Welcome, everyone. Today is the first of the ASAP live series for this year. Today our first program is going to be, you know, diabetes. Just to introduce myself, maybe you can go to the next slide. So my name is Elias Siraj. I am the editor-in-chief of the ASAP product. And this ASAP live was conceived in collaboration with my colleague, Dr. Gopalakrishnan, who was the chair of the Fellows Education Committee at that time. So we started this program to complement the ASAP full product. And so, next slide. So with that in mind, as I said, today's program is going to be diabetes number one. We have two sessions of diabetes. And then we will have one session each for the other subspecialties. We'll have thyroid, we'll have bone, lipids, we'll have adrenal and pituitary, and we'll have reproductive endocrinology as well. Today's speakers will be Dr. Arshin Asadu, who is the director of the diabetes program at Houston Methodist and also assistant clinical professor at Weill Cornell Medical College. And then our second presenter will be Dr. Viral Shah, who is associate professor of medicine and pediatrics at the Barbara Davis Center for Diabetes at University of Colorado. So that said, I hope this year's ASAP series will be as productive as it was over the last couple of years. And I hope it will be very interactive. Those of you attending, use the opportunity to interact and ask and also give us feedback so that how we can make it better. So that said, I will give the podium to Dr. Shah. Thank you so much, Dr. Siraj for opening up this, the first module of the ASAP diabetes one. Nice introduction. So here are the disclosures from Dr. Asadu and me, not really relevant to this ASAP. As Dr. Siraj mentioned, just make sure that you ask us questions. So, you know, feel free to ask us either in a Q&A box while we are presenting the case or after that. But let's make it interactive rather than just the boring one-sided talk. At the end of the question, I believe that the Zoom poll will open up so that you can answer that question. And then there are no right and wrong. We'll discuss that. Of course, there will be one best choice, one best answer. But it will be good to discuss what you think and what is the right answer. With that, what we're going to do is that we will switch between Dr. Asadu and me about the case presentation and the first case will be discussed by Dr. Asadu. Now the stage to you. Do you want me to do that? OK, all right, let's do that. OK, so the way we're going to do is that I'm going to read this case and then Dr. Asadu will discuss the right answers or wrong answers. My laptop screen is a little smaller, so I'm going to probably move some of the part. OK, there we go. So this is the first case, 58-year-old man with type 2 diabetes for 12 years, underwent bariatric surgery about two years ago. Before surgery, he was taking metformin 1,000 milligrams twice a day. Cetagliptin, that's a DPP-4 inhibitor, 100 milligrams a day. Depagliflozin, that's a SGLT-2 inhibitor, 10 milligrams a day, and 20 units of insulin glargine, that's a long-acting insulin at bedtime. His glycated hemoglobin, that's an A1C, levels were between 6.8 to 7.4 percent, not bad, but can do better. He also had a history of well-controlled hypertension, hyperlipidemia, BMI of 42 kilograms per meter square. Before surgery, blood pressure was 139 over 75 with a pulse of 84, respiratory rate of 16. Sounds like everything was normal. Physical examination was unremarkable except for obesity. Surgery went well. He had no complication. Blood glucose was 144 milligrams per deciliter. If you like nanomole or millimoles, that's eight millimoles. Before surgery and 168. Two hours after surgery, the anti-diabetic drugs were stopped on the day of surgery except for the correction doses with the Lyspro every six hours. Since surgery, the patient's blood glucose ranged from 120 to 220 milligrams per deciliter. In the evening of the second post-operative day, the patient developed tachycardia, mild dyspnea, and fatigue, but he denied chest pain. His blood pressure was 100 over 74, respiratory rate of 18. He was ephebrile. The state EKG was reported as a sinus tachycardia. Without any specific other changes, the patient had normal cardiac enzymes and negative chest X-ray. Now, despite an intravenous bolus of normal saline of 500 ml for over two hours and the hydration at the rate of 200 ml per hour, he remained tachycardiac and mild shortness of breath and the diffuse abdominal pain. The blood glucose continued to be around 160 to 240 milligrams per deciliter. Here are the labs. Hematocrit 42%, fasting glucose 168 with the A1C of 7.2, sodium 145, potassium of 3.8, venous pH, current pH 7.2, bicarb of 16 currently, 22 previously, anion gap of 20, so anion gap is increased, bicarb low. Serum osmolality 308 currently, and lactate of 5. So you have got all these labs in front of you, and here are the options for the questions. Which of the following diagnostic tests would you like to order? Option A, that's a pulmonary CD angiogram to rule out pulmonary embolism. B, repeated cardiac enzymes, and B and P if you are suspecting heart failure, salicylic acid level, and then plasma beta hydroxybutyrate level. Options are in front of you. Take your time and answer those appropriate choices. And then we'll see what Dr. Sadhu thinks about this case. Pretty long case. Lots of details. A lot of details, yeah. And I see something in a chat field. Okay. Nothing specific. All right. Okay. Wonderful. All of you, 100% says plasma beta hydroxybutyrate level. Yay, we definitely have an endocrine crowd for sure, right? No surgeons out there thinking about post-op complications. Yes, so this was pretty obvious because of the NIN gap being elevated, the pH being low, and the bicarb being low, with normal to only mildly elevated glucose, and that is the key to this type of DKA. And a plasma beta hydroxybutyrate level will clinch the diagnosis. Now, I don't know how many of you noticed, but the lactate level was five, which in that range was also elevated. So certainly, post-operative sepsis is in the differential. But if you go back to the history, one of the key statements made, which was right here, very last, is his antidiabetic drugs were stopped on the day of surgery. And so what were his antidiabetic drugs? They were metformin, acetagliptin, adapagliflozin, and glargine insulin. And the use of those SGLT2 inhibitors, without holding them for at least three days in the case of adapagliflozin, and four days in the case of one drug, which is erdigliflozin, you're at risk for euglycemic DKA, which is what the labs showed. And the risk for euglycemic DKA really happens most often when the patient is restricted from eating, particularly a carbohydrate ingestion. And obviously, for surgery of any kind, patients are made NPO. And even more particular, this patient had bariatric surgery, and they had very limited PO intake immediately post-op as well. So this is a national issue that has lots of conversations. And in fact, because I do a lot of diabetes quality for our hospital system, we have a project in place right now on how to handle SGLT2 inhibitors in the perioperative setting. As I mentioned, the FDA, a couple of years ago, did issue a warning and recommended that these drugs be held before any planned procedures. But sometimes the procedures are not planned and are emergent, or maybe the patient didn't follow through. And so whenever this drug is on board and patients are made to have restricted PO intake, you should be looking at labs regularly and looking for this. It's very covert, especially for the non-endocrinologists, because they're expecting high glucoses, 5, 6, 7, 800s when they're thinking DKA. But it's happening with relatively normal glucoses. Now, of course, PE post-op is a common part of the differential. However, it wouldn't result in an anti-gap acidosis. And of course, you'd want to think of post-operative cardiovascular outcomes. But again, that wasn't consistent with the labs. And also the patient didn't have a chest pain or any other complaints other than just... Right. Yes. And then when we think about what his presentation was, it's tachycardia, some shortness of breath or dyspnea, and abdominal pain, which is very classic for DKA. Salicylate levels, yeah, you could get an NNN, yeah, but the patient wouldn't normally be overdosed on that in the hospital setting. And he did come in with the normal labs when he went at baseline. So that seems really less impossible. So those are the key things, I think, to think about this case. And as all of you have identified, very important to be aware and monitor for patients who are on these drugs at home and who are in the hospital with acute illness. Other situations where it might occur besides just decreased PO intake has been severe illness. So sepsis and other types of severe infections. Patients are also getting noted to have associations with euglycemic DKA. So let me ask, not to you, but to the fellows, if they are watching this presentation, is that, let's say if you give an option of a plasma versus the urine ketone testing, what you would select? So plasma beta-hydroxybutyrate is much more specific for DKA. You can get a urine, but it's not as gold standard as BHB. So it is recommended by all the guidelines to get a BHB. Okay, that's a wonderful explanation for all those things. We are not going to read this detailed explanation that are here in a slide. You can see, you can find that in a printed copy or the electronic copy of the essay and feel free to read that. But essentially, it's the same thing that what we are discussing here. I just wanted to also mention the use of SGLT2 inhibitors in type 1, which is really contraindicated because of its high potential for euglycemic DKA. When this class of drugs first came out, it was actually being used off-label quite a bit for type 1 to help because it's such a non-islet, non-insulin mechanism of action, thinking that it would help them get glycemic control, but the euglycemic DKA was a high-risk factor. Yeah, and I'm sure that many of us still use that, but we have to keep that possibility in our mind. We need to discuss that with the patient about the possibility of euglycemic DKA and how to prevent that. Education to the patient when you prescribe this drug is really key, and that education about holding it for procedures is also very important. Right. All right, we're going to move on to the case 2. I'm going to read the case again, and Dr. Sadu will probably provide some possible explanation for the right choice. This is a 40-year-old man referred by his internist for an eye examination. The patient complains of a blurry and wavy central vision that has been versioning over the last six months with a difficulty reading. He was recently diagnosed with type 2 diabetes with an A1C of 11%. He has obesity with a BMI of 32 and denies smoking. His last eye examination was about three years back, and at the time, he was told that he had only mild myopia, but probably no retinopathy. On examination, his best corrected visual acuity is 20-80 on the right, 20-30 on the left with the normal intraocular pressures. He had mild cataracts in both eyes. Dilated fundus examination shows multiple dot-plot retinal hemorrhages and microaneurysms in the peripheral retina. The macula in both eyes had a lipid exudation along with the retinal thickening, with the right eye being worse than the left eye. He's counseled on the importance of controlling his diabetes, blood pressure, cholesterol, the importance of regular exercise, and maintaining a normal body weight is also stressed. What is the most likely cause of his visual impairment? And the options are A, cataracts, B, neovascularization due to diabetes, neovascularization meaning by that proliferative diabetic retinopathy, dot-plot retinal hemorrhages, and option D is the diabetic macular edema. Let's see what you guys think. We're going to keep this here for about 30 seconds. Easy peasy. And again, feel free to ask us any questions you have while I'm reading this case or while we are discussing about this different options and answers. That's right. Don't be shy. Use the chat screen. Yes. Okay. So we got a split audience here and we like that. So we can have a really good discussion here. Some of them cataracts, majority diabetic macular edema. What do you think Dr. Sadhu? Well, certainly all of these are findings in patients with diabetes on eye exams, right? They do get early cataracts and they get them at younger ages than the general population. He was like 40, I think, and was found to have cataracts. Neovascularization, of course, that happens and we know that it's through the mechanism of VEGF and we use antiangiogenesis factors as therapy for neovascularization and that's related to hemorrhages as well. Doppler retinal hemorrhages, again, damage to these blood vessels from the constant hyperglycemia effects is another finding that we see on retinal exam. And of course, diabetic macular edema is noted as well. So how do you figure out which one of these is responsible for this patient's symptoms? You look at what are the symptoms with the correct answer really relates to what the patient came in with, which is a blurry and wavy disruption of the central vision. So whenever we're talking central vision, we're talking about the macula. And so that's where this patient's symptomatology came from. He was found to have some of these other findings as well in the periphery, the retinal, the Doppler retinal hemorrhages, neovascularization, as well as cataracts, but it's the lipid exudation, which are the hard exudates, and the retinal thickening that was found in the macula for both eyes, one was a little worse than the other, that is really causing the vision impairment in this patient. The hemorrhage and vitreal detachments can happen, of course. They're more related to a sudden vision loss, and usually the patients may complain of some floaters where those happen. I find it interesting in this case that actually the case states three years ago, they did have a retinal exam, and Dr. Shah, you assumed he had an eye exam. We assume he had a retinal exam, but just in three years for them to develop all of these findings, it's a little suspicious. Although the A1C was very high and it was recently diagnosed at 11 percent. But usually these findings take some time. But the correct answer to this question is in the macula and the diabetic macular endema. Yeah. I think thanks for the clarification because I agree with you that it wasn't just the eye examination, probably not full detailed retinal examination. It's unlikely to have that kind of a fast progression. But again, people who have a pretty high A1C for a long time, remember type 2 diabetes, many people are not diagnosed till pretty late stage. When you treat them aggressively, it's quite possible that they do have a versioning of retinopathy, even from a no retinopathy to some kind of a mild to moderate proliferative retinopathy. But again, it is temporary in one way because good glycemic control helps in the long run. Despite that changes, I would still stress on good glycemic control. Yes. We see this in our patients who are pregnant with diabetes, pre-existing diabetes, and now they're pregnant and they're highly motivated to have a healthy baby and improve their diabetes control with intensive therapy, and they can actually get worsening retinopathy as well. As well as one of our newer classes of drugs, semaglutide has been associated with worsening retinopathy after initiation. That's because they do get a dramatic improvement quickly in their glycemic control, and anything that causes this dramatic improvement seems to worsen the retinopathy. But not a reason not to control them, but just to have their baseline vision exam and follow-up exams, retinal exams specifically, not vision. I stand corrected because I think that's what happened to this patient. He just might have gone to an optometrist for glasses or not a vision exam, but not a retinal exam. It's very important to have these on a regular basis. Interestingly, we're really developing the technology of retinal exams. I recently reviewed some papers and spoke with a manufacturer for retinal camera, which is now FDA approved using AI to detect some of these diabetic eye findings in the office in a quick screen. Very important, of course, to save vision for our patients and to recognize these early and get them treated at their ophthalmologist. All right. Just one more point that I think one of you mentioned about the cataracts. Yes, it can reduce the visual acuity, but here it sounds like the patient has a more impairment on the right than the left, which matches with more macular edema on the right than the left. Probably, that's unlikely in this case. Cataracts also wouldn't cause that wavy disruption as well. Yeah. Just be a cloudy vision. All right. Here are the explanation. Again, as we discussed earlier, mentioned earlier that we're not going to read all these things, but we already discussed that part to make it more interactive. I'm going to skip that part. There are references. Again, everything is in ASAP. You guys can read that. We're going to move on to the case 3. This is a 42-year-old female is referred to you for an evaluation. She has the symptoms of hypoglycemia, and both the fasting as well as the post-trandial period, she presents with the documented hyperinsulinemic hypoglycemia. Laboratory test results shows in a figure number 1, were obtained during an episode in which the patient was diaphoretic and confused. I don't see figure number 1 here, but I guess. Next slide. Yeah. Probably. The patient's medical history is otherwise not notable. She has no prior surgery. She has a regular menstrual cycle. Her calcium is normal. Rest of the evaluation is normal. Results of a triphasic CD of abdomen and the endoscopic ultrasound are both normal. So it's quite extensively worked up case, sounds like. After consulting with an endocrine surgeon, you are asked to order a selective arterial calcium stimulation test. To recognize the presumed insulinoma, figure number 2 shows the concentration of insulin in the hepatic venous blood after an intra-arterial calcium into the gastrointestinal superior mesentery and splenic arteries. And I'm going to go into this here. I think I'm guessing this is a figure number 1, where it shows you the glucose of 39 during that hypoglycemia. The C-peptide was 3.3, pretty high. Insulin of 10, normal is 2.6 to 24. But remember, during hypoglycemia, it should not be detectable. So this is pretty high. So it's a hyperinsulinemic hypoglycemia. And this is the result of that calcium stimulation test. Honestly, I don't have much experience with this kind of a test, so I don't know how to interpret that part. But I'm going to just say gastrointestinal artery here, superior mesentery, and splenic, and the data is provided at baseline, 20, 40, and 60 minutes. You guys can have a look at that for a couple of seconds. It sounds like there is an increase in a gradient at the splenic from a 31 at baseline to 556. That's a lot of insulin at 60 minutes. Superior and the gastrointestinal, I see, but the gradient is in kind of a different direction or no change. So that kind of a picture. Now, the question for you is that which of the following is the most appropriate next step? Proceed with surgery with a plan to resect the head of pancreas. That's option A. Perform a trans-abdominal ultrasonography. Option C is proceed with surgery with a particular exploration of the tail of pancreas. And option D is measure the PTH and prolactin concentrations. Let's see what you guys think. Even though I'm not an expert in insulinoma, but I think based on this options, I can guess what is going to be correct answer here. So the laboratory data, not the stimulation test, but the actual data at the point of patient's symptoms was very diagnostic. So that's important. And then, of course, diagnosis of any hypoglycemia. Differential starts with Whipple's triad. We kind of skipped all of that and just started with the case where patient has hyperinsulinemia endogenous. Yeah, so let's presume that patient met that Whipple's triad. It's documented. It's a thoroughly worked up case. OK, so there are two selections here by you. One person have performed trans-abdominal ultrasonography. And C, that's by three of you, proceed with the surgery with a particular exploration of tail of pancreas. Now, Dr. Sadhu, tell us what to do here. OK, so if you can go back to one slide before. OK, give me one second. Yep. Yeah, so as you mentioned, the pancreas is blood supply comes from three different sources, the gastrointestinal, the superior mesenteric, and the splenic. And generally, the gastrointestinal artery supplies the head of the pancreas, the SMA, the body of the pancreas, and the splenic, the tail of the pancreas. So what we're looking for when we do this stimulation test is a gradient, as Dr. Shah mentioned, in the hepatic vein after injection of calcium, which causes instant secretion. And the most dramatic effect was seen in the distribution of the splenic artery, where the baseline was 31, and it went all the way up to 556. And so that kind of tells you that this lesion is in the tail of the pancreas. If you can skip and move forward to the answers, we can discuss each of the answers. So the first question is the head of the pancreas. We didn't see that gradient in the gastrointestinal artery distribution, so that's kind of incorrect. We can perform a transabdominal ultrasound, but what would that do after we have already had the tripasic CT and other imaging? Really, I mean, sometimes you don't even visualize the pancreas and transabdominal ultrasound. So that's really no good. An intraoperative ultrasound might be much more sensitive to pick up these small insulin amylations, but a transabdominal ultrasound is pretty nonspecific. The answer C, proceed with exploration of the tail, that makes a lot of sense because that's where we saw the distribution gradient the highest, from 30 to 550. So even if you didn't have the ability to do an intraoperative ultrasound or any further imaging at all, the answer would be you get a good surgeon to go and explore and find that lesion in the tail of the pancreas or just remove that section of the pancreas entirely. Sometimes they're very, very small, really hard to visualize, and sometimes they'll just palpate the actual pancreas along until they feel it in their hands to see where the lesion might be. But exploring and removing the tail of the pancreas would probably be the best effective method. Now, measuring parathyroid hormone and prolactin concentrations, that is a valid thing to do. It may not be the next step in curing their insulinoma, for sure, but we're alluding to MEN1 here with hyperparathyroidism, a pituitary tumor, and a pancreatic tumor. This, when you look at the case history, they do say the patient had normal menses, so hyperprolactinemia, probably not an issue. And they also state specifically that the calcium was normal. So we would steer it away from answer D. Very important to get a good proceduralist of someone who's experienced in doing this. Make sure their catheters are in the right place and measuring exactly what you did, the section of the vascular distribution. It's a tough, it's a very tough procedure to do, so you want to make sure that someone experienced is doing that. And then surgeons can go in and kind of use that segment that's identified in the stimulation test. So let me ask you this, that if you open up the abdomen and then you explore the tail of pancreas, or you do an intraoperative ultrasonography of tail of the pancreas, and if you don't find any tumor, would you still go ahead with the surgery? Yeah, because this patient clearly has an insulinoma. We've clearly demonstrated that it is in the tail. And even if you can't visualize it or palpate it, you can get a partial pancreatectomy from that area and have some chance of cure. Otherwise, you're just leaving the patient with an insulinoma and that's going to be deadly for the patient. Right, so for fellows, this is a very important thing, that limitations of imaging in endocrine situations, right? That you rely more on our hormonal stimulation test than imaging techniques. All right, with that, we're going to move on to the next one. So again, all this explanation with the rationale and the references are provided in ASAP. Please read them. Case number four. We are switching the role here or? Yes, so I am going to put Dr. Shah on the hot seat now. And please ask questions now at least, because we've been a quiet group and I want him to work tonight. Okay, case number four is a 65-year-old Chinese woman, comes into the office for evaluation. She has a hemoglobin A1C of 6% and a fasting glucose of 105 milligrams per deciliter or in millimoles per liter as listed. Her medical history is significant for an MI five years ago and she takes a torpostatin max dose, aspirin and metoprolol for her cardiac disease. And the rest of her exam is pretty unremarkable except for a BMI of 24. So knowing that, the patient has clearly met criteria for pre-diabetes, but what would you want to do next to address her pre-diabetes? You can advise her to stop her statin and then recheck the blood test in three months and maybe she'll be better. You can obtain a GAD at 65 antibody level. You can start her on therapy with some glutide and of course, along with dietary modifications and weight loss recommendations of 10%. And then you can advise her to engage in 150 minutes of moderate strenuous activity. So what is the next best approach for pre-diabetes? All right, so the, you know. Now there are nine of you on this session but I only see three to four votes per question. So you will not be called out if the answer is wrong. So just vote what you think is the best answer. All right, so I think some divided opinions here. Between C, yeah, C and D, okay. So Dr. Shah, give us some insight. So I think, you know, the first thing is that regarding the pre-diabetes, how many of you think that this is a confirmed case of a pre-diabetes and you're not thinking about something else here? I don't know, I think this is a pretty quiet group here but you can put your thoughts into Q and A. And it's very interesting in this case that they provided you that she is taking a pretty high dose of an atrovastatin and you might think that the statin may be making this individual on the age of pre-diabetes. I see someone has typed something, so let me read that. The chat is disabled. I don't know. I don't know. But you can type in your Q and A, sorry. Beth, are you there? Is the chat disabled or? Okay. It's okay, I think you can write down in the Q and A at this moment. Yeah, you can use the Q and A as well. Sorry for the technical issues here. I am struggling with my own computer here, okay. Okay, so we talked about that part. So, you know, again, A1C fasting, they go pretty hand to hand. Age 65 year, Asian individuals who are at higher risk of pre-diabetes. Sometimes think about the BMI. The BMI definition and cutoffs are different for Asians compared to Caucasians. So we have a 25 and higher for overweight, but for Asia, it's a 23 and higher. So this person has overweight. I think everything that meets the criteria and definition for pre-diabetes. I don't think that I would doubt the diagnosis of pre-diabetes here. So once you think about pre-diabetes in presence of myocardial infarction, what is the next best step here is that, so let's think about the first one, stop the atrovastatin. I would not do that because patient had a previous history of coronary artery disease. That's priority number one, right? You don't want to stop that and have the patient at the high risk of reinfarction. So I would not do that. There is something in a chat field. Just let me have a look. Chat is showing on me. So I don't know about things that chat function is working. So I don't know. All right. So this option is not correct in my opinion. Again, you can debate that, that atrovastatin might be responsible for some hyperglycemia here, but still it's an essential drug in person with a history of cardiovascular disease. Obtaining again, they didn't provide us any family history at this age, again, Asian, the likelihood of type one diabetes is pretty low. Not that it is not possible, but it's pretty low. So probably I would say that this option again doesn't make a whole lot sense here. Starting a semaglutide and encourage the dietary changes to achieve 10% weight loss. GLP-1 analogs are wonderful drugs for weight loss, for managing type 2 diabetes in presence of cardiovascular disease. No doubt about that part, but this person has pre-diabetes, not type 2 diabetes. And so at this stage, I would say that may not be the best option to start the semaglutide because we haven't even talked about the lifestyle first, right? So option B is the best option here where you can encourage this individual to do a lifestyle modification by changing some of the dietary carbohydrate intake, also telling them to engage in 150 minutes of moderately strenuous physical activity per week. And that's the best option in my opinion. And that's the recommended treatment for pre-diabetes. If now that individual fails on that or progress from pre-diabetes to type 2 diabetes, then you can always explore other options. Great. Thank you. Just to comment on GAD antibodies, you know, and LADA, can you talk a little bit about that and when should we be checking for that? And when is the presentation more common for those? So when to do a GAD antibody? Yeah. Yeah. So something that I would think about is that, let's say if they have provided history like this, that it's a Caucasian, young individuals have a family history of type 1 diabetes. Those things I think would make me in favor of doing GAD. Other is that the presentation is not typical as pre-diabetes, right? You have a pretty severe hyperglycemia as a presentation, doesn't fit as a typical presentation in older individuals, then probably you want to look up at that option as well. But that's what I would think, yeah. Yeah. I mean, atorvastatin-induced hyperglycemia is a pretty real thing, right? There's an increased risk. It's something like 0.2% per year or something. But in this individual who has already an atherosclerotic event, it's really not an option to not be on a statin. You're right. Yeah. Okay. Now I see a question, when do we check for the insulin antibody? Can it be falsely positive in someone who is already on insulin? So I'm guessing this question is outside this case, but again, when you are suspecting type 1 diabetes, and in my opinion, my practice, what I do is that I generally test most young individuals, just making sure that I'm not misdiagnosing someone as type 2 diabetes, right? Also, I think we are type 1 center, so we are a little biased towards checking more than not checking. Yes, it is possible that if someone is already on insulin, then insulin-specific antibody, that's an MIAA, could be positive. It's not false positive, it is positive, but it's related to the insulin therapy rather than the diagnostic per se. Again, insulin antibodies are more common in children. In adults, actually, the GAD is more common. So if you test that in someone who is 30-year, 40-year-old, most likely that you're going to find GAD positive, and that's why the consensus by the American Diabetes Association and EASD in a management of type 1 diabetes recommended to check GAD first, because that's where you're going to have more yield rather than checking for all four. Now, if you have resources, for sure, go for it, but otherwise, the GAD is the first one rather than insulin. I hope that answers your question. Most bang for your buck would be GAD. Okay, we'll go on to the next question. If there's nothing else in the chat, I don't see anything. Sorry about the technical difficulties, but the Q&A is working, so please use that one. Do case 5? So let's move on. There we go. Case 5. All right. So case 5 is a 64-year-old man with a history of TIAs, stable angina, and type 2 diabetes for 20 years. He comes for an evaluation. He has had two episodes of TKA in the past three years, and they were all associated with severe UTIs. He is on aspirin, baby aspirin, metoprolol, sublingual nitroglycerin for his angina, max-dose atorvastatin, venazapril, and metformin, glipizide, and clargine insulin nightly for his diabetes management, but his A1C continues to be high at 8.5 percent. I have some issues on my side, too. Okay, all right. I think it's Zoom today. Zoom is just acting up. So what is the most appropriate pharmacological agent to recommend for this patient at this point? A is you start epigliflozin at 10 milligrams a day. B, add prandial lisproinsulin five units along with his clargine before meals, or C, start semaglutide at 0.25 milligrams weekly and then titrate the dose as tolerated, or D, start linagliptin at five milligrams a day. Okay, this is like all nine of you to vote this time. And this is easy peasy. So I'm guessing that you guys will have a consensus on a one right answer, a best choice. Okay, some split work here. Beginner lispro five units three times a day before meals. So you want to start the prandial insulin. Other, begin semaglutide 0.25 milligrams. That's, that's not a bad split. I mean, I could see both of those being options. And then, you know, there's one best option here. One best option, right? Yeah. And this is like, That's how you approach these tests, the one best option. Yeah. I'm going to take you back a little bit. So think about that, this guy type two diabetes. The important part here is the history of transient ischemic attack with the stable angina. So cardiovascular disease. Two history or two episodes of DKA in the past. Now this is the key here associated with severe UTIs. Okay. So now it makes sense that probably starting an SGLT2 inhibitor in this individual probably will put him at the high risk of DKA again, again, UTIs, because these are the two common side effects of SGLT2 inhibitors. Again, it's a good drug in presence of cardiovascular disease, but it would be a relatively contraindicated in this individual. So I would not use that. So option A, I would say, no, that's not the right answer. Lispro five, that's a prandial coverage. Again, not a bad option at all. But remember that here you have to select the best right answer, right? So what is the better than Lispro? And Lispro will cover only the prandial, not the basal, not the best therapy. So semaglutide GLP-1 analogs, this is a weekly GLP-1 analogs has been shown to improve to improve cardiac outcomes by a three point mass. This is similar like other GLP-1 as well. Liraglutide has been shown again to be cardiovascular beneficial. Dilaglutide, same thing. So GLP as a class, I think predominantly long acting GLP-1 analogs are pretty good drug in presence of a cardiovascular disease in people with type 2 diabetes. So the hint here is that patient has cardiovascular disease, has type 2 diabetes. You've got a probably two best choice, SGLT-2, GLP-1. SGLT-2 is not a best option here because of an UTI, DKA. So I would go with the GLP-1 analog for ASIP. Now in a clinical situation, it's quite possible that someone say that I don't want to be in a GLP-1 analog or could not tolerate that in the past, did not cover by insurance. I'm sure that you're going to start the insulin in this individual as well, but that's a real life. Nowadays, DPP-4 is never a right answer for any question. Well, no, no. Our elderly who are at high risk for hypoglycemia, in the presence of some kidney disease, limited lifespan, simplified regimen, that could be appropriate. Yeah. But in this, again, case where you know that it's established cardiovascular disease, the data is pretty strong about GLP-1 analogs than DPP-4. DPP-4 are neutral drug in terms of the cardiovascular outcomes. So again, GLP-1 option C would be the best choice here. So Dr. Shah, let me ask you, what if the A1C was 6.7? So that's a, that's a, I know you got, you are making it a little complicated. Now remember that part that- Interesting, interesting. In, even though someone will have a good glycemic control, the benefit of both actually is GLP-2 inhibitors and GLP-1 analogs on cardiovascular outcome. With the HGLT-2 heart failure, predominantly with the GLP-1, it's a mess. It's pretty strong and it's an independent of glycemic control. So even though if someone has a good glycemic control, I would be in a favor of starting GLP-1. If there are no contraindication in this case, HGLT-2 as well. And probably I would either reduce the dose of other drug or stop it. And I would maximize the benefit by giving in GLP-1 analogs. Exactly. And I think that's where all the guidelines in this standard of practice is going, is we are looking at complication-centric management beyond just glycemic control management. It's more than just the A1C. And similarly, if this patient, let's exclude the history of the DKA, but let's say they already had chronic kidney disease, stage 3B, you should add ampicloplasm to their regimen and reduce their other glucose-lowering agents so that they don't get hypoglycemic, obviously, because the patient is uninspun as well. But we are looking to, it's nice to have a pretty A1C, but what we're really looking for is the reduction in complications, whether we do the A1C or their inherent disease. Thank you. Thank you for that interesting discussion. So we'll go on to our last question. We're great on time, last few nine minutes here for question number six. This is a 35-year-old Asian woman at 28 weeks gestation who presents to the clinic for a routine prenatal visit. She has had a previous pregnancy without any complications, and it resulted in a live birth of a boy who's now four years old. She's feeling well, no symptoms, her BMI for her second pregnancy, oh sorry, before the pregnancy was 31, which she attributes to weight gain during her first pregnancy that she just couldn't lose. Not surprising. She has no family history of diabetes, hypertension, or cardiovascular disease, and she's taking her prenatal vitamins regularly. On exam, really nothing remarkable for vitals. Fundal height is 32 centimeters, which is maybe just a little bit bigger than for her gestational age. At 26 weeks, she did a 50-gram glucose tolerance test, and her one hour was 141 milligrams per deciliter. So because that was a little abnormal, she got a 100-gram oral glucose tolerance test after an overnight fast. And these are the results of that 100-gram OGTT. Fasting was 101, one hour was 181, two hour 160, and three hour 138. So based on these results, she is diagnosed as having gestational diabetes. So what is the next best step for the management of GDM in this patient? Is it A, lifestyle modification, B, metformin, C, glideri, or D, insulin therapy? Yeah, I think in this case, they made it very clear that it's a gestational diabetes, you know, so I think it's easier for you not to think about those different criteria between 50 grams, 75 grams, and 100 grams. American Diabetes Association recommends 75 versus the Obstetrics and Gynecology Associations are more in favor of 100. Again, one step versus two steps, yes. One versus two steps, yeah. But regardless of that, I think here the picture is pretty clear that it's a gestational diabetes. So now, wonderful. Everybody is in opinion of lifestyle modification, 100%. So I don't think I need to explain anything about this. So just comment on, you know, the use of metformin. So I think, you know, I agree 100% with all of you that lifestyle modification is the first step on managing gestational diabetes, and it's pretty consistent by all these different societies, whether you look at the ADA Standard of Care or the Endocrine Society or ACOG. But then the guidelines are slightly divided in terms of the evidences between the metformin and glideride. The Endocrine Society clearly states that there are not enough evidence to really recommend metformin or glideride for management of gestational diabetes, except certain circumstances where patient prefers that over insulin therapy. But the first thing to start with the lifestyle modification, and the lifestyle modification, meaning by that, try to tell them to reduce the carbohydrates a little bit. So 30 to 40% of carbohydrates should be coming from a total diet, and rest should be have proteins and fat and some of the micronutrients. Exercise, that's a physical activity. As we discussed in pre-diabetes, it remains pretty much the same principle here in gestational. And despite that, if the patient remains hyperglycemic, which is by those criteria, whatever you want to use that 50, 70 or 100, then the next option would be insulin therapy. And again, as I mentioned that we do not have really great evidences around metformin and glideride, but in certain circumstances, it can be used. But the first thing first, lifestyle modification, and that's the correct answer here. And how long would you give them the lifestyle modification before you escalate there? That's a good question. And I think this is going to be my opinion. It's a minute, it's about a six weeks before we change to the insulin therapy. That's what you would do. Well, I think in this patient, she's well far along, right? She's 26 weeks gestation. Maybe her fundal height is just a little bit big already. I would probably do it just two or three weeks. Two to three weeks. Okay. You just want to be aggressive so that the baby, we don't have a large for gestational age baby complications. I totally agree with you. And I missed that fundal height. Yes. So it's a 32 already. So in this case, you want to be more aggressive than broadcasting that. I mean, most of this is happening probably in the OB's office before they can even get in to see one of us. All right. So those are great questions. I think we just have the last few slides, a little bit more of discussion, but I'd like to leave a minute or two left for questions from the group or comments and just let us know how you enjoyed this presentation or what we could do better for you next time. Yeah. And again, when you are preparing for ASAP, the board exams, don't think about what you do in a clinical practice. That's, I would say that the key or success, you know, theoretical go by guidelines, even though I think there is a one more question. Okay. Someone just says, thank you very much. Our pleasure. Of course. Feel free to reach out to us if you have any questions. And again, you see that sometimes even between me and Dr. Sadhu, there are some differences in opinion because we do differently sometimes, right? Yeah. That's okay. That's okay. That's totally fine. That's the science, right? Yeah. And then, but for the answers on the test. Yes. One best answer. Remember that one. One best answer. All right. Have a great night, everyone. Thanks for joining us and we'll see you at the next session. Thank you. Thank you everyone.

pharmacological agent

recommendation

patient

lifestyle modification

gestational diabetes

American Diabetes Association

Endocrine Society

American College of Obstetricians and Gynecologists

diet and exercise