Welcome to the Today Webinar hosted by the ADA Clinical Centers and Program Interest Group. I'm Ninh Ninh Aung. I'm one of the diabetologists from Mohawk Valley Health System in upstate New York. And I'm a program director of the Diabetes Fellowship Program and co-leader of the Inpatient Glycemic Management Team, which is a quality improvement team and responsible for updating and creating the inpatient glycemic order set protocols. So today we are going to go over some agenda first. I will start with some housekeeping items and some announcement, and then I'll introduce the panel. Who are the top experts in the field? So it will be very little need to introduce them, but I just want to mention some of the achievement from the short biography, and then we'll have a presentation. So we have a dynamic presentation today. So we'll start, the panelists will start talking about the background, historical background of the hyperglycemic crisis guidelines, diagnosis and treatment guidelines. And then the panelists will focus on the latest consensus report, which is published this year and endorsed by multiple professional organization, including ADA and other US and European counterparts. And then the program will be concluded with a question and answer segment. So if you look at in your control panel, you are going to see two main things. So one is a chat box and the other one is a Q&A. So chat box is for the announcement and link, which will be sent to you by the ADA officers. And you can use that chat box to communicate with your fellow audience, if you want to introduce yourself or whatever you need to talk to your fellow audience. We will be taking questions, the panelists will be taking questions at the end of the presentation. However, I would like to request everyone to put in the questions that you have or comments in the Q&A box during the presentation. So we can start the Q&A section as soon as we are done with the presentation. So we don't need to wait for the questions to come up. So if anytime, if you have any questions or comment you want to make during the presentation, please use the Q&A box and please put that in. And we just had a very informative and great presentation about perioperative care of patients using wearable diabetes device, which is again hosted by the Clinical Center and Program Interest Group. And if you miss it, or if you want to re-listen it again, it is available in the ADA's Institute of Learning platform. And you can see a lot of other different webinars in there as well. This is the ADA member-exclusive benefit. So I would like to ask everyone to utilize that. Another announcement I want to make is the ADA member forum. So this is where you can share your thoughts. You can continue the discussion you want to continue from this webinar, or if you want to communicate to your other fellow members for questions, or if you want to collaborate with the research or clinical initiative, that is a very good communication forum. I have benefited myself a lot from it. So I would like to ask everyone to utilize this Diabetes Pro member forum to communicate with other members. Now I would like to take some time to introduce our panelists. So they are very well-known, they are experts in this field, but I just want to mention some of the achievements. It will not be all, I won't be able to capture everything, but I just want to mention some of them. So let's start with Dr. Robert Ushakov. He is the Medical Director for Inpatient Diabetes and a Professor of Medicine at UCSF. For the first 30 years, his activities have evolved around the education and research to improve the management and outcomes for inpatients with diabetes. He has pioneered the internet interactive mandatory training for physicians, nurses, and the pharmacists, and he continues introducing the new innovation in all area of inpatient diabetes management, including virtual inpatient diabetes service, automating insulin dosing. He was a member of the Endocrine Society Committee, writing a new guideline for inpatient diabetes management, and those guidelines were published in 2022. The second panelist is Dr. Guillermo Umpirius. He is a Professor of Medicine in the Division of Endocrinology in Emory, and he is the first President of the ADA Medicine in Science 2022. Dr. Umpirius' research has made significant contribution to the field of endocrinology and diabetes, and his interest spans a wide range from studying the mechanism for beta cell dysfunction in minority populations to preventing acute and chronic diabetes complications. He has shared his findings through more than 500 scientific manuscripts and book chapters, and has presented over 400 research abstracts at national and international scientific meetings. He chaired the writing format for the consensus guidelines he is going to go over, which is published this year and endorsed by ADA and many U.S. and European organizations. Last but not the least, the last panelist is Dr. Cecilia Lo Wang. She is the Professor of Medicine at University of Colorado Anschutz Medical Campus School of Medicine. Dr. Lo Wang earned her MD degree at the University of Rochester, did her intermedicine residency and chief residency at the University of Utah, and endocrinology fellowship at the University of Colorado. She then joined the University of Colorado faculty at VA and currently serves as medical director for glucose management team at the University of Colorado Hospital. She contributes to various diabetes and glucose management efforts across the system and sees patients in endocrine and transplant metabolic clinics. She co-founded and is the program director for the University of Colorado Diabetes Fellowship Program, and she is the associate director for the School of Medicine Brown Student-Aligned Mentored Scholarly Activity and senior fellow of the Academy of Medical Educators. Her research interests include hospital glycemic management, the use of the diabetes technology, complications and digital health for underserved population. She is experienced in regulatory aspects of the clinical research and clinical trials, end point education, data safety and monitoring. She served as a chair of FDA advisory committee for endocrinologic and metabolic drugs and medical director for CUAMC INDE IDE office. She holds the leadership role at the Endocrine Society and American Association of Clinical Endocrinology. She co-founded and served on the executive board of the American College of Diabetology. She has published numerous original manuscripts, reviews, chapters, and co-edited two books published by ADA. She is dedicated to advancing the care of the individual affected by diabetes and diabetes related complication through training, research and enhancing the care delivery. So thank you very much all the panelists to contribute to this webinar and share your expertise and thank you very much everyone to join and listen and participate in the discussion and question and answer. So let's welcome Dr. Ruchakoff to present his presentation. Great. Thanks so much. Let me just get this started. Okay. So the first thing is thank you for asking me to be part of this. If anyone wants to see the details on the slides that I'm showing, just let me know and I'll send them to you. This is part of a talk I gave a while back and it's on the history of DKA. And I thought that it would be a nice place to start as you're going to learn about all the new things, mainly from Guillermo in just a few minutes. This talk actually starts back in 1886 with the Bradshaw lecture from a person named Julius Drushfield. And in that he talked about the history of DKA at that time. Basically he thought that this was a small group of people, but it was interesting to both physicians and pathologists. That tells you a lot when it's the pathologists that the diabetic coma was a peculiar group of symptoms that comes on suddenly, characterized by coma and generally entering in fatality. They had three different types of diabetes. I'm sorry to interrupt, Dr. Rushidov. We cannot see the slides. So if you can... You really can't see the slides. Oh my gosh. Whoa. Let's try this again. How about now? Yep. It's loading. Yep. We can see now. Thank you. Okay. And let me start over. Oh my gosh. I apologize so much. And then... Okay. Do you see them now? Okay. Yep. We can see them. Okay. Sorry about that. That is so strange. Anyway. So this is... There were three forms of diabetic coma that they discussed at that time. The first was chiefly characterized by drowsiness and the patients would soon pass into coma. The second kind of was like an alcoholic intoxication. The patients were in this excited state, had drowsiness and then coma, a staggering gait. So I'm really unclear what this is. A third group was the main group that had dyspnea, the breath of the patient and the urine showed a characteristic color and odor of acetone and the patients had coma. So we kind of talk about these specifically because it'll be interesting when you think about the way we look at patients now. The first group that they talked about with diabetic collapse, they had drowsiness and excessive weakness. Their extremities became cold, they had quick pulses. The respirations were only slightly quickened, shallow, but not much dyspnea. They had a gradual falling of their temperature and death ensued from collapse within 10 to 20 hours generally. They tended not to have delirium or convulsions. This is now from Dr. Hoffman and this group was mainly in people who are over the age of 40. They'd had symptoms for some time. They were generally stout and well-nourished at the time of their attack and they called this constitutional diabetes or diabetes of stout people where the course of disease was slow and protracted. This is obviously what's going on in type 2 diabetes patients. The alcoholic form, I'm going to skip over here for time, but it kind of resembled this alcoholic intoxication. It's unclear what's going on and actually when they looked at the urine, it contained alcohol, but it was unclear what the underlying etiology really was in these patients. I'll just skip over that and let you look at this if you want to in the future. The third group now discussed by Kusmal, so that should tell you a lot right there. So this was coma from acetonemia and he was the first to describe this. So the patients had lassitudes and dyspnea, gastric pain with vomiting. They pass into a state of drowsiness with marked dyspnea soon followed by coma and death. They could have delirium, abdominal pain and severe symptoms to simulate peritonitis, which is again what we talk about when we're discussing a DKA. They become pale and flushed. They have quick, small thread-like pulses. Their veins are not distended in their neck and as far as a respiratory status, they have marked dyspnea and what we've learned is Kusmal respirations. It's all described here as he described it in the first place. The third part of this again, now this is from Dr. Foster, was the patients again had loss of appetite, nausea, the vomiting always shows here of copious masses, the temperature initially increases and decreases and can be as low as 90 degrees at that point. 90% of these people were, it was fatal generally within just a couple of days, but again, in the type 2 patients that we think of now in the stout group, it could be preceded for months before they develop the problem. Now our next player is Charcot, I'm sure you, that name all shows up for many things in our diabetes. He had a series of 4,000 cases, 55% were age 40 to 60, another series at age 20 to 40 and again, the younger patients had coma that occurred about 6 to 12 months after the initial symptoms and the older people, it had been much, much longer and in the patients who were younger and it was quicker, they didn't have sugar in their urine even just a short time before they went into coma. These three group people described what they thought were the cause of DKA and coma, excessive physical activity, mental shock or a change in diet to nitrogenous diets or after surgery or febrile illness. Some of that sort of makes sense, but the treatment was interesting because they wanted people to avoid physical activity, avoid mental worry, avoid mental shock and avoid changes in diet, but basically it was a gloomy outlook and people died from this no matter what. So let's move forward a little bit to about 50 years ago and start looking at what were the causes of DKA at that point and at that point, we had generally the main thing was patients who admitted their insulin mainly from the patient, sometimes by physicians. Now it's for a mission, it's usually social or economic, homelessness could be the initial manifestation and one of the main things that we're all interested in these days are the medications SGLT2 inhibitors and checkpoint inhibitors for us in 2024. You look at the description of DKA by Howard Root who was a president of the American Diabetes Association in Boston a long time ago and they compared patients from 1923 to 1940, 1940 to 1944 when they changed how they made their interventions. The percentage of people who died went from 12% to 1.6% and the main thing was how much insulin they gave in the first three hours, it went from 83 units to 216 units in the first three hours of treatment and they actually had sort of this diabetic coma wartime service where they had a lab service available 24 hours a day, a coma bed, special diabetes nurse. Initially, as they were coming to the hospital, they got 20 to 60 units of insulin up to 1,200 units of insulin in the first 24 hours, four to seven liters of fluid, repeated enemas. They started feeding them in about six hours and if they weren't eating, they would give them glucose but if they gave them glucose at the start, there was an increase in mortality. So this takes us then to why we've moved toward these massive doses of insulin closer to where we are now and this is from Annals of Internal Medicine in 1976. So they seem like a long time ago but this is basically just a year before I started medical school so it doesn't seem so long ago to me but this is showing that at the time, people who had high blood sugars, let's say over 1,000, they gave them a 50 units IV plus 100 units sub-Q to start versus a low dose group where they got 0.1 units per pound and then followed them every hour and the group that still had high blood sugars, they got 50 units more every hour as opposed to the low dose group that got five units IM per hour and once the glucose got lower, they would start giving them dextrose. So you can see the difference in how much glucose insulin they got, 263 versus 46 units and actually the only difference here, these weren't statistically significant for the time to glucose under 250, the time to bicarb coming up. The difference was people got all this insulin, had a lot more hypoglycemia and hypokalemia. What about the move towards sub-Q insulin that you're going to be hearing about? Well, this was being looked at back in 1977 too and if you compared IV insulin to IM insulin sub-Q insulin, it didn't make any difference way back then. I think most of us then learned to use IV insulin because it was a lot easier to adjust, but if you look at the data, it didn't really make any difference. If you look at electrolytes and fluids, people have shown for years that what the urinary loss is here of six and a half liters of free water in the first 24 hours here and what do we make of this? Well, because again, back in the late 1970s, it showed just giving fluid helped the resolution of the DKA. So we have blood glucose just being treated with fluids and here it's up in the 500s to 600 coming down to about 360 over 20 hours, just giving the fluids, not actually giving any insulin during that time, showing just how important fluid replacement is. What about bicarb? These used to be all the indications for bicarb, pH under seven, coma, hyperventilation. Turns out that basically none of those are particularly true. Maybe hypotension unresponsive to IV fluids or cardiac arrhythmia, but it can be dangerous if the potassium is already low and you give bicarb that can lead to hypokalemic respiratory paralysis. So generally bicarb isn't used. And actually it doesn't make much difference whether you give it or not. This is showing a change in glucose. This isn't actually statistically significant. And this is showing there's actually a no change in pH, whether you gave bicarb or not. The other thing with bicarb, just to be complete, is this is looking in kids, looking at cerebral edema, this is ventricular size during DKA and in resolution. And with resolution, the ventricular size returns to normal. So you can have this, again, generally subclinical edema. But what we know is if you give bicarb to rabbits, you can actually increase edema. So we tend not to want to use bicarb. So basically I gave you just a little background just to show where things have been, how things have progressed over time before you start hearing where things are now and where we're moving to in the next short time. I guess the question is, you know, 20, 30 years from now, when people look back, are they going to be laughing at what we're doing now? Just like we're sort of laughing at what they were doing way back when. So and again, I'll share any slides you want in the future. Thank you. Thank you very much, Dr. Yusufov. So now is Dr. Pires. I just I forgot to mention one thing is he is out of all the country. However, he is gracious enough to pre-record his lecture and we are going to share his pre-record lectures and he will try to join for the question and answer section. Hello, I'm Guillermo Pires. I'm a professor of medicine at Emory University School of Medicine in Atlanta. And it's during the next 25 minutes, we will update you on the management of hyperglycemic crisis in adults with diabetes. And this was the publications that we worked together with different societies, including, of course, the American Diabetes Association, the European Association of Diabetes, the Joint British Society in Patient Diabetes Care, ACE, and Diabetes Technology Society. Before we start, here are potential disclosures and conflict of interest. And this new consensus statement, the objective is to provide up-to-date knowledge about the epidemiology, pathophysiology, clinical presentation and recommendations on diagnosis treatment of both diabetic ketoacidosis and hyperglycemic hypersmaller state. And we have reviewed the literature from 2009, the last ADA update, to November of last year. And the audience is full spectrum of diabetes healthcare professional, everybody who is involved in diabetes care. The first consensus statement of the American Diabetes Association was published in 2001. The second we updated in 2006, and the third one in 2009. So during the past 15 years, we didn't have much update on how best to manage patients with hyperglycemic crisis. So in this update, we divided the consensus in eight sections. First, a discussion of epidemiology and clinical outcome, pathogenesis, diagnostic criteria, recommendation for treatment, both in the hospital and after hospital discharge, discuss about complications and how to prevent complications during treatment. And we have two sessions, one special population and future research, that we'll not discuss today, but they are in the public cases. So with respect to epidemiology, it's clear that both in the United States and Europe, there had been a significant increase in the number of admissions of adults with both type one and type two diabetes. No population level data is on hyperglycemic crisis on HHS, or in mixed DKA and HHS. This is the area that we need to discuss in the future and do research to determine what's the difference between DKA and HHS and outcome. We also have noticed that repeated episodes of diabetic ketoacidosis admission both in the United States and in Europe. We also describe the increased number of people with type two diabetes admitted with DKA. Over half of newly diagnosed African-American Hispanics in the United States with unprovoked DKA are now known to have type two diabetes and recognized as ketosis-prone type two diabetes. And of course, good news, from over 95% mortality before the discovery of insulin, mortality reported in Europe and in the United States is less than 1%. As you notice that mortality of HHS is five to 10 fold higher in individuals compared to DKA. This is just one of the examples on the increased prevalence of hyperglycemic crisis. This data comes from the UK. To the left is type one diabetes and to the right, the prevalence of type two diabetes. And in both, the increased number have been noticed during the past 20 years, despite that this should be a preventable complications. We also have noticed that for many years, we have DKA and HHS like two different entities. But recent publications suggest that 38% have pure DKA, 27% HHS, but there is a combination of both. So it is hard to describe or try to divide them as two different entities. There are two expressions for the decompensation of type one and type two diabetes. We discuss in this publication, the precipitating costs and the changes in different countries. For example, in the United States, here at the bottom of this table, the number one is insulin omissions. In other countries too, newly diagnosed or more importantly infections in many countries, the number one cause. So it is important to recognize the reason why the precipitating costs and different populations that will help us in prevention and treatment of patient with diabetes, with diabetic ketoacidosis. In the last three years, we also recognize the role of SGLT2 inhibitors, the association of SGLT2 inhibitors and diabetic ketoacidosis in type one. And in patients with type one, several studies have shown an increased risk of two to fourfold the risk of diabetic ketoacidosis which led the FDA not to approve SGLT2 inhibitors in patients with type one diabetes. And it's not only type one, the risk of DKA is in patient with type two and we describe risk factors that may precipitate DKA in type two such as prolonged fasting, ketones diet. So it is important to recognize that both SGLT2s increase the risk of DKA in both type one and type two diabetes. Good news as I mentioned before is the significant reduction in mortality and now in general is less than 1% but it depends on what is the precipitating cause. Of course, if you have a DKA that is precipitated with acute myocardial infarction or GI bleed or cerebral infarction, well mortality is much higher. Also mortality in HHS is higher, but in general mortality rates has come down to 1% despite the increased rate of hospitalizations. We highlight the importance of repeated episode of diabetic ketoacidosis. To the left this graph shows in blue those patients with one episode, two to five in green and in red more than five episode of DKA. Those patients with repeated episode of recurrence episode of DKA that are associated with four, three, four, five fold increase in mortality. So if we look at somebody who is re-admitted with DKA, we need to find out why and trying to prevent it because there is an increase, significant increase in mortality. And finally, well, the combination of DKA and HHS have higher mortality compared to DKA or HHS alone. So those are the individuals that have to be careful because there are higher sort of mortality, not less than 1%, but mortality may be between five to 10%. In respect to diagnosis, so we discussed with these different societies if we need to change or not the diagnostic criteria. First, we put together this table, the clinical presentation of DKA and HHS. So DKA develops over a few hours to days. HHS is more slowly processed, usually several days. Most patients are alert, stuporous, but HHS has greater impairment of mental status. The poliurea, the polydipsia, weight loss, and semen, both. Clinical characteristic, those patients with nausea, vomiting, abdominal pain, suggests DKA. HHS per se is not associated with nausea, vomiting, or abdominal pain. So that's something to keep in mind when we see these patients. They need or not to be worked out for potential complications that may lead to diabetic ketoacidosis. And finally, good smile breathing. The increased inspiration and expiration to produce respiratory alkalosis to compensate for the metabolic acidosis is seen in patients with DKA. Again, keep in mind that up to one third of patients has a hybrid representation, both DKA and HHS. So you have to keep that in mind when you decide about the diagnostic criteria. So with respect to diagnostic criteria, we make minor change. With respect to hyperglycemia, it's still on the top as one of the criteria, but we know that 10% of patients with DKA present with glucose less than 200, 250. So we have changed from 250. Now we recognize that 200 should be the way to diagnose DKA. So why is that? Not only that 10% have lower blood glucose, but the diagnosis of diabetes is with a glucose greater than 200. So we decided that instead of 250 should be 200, or a prior history of diabetes. So you can have type 1 diabetes and a glucose of 180, 150, but if you are metabolic acidosis and ketosis, you have DKA. So hyperglycemia is important, but in those patients who have prior history of type 1 or type 2 diabetes presented with metabolic acidosis and high ketones have a lower value in the diagnostic criteria. Ketosis, we would like to have an increased rate of measuring beta-hydroxybutyrate, the main ketone's body in patients with diabetic ketoacidosis. And the beta-hydroxybutyrate should be greater than three. We recognize that about half of the hospitals in the United States, they will still use urine ketones for diagnostics or diagnosis of DKA. And that's okay. The sensitivity of 2 plus urine ketones in relation to beta-hydroxybutyrate is quite high, more than 90%. Then we want to highlight the importance that urine ketones is good for diagnosis, is greater than 2 plus, but it's not good to assess resolution of DKA because half of the patients who has already corrected the acid-base disorder still have positive urinary ketones. The metabolic acidosis is described as a pH less than 7.3 and bicarbonate less than 18, not 15, 18. So what's new in DKA? Definition, lower blood glucose level from 250 to 200, added a prior history of diabetes irrespective of glucose levels. Consider that 10% of those patients has near normal, ill-glycemia or near normal glycemia. So that was the reason to change the cutoff limit of glucose. With respect to ketones, again, we would like to increase utilization of beta-hydroxybutyrate. It should be greater than 3. You can still use ketones for diagnosis, but not for resolution. When you resolve DKA, the beta-hydroxybutyrate converted to acetoacetate, so you can still have positive ketones. So the other thing that we recognize is that the use of anion gap. It used to be a strong criteria. Now it helped to diagnose because most people present with high anion gap metabolic acidosis. But one third of patients has a mixed acid-base disorder and they present with not a high anion gap. So it helps you, especially if you don't have beta-hydroxybutyrate, that it was not a strong criteria as we had it before in 2009. So we have this table to guide doctors about where to admit patients to the hospital. We had similar table in 2009. There have been minor changes. The glucose now is 200, as we mentioned before. The level of ketones now less more than six suggests severe DKA. The metabolic acidosis, this is the most important criteria. That's right, beta-hydroxybutyrate and acid-base disorder. A pH less than seven suggests severe DKA, seven to five moderate. And the same thing for bicarbonate, less than 10 millimoles suggests severe diabetic ketoacidosis. Mental status is extremely important because those patients who are admitted with stupor and coma have an eight to 10% mortality, much higher than those patients who are alert. And in this table, we said those patients with mild DKA should be treated or can be treated in a regular floor in the emergency room observation unit. Those who have severe DKA suggest to be admitted to the intensive care unit because it's associated with higher mortality. But again, location is a clinical decision. Look at what is the precipitating cost. Those patients with a precipitating cost severe like surgery, acute myocardial infarction, et cetera, should be admitted to the unit. Regarding the diagnostic criteria for HHS, hyperglycemia was not changed, 600 milligrams. Hyperosmolality was a big discussion. In the year 2001, we used total serum osmolality, that is sodium times two, glucose divided by 18 milligrams, urea by 2.8. If you use mil-osmol, this formula is in front of you. In 2009, we changed to effective serum osmolality not taking in consideration urea. And because we explained that maybe urea doesn't really produce alteration of mental status. It just flow freely inside, outside the cell. Now we have data suggested that either one, effective greater than 300 or total serum osmolality more than 320 account for the diagnosis of HHS because it has the same impact on outcome. Significant absence of significant ketonemia, less than three or less than two plus ketones, absence of severe metabolic acidosis, so the pH should be more than 7.3 by coming to more than 15. But remember that one third of patients have a combination of DKA, HHS. So use your clinical criteria. And they are not different entities. They are two expressions of the severe metabolic decompensation. Respect to management, we've made some changes and recommendation for treatment. In the past, we have four columns, IV fluids, insulin, and potassium. And we also have bicarbonate. Now we took bicarbonate because very little goal is to correct metabolic acidosis with bicarbonate administration. So different recommendation for IV fluids. First, you assess the hydration status. That in the IV fluids, we always recommend that since 2001, the use of normal saline. There are eight or 10 different randomized controlled studies published in the literature suggesting that the use of balanced crystallized solutions such as Ringer Lactate have faster resolution, shorter hospital stay, less frequent development, what is called hyperchloremic metabolic acidosis. So you use normal saline or Lactate or Crystalloid. It's up to you, whatever is available in your institution. The fluid replacement should be corrected in the first 48 hours. So there's strong recommendations and very clear and detailed recommendation how to use fluids in different situations. For example, if you have chronic kidney disease or congestive heart failure, how do you manage with the detail that in the publications. With respect to insulin, there are minor changes. However, we recommend that those patients with mild decay, so pH, not bad, 7.28, 7.25, not really decompensated, no precipitating cause can be treated with sub-Q insulin. And there are several papers and even in meta-analysis suggesting that in mild decay, you can use sub-Q rapid-acting insulin analogs. You can still use IV insulin for mild, moderate, severe decay. And we've made recommendations on how to manage and how to adjust insulin to start 0.1 units per kilo. If you want to use both, okay, if not, okay too. And how do you have to adjust the insulin and glucose infusion to correct the hyperglycemia, correct the increased ketones and free fatty acid in patient with DKA due to insulin deficiency. So, and how to prevent hypoglycemia. In potassium recommendation, we make clear that if somebody is meted with GKA and HHS, there is a reduction of serum potassium between one to two millimole within the first 24, 48 hours. And this is because the sodium potassium pump that regulates transport of potassium inside outside the cells is controlled by insulin. And when you start insulin infusion, you start fluid, you start excreting potassium in the urine, there is a reduction of one to two millimole. So if somebody is admitted like shown here in the bottom with potassium more than five, six, no need to be treated, just start insulin and fluid. But in the other hand, if you have somebody who is admitted with a potassium of 3, 3.5 or less, this is somebody who may develop significant hypokalemia associated with increased morbidity and mortality. So we recommend to look at potassium, measure potassium frequently to prevent hypokalemia. As I mentioned before, bicarbonate, we don't have good data with those patients with pH less than 6.9 or 7. We don't usually use bicarbonate anymore. In most people, in most patients admitted with diabetic ketoacidosis. And phosphorus, we used to change potassium, but phosphorus with chloride or KCL or KFOS, we don't recommend much the administration of phosphorus except for those patients with severe hypophosphatidin. Regarding the resolution criteria of the TKA, we want improvement of glucose level, hopefully less than 200, 250 and resolution of the acid-base disorders. If D-NOS pH more than 7.3, the bicarbonate more than 18. And if you are measuring ketones, and now we have ketones by finger sticks who are very accurate, that's what they use in Europe. Or continuous ketones soon to be available. You want to be less than 0.6 millimoles more. And for HHS criteria, they have not changed. Bring down osmolality less than 300. Bring the blood glucose down to a 250 and an improvement of cognitive status. And of course we want, because we know that for HHS, the main problem is dehydration. We want to make sure kidney function is improved and patient urine output is greater than 0.5 ml per kilo. We spent a lot of time discussing and providing recommendations about transition of care. First, keep in mind, most people are treated with IV insulin or frequent doses of sub-Q, that half-life of IV insulin is less than 10 minutes. So we have to give sub-Q, basal insulin or rapid-acting insulin before you discontinue the IV insulin about two to four hours before. How do you calculate the insulin dosage? We provide three ways to do it. The most common form is a weight-based, especially for those patients with newly diagnosed. And we start on 0.5, 0.6 units per kilo. We divide half basal, half boluses. Or you can look at pre-admission insulin requirements. So if the patient just stopped insulin because it just stopped for a couple of days, developed GKA, consider that. And of course, most people present with decompensated, very high hemoglobin A1C, so you have to adjust insulin. You can also look at the insulin requirements per hour to calculate the insulin doses. We'll have a long discussions about what do you do with some patients, for example, with ACLT2 treatment. First, stop it. Don't use it in type one. Then if they're type two after a period of discharge, can you use it? Well, the recommendation depends on what the patient is going on. That's right. They achieve good glycemic control. They're stable. two or three months after discharge, they have kidney problems, heart failure, well, you may consider use, but make sure they're not type 1. 40%, according to a standard of care, of patients with type 1 diabetes are misdiagnosed as type 2. So we want to bring to your attention that you can use them, but just be careful about that. There's also several publications suggesting that you can add basal insulin early on in the treatment of diabetic ketoacidosis, and yes, you can do that. It may help a little bit in resolution, but what has been shown is that prevent rebound hyperglycemia. That is institution-dependent in our unit, we don't use too much basal at the beginning of treatment, but we do start basal insulin two to four hours before we stop the IV on the transition period. Finally, let me discuss with you some important aspects about complications and the transition of care. First, hypoglycemia. Unfortunately, very common, between 15 to 30% of patients have severe hypoglycemia at less than 40. So imagine this brain, who has a little bit with a glucose of 600, you drop to 40 in the matter of four, six, eight hours. So that creates a significant inflammatory state, reactive oxygen species, and it's associated with two to four-fold increase in mortality. So we want you to measure glucose every one or two hours, basically every one hour, and see that the patient is responding to therapy. Regarding hypoglycemia, I mentioned before, you reduce potassium from one to two millismal in the first 12 to 24 hours. They'll bring potassium from outside, inside the cell. And if you develop significant hypoglycemia, the rate of mortality increase by two to four-fold. So what we want you to measure potassium, if it's low in two hours, then every four hours during treatment, and potassium replacement should be added to every fluids, because most people will have a significant reduction in potassium levels. We don't have much data on thrombosis. However, we recommend that this patient, because of the inflammatory, they are dehydrated. The risk of thrombosis may be increased. We need more data. We would recommend to use low molecular weight heparin to prevent potential thrombosis or DVT in these patients. Cerebral edema and osmotic demyelination syndrome is uncommon in patient, in adult subject, but it's present in type one. It's, well, we want, it took hours to day, it's two weeks to glucose to go that high and have a hypoglycemic state. Take your time, slow down. There's no need to rush. And finally, acute kidney injury. It's due to pre-renal anesthesia and dehydration or lack of the fluids during treatment. It's associated with significant increase in morbidity and mortality. So look at this kidney function. Check labs every four hours during treatment. Those are the treatment in patients, but at this charge, we wanted to make sure that when the patient go home first are educated, have enough insulin, have enough prescription. Look at precipitating factors for those patients with one or multiple episode of GKA. I already told you, mortality increased by three to five fold. So those patients who are repeated offenders, well, look at why. Are they depressed? Are there substance abuse? They're psychotic. What is going on trying to prevent recurrence of GKA that may decrease morbidity and mortality? Offer appropriate education, make sure they have these charts. And finally, what about the use of CGN? We recommend that those patients with type one and those patients with type two that want to be treated with insulin should be considered candidate for the use of continuous glucose monitoring. There's data from Europe that they significantly decreased readmission rates. So make sure you provide enough supplies, consider CGM for those patients admitted with diabetic ketoacidosis. We have sections and details about how to manage the frail, the older adult. Should they be managed in the same way like young people? No. So we make significant recommendations already mentioned about HCLT2 inhibitors. Those patients with end-state kidney disease, how do you manage fluid? How do you manage potassium in these patients? So we make significant recommendations for your consideration. Pre-pregnancy diagnosis of type one and type two diabetes increase the risk of diabetic ketoacidosis and diabetic decompensation during pregnancy. So we make recommendation how to manage this patient. I hope that we don't ever have the COVID pandemic again, but of course we have this section. How do you manage this patient, especially during the transition period, long-term, short-term? So I thank you very, very much for the opportunity to discuss the management of the new update of hyperglycemic emergencies in those patients with diabetic ketoacidosis and HHS. Thank you so much. So now we have learned something about the historical background and the latest consensus paper. So I would like to invite Dr. Lo Wang to give us some practical tips and tricks of implementation and treatment. Oh, thank you. Actually, what I'm gonna do, let me go ahead and share my slides. I would like to focus a little bit on euglycemic DKA. So first of all, thank you for this opportunity to talk about this and thank you to everyone for logging in. So I'll talk a little bit about the background and then SGLT2 inhibitors and DKA and euglycemic DKA. I'll highlight some of the things about euglycemic DKA in the new consensus report, as well as some papers I was able to pull on management. And then the situation of, what if there's a patient at high risk, but not in euglycemic DKA? For example, we have many situations where we have patients who didn't hold an SGLT2 prior to a planned procedure, or maybe they had an unplanned procedure. And so how do we monitor? And then I'll go over a few barriers to care and then gaps in knowledge. And I think this will probably take about 10, no more than 15 minutes. So this is the publication that highlighted this problem of euglycemic DKA with our use of SGLT2 inhibitors. So I wanted to pull this out. It was published back in 2015 in Diabetes Care by a number of our leaders in diabetes. And so this was the observation that SGLT2 inhibitors seem to be associated with euglycemic DKA and ketosis. And we didn't really know the mechanisms and we still don't really know the mechanisms, but the thought was there was hyperglucanemia, volume depletion, and we should be aware of this in patients with type 1 and type 2 diabetes. So this is a diagram that shows maybe some of the mechanisms. So it's thought that there are probably some indirect as well as direct mechanisms. So the indirect mechanisms would be the decrease in plasma glucose, causing decrease in insulin, and then causing an increase in the glucagon to insulin ratio with increased lipolysis, free fatty acid production, ketone body production. And then direct effects may be that SGLT2 inhibitors could be acting directly on alpha cells to increase glucagon production, as well as to increase ketone body reabsorption by the kidney. So many of the reports about SGLT2 inhibitors and DKA are either case series or case reports. There've been some meta-analyses and then also some reviews of the FDA adverse event database. So I just pulled out a couple of these. One is a meta-analysis of 16 different randomized control trials of SGLT2 inhibitors. And so this was mainly the randomized control trials of SGLT2 inhibitors with type 2 diabetes. And about 19,000 patients were on SGLT2 inhibitors, about 12,000 on placebo. And the pooled relative risk of DKA, so this is all DKA, not just euglycemic DKA, was about 3.7. So this is pretty close to the numbers that Dr. Impera has mentioned and that are quoted in the hyperglycemic consensus report. And then if we take a look at the FDA adverse event database, so this is people and providers who submitted cases to this adverse event database, looking at about 10,000 cases of DKA, around 1,700 of these were euglycemic and about 8,500 were DKA associated with SGLT2 inhibitors. What this group of authors was focusing on was really just trying to look at median onset of time between euglycemic DKA and DKA, and then to see if there were differences between the different SGLT2 inhibitors. So what they found is that the median onset time for DKA and euglycemic DKA in patients on SGLT2 inhibitors was about 31 days, but it did seem to be longer for patients on canagliflozin, and that was longer than patients on dapagliflozin or empagliflozin. And it did seem that patients who were entered into this database with euglycemic DKA on SGLT2 inhibitors tended to also have vomiting. And those who didn't have euglycemic DKA, there's a lot of acute kidney injury reported. So just recently, this was a topic of discussion at a recent FDA Endocrine Metabolic Drugs Advisory Committee meeting. And so I pulled out a little bit of the analysis that was presented at that meeting. And so this was an FDA Sentinel analysis of SGLT2 inhibitor use in type 1 diabetes from 2014 to 2023. So of course, this is off-label. And so what the FDA found in this analysis is that the proportion of new users of SGLT2 inhibitors who met the criteria for type 1 diabetes decreased during this period of time. So it was 2.2% back in 2014, and then down to 0.5% in 2023. And this kind of depended on how you defined type 1 diabetes. So if you used a more broad criterion or narrow criteria. And so you can see kind of the difference between the ways of detecting or pulling type 1 diabetes diagnoses from the databases. It also seems that the proportion of new users of SGLT2 inhibitors was highly age-dependent. And so the use was much higher in people who had type 1 diabetes and were between the ages of 19 and 24, and a lot lower in those who were 65 and above, so you can see the numbers here. And of course, there was an FDA warning that came out as a result of that initial report that I showed you back in 2015 about SGLT2 inhibitors and the risk for DKA. And of course, we've also seen publications of various monitoring protocols to address potential, this potential risk in patients with type 1 diabetes on SGLT2 inhibitors, such as the STOP-DKA and STITCH protocols. But the incidence of DKA in type 1 and SGLT2 inhibitor use didn't change during this time. So this is also from the FDA sentinel analysis. So ranging from about 2014 through 2024, this is the DKA cases per 100 patient years. So it really hasn't changed despite these warnings and despite the decrease in use. And then here's a separate study looking at, it was a pharmacovigilant study looking at SGLT2 inhibitors and individual different SGLT2 inhibitors and euglycemic DKA incidence. So you can see that they vary between EMPA, DAPA, and CANNA are the ones that I pulled out here. So euglycemic DKA is significant, but it really seems to vary among the different SGLT2 inhibitors and DKA is definitely more prevalent. So how is euglycemic DKA different from DKA? So how do those patients look? Are there different times, like in terms of mean time on insulin infusion, mean length of stay? What about severity of the DKA? So here's a study where at a single center, they did a retrospective review of patients with DKA between the years 2015 and 2022. And it was University of Michigan. So they looked at the use of the two bag order set for DKA and then stratified patients by a glucose of 250 or less than 250 on presentation. And so out of this, they were able to pull 629 patient charts and 44 of those kind of fit their definition of euglycemic DKA. So presenting with a glucose of 250 or lower and 585 with a glucose of greater than 250. And looking at the differences between these groups, there really weren't that many differences. And so the presenting pH was similar, bicarb was similar, mean time on infusion was maybe a bit longer with the hyperglycemic DKA, but hours to the first bicarb of over 18 was similar. And then the mean length of stay was also fairly similar. So going back to the hyperglycemic crisis consensus report, as Dr. Ramakiris mentioned, there is this recognition that there's this wide range of glucose concentration in people presenting with DKA. So the DKA diagnostic criterion, the glucose one was revised. So it includes that lower glucose value of 200 and a prior history of diabetes irrespective of the glucose. And it's estimated that possibly about 10% of patients with DKA are presenting with euglycemic DKA. So here's the definition and there are a number of different causes. So it could be spontaneous, it could be because of those insulin dose reductions, omission of insulin, prolonged fasting, acute illness, reduced PO intake, pregnancy, impaired gluconeogenesis due to either alcohol use or liver failure. But it really seems like recently it's been SGLT2 inhibitor use in type one and type two diabetes that accounted for most of the euglycemic DKA. So what about the management? So the consensus report recommends that the SGLT2 inhibitors are stopped on admission and we use D5 or D10 added to the IV fluids at the same time as NS. And the acute management is really the same as for general DKA. And I thought this was interesting. So this was a proposal that was published not too long ago by a group, Dr. Chow, Clements and Garg that mentioned, that kind of proposed some different infusion rates. So for example, an IV insulin infusion rate of one to two units an hour, D5 or D10 to maintain a glucose of 120 to 180 and advancing the diet and or giving carbs to replenish glycogen and then trending the ketones and the anion gap. This was of course, before the publication of the consensus report. And so this I thought was interesting. We haven't, we really don't have studies of management of DKA, of euglycemic DKA. And then in terms of future considerations in euglycemic DKA, what's already been mentioned is that for patients with type one, not to restart the SGLT2 inhibitor and then to protect two, really not routinely initiating or continuing that therapy after the DKA resolution. Although there might be situations a few months down the road, if there are, it's thought to be, the benefit is thought to be much greater than the risk. So for example, the patient has heart failure or CKD, maybe consideration could be given to restarting, but really it's an individual patient centered decision. And then not specific to euglycemic DKA was the recommendation that CGM could be offered or should be offered to people admitted with DKA after discharge. So what about that situation? Like what do we tell patients around the time of procedures? So really ideally we would be instructing our patients to hold their SGLT2 inhibitor either three or four days prior to the procedure. Our center is thinking about just keeping things simple. And even though there aren't that many patients on urticliflozin, changing it all to four days prior and having people come in for a pre-op procedural services appointment so that all of these instructions can be reviewed, medications can be reviewed with a patient. And then what we're probably going to institute is that everyone who's on an SGLT2 inhibitor to receive a confirmatory phone call a week prior to their procedure if we can. And if for whatever reason the patient had an urgent or emergency procedure, so the SGLT2 would take in or they didn't follow the instructions, then we are going to recommend some protocol of checking ketones. And then if the ketones are elevated then checking a blood gas. And this is kind of a potential monitoring protocol that was proposed in this publication down here. And then what about in the hospital? So for those patients who undergo an emergency or urgent procedure and didn't stop the SGLT2 inhibitor, how would we monitor? So this isn't super clear, but we're probably going to set up a protocol where we monitor patients. And so I think this was actually proposed by Dr. Ruchikoff and his group where they are doing real-time monitoring of the EMR for patients on SGLT2s prior to or during their admission. And then so they're looking for increased anion gap, decreased bicarb, elevated serum beta-hydroxybutyrates or low pHs, which would result in a text page to the endocrine service, review of a chart by the endocrine provider, and then potentially offering an endocrine consult to the primary service. And so I think there are still some barriers to care. This is still a big issue in question in our hospital. And we are getting lots of requests from the hospitalists and other services and lots of problems related to development of euglycemic DKA. And so recognizing the euglycemic DKA, having a protocol for those at high risk and close monitoring. And then in terms of management gaps, there should we be using sub-Q insulin? So many of the initial reports really talked about prolonged DKA in our patients with euglycemic DKA, sometimes lasting as long as a week or two. And so could we be using sub-Q insulin? And what dextrose infusion rates should we be using? Should we use a standard low insulin infusion rate? And then should we be allowing people to eat early? So in summary, I think I just wanted to highlight euglycemic DKA and just a little bit of information that was out there about DKA and SGLT2 inhibitors. So euglycemic DKA accounts for about 10% of all DKA estimated. Recognition of euglycemic DKA is often delayed and awareness of those risk factors and the higher risk populations can improve detection. We have to start dextrose infusion early. Oftentimes those patients are presenting with glucoses where we'd be starting dextrose anyway with the insulin infusion. And then we should be screening those, probably should be screening those at high risk and monitoring, and there are still some evidence gaps. So that is the end of my presentation. And I think that we have a lot of time for Q and A. So let me stop sharing my screen. Thank you very much. So before we go back to Dr. Arushaka for the final thoughts, I just want to urge everyone to put in the questions so that we can start the question and answer section as soon as Dr. Arushaka's final section is done. So I just want to welcome Dr. Arushaka again. Great. Great. Thanks so much. Hopefully you can see it to start with this time. Okay. This is going to be very quick. I just want to talk a little bit about actual implementation of protocols. This is one of the British publications. They have these enormous publications on every area of diabetes management. This is their last one on DKA. It's about 50 pages long. This is the one-way pathway for DKA treatment and a couple one-page items for implementation. The reason I'm showing this to you is not to say, wow, this is great, you should blow this up and look at it. It's because you've heard a lot about pathways and generalities so far. The problem is you've got to go a lot farther than that. With this and these big publications, there was a presentation about a year and a half ago at the ADA meeting looking at outcomes and the appropriate treatment of DKA in hospitals in the United Kingdom and found that it was not very good. That was despite these great pathways that are present and all the work that went into it. It turns out when I spoke to the speaker after the presentation, it's because they don't use, for the most part, standard order sets, EMR order sets, that actually help people manage this. It was all ad hoc orders that people did. That's the problem. Let me just go back over what we should be doing, where we've been, and where we're going with actual order sets on these things. Obviously, in a DKA order sheet, you need laboratory tests, the fluid orders, the glucose monitoring orders, the insulin orders, some guidelines or easy ways of adjusting fluids and insulin. Those are all the key items. We've actually had paper order sets in the past that were put in for DKA that started in the early 1990s. The order sets were simple and easy. We talk about it in a generality that someone who had been a physician 30 years earlier, they were taught to sit by the bed when the patient was being treated for DKA. You could be in your own bed and be treating the patient for DKA because it really was not so hard when you have the right orders in place. The patients were DKA. We worried about gastroparesis and made them NPO initially, had appropriate lab tests that were all standard, standard times for follow-up lab tests. We gave them some guidelines again for fluids, and then they put in their own fluids, but there were only a couple of choices that they could use, told to when to change the D5 to add to the fluids when the blood glucose was under 200. Very simple insulin orders. These were not very exciting. Initially, there was an initial bolus because that was the style at the time. We got rid of that many, many years ago. Then we gave everyone just five units an hour. We weren't using anything weight-based. This was based on that five units IM that I showed you earlier. That was the way I was taught, and that's the way we did it. Then gave them simple way of following the patient. Then if it were too high or coming down too quickly or not quickly enough, they could adjust the rate. That was our initial paper order set way back when. Then once the blood sugar got under 200, they were put on the IV insulin protocol that we were using at the time to maintain the blood sugar P120 to 180 until their DKA resolved, and then got moved over to sub-q insulin. The back of that paper order set had very basic information on what was DKA and what all the different electrolytes and bicarbonate and stuff it meant. Now that we're on to our EMR, the same kind of one page can be opened up at the top of all the DKA order set. That still remains to this point. The key thing is you can put in, again, all the kinds of paper stuff in the past now EMR-based, but you still need to train everyone to do this. We've been doing physician and now nurse practitioner training for a long time back in the 1990s. We had monthly ICU lectures starting around 2000. We've had online interactive modules to teach everything there is about DKA management. Now we have to do some updates after all the things you've learned today because we haven't put those in yet. Now we're updating. We put in our DKA order set years ago online, and now we're updating them based on everything you've heard today. Let me just kind of go through a few of those things. As far as that goes, again, you have to have all your basic lab tests that are needed with how often they're done, when you should stop doing them. We've now added beta-hydroxybutyrate as a stat lab. You've heard that you can do a point-of-care beta-hydroxybutyrate, but not in the United States. They're not FDA approved for use in the hospital. Then we've just changed all our fluids. We had too many fluid options, and we've moved to lactated ringers for the reason you heard earlier, because it does appear to be a little bit quicker resolution of the DKA. The people in Nebraska have shown that nicely. Then you have all your nursing orders and your IV insulin orders. Now, as opposed to in the past when we gave recommendations, it's automatic whether if the blood sugar is not coming down quickly enough to adjust the insulin automatically. All these things are in the order set. No one has to think about it. No one has to write new orders. It's all done automatically. It's very important because people will get confused when they have to make their own decisions. We just added a DKA initial workup panel for the emergency room, because people would flail at ordering the test to figure out if someone's actually in DKA or not. Now, the ER physicians can just click on the DKA initial workup, and it'll get all their tests that they need at that point to have the initial test to show if it's a patient in DKA or not. Then I'm actually just going to end here, because the real changes we're making you'll have to email me about in about three or four months, because our DKA order sets are changing entirely right now. When you go into the EMR, you're not going to see this massive list of stuff. You're only going to see initially three different things. One will be intravenous insulin protocol, the subcutaneous insulin protocol, and probably we'll have euglycemic DKA protocol, because it'll be just a little bit different than the others. Next to each of these, there'll be the inclusion criteria, exclusion criteria to guide which patient should be on this or that. Once they open this, the full treatment protocol will open up specific for the IV or the subcute or the euglycemic. In each of the order sets, we hadn't had basal insulin before, but really based on the work from Colorado especially, we're adding this so that patients can get started on basal insulin right as they present with their DKA with different options that are weight-based or based on their home dosing. And we think that's important not only for the bounce back so they don't go back into DKA when they stop the IV insulin and have to deal with that, but because there's some data showing that you have a bit quicker resolution of the DKA in that case. In addition, in the EMRs, to have multiple order sets to start basal insulin after the IV is ordered and do it before the IV is stopped is a nightmare. So having all this in place up front makes life really easy. So I didn't show you an hour of each line of an order set, and you can touch base with me in a few months when we have all our new protocols completely programmed and online. But this is kind of where we're going to make this as simple and easy as possible for the people treating DKA because it's really not hard to treat DKA. And I'm going to leave it there and open it up for questions for everyone. Thank you. Thank you very much, all the panelists. That is a very informative and dynamic presentation. We have some questions, so we'll try to get through it as much as possible. And if we want to continue the discussion, as I mentioned in the initial introduction, please use the forum so that you will be able to get other opinions. And if you want to, if you are creating a new order set protocol in your institution, if you need help, I got a lot of help when I do that at my institution. So please use the forum. You have a panelist email too, so you can, you're welcome to shoot the email directly as well. So first question is about SGLT2 inhibitors. So I will just pose that question to both panelists. So one thing is the use of SGLT2 inhibitors for renal or heart failure indication in patients without diabetes. Do they have a eucalyptus DKA? Are they at risk for eucalyptus DKA? And are they still recommend to hold that SGLT2 inhibitors three or four days before the procedure? So maybe I'll start. So if you look at the trials, and I went back, I saw this question, so I looked up some of the trials, DAPA kidney, DAPA HF, and the kidney, and the reported DKA in those trials is extremely low. So again, these were trials of heart failure and CKD with or without diabetes. And so the percentage or proportion of patients with diabetes in the trials ranged anywhere from about 40% up to 67% in those three trials I mentioned. And they lasted between 18 months and two and a half years. And the incidence was extremely low. So this is mainly, this is all type two, so like very, very little type one or no diabetes. And the incidence of DKA ranged anywhere from zero in DAPA kidney to 0.2%, and so extremely low. And I think the question of whether or not SGLT2s should be held, we hold them across the board, no matter what patients are taking them for. I think that we, I think the actual incidence in the studies is quite low, but I'd love to hear what other people are doing, but we're holding them across the board. Yeah, I'm not really sure. I mean, we generally don't see the patients and haven't made recommendations on patients who come in on SGLT2s who don't have diabetes. We had been successful in banning them from the institution until just a couple of years ago, but did have to give in finally to, first it was a cardiologist and then the nephrologist and then everyone on earth. But we haven't really run into this yet. As far as just stopping them in general, yeah, I mean, in that paper that you quoted, I mean, that was of ours. I mean, we showed that stopping the SGLT2 inhibitors three days before procedures really reduced the risk of perioperative euglycemic DKA down to basically just about none. So yeah, but that was for diabetes patients, for sure. So I just have a one follow-up question on the SGLT2 inhibitors. So if the patient develop euglycemic DKA while on the SGLT2 inhibitors, will you resume it again, especially in patients with type 2 or maybe if there's some patients without any diabetes history? I would say for us, I mean, we would be extremely hesitant to restart it. So certainly not on that admission. And then I think that what we're really looking at is how much of a benefit do you think the person's going to get either for their heart failure or their CKD or both or cardiovascular disease or cardiovascular death, et cetera, versus the risk of the DKA. So to me, I mean, I feel like if the person came in with DKA on the SGLT2 and maybe there are some other factors, so like they went on a ketotic diet or they went on, I don't know, there are some other things, some added factors, maybe I would be a little bit more willing than if they were going along just taking their SGLT2, nothing else was going on and they suddenly developed DKA. But I think you're balancing both the potential benefit versus that risk of getting DKA. And I feel like if there were factors that could have led or increased the risk of the DKA other than being on the SGLT2, then maybe I'd be a little more willing to. But- Yeah, I think that, I mean, if there was no obvious precipitating factor, then you wouldn't put them back on, I think. But there are patients who have presented with euglycemic DKA at the time of their colonoscopy, because they've been in the prep for a few days and such. And so that was the precipitating factor really. And so I think it's likely safe like in that patient to be back on it and just make sure they don't go back, they stop it next time when they have their colonoscopy. But I think you have to take it case by case. So before moving to the next topic, there's one more question. If the patient is on SGLT2 do you need to monitor something to prevent euglycemic DKA? Do you need to do any labs or anything routinely? Yeah, I'm looking at this question. So it's someone with type 2 in an outpatient homeless clinic, routine labs. So I think, first of all, I don't know that you need to do routine labs and monitoring. I know that for type 1, there is continuous ketone monitoring that's being kind of looked at and studied, and maybe it's going to come out at some point. And the thought is that if you can monitor ketones continuously, then you can safely have people with type 1 on SGLT2s. The rate of euglycemic DKA in type 2 diabetes and SGLT2s is lower. I don't know that I would continuously be monitoring. To me, it would be more related to if the person had symptoms, nausea, vomiting, abdominal pain, other reasons to think that they might be in DKA, even if their glucose isn't elevated, then I feel like you should check ketones at that point. But I think the hard part is, you know, for someone who is unhoused and doesn't really have a lot of these resources, it can be difficult to get those ketone strips and get monitored. And patients who are on SGLT2 inhibitors are often mildly ketotic all the time. So you have to keep that in mind. So in a sense, you'd have to do baseline testing on the medication when they're just fine, and then test when there's some issue. So it gets to be a little complicated. Yeah, no, I think that's a good point. So if you had mild ketones and no symptoms, what does that really mean? Probably not much. Probably not much. Thank you. So let's move on to the next topic, which is about subcute insulin, use of subcute insulin in the DKA management. I don't know whether any of you have experience. So the question is mostly, you know, can we use Q4 hours instead of Q2 hours? And there's some questions about transition from subcute DKA protocol to regular baseline models. So, yeah, I mean, I think, I mean, there's no problem using it. I think people, even though we haven't had it as a protocol, people have been doing it anyway, no matter what, it was just done in a haphazard way. And then as far as Q2 versus Q4, I've seen both protocols out there. And when I presented it to the different committees, I presented both as possibilities for use here. And then I think, you know, especially for the group that's in this, who take care of patients, I think many of us have taken care of patients who are certainly in mild DKA at home. You know, they call up, they're clearly in DKA, but you give them their subcute insulin every couple hours and they get through it. So, I mean, we all have experience with subcute. Yeah. And, you know, if you look at the initial studies, many of them were published by Guillermo's group. There's Q1 hour, Q2 hour, Q4 hour protocols. And we started using the Q2 hour protocol in our ER-CDU a few years ago. It's been working great. There was initial growing pains to try to figure out the right patients to use them on, and then to get people used to using them. But it's worked out very, very well. So people get discharged from the OBS unit, which is our CDU, clinical decision unit. And we haven't moved it to our floors yet, but certainly there is a protocol out there for Q4 hours. And as Rob mentioned, I mean, we have ketone monitoring for our patients, you know, who are in mild DKA as outpatients, and it's just when they can't keep the fluids down or they can't, I don't know, they continue to feel worse that we ask them to come in. Right. Thank you. So maybe the last questions I can put it in is use of the serum as a dough. So I think the latest consensus guidelines mostly talk about the beta-hydroxybutyrate, but some institution, it is a sent out. So can we use the serum as a dough and it will be the same as a urine ketone in terms of, you know, resolution of the DKA? No. I mean, because acetoacetate is cleared more rapidly and then it won't tell you what's going on. So you really need to be using beta-hydroxybutyrate. And yeah, I mean, even for us, I mean, right now we have three, we assume five hospitals in the UCSF system. And one of them right now, you can't get a stat beta-hydroxybutyrate. So you use, you know, a gap like we've always done. And that's, and that they didn't really, in the guidelines when they presented that at the ADA meetings in June, they were roundly criticized for, you know, saying that's beta-hydroxybutyrate or nothing, almost when most places really couldn't do it. So, and they didn't even realize it. It was amazing. They didn't really realize it. Yeah. There's no point of care testing for the U.S. So it's a, it's a transition period for us, I think. Yeah. So I agree. I don't have anything to add. Yeah. You're muted. Thank you. So I think it's almost time. So thank you very much, all the panelists and all, all of the participants. So if you have any more questions, I think you already got the email of the panelists and you are welcome to use our interest group forum for further discussion. Thank you very much. Thank you. Take care. Have a good night.

ADA webinar

hyperglycemic crises

diabetic ketoacidosis

DKA

hyperglycemic hyperosmolar state

HHS

SGLT2 inhibitors

euglycemic DKA

lactated Ringer's

beta-hydroxybutyrate

subcutaneous insulin

glycemic order protocols