during our discussion section. With that, I'll pass it over to Nia to get us started off. I just want to clarify that you're seeing the correct screen right now? Yeah. Okay, great. So thank you. I'm going to talk to you today about very low carbohydrate diets for management of type 2 diabetes. But first, I'll start with the case. DR is a 65-year-old male who was referred to the Weight Management Clinic by his PCP. In terms of his vital signs, his blood pressure was elevated at 149 over 76, and his weight was 423 pounds and his BMI was 59 kilograms per meter squared. He was on alfuzosin, atorvastatin, and metformin, and in terms of his labs, his hemoglobin A1c was 6.4. In terms of his cholesterol, his LDL was 40, his HDL was 50, and his triglycerides were 136, but he was on atorvastatin, and he had normal thyroid function tests, liver function tests, and creatinine. Let's look at the carbohydrate insulin model. So this says that dietary carbs lead to increased serum glucose and serum insulin, and endogenous insulin. On a low-carb diet, you get less serum glucose, so then less endogenous insulin. And then insulin actually leads to lipogenesis, or the creation of fat cells, and decreased lipolysis, or the destruction of fat cells. Decreased insulin then would lead to increased lipolysis and decreased body weight. So we'll look at the management of hypoglycemia in type 2 diabetes with the 2022 consensus report by the ADA and the European Association for the Study of Diabetes. So in this recommendation, they recommend that we take a holistic, person-centered approach to treat type 2 diabetes, and using four components of care. These four components would be medication for glycemic management, weight management, cardiovascular risk management, and cardio-renal protective glucose-lowering medication. I'm going to say instead of medications for glycemic management, we'll just use glycemic management. And by that, I mean a low-carb diet. So it's also important to note that there's actually no standard definition for a very low-carb diet. So here we have four definitions from four different studies. The first is that a diet would be 10% of the calories from carbohydrates, another that less than 26% of the total calories, another that says less than 50 grams of carbs per day, and another between 20 and 70 grams of carbs per day. But in terms of glycemic management, how do carb-restricted diets actually affect hemoglobin A1C? So for that, first, we'll be looking at a study of the effect of dietary carbohydrate restriction on glycemic control in adults with diabetes, a systematic review and meta-analysis that was published in 2018. In this study, the primary outcome was change in hemoglobin A1C. The secondary outcomes were weight change, cardiovascular disease risk factors, and diabetes medications. So in this study, the prescribed diets were put into three categories, very low-carb slash ketogenic diets, which meant that there were less than 10% of their energy was from carbohydrates or less than or equal to 50 grams of carbs per day, a low-carb diet, which was less than 26% of energy from carbohydrates or less than 130 grams of carbs per day, and then moderate-carb diets, which lead to 26% to 45% total energy or 130 to 225 grams of carbs per day. So we'll look at the outcomes at three months. At three months, very low-carb diets and low-carb diets actually showed greater improvements in hemoglobin A1C. So here, you can see this forest plot. The first four studies were very low- and low-carb diets, and the hemoglobin A1C came down by 0.47, and this was statistically significant. For these eight studies with moderate-carb diets, you can see that the hemoglobin A1C did come down, but it wasn't statistically significant. And then when you look at all 12 studies, the hemoglobin A1C came down by 0.19, and that, in total, was statistically significant. When we look at very low-carb diets, I'm sorry, at six months, very low-carb diets and low-carb diets still showed greater improvement in hemoglobin A1C. So again, here, we have the five studies, and with the A1C dropping by 0.36, these six studies for moderate carbs, the A1C went down, but it was not statistically significant. And then when you look at all 11 studies, at six months, there was no statistical significance. And at 12 months, there was actually no difference in changes to A1C, even in the very low- and low-carb diets. And you can see here that the diamond crosses zero for the low-carb, moderate-carb, and all studies. The next study we'll look at is the efficacy and safety of low- and very low-carb diets for type 2 diabetes remission, a systematic review and meta-analysis of published and unpublished randomized trial data that was published in VMJ in 2021. Primary outcomes in this study are remission of diabetes, weight change, change in hemoglobin A1C, fasting glucose, and adverse events. So type 2 diabetes remission is defined as either with or without the use of diabetes medication, hemoglobin A1C is 6.5%, or a fasting glucose of less than 7 millimoles per liter, or less than 126 milligrams per deciliter. So at six months, low-carb diets actually led to more remission of type 2 diabetes. So you can see that this looked at eight studies of 264 individuals, and we were at 0.32. And this was independent of medication use, but low-carb diets actually led to remission of type 2 diabetes. So in another study, diabetes remission was more likely with low-carb diets at six months. So here we have the relative risk and 95% confidence interval, and at six months, we're at 1.87, so 87% more likely to go into diabetes remission with a low-carb diet. But at 12 months, this was only 27%, and it was not statistically significant. So how do low-carb diets affect hemoglobin A1C? Well compared to high-carb diets, very low-carb diet and low-carb diets show greater improvements of A1C at three and six months, and the carb restriction improves A1C in the short term. So now we'll look at diabetes medications. How do very low-carb diets and low-carb diets affect dose or the use of diabetes medications? So in this table, you'll see very low-carb diets actually showed greater medication elimination. So in the first column, you'll see several classes of diabetes medications, and then in the second column, the amount of people who actually eliminated medication if they were on a very low-carb diet and the usual care group in the third column. So 100% of people compared on sulfonylureas, 100% on very low-carb diets compared to 16.7% in usual care. For insulin, 47.6% of people eliminated medication versus 7% in usual care. STLT2 inhibitors, 91% versus 20% of usual care. But what I want to point out on this slide is that when I have a patient who is on an STLT2 inhibitor, I do not place them on a very low-carb diet because of the concern for developing normal glycemic DKA. The problem with DKA is that insulin actually helps prevent DKA from happening, and because insulin levels are so low with both an STLT2 inhibitor and a very low-carb diet, I think that would increase the risk. So I do not recommend placing someone on a very low-carb diet or a low-carb diet if they are on an STLT2 inhibitor. But again, back to this slide with TDZs, 80% were able to eliminate their TZDs on a very low-carb diet compared to 0% for usual care. And for DPP4s, almost 55% compared to 10%. And for GLP-1 agonists, 28% versus 16%, and for metformin, 18% versus 10%. So carb-restricted diets showed greater medication reduction. Compared to high-carb diets, carb restriction reduced the dose or eliminated oral medications or insulin. Now we'll look at weight management. How do carb-restricted diets affect weight management? So the ADA recommendation for weight management is as follows. They first recommend general lifestyle advice and a medical or medical nutrition therapy or different eating patterns, and in this case, we're going to discuss the very low-carb and low-carb diets, physical activity. And then they also recommend an intensive evidence-based structured weight management program with less medications or metabolic surgery. So here we can see that very low-carb diets and low-carb diets had more weight loss at three months. So here at three months, we can see, and this is a weighted mean difference in kilograms, loss of 2.5 kilograms, and this is statistically significant. Moderate-carb diets, not so much, because these are not significant. And then at six months, you can see we're still at like about one kilo loss, but it's not statistically significant, and the moderate-carb diet's not significant. Interestingly, when we get to 12 months, the weight change for low-carb diets is actually, very low-carb diets is an increase of about half a kilo, but again, not significant. But for moderate-carb diets, it finally shows some significance with a loss of about 0.6 kilos. And here's another chart that says more weight loss at six months with low-carb diets. So here's our forest plot, and again, six studies, and the percentage weight loss is 7.41% loss in the very low-carb and low-carb diet. And here in these 12 studies in the moderate-carb diet, we can see a weight loss of 2.27%. And in all 18 studies in total, 3.36% weight loss. So how do carb-restricted diets affect weight? So compared to high-carb diets, at three months, very low-carb diets show more weight loss. At 12 months, moderate-carb diets actually showed a small improvement in weight, but carb restriction improves weight in the short term. So what about cardiovascular risk factor management? How do carb-restricted diets affect lipids and blood pressure? Because one of the things you'll frequently hear is, well, if people are eating all this bacon all the time, certainly their cholesterol is going to go up and their blood pressure is going to go up. So here at three to six months, there's no definitive difference in lipids or blood pressure. So here we see the cholesterol, and you see the LDL, there's actually either no change or a very small decrease in LDL in a carb-restricted versus a high-carb diet. The HDL, you can see that there's an increase in nine of 20 studies and a significant increase in HDL in three of these studies. And triglycerides are significantly decreased in one of these studies. And in terms of blood pressure, both the systolic and diastolic blood pressure go down. For some patients, it's a little. For some patients, it's quite a bit. And it's significantly decreased in one study. And then at 12 to 24 months, we're looking at the cholesterol, and you see that it increases significantly in six studies. The HDL significantly increases in six studies, and triglycerides are significantly decreased in five studies. So in another study, if you're looking at low-carb diets, improved triglycerides, but possibly worse in the LDL. So here we have the LDL at six months, and you can see there's really no difference between a high-carb diet and a low-carb diet. And at 12 months, you can see that there might be, this was listed as statistically significant, but when I learned about these things, I'm like, if there was a minus sign and a plus sign, then that meant that there was no significant difference. But again, it was listed as a significant difference. You can see in the HDL, there was no significant difference was seen. And then at the triglycerides, there were seen as a decrease at both six months and 12 months. So how do low-carb diets affect lipids? Well, compared to high-carb diets, at 12 months, low-carb diets showed improvements in triglycerides and HDL. Low-carb diets may also show a worse LDL, but I think it's important to note that most patients with diabetes are prescribed statins to improve their lipid profiles. So how do low-carb diets affect blood pressure? Well, compared to high-carb diets, low-carb diets do not seem to adversely affect blood pressure. Again, it is also important to note that most patients with diabetes are prescribed ACE inhibitors or ARBs to treat their blood pressure and to protect their hearts and kidneys. So very low-carb diets to manage type 2 diabetes. In terms of glycemic management, the carb restriction improves hemoglobin A1C and fasting glucose in the short term. Carb restrictions can reduce or eliminate diabetes medications. In terms of weight management, carb restriction improves weight in the short term. And the cardiovascular disease risk factor management, low-carb diets showed improvements in triglycerides and HDL and do not adversely affect blood pressure. So just to go back to our case to remember, his blood pressure was elevated. His weight started out at 423 pounds and a BMI of 59, and his A1C was 6.4. So we started him on a very low-carb diet, which was less than 20 grams of carbs per day. And he could have unrestricted amounts of meat and eggs, up to four ounces of hard cheese, two cups of salad per day, and one cup of low carbohydrate vegetables per day. Calories were not restricted. He was also told to take a daily vitamin and drink plenty of fluids. So when we started to see, and I started to see him in February of 2018, this is where we were. And you can see he did really well. And then March of 2020, you know, everything shut down because of the pandemic. And so I didn't see him for a while, but he only gained, you know, he gained less than 20 pounds during that time. And then I saw him again and he started going down again. I will say that I saw him a couple of weeks ago in clinic and he's back up to about 338. But again, still he's had a significant amount of weight loss. He would like to lose another 100 pounds, but he doesn't want to try medications. And so we sort of stabilized where we are. So finally, the takeaway points are that very low carb diets and low carb diets can be used to manage diabetes because they first lower A1C and lower weight and do not necessarily adversely affect lipids. And then I'm going to pass it over to the next speaker. All right. Thank you, Dr. Mitchell. That was awesome. All right. Can everyone see my screen? I'm going to assume that's a go, unless someone speaks up. All right. Excellent. Perfect. All right. So I'm going to be discussing going quote keto for type one diabetes, evaluating the evidence of therapeutic carbohydrate reduction. And just to quickly describe what that means, that means exactly what Dr. Mitchell had said. I think it was in slide three or four, which is less than 26% of total calories coming from carbohydrates. And those are the diets we're going to be talking about. First of slide, my disclosures. And so let's jump right into it. Why would someone with type one diabetes consider therapeutic carbohydrate reduction? Well, the graph on the left-hand side goes back about a half century, looking at the insulin requirements of carbohydrates. And you see that this is a rather rapid elevation in insulin that peaks around 30 minutes. Now, what happens if you're a patient with type one diabetes and you lack endogenous insulin production? Well, you're almost completely or completely reliant on exogenous forms of insulin and typically utilizing rapid acting insulins, which are shown here. When you actually model the kinetics curve of exogenous insulin directly on top of this graph, we see there's an issue. There's a clear three to four fold mismatch between carbohydrates and insulin, at least the kinetics required to metabolize carbohydrates. Now, when you consider the average carbohydrate intake in the diet of someone with type one diabetes has been reported at around 45% of total calories and you amplify the mismatch by daily lifestyle variability, things like change in insulin absorption or insulin sensitivity, it's not surprising that a typical patient with type one diabetes lives with very high and variable glucose levels, as illustrated in a CGM graph on the right-hand side of a patient with type one diabetes. But what about these other macronutrients, such as protein and or fat? Well, to illustrate that, we can compare some of the glucose and insulin area under the curves and specifically protein, as you can see on the left-hand side is much slower. It's a much lower peak and also much slower kinetics. Now in this study, they showed a four to nine fold reduction and blood glucose areas under the curve for protein with no effect from fat, although there's a pretty clear effect on fat and carbohydrates. And then ultimately a 2.5 fold reduction in insulin, which ultimately leads to less insulin and slower kinetics, which can allow for some of the currently available insulins to potentially match these kinetics. Now, evidence for this is actually looking at next generation automatic insulin delivery. These are tools that couple continuous glucose monitoring with insulin pumps through a computer algorithm to automatically administer insulin, sometimes with minimal or no user input. And when you look at the mean glucose graphs at the top two graphs from the two studies presented at the top and time and range from two separate studies, looking at three to 12 months studies, rigorously conducted randomized controlled trials of hybrid closed loop, you can see that when patients are not eating food, that these tools work remarkably well. In fact, you can see on the top left-hand graph, this patient or these patients in this study are getting pretty close with hybrid closed loop to around 120 and right around that number on these graphs. Whereas time and range on the bottom is getting north of 95% in closed loop. However, when food is in the mix and you have this carbohydrate insulin mismatch, you see almost all the therapeutic value of hybrid closed loop deteriorates and goes away. No matter what study you're looking at or which graph you look at, again, validating these carbohydrate insulin kinetic mismatch. But what is ultimately the reason a patient who loses endogenous insulin control and ultimately has very consistently reported hyperglycemia? Well, we know there's a number of high profile reports. These are just some examples that ultimately illustrate pretty clear evidence that patients with type 1 diabetes are at significantly increased risk for microvascular and macrovascular disease, as well as an estimated mean 11 to 18 year reduced life expectancy. Again, all of these are directly linked to glycemic control and in the DCC and EDIC, some of that is causally linked to glycemic control. So of course the goal in type 1 diabetes is to pretty simply put, safely bring glycemic control to as normal as possible. But that sounds great, right? Okay, obviously the kinetics are mismatched. Let's use foods that have slower kinetics that should match the insulins better and that'll make improved outcomes, right? But there had never been a systematic analysis that really included all studies, both high, moderate, low, and very low carbohydrate diets as defined by Dr. Mitchell earlier. So we attempted to do that. This is a very long, exhaustive effort in collaboration with Boston Children's, Harvard Med, University of Washington, Queens University, where we pulled every study. The ultimate inclusion included almost 46,000 patients with type 1 diabetes and over a hundred studies. So to first describe glycemic control using a measure of HbA1c, which is a measure of average glucose control over a two to three month period of time, we only included carbohydrate or data from patients that had a reported carbohydrate intake of at least two months. Of course, HbA1c is only valid if it has occurred over a two to three month period of time. That still included over 44,000 patients and 97 reports. And what we see when we actually look at this data is that there's no association between carbohydrate intake if you go from the mean intake of carbohydrates to even higher carbohydrate intake. But it's a much different story when you talk about carbohydrate reduction or therapeutic carbohydrate reduction, wherein this data across all studies ever published reporting a carbohydrate intake in patients with type 1 diabetes of at least two months or greater on HbA1c, there's a clear reduction in carbohydrate intake that is associated with a reduction in HbA1c. And in this analysis, it came out, at least in this regression to a reduction in HbA1c for every 50 grams of carbohydrates reduced at a negative 0.5% HbA1c. Now, in theory, if a patient were to go from the mean intake of carbohydrates around 244 to 245 in patients with type 1 diabetes and go down to a very low carbohydrate or sometimes termed ketogenic diet, these patients would experience up to, at least in theory, a 2% reduction in HbA1c, which is remarkable. Now, when we talk about how does that play out when we talk about the ADA targets of less than 7% HbA1c? Well, when looking at high carbohydrate diets, only 10% of all high carbohydrate diets actually reported hitting these ADA targets. We're similar to Dr. Mitchell's story in type 2 diabetes, moderate carbohydrate diets, sort of slight improvement compared to high carb diets. However, when you go to low carbohydrate diets, which is less than 26% of the total calories coming from carbohydrates, that is a three to eight fold higher incidence of patients actually seeing a less than 7% HbA1c at close to 80% of the cohorts where 100% of reports in the very low carbohydrate, sometimes termed ketogenic diet group, achieved these values. In fact, if you look at this data, you actually see that over 70% of these reports, patients with type 1 diabetes achieved normal glycemia, which is less than 5.7% HbA1c. And the importance of this cannot be understated. There is not a medication or technology available to patients with type 1 diabetes that currently reliably gets patients to these values. So this is quite remarkable, observing something like a diet can have an impact on HbA1c like this. But what about insulin? When we looked at insulin of at least a week on the diet, we know insulin changes due to carbohydrate restriction can actually happen within the first day. And so we only modeled those within a carbohydrate restricted diets for over seven days, or sorry, all diets for at least seven days, and a similar story. Mean carbohydrate intake, no association if you go higher, but if you go from mean carbohydrate intake lower, you see a reduction in insulin, whether it's relative insulin based on body weight or absolute insulin load, showing a very similar story. So what this data illustrates is it appears that therapeutic carbohydrate reduction diets clearly appear to be evidence-based solutions to improving glycemic control, sometimes to remarkable levels, but also reducing insulin load, the primary medication used in patients with type 1 diabetes. But there have also been a number of concerns or knowledge gaps that have been described on the left-hand side. And many of these I will, us and others have published on this topic describing some hypothetical clinical concerns, such as, well, if you're on a ketogenic diet, wouldn't you increase your risk for ketoacidosis? Or if you're eating less carbs, wouldn't you increase your risk for hyperglycemia? But the list goes to pediatric growth, cardiovascular disease risk, kidney dysfunction, compliance, quality of life, and eating disorders. This could be, frankly, its own webinar, an hour in length to do justice to this topic and really dive into each one of these. But suffice it to say, there is not sufficient evidence to say whether these are real risk or not real risk in the context of type 1 diabetes. We really need long-term randomized control trials to answer these questions, to validate or invalidate these concerns. But there's some key clinical gaps that I really wanna highlight here, specifically to the audience of the American Diabetes Association. We recently, and are still ongoing, I'm gonna show you some preliminary results from a survey we conducted in collaboration with University of British Columbia, with support from JDRF and others, from Annalyn Conkling's group and Dr. Jim Johnson, looking at the patient and caregiver experience with food. We've had over 800 people respond and hoping to get more people give their input on how food affects their diabetes. And what we see here is that, from the at least preliminary results, that nearly all patients or caregivers considered food important for managing their disease. Two thirds were willing to change their diet to stabilize blood glucose levels, showing a clear willingness from the patient to want to be actionable to improve their outcomes. But a clear concern that came out of these results is that over half patients felt they didn't receive adequate resources from their healthcare team on food's impact on glycemic control, something that I hope we can work to address. As well as 25%, or a little over 25% of patients felt that their dietary choice was not supported by their healthcare team. Well, what's also important to illustrate is this isn't a topic where diet is frankly going away. This is, in this survey, we found that therapeutic carbohydrate reduction was the most commonly utilized diet strategy in this survey respondents. We also know that there's cited literature showing that this is one of the most popular topics in type 1 diabetes. And if you look on things like PubMed or Google Trends, you see that this is one of the most popular dietary strategies since the origin of Google Trends. So it's clearly a popular topic and many patients are frankly doing it, at least based on the evidence. Another thing to describe here is that Inel and Conkins group also surveyed dieticians in the pre-COVID pandemic era, published two years ago, looking at dieticians and how they felt at least supported or their ability to implement therapeutic carbohydrate reduction. But unfortunately, 66% of at least this survey respondent group, so maybe not systemic, but just within this respondent group, felt unsupported or unprepared to implement therapeutic carbohydrate reduction. And when actually looking at the systematic analysis we conducted on the very low carbohydrate ketogenic end, we see that over half the reports that patients reported doing these therapeutic carbohydrate reduction approaches with minimal or no healthcare support. Clearly, this is not a safe scenario for patients and it's also failing both sides of the equation, both the patient and the healthcare provider, which I hope we can all work to address as we know that there are guidelines out there for what you should consume nutritionally from the ADA in 2019. We also know there's a pamphlet on very low carbohydrate eating patterns for adults, specifically more so for type two diabetes, but we really lack any guidelines in type one diabetes. What are we supposed to do for type one diabetes specifically on these therapeutic carbohydrate reduction approaches? And why that is so important is because we know that these therapeutic strategies have common pitfalls, but they are both predictable and preventable. We know that oftentimes when people go on these approaches, they can lead to poor diet formulation. Many people inadvertently calorically restrict, as Dr. Mitchell showed, a patient lost weight, which sometimes is intentional, but many times it's not intentional, specifically in kids. We also know that you wanna consider phytonutrients, fiber, other micronutrients in the diet, and oftentimes there's no evidence-based guidelines for type one diabetes on how to do that. We also know that there's a real lack of understanding on the insulin adaptations to these approaches. In type one diabetes, we know that you often require not only an insulin reduction, but also changes in the type of insulin. Many patients move from rapid-acting insulin to regular insulin, or change from a typical bolus approach for pre-meal to a dual-wave bolus and beyond, all to try and manage a different strategy. So it does not only require different insulin dose, but often different insulin types and kinetics. There's also the concern of counseling patients on hypoglycemia. Many patients will do this approach and achieve a remarkable improvement in their standard deviation around their mean, but then they'll push it low enough to where they're at increased risk for hypoglycemia, and this can be something that could be addressed upfront if pre-screened and working with a healthcare provider on how to manage that. We also know, as Dr. Mitchell has spoke about, the reduction in medication requirements, often in patients in type one diabetes who often aren't only using insulin. Sometimes they're using Metformin and SGLT2 inhibitors, and now the emergence of GLP-1s. Which have kind of hit a peak interest recently. We have to consider the medication adjustments that need to happen in these patients. And we know that when we talk about a very low-carbohydrate diet, there's a clear metabolic adaptation that occurs. We've written about this and many others have. The hormonal changes, the mineral load changes that take up to three to four weeks to really reach homeostasis, oftentimes for patients. And preparing the patient upfront for that helps mitigate symptoms and leads to, often can hypothetically lead to better success. We also know that it's important to pre-screen patients. Understand who may be a ideal candidate, or if someone wants to do this dietary strategy, or maybe has risk factors that they're managed upfront. Such as if a patient has a history of being diagnosed with an eating disorder or unstable weight. So in summary, we know there's a mismatch between carbohydrates and exogenous insulin, which is amplified by the moment by moment, and often day-by-day lifestyle variability in patients with type one diabetes. Ultimately to increase risk for long-term complications and shorten life expectancy in patients, which I am one. I am a patient with type one diabetes as well. Therapeutic carbohydrate reduction is an evidence-based approach to regulating glycemic control and insulin with a hundred percent of studies in this very low-carbohydrate category, sometimes called a ketogenic diet, achieving the ADA targets of less than 7% HbA1c. But there are hypothetical clinical concerns that have been raised that do clearly require more rigorous evidence to understand, are these risks real? And how do we mitigate or manage those? Because patients are doing these diets anyways. And there's a clear need for critical and immediate action to provide resources for patients and healthcare practitioners to help guide patients on this journey and have the right resources to inform them on what to do. And that means formulation of guidelines specific to type one and therapeutic carbohydrate reduction that can avoid these pitfalls that are both predictable, I'm sorry, predictable and preventable. And with that, just like to thank the team at Sansum Diabetes Research Institute, the collaborators, the prior funding, and call to action anyone who's interested in taking this survey. I'll put it at the top of my Twitter so anyone can take it. We want to hear from the patient and caregivers on their lived experience. With that, I want to thank everyone. I'm Elisabetta Bonitti, a diabetes educator, and I'm the last panelist for today. I just want to confirm that you can see my slides. My topic is Counseling Insight and Tips for the Keto Page Diet Patients. And from previous presentation by Dr. Mitchell and by Dr. Kutnick, it's obvious that the most challenging thing with keto diet is long-term adherence. It seems to be more challenging than other approaches, so I want to discuss what could be possible reason for that. I'm then going to present a case study with a patient with type 2 diabetes, a case study with a patient with type 1 diabetes, and share some of the counseling tips based on my clinical experience. I wish when I meet with patients, I have a crystal ball and to know what is going to be the best approach for them. Is it going to be the ketogenic diet, which seems to really help suppress hunger? Or is it going to be a more moderate approach, which seems to be more sustainable? There are factors that seem to predict what option is the best for different patients. If I have someone who really likes fruit and starches, I would go with a moderate carb, the same if they have a preference for a vegetarian or vegan diet. But if their problem is more excess hunger and post-prandial glycemic excursion, then the keto diet seems to provide additional benefits. And I do like when I teach the keto diet that it seems to be very straightforward. In some of the patients I work with like clear instruction and not a lot of choices. I emphasize the importance of eating as much they need and not as much as they want. But we do see that there is bad appetite suppression effect. And then the diet consists mainly on protein, oil and condiments, salad, nuts. It's important to emphasize water intake and they might need extra sodium to compensate for the diuresis that occurs during the first few days. I normally do not discuss reintroducing carbohydrate for those on the keto diet unless they bring it up to me. I think it's safe when they're monitored closely for side effects to continue on about 10% of the calories from carbohydrates. If they do bring it up to, I do recommend moderate, very gradual addition of about five grams per day based on the food that they seem to prefer. I wanna spend a couple of time reflecting, a little bit reflecting on psychological implication of changing a diet and what brings to the patients. I have seen frequently within my clinical experience that patients were recommended a keto diet which might be significantly different from what they were doing prior to the recommendation. Our expectation is that they will go home and they will start the next day. But as Prochaska and DiClemente show, we need to give them some time. We need to understand that they would need to have time to check what they have in their kitchen, to go grocery shopping, to plan their meals. So that sometime takes a couple of weeks, sometimes a month. So there is always a contemplation phase before we can go into action. The other reflection that I've frequently seen is that the first time that you do something, you tend to be very compliant. That compliance becomes a little bit more challenging after relapse. Saying that, I'm gonna show you my two case studies. These are patients I've worked for a little over a year in the last few years. This first patient is a 64-year-old woman referred by her PCP. She has a BMI of 35.6. She has several key health issues ranging from acquired hypothyroidism to type 2 diabetes, which when I started working with her was diet control. She also has obstructive sleep apnea. She suffered from a rheumatological condition and has some behavioral health issue, including she's a smoker, which is something that we never address during our meetings. She is post-menopausal. And unfortunately, the typical client who would have trouble losing weight because of not being very tall, being a woman and having several condition, her list of medication is quite long. And I think that led to her inspiration to change, which was to reverse diabetes with diet and exercise. She didn't want to add any medications. She noticed during our first appointment, she had gained 40 pounds over the last 10 years. She attributed the weight gain to being diagnosed with hyperthyroidism, followed by surgery and thyroid medication therapy, and the undifferentiated connective tissue disease had impacted her energy. This is a reflection of how she gained about 40 pounds from 2010 to 2020. When we started working, she was really interested in the keto diet. So she came up with a plan. She wanted to also monitor her calorie intake, which I didn't encourage her to do, but she wanted to do it. She came up with a plan that was easy to follow and didn't require a lot of cooking. I was very impressed by her improvement in fitness over the year that we worked together. She gradually, but consistently became more active, also adding a variety of different exercises to her routine. And she almost doubled the steps that she did in about six months. In spite of the prejudice that it's hard for post-menopausal women to lose weight, she had an excellent weight loss during the time that we worked together, six months, and she regained a little bit of weight later, but she was able to maintain it. I wanna point out that her A1C had improved prior to working together. So when we started working together, her A1C was just down from 6.7 to 6.5, and she reduced it even further. Also, her LDL went down from 193 to 121, which was something that she was very pleased about. And now my second case is a type 1 diabetes. This is a 22-year-old man, is a college student referred by his primary care physician. He had type 1 diabetes since age 13. He also suffered from ADHD. When I started working with him, was on Adderall and Ritalin, and insulin Lispro up to 80 units per day via pump. He had a CGM and a pump. And after a month of being instructed, he was following low carb. The main challenge from a nutrition standpoint with this client was to help him eat more vegetable, which really didn't like vegetable, but he came around, and after some months he was picking up a few choices. But definitely his food intake decreased on low carb. His main issue was thought was compliance. And after about 13 months of working together, his weight loss was not excellent. He had lost about 10 pounds. But his A1C had improved dramatically and reduced considerably. LDL also improved, but his primary care physician put it on a statin starting October of 2023, which led to further reduction. I thought what was interesting with this particular patient is that he didn't suffer from hypoglycemia because the CGM and the pump allowed him to control tightly his blood sugar. Insulin was reduced by half. And what I thought was really interesting is that his ADHD seems to improve with better control blood sugar. Also no experience with DKA. Just want to briefly breeze through counseling strategies. I think it's important to provide meal planning skeleton for clients who follow low carb to a level of about 20 grams a day or 10% of its total calories. Some people would rely on meal delivery services and they can be ready to be eaten. And some of them, they can have recipes to be prepared or some of them would just benefit from some meal suggestions. Tracking carbohydrate is important. So here's just some available apps. An additional strategy could be help them upsetting plans, identify barriers, avoid all or nothing mentality, which is common. Either they are on keto or they are not and they eat a lot of carbohydrates. Attitude adjustments might help. The same with environmental restructuring, making sure that the environment that you are around supports you. And also the support of the people they live with. Above all, I think it's about progress, not perfection. And the success is the sum of small efforts, repeated day in and day out. Okay, wonderful. Thank you to all the speakers. We'll move on to our question and answer section of the webinar. Just a reminder to put your question and answers in the Q&A box if you have any. This first question, I believe this is directed towards Dr. Mitchell. Do the studies make differentiation on the type of carbs? So no, the studies that I talked about did not talk about the different types of carbs. I would say that one of the, I asked a question at a talk once about a vegetarian diet and a low carb diet. And I just, I don't see a path. I will say, I just think it's just too hard to do. And I think, Elisabetta might be able to speak to that, but I think most times, again, it's a lot of meat and eggs. It just really is. It's a lot of meat. All right, the next question is also directed to Dr. Mitchell. What about the lack of fiber in this diet and the impact on gut microbiome and digestive health with such a low fiber diet? So I cannot speak to the impact on the microbiome because I don't know. But in terms of digestive health, that is real. We often, you know, because it is low fiber, I think people end up getting, can get constipated. Sometimes we tell them they can either try things like chewing gum that has like sugar alcohols in it, because that can cause people to, the bowels to move. We certainly talk about drinking a lot of fluid. You know, occasionally I do have people take like polyethylene glycol to get things moving. But I will say, honestly, for the most part, people don't complain about that. And I don't know if they're like, who cares if I'm constipated because I'm losing weight, but I don't really get a lot of complaints about constipation. Elisabetta, do you get a lot of complaints about constipation? Actually, interestingly, I find that the keto diet that tends to be high in fat helps move things along. So sometimes, yes, there's less fiber, but there's more fat and that compensates. So certainly not as much as with GLP-1, I have to say. GLP-1 seems to cause more constipation than not the low carb diet. All right, and the next question, I'm not sure who this is directed to, so anyone feel free to jump in. The study results are positive, but how sustainable is this diet? How many patients drop out of the study due to their inability to continue on a very low carb diet? I'll jump in. I took some slides out of my presentation about adherence. And so one of the things I will say is that, people are like, no one can stick to a low carb diet. Here's the deal, no one can stick to any diet, otherwise I wouldn't have a job, right? And so they've been in the DIRECT trial, and I can't remember what DIRECT stands for, I apologize. But they actually looked, there was actually no difference between a low carb versus a low fat diet in terms of adherence. And there, I think there was another study that looked at, and it said that basically it might've been that people were less likely to stick with a low carb diet. But again, people weren't sticking with the other diets all that much either. So I just think that, I understand, I tell people all the time, we live in a carb centric world. And so it might be harder for people, especially if you live with somebody who does not have to be on a low carb diet or refuses to be on a low carb diet with you. If you live with kids who, you know, you're feeding fruit all the time, that's gonna make it more challenging, no question. But I also say to people, if you have diabetes or prediabetes, your body's already telling you, it does not process carbs well, and we need to work on reducing them. We don't necessarily need to go full keto, but we definitely need to work on reducing the carbs to help you lose weight and help your health. Okay, the next question is, and how do you address concerns from patients about environmental impact of this high animal product diet? Well, yesterday was just Earth Day. So I think it's a good question. I do think that what seems to be highest in carbon emission is really beef and lamb. So switching to a low carb diet will focus more on seafood and poultry can certainly help. And then we have the vegetables, but yes, that is certainly a concern, although there are ways to work around it. Okay, and next question for Dr. Mitchell, how do you know if your patient's weight loss is not a result of lean muscle mass and not fat? And if your patient was eating a true keto diet, did he do strength training to maintain muscle mass? And lastly, did your patient's HGL improve lower triglycerides or lower triglycerides? Thank you. Hey, there's a lot there. So we know that when people lose weight, they will lose muscle. There's no question, but I don't think he lost a hundred pounds worth of muscle. And so I think, you know, I can certainly see, I look at him and I wish I had a before picture of him now because it is like night and day. And again, he could still lose a hundred pounds. So we know that he loses muscle. I recommend that everyone, no matter what their size, that they do strength training. The thing of it is, is that, you know, how much people follow that recommendation, I can't tell. So no, did I do, I didn't do any DEXA scan on him to see what his body composition was. So I'm sure that he lost muscle, but he also had a lot of fat to lose and he lost quite a bit. But I do think that that is something for everyone. Everyone needs to do, like I always tell people, everyone needs to exercise and everybody needs to do resistance training. And if you're a woman and you're post-menopausal, you need to do more resistance training. So I really, I really do harp on that. And what would the other question, there was muscle mass. What was the other question? I'm sorry. Oh, no, that's okay. Did your patient's HDL improve and did they lower their triglycerides? I don't recall if the HDL improved. I do know that he was already on atorvastatin. So I wasn't that worried about his, I wasn't that worried about his cholesterol, but I don't, I should check that, but I don't recall. Can I comment one second on the muscle mass? Because we've published studies and actually evaluated patients going on these approaches over time. And what we see in the literature pretty consistently, at least that way to the evidence is that there's no, this diet doesn't perceivably cause more muscle mass loss. There's been hypothetical preservation, but typically what you're seeing is a four to one ratio, which is very normal for weight loss. Actually, that would be seemingly good compared to some of the other rapid weight loss trials. And on the compliance issue, at least in type one diabetes, just to comment on that, what the literature actually says, the evidence I presented was when patients did it, right? So they already did the diet. And so that the compliance is a completely untapped area in type one diabetes. Of course, you have to do the diet to see it. From the vegetarian side of things, there is something termed an eco-Atkins approach, which is a pure vegetation, a vegetarian based low carb diet that has frankly been largely understudied. I do know a number of individuals in type one who actually do this approach and are eating vegetarian, although you are eliminating a lot of carbs and then a lot of other things on top of it. So it's a barrier, but I just wanted to present those as well. All right, the next question is, I think I don't know how to read it, but it seems like the person is asking about a condition here. So a person type one who tried keto and became concerned when she noticed her urinary ketone levels were elevated. And this is not like a DKA, but what do you tell patients? I tell patients that ketosis is different from diabetic ketoacidosis. That's what I tell them. And so, you know, diabetic ketoacidosis is dangerous and we want to avoid that, but ketosis is okay, but ketosis actually shows that we're burning fat. And so, you know, again, I think that we need to educate people on it and like, what is the difference between ketoacidosis and ketosis? Because they are not the same, but I understand why patients get confused. All right, and then, oh, sorry, did somebody else want to jump in? Well, I just wanted to add that actually ketosis is, the ketosis that occurs with a ketogenic diet, it's how the appetite is suppressed and it's a good phenomenon. And of course, thanks to checking blood sugar, patients will be able to know which one is which. We also wrote in a JCI article that I cited in there, so if you want to go back and look at the webinar, we actually put a definition for both of them in the back in the context of type 1 diabetes, I think supplemental figure one or two, if anyone's interested, so. All right, we have time for maybe one or two more. One question, do you counsel patients to make a majority of their fat intake to be from unsaturated sources? So anybody can answer that. I would say yes, that's preferable because we know that unsaturated sources are the one that tend to not increase LDL, which is a concern that Dr. Mitchell brought up. And I think, were you concerned about doing keto in a more heart-healthy way by choosing fish and healthy fats? I actually don't tell people to do unsaturated. I do something like eat what you want, because again, we haven't really seen, at least in the States, haven't seen the LDL go up too much. I also think we haven't, and again, most of these people want statins anyway. So I just don't worry about it. I didn't present this data, but to Dr. Mitchell's point, we did run the analysis on libids. I just didn't have time to present it. There was no significant effect on LDL with these diets as you restricted further. Now we know in randomized control trials and other settings, you see that, but in type one, we weren't seeing that. So we don't see a deterioration in LDL in that context. Although I suspect, you know, either way, just whatever it's worth. All right. I think we're about out of time. So this includes today's webinar, but I'd like to thank our speakers for their excellent presentations. And thank you everyone for joining.

ketogenic diet

diabetes management

type 2 diabetes

type 1 diabetes

therapeutic carbohydrate reduction

counseling strategies

glycemic control

weight loss

lipid profiles