My name is Diane Chun. I'm a clinical endocrinologist at UCLA in California. I'm also the president of the Clinical Association of California Endocrinologists. And I'm honored today to discuss with you the usual and not so usual cases in type 2 diabetes. What do you recommend? Or shall I say, what do I recommend? There's no financial disclosures. So really, I wanna use this session to do a case-based approach to managing type 2 diabetes to really emphasize that one size does not fit all. Over the course of the last few years, we have really come about new medications that we know are not just for glycemic control, but they are also for the complications of diabetes. So I wanna go through these four tenets. And throughout the talk and throughout all the cases, you'll see that I kind of revisit these to just remind us that this is how we should be thinking about in terms of managing type 2 diabetes. Number one is individualizing care in our patients. Thinking about not just their diabetes, but also the complications. And I'm talking about cardiovascular disease, CKD, and heart failure. Number two is the guidelines that we use in practice. Whichever guidelines are the ones that you like, whether it is the ADA, the ACE guidelines, the BASD guidelines, understanding how we can utilize these guidelines in our practice, but also identifying the potential barriers we might have for success. Such as access and cost, which are big issues for our patients, wherever you practice. Number three is thinking about those new therapies. Obviously those are cost prohibitive for a lot of our patients. And that is the SGLT2 inhibitors, GLP1 receptor agonist, as well as of course the dual agonist, GLP1 and TDIP dual agonist. And of course, lastly, let's not forget about our diabetes technology. Obviously there are both continuous glucose monitors, as well as hybrid glucose pumps. But for the purposes of this talk, I will be focusing on using CGMs in our practice, and how I utilize these to identify the best course of actions for each of the cases, and how I make those treatment decisions. I'd like to just remind you of Dr. Ralph DeFranco's famous ominous octet, where he's really focusing on the multifactorial pathophysiology of type 2 diabetes. This slide does need to be updated, because we do have dual agonists now, GLP1 and TDIP, and in the future perhaps even the dual agonists coming out. But what this is really telling us is that, before we even think about insulin, we have other choices, and you can use them in isolation, and you can use them in combination, to achieve normal glycemia in your patient. Now the choice of the medications of course, is gonna be really based on if, not just their glycemic control, but if they have associate conditions that we also need to worry about. This is the ADA guidelines from 2023, we will soon get the new ones as well. But in the last few years, the guidelines have been very similar, and it doesn't matter which organization, because what it does really stress is yes, lifestyle modification is key, metformin is still considered a first choice for us, although some would argue maybe we should use some of the newer agents as first choice. But now you could see right here with my pointer, that we're talking about if the patients have ASCVD, they have risk factors that we worry about for heart disease such as age greater than 55, obesity, hypertension, smoking, dyslipidemia, or even albuminuria, they have a history of heart failure or risk for it, or CKD, and that will guide us with our treatment decisions beyond the lifestyle and metformin, as we make these treatment decisions for our patients. This is another part of those guidelines, and it does also emphasize that during the treatment decisions that we make, we have to decide on the medication or combination of medications that minimize hyperglycemia in our patients. While trying to minimize weight gain, very important obviously with the craze of the GLP-1 receptor agonist and dual agonist, we now have patients really want to try to get their weight down as they should, but we also have to think about cost and access to these medications, and that maybe you practice in a location or a country or a state where patients just really cannot afford these medications. You can still use insulin, it is quite affordable now, and you can still have to use solanurias or secretogogs, and you may need to use pioglitazone because these are more easy to get access and the cost is low, but to utilize these medications to minimize the hyperglycemia and the weight gain is key. This is the ACE guidelines, very similar in terms of identifying not just that they have diabetes that needs to reach a A1c target, but what else do they have? And you can see on the ACE guidelines, they actually have a separate column for stroke and TIA, but very similar in terms of concept. We see this as also another part of the ACE guidelines where they think about the glycemic control, and they do think about access and cost, and they also think about what if the blood sugars are very high? Well, at that point, you might want to start insulin before you start any of the other agents. So it is a combination of medications, a combination of drugs, individualizing care. So the basic principles in diabetes guidelines is really lifestyle modification is key. Metformin is preferred first line, but individualize the care for our patients. And metformin, once you start, it should be continued as long as possible, unless it's contraindicated or the patient cannot tolerate it. Early combination therapy is key if they need to add a second or a third agent. Don't be afraid to start insulin if the patient has these urgent warning signs of metabolism, hyperglycemia. I think sometimes we have patients that are very apprehensive of starting insulin, but at least basal insulin, I found in my practice is not so difficult if you are sitting there teaching them, identifying the reason why they need to start it first, and then perhaps at that point, add a GLP instead of adding even more insulin to that regimen. So you do want to individualize care and see if they have cardiovascular disease, heart failure, or CKD, but also address if cost is an issue or if the patient has a preference. For instance, they just don't want to do shots. Consider SGLT2 inhibitor or GLP-1 receptor agonist independent of glycemic control, and you'll see that in some of the cases where the A1Cs are low, but the patients have one of those three conditions or more, and they would benefit further by being on the newer agents. Want to intensify treatment. I cannot tell you how many times I have seen patients refer to me that are on the smallest doses of some of the newer therapies, and they have not been maximized. Do not feel worried about it in terms of side effects. We'll talk about that to lessen those side effects to minimize them. And most importantly, if you're going to use insulin, which I use a lot of insulin in my practice, do not over-insulinize the patient. So let's talk about the usual cases of type 2 diabetes. They're usual, but they have just a little twist. And I'm hoping that you'll get some clinical pearls for these cases. So these are cases from my own practice here at UCLA. It's a 66-year-old female. She's not type 2 diabetes, and she's on metformin already, but she is really not well-controlled. She was pre-diabetic for a while, and then all of a sudden her A1C went up to 8.2%. Now she has a type 2 diabetes. She has a high BMI, so she's obese with a BMI of 35. She's then taking her metformin at the maximum dose of 1,000 trace daily, and also a statin, receded statin, and lozartan. So she is on her statin and her ARB. Her A1C 12 months before was pretty good, 6.2%. It's a very common story. And then all of a sudden, and she was doing fine on metformin, and she was started early on it. And she was exercising a lot, and a walker and swimmer, but all of a sudden she got pandemic stress, and she didn't want to go out, and she was scared. She stopped exercising. She was very inactive and obviously stress eating. So you could see that she started gaining weight over time, 12 pounds. She was only occasionally checking her sugars, and they were averaging about 132 milligrams per deciliter, and they were ranging 120 to 160. She actually presented to an urgent care for a urinary tract infection, a random glucose of 200 pounds. She was treated with an antibiotic for UTI. And at that point, at the urgent care, because they were very concerned that she may have gotten that UTI, because she had out of control diabetes, they gave her a vargin, a basal insulin of 20 units at bedtime. She refused to start insulin, and she presents to the endocrine clinic now with poorly controlled type 2 diabetes. So when we look back at the guidelines, we see that number one on the very top of the guidelines is that lifestyle behavior modification is number one. And you can see that before she got stressed, she did all of that. She did the lifestyle modifications with metformin, and she put that goal A1C, whether you look at goals of less than 7% or 6.5%, she was there. But because of the stressor, because of what has happened in terms of her inactivity, she, quote, fell off the wagon. So it's very important to think about, well, what do we do at this point? Do we jump into the new medications or do we give her another chance? So when we think about lifestyle modifications, this is a very famous graph from the Diabetes Prevention Program. And we're looking at placebo versus metformin versus lifestyle modification. And lifestyle modification had a 58% decrease in incidence of diabetes in our patients, much better than just metformin alone. So really doing 150 minutes per week, minimum of moderate to intense physical activity, having the patient meet with a dietician, go on a diet plan, it can actually do wonders. So for our patient, we did that. I referred her to our dietician, diabetes educator, and she actually met with her immediately. And we do telemedicine at UCLA quite frequently, so we were able to get her in. And she was started on a carb-controlled diet and an exercise plan. And I also wanted her to see the data. Remember, in the beginning of my talk, I talked about using diabetes technology. So I had to put on a CGM professional trial. She was given an option of whether or not she wanted to see the data on her phone, or she wanted to do a blinded trial. She really didn't want to see what the sugars were, so we did a blinded trial. And she was able to keep the Libre Professional CGM on for about nine days out of the 14-day trial. And so it gave me enough information. But she did write a food diary, and she was okay with pricking her finger and writing her glucose numbers from a finger stick glucose. And she started recording how often she was walking. She wore a Fitbit that she found in her drawer. And this was her CGM, and I did nothing. I did not add beyond what Metformin she was already on. And you can see on here that her time and range was 97%. That's amazing. That's 6.2% GMI is an estimated A1C. And she did fantastic. And again, this proves that DPP program's percentage showing that lifestyle modification may be all your patients need before we go for the more expensive drugs. So three months of lifestyle modification, her A1C did come down. Now it's 7.2%, so it's not in the eighth. Despite glycemic control, she was not able to lose much weight though. Her BMI still is high. So what do we do next? So when we're looking at the guidelines, she had a lot of risk factors, right? And that's the circle on the top. And then we're gonna talk about starting a GLP-1 receptor agonist or an SGLT2 inhibitor. Target less than 7% for her. You could argue it was pretty darn close, but she really was very concerned that she may not be able to maintain her lifestyle modification if she wanted to get the rate down. So we tried a GLP-1 receptor agonist. I tried her on semaglutatide. We started on the 0.25 milligram dose for four weeks and then intensified to the 0.5 milligrams of our once weekly dose. She actually had minimal side effects, a little nausea, a little diarrhea. Many of you know that that nausea would be as high as 40% in some of the studies. She did great though, and her A1C came down to 6.8%. She's lost a little bit of weight now. She's back for following up and she wants to get to her next goal, which is to try to get that BMI to below 25. And we suspect going up. Now in the package of all the GLPs, they say it can go up every four weeks. I really play it by ear in terms of patients and in terms of how they're tolerating it. I've had patients on the low doses of the GLP-1 receptor agonist lose a significant amount of weight and reach their A1C goals. And I've had to push up some other patients to the highest doses to reach the same goal. So it's a visualized care. So also thinking about what if we go up to the higher dose, she can't tolerate it. What do we do next? And so again, when we think about this and say we push her up and she's not reaching goal, we can consider adding an SGLT2 inhibitor as well. So she didn't tolerate the higher dose. So we just kept her at 0.5 milligrams. She got a lot of nausea from it. So I added an SGLT2 inhibitor and I added what was covered by her insurance, Temporal Fluorphosin. We did the small dose first at 10 milligrams. I tended to do that because some of the patients may not tolerate well at the higher doses. And for her, she had had a UTI before. This is not a contraindication. I think a lot of our diabetics, men and women have had UTIs, but you just need to discuss the risk and to educate about hydration and good hygiene. You might want to reduce any blood pressure medications they may have, including the ARB, because we know the hyperkalemia is an issue when you're doing SGLT2 inhibitors in some of our patients. I had her come back in six weeks because I was just worried that she may not tolerate it very well. And she did pretty well, actually. Her volume status was great. Sometimes I order a BMP within the six weeks. Sometimes I don't. I did for her because I was worried about her dehydrating. She did great. The labs were fine. You do want to inform a patient that if you're checking a UA, because you're worried they might have a UTI, that the three or four plus glucose is normal that we expect glucosuria. That'll spare you a lot of phone calls. So that's what we did for her, and she did great. This case, though, is a little bit different. So the patient's already on metformin, so type 2 diabetic. She has perfect lysine control. So what else do we, why would we even address this anymore? Well, I'll tell you why. So she's a 75-year-old female with type 2 diabetes, hypertension, osteopenia. I actually saw her for primary hyperparathyroidism. Half my practice is thyroid and parathyroid. And that's what I saw her for. And she had surgery with our parathyroid surgeon. After that workup, I could have sent her back to her primary, who was managing her mild diabetes, because her A1C was great, 6 to 6.3%. But she had a BMI of about 29. She was on a little bit of metformin. She had a lot of blood pressure medications. That is what really disturbed me, that she was on carbadol, valsartan, nifedipine, high doses. And of course she was on a statin, as she should be. Every time she came to my office, the blood pressure was high. And then she tells me, no, it's fine at home. How many of us have those patients? We do, but I was just very concerned about three blood pressure medications. She has no history of retinopathy, and she does have regular follow-ups with her ophthalmologist. And all her blood work have shown regular or normal creatinine levels and HFR. So the question is, are we done? We should send her back to her primary. Well, you know, this is the case, so we're not done. So these are the labs that if you're just doing blood work, this is what you're gonna see, everything looks perfect. But if you do a urine, urine, whether it's a UA or a microalbumin creatinine ratio, you can see she has significant proteinuria. It's not even micro at this point. So always check the urine for this patient. So the ADA and the kidney docs, the ADA-CDGO did a consensus statement in 2022, and I'm sure we'll be updating that soon as well, that says that first-line therapy in our patients with diabetes and CKD is to consider an SGLT2 inhibitor in addition to the RAS inhibitor, and that metformin's okay to use all the way down to an HFR of 30. So that is very important in this class of patients, and especially in this patient. So this is just to illustrate to you what happened with this patient. I started her on dapagliflozin, and you could see this is in the thousands for albumin creatinine ratio. I tried to go up on it, and I had to lower her blood pressure medications at that time. I lowered the dapa a little bit because she started getting very dizzy. I then moved and I continued to lower her blood pressure medication. You can see she had regular follow-ups every two or three months, and then she just couldn't tolerate anymore. She started getting cold. So then we changed it to ampliflozin. So if one doesn't work in the same class, try a different one. Then I went up slowly. I didn't go from 10 to 25. I took a 25 and I had her cut it in half. She seemed to tolerate that well, and then we went up to the 25 milligrams, and at UCLA, C-COMET means that it's zero undetectable, and you could see that during that whole course, I was lowering blood pressure medications. I usually do diuretics first, and if they're not on a diuretic, I kind of start lowering things down, and the take-home point of this is that low-dose SGLT2 inhibitors can work. It does take time, so you could see that it actually took about three months at a time for it to come down. So you gotta be patient. Titrate slowly, adjust the blood pressure medications, and if they're on diuretics, adjust those to avoid hypotension. If one doesn't work, try another. So this is something that takes patience, but it's extremely rewarding. Now, my albumin-creonine ratio is gonna bounce up a little bit, but it does stay down, and I have seen her since these labs were drawn, and I can tell you she has stayed relatively low, under 100 on the albumin-creonine ratio, on the same regimen. So you can see the success she can have with an SGLT. So the next is actually someone who is metformin intolerant now, so they can't be on metformin, and he wants to try something new. So this is a 62-year-old male with type 2 diabetes, 15 years, and he presents to a clinic with an A1C of 8.4%, currently on no diabetes therapy, and he says he has no history of cardiovascular disease, CHF, or CKD, but he is an avid runner, and I believed five miles a day, he had a decent BMI, but both his parents were insulin-dependent diabetics in their 60s, and he's just feeling like he's doomed, no matter what he does, because it seems like that's the case, although he admits to occasionally indulging on sweets and wine, definition is occasional, I don't know, but he reports a very high protein, very low-carb diet, and he reports that he takes in about 1,500 calories a day, I don't know if he counts the sweets and wine, but that's what he says. He does check his sugars, the fastings are high, 110 or 130, and the two-hour post meals, they're still high, no matter what he eats, or whatever, what he does. So this is making him very, very upset. Trials for metformin a few years ago led to diarrhea, and a high upset, and what was more important is that it led to severe erectile dysfunction, so that was discontinued, he will not go on that medication again. He was on pioblitazone, up to 30 milligrams, but he gained weight and his sugars did not improve much, so he stopped taking it. He is on a statin and he is on an ACE inhibitor. SGLT2 inhibitor was prescribed. That was just kind of the next step in this patient. And he started on empical flows in 10 milligrams. He was educated on all the side effects, hydrate, eating correctly, and things came down in terms of his A1C and his glucose readings, and we went up to the higher dose of 25 milligrams as tolerated. Three months later, though, that everything was going well, and then he ended up with flu-like symptoms, which led to dehydration and decrease in appetite. I think you guys all know what I'm getting at. This has probably happened to your patients. However, the patient continued to take his medications, including his empical flows, and he was just going to be a good student doing that. However, he didn't feel well in the GI and the stomach, so he needed to calm his stomach, and he started drinking wine nightly, a few glasses, he says. And because he was so tired and not sleeping well at night, he actually started drinking more coffee than usual during the day to stay awake. He was sick for days. He stopped eating, and his sugars never really got very high, so he didn't think anything of it. Mid-200s at the most, generally less than 200, but he started vomiting, and his wife was very concerned. She drove him to the ED, and the patient was admitted to the hospital. He was found to have euglycemic DKA, so he had a whole anion gap. He had hydroxybutyrate. Acid was high, and this is defined as less than 200 milligrams per deciliter with DKA. You can look in the literature. Some people say 250. Some people say 300. There will be an upcoming joint society statement, and by the time you see this, if you're watching the recording, maybe it will be out that it's generally going to be considered less than 200. So that was the reason why we get fooled by this, and it is euglycemic DKA. I encourage you to read this paper by Rosenthal, Stock, and Ferronini that really talks about how SGLT2 inhibitors can lead to euglycemic DKA. So what happens is that we know that SGLT2 receptors are on the proximal tubule of the kidneys, that if we inhibit SGLT2, we are inhibiting the reuptake, 90% of reuptake of glucose back into the blood, and that you induce glucosuria, and that is the reason why we get fooled, and we don't see the elevated blood sugar, so we don't see the DKA coming, and what happens is SGLT2 inhibitors increase lipid oxidation, lipolysis, and glucagon. You're mobilizing the free fatty acids. Ketogenesis starts. Beta-hydroxybutyrate happens. The process speeds up even more when you're not eating, you're not drinking, and in patients who might be on the brink of needing insulin or they have insulampenia, that just makes it worse, and it's this vicious cycle that leads to rapid DKA in our patients, and it is a two-hit hypothesis where dehydration, insulampenia then leads to this euglycemic DKA, a type of DKA, those of you that do hospital medicine, that you know you can get fooled when the gap closes, but then the patient, you think, oh, I can get them off of the insulin drip, and then they go right back into it, so it's very different, and that's just because the SGLT2 inhibitor also stays in the system for a while even if you stop the medication, so it's very important to think about the predisposing factors and think about it in your patient. We do know that this particular patient was someone who liked alcohol, someone who was very into a high-protein, low-carb diet, and wasn't exactly the best student in terms of his lifestyle, so education is key, but life happens and patients can get sick, so it's really difficult for us to predict, but it's very important to try to predict, try to detect, and try to prevent, but not to be afraid to use medication because of the benefits, cardiovascular, heart failure, and CPT, so he presents to the endocrine clinic four weeks after his hospitalization. He's on insulin. He's on basal. He's on pandolins, and though his gap closed, his glucose still stayed high, and I did check him for type 1 antibodies. I know everyone's wondering because of his parents' history. They were negative. Random lab glucose was 190. His peptide was a little low, and of course, he had gone through a DKA. We all can see that in our patients that they might not be taking a lot of insulin at the beginning, and he still had the blurred vision, the polyuria, the malaise, kind of the warning signs, but so at this point, we're not going to take him off insulin. We're going to maximize the therapy. That is seen at both the ADA and ACE guidelines. It's just a pretty illustration of how to maximize insulin that I'll let you review, and many of you probably already know how to do this, so with us, education is key, so I had him meet with our dietician and our educator again. He did stop drinking altogether. He eats a more balanced carb-controlled diet with his daily exercise. We went ahead because he is, and I probably never said, but he's an engineer, which probably made it easier to convert him to carb count, and so he did carb counting, and he was put on Lispro in the correction, and he got a CGM. At the time of this, we didn't have two sevens. This was a two six, so yeah, so he did great, and he was 99% in range. 70 to 180 is the time and range, and he did fantastic. It's a straight line, and this is just on insulin, basal and perennial, and it's not on a pop. He's actually doing multiple daily injections or MDI, so what did we do next for him? Nothing. He's perfectly controlled. Do we try the SGLT2 inhibitor again? Do we try GLP-1 receptor agonist? Do we try PIO or metformin, and remember, he had side effects. What would you start him on? A sulfonylurea and discontinue the perennial insulin to minimize insulin use. I think your answer is really in terms of, obviously, cost and what the patient's willing to do. Is he willing to do more shots? What does the guidelines say? The guidelines say to consider a GLP-1 receptor agonist if we're not going to do an SGLT2 inhibitor again, and what you want to do when you do this is you want to lower the insulin to avoid tight control, so if a patient's already on insulin, you're going to add GLP. You want to make sure that you're lowering both the basal and the perennial. Close monitoring is very important as you're trying to dial down that insulin. Cost could be prohibitive, not for this particular patient, but for some patients, so you might want to just keep him on insulin if he's well controlling, tolerating if cost is an issue. So, could we restart? You know, I don't know. With the SGLT2 inhibitors, there's really no clear guidance on this. There's a lot of case reports that have been published that suggest the pharmacologic effects of an SGLT2 inhibitor persist beyond five half-lives of elimination, so two to three days, with glucosuria and ketaminia lasting as long as nine to ten days, so if you do decide that you want to start him off again, education is key, and this patient, I just did not feel like he was a great candidate to get back on it. You want to talk about the benefits versus the risks for each patient. Okay, so now we're going to talk about a different kind of patient, so this is an out-of-control type 2 diabetic. We see these all the time in our programs. This is a 52-year-old with type 2 diabetes, five-year history for the control, 13.9 percent. He was referred by his primary care provider, 410 blood sugar on the visit, and he had just ate lunch. Currently taking just metformin, 750 milligrams, one pill daily. He says he just cannot tolerate more. He gets severe diarrhea, and this was the extended studies on, has been resistant to adding new diabetes medications offered by his primary. Now he's experiencing those warning signs, right, the polyuria, the polydysplasia, the polyphagia, blurred vision, neuropathy, pain in his feet. He eats a large amount of carbs and sweets, and he travels a lot, so he has a terrible diet, does not exercise, and of course he is on a statin, and he is on an ACE inhibitor. So these are actually his labs, and you could see that how quickly his A1C went out of control. He seems to have had these patterns of doing this in the past, which you could see a few years before. His presentation with me had done this as well with an A1C of 11.8 percent. His BMI is actually not bad, 23.4. Remember, he's got out-of-control type 2 diabetes. He lost weight because of it, and he's got trace ketones now. The anion gap is actually okay. He's got 3 plus glucose in the urine, so this guy's in trouble. So those are all his troubling signs. So we went ahead and, you know, for me, I did the antibodies because I seem to have a very large amount of LADAs, and we'll talk about that later at the end of the talk, but he was negative in the antibodies. He was still producing insulin, but he had very high sugars. So with him, I went ahead, and because he had all the warning signs that looked like he really just needed to start insulin, I started Degludec 30 units daily, and then I also added Lispro with his meals. He was really not like my other patient. He really didn't want a carb count. We designed a fine scale with set amounts of carbs per meal. He seemed to do fine with that after meeting with my dietician educator. He enjoyed lifestyle modifications with a carb-controlled diet and adding protein to his meals, and he was scheduled to return a month later. So this is what we see in our patients, whether they're handwriting them or we're downloading it on our glucose readers. This is gluco. We're getting sporadic numbers. It's very difficult to make treatment decisions based on just kind of numbers scattered. He checked about three times a day, which was I had him do fasting in two hours after lunch and two hours after dinner, and it gave me some information. So he was agreed to do a CGM. He actually got a professional one as well, professional trial. So this was a blinded trial, and he did continue to just check his own sugar. He started getting hypoglycemic when he was starting to eat a little better and exercise. So the basal and the cranial insulin was lowered, and we could see that he's actually pretty well controlled with a 95% time and range now, which is fantastic, and he wants his own. So we did it, and we were able to get that approved. He chose the Libre and 95% time and range for this patient, and he continued to self-reduce with my instructions on his insulin, and we then added a GLP-1 receptor agonist. He stopped his cranial insulin. I went ahead and maximized the semaglutatide from 0.25 after four weeks to 0.5. Did well, and again, don't forget to even lower the basal insulin. So he went ahead and lowered that, and he lowered it even more. So we went from 20 to 68 units. All along, he's getting this information. I'm getting this information. We educate our patients to learn how to use their CTM, and I also have them titrate. I can't see them every day, so they're doing a great job. This guy is fantastic. So now his time and range is 98%, and he's only on eight units of Gluteglutec now, 0.5 of sema. He's off of Lispro. Still on metformin, what he could tolerate. However, he fell off the wagon. He went on vacation. He forgot his semaglutatide. Had been off for four weeks. He did continue to take his insulin, so he had Deglutec, and he continued the eight units and the metformin, but he forgot to bring his extra sensor, so he was off the center for a week because he didn't know what his sugars were. He wasn't checking on finger sticks or had one. He fell out of control, and you could see how quickly these patients can fall out of control and how quickly his sugars can go up. So it's important for us to utilize CGM in our practice. Patients actually rely on it a lot, which is a great thing. I always say it's actually good to be addicted to your CGM. That's the one thing that's a good addiction because patients are actually being very involved in their own care when they are wearing this. 70% time range is coming from this paper. That's kind of the goal that we're aiming for, for a 70 to 180 range of blood sugars, milligrams per deciliter. The problem is that when we rely on A1Cs, A1C reflects average glucose, but it lacks any information about the in-between. You know, we're talking about three months reflection. We're not talking about what's happening on a day-to-day basis like a CGM gives us. There's also disparities in terms of medical conditions patients have that can make an A1C inaccurate as well as disparities. The red cell survival can vary. You can get a falsely high A1C if your turnover is low. You can get a falsely low value of A1C if your turnover is rapid. So again, A1C is probably not the best for some of our patients and maybe many of our patients. So when we look at CGM, 70% time range is susceptible for most of our type 2 diabetics, but if you have older patients, you may want to just aim for 50% because at that rate, you know, my 80-year-olds, my 90-year-olds, patients who have cancer or a high risk of hypoglycemia, I'm happy with 50% time and range. You do want to keep below 4% in terms of lows under 70 milligrams per deciliter. Patients with pregnancy, you might want to aim for a higher time and range, even all the way up to greater than 90% time. And so CGM is an estimate of A1C and average glucose and the GMI that you see in all the readings, all of you know probably that it's an estimate of A1C based on the average CGM glucose data. Obviously, many of you may say that not all the CGM data is accurate. I do have my patients, but I'm not sure how accurate they are. I do tell them if it's within 10 to 15 points, that's definitely fine. I do have patients who have reported 40 to 50 points difference and at that point, maybe CGM may not be a good option for them. All right, so moving on. So now, this is another kind of patient you probably see. It's a type 2 diabetic, new to practice, and has type 2 diabetes, obesity, BMI 36, CKD, and he's got persistent microalbuminuria, and he just needs refills because his doctor retired. He's on all these medications, pilotazole, metformin, glipizide, arginine, atorvastatin, losartan, hydrochlorothiazide, so a lot of medications. His A1C is actually pretty decent, 7.2%. He doesn't check his sugars. He just relies on his every three or four month visits and says, my A1C is always the same and I just want my refills, and he wants to just have you refill and go, and I'm sure many of you will say, no, that's not what we do. So what we do next, physical exam, very important. So I noticed that he had a lot of lower extremity edema, pitting 2 plus to mid-cap, and I had him do a microalbumin creatinine ratio and give me a urine, and you could see it's high. He does also report when you ask for a history of apnea, he needs to sleep with several pillows. Frequent bounce of hunger during the day, lightheaded, he's relieved by eating, so you know that he's getting hypoglycemic on this stretch. He reports that he had seen a cardiologist a few years ago. He was given a test. He thinks it was an echo. He was told to take parosamide for some time. He's not on it anymore. He does not know if he had heart failure. So what does he have? So he looks like he has heart failure now, and so when we looked at that med list, you want to think about the medications that someone with CHF risk you want to eliminate, and that includes the TZDs, so pyoglitazone, the secretagogues, and trying to minimize the use of insulin in these patients. So we did find his echo. He actually has a reduced EF, so definition of reduced EF, as many of you know, is to be less than or equal to 40 percent, and he was at 35 to 40 percent. His repeat was the same, so we went ahead and we took off his pyoglitazone, his lipozide, and I added dapagliflozin 10 milligrams daily. No rhyme or reason. I could have done EMFA, so what was covered by his insurance, and so we're here in the ADA guidelines with the heart failure. I'm seeing in the other guidelines that your next choice, other than if they were on that formin, is to go ahead and add an inhibitor, but you need to consider, and obviously with the previous case, we had to worry about euglycine and DKA, but for this patient, as well as all patients, think about dehydration. Now, of course, it's going to be hard to tell someone with heart failure to drink lots of water, but it's important to stress that they should hydrate, you know, and work with your cardiologist in terms of how much they can hydrate, and if they're on diuretics, you may want to adjust them if you're adding an SGLT2 inhibitor. Hyperglycemia on insulin can occur when you add an SGLT2 inhibitor. SGLT2 inhibitors by themselves will not, right, because of the nature of what it is. It's a blemish area, right, but when you add it to insulin, it can, so I usually reduce both basal and perennial by 10 to 20 percent when I initiate. Monitor the EGFR because they can get AKI on top of CKG. Just hydrate. Look for hyperkalemia. This can be an issue, especially if they're on an ACE and an ARB, so do check, and this might be when you want to bring them back to the clinic in a couple of weeks or four weeks or six weeks, and check their basic metabolic panels or kidney functions and potassiums. You want to monitor for UTIs and mycotic infections and, of course, those ketoacidosis risks, and it is the same as that case before. If they stop eating, they stop drinking, tell them to stop. This is the medicine to stop, and I do put it on the after-visit summary of every visit of all SGLT2 inhibitor patients to remind them and educate. So, three months later, after starting dapagliflozin, 10 milligrams, the patient did great. A1C is 6.8%. Denies hypoglycemia. He's lost weight, actually. We took him off of all those medications that cause weight gain, right, and we reduced glardine to 20 units daily. Lower extremity edema has improved. Orthopnea has resolved, and you could see, actually, the patient was experiencing a little lightheadedness, so I took the hydrochlorothiazide off, and after three months, you could already see the improvement in the microalbumin-creatinine ratio in this patient. Now, like I said, just have a little patience. It's not going to happen in two weeks. It may not even happen in a month, but you'll see it in the urine after about three months or so. So, next case, however, is a patient who's already on insulin, and what do we do? So, this is a type 2 diabetic. For 15 years, insulin-dependent with multiple drug intolerances. She died of intolerance to metformin, nausea, severe diarrhea, and very hesitant to try more options for the GLP-1 receptor agonist or even a dual agonist due to side effects. This woman is traumatized. She has tried dulacotide and itching and rash. She's tried exenatide. She got dizziness. She's tried baractide and semaglutatide. She had severe nausea and vomiting, but she says her glucose improved on them, but she just does not want to have that experience again. She has tried an SGLT-2 inhibitor, canaglucosin, and she had repeated yeast infections that were very difficult to treat, so she does not want to go on an SGLT-2 inhibitor. She's currently on pioglitazone. That seems to be the only thing that works at a low dose, and she's on basal and prandial insulin. So, you can see that she's on quite a bit. When patients are on high doses of insulin, I do sometimes split that insulin, so she is on a split dose of that, and it seems to work pretty well for her. She's also on Lispro, fine scale, 20 to 30 units before each meal. She has a very high BMI of 34 and she continues to, that's a typo, gain weight. Her A1c is 9.2 percent. And so you could see that when we look at this paper, the once weekly semi-glutatide paper, and we're looking at these GI side effects that these patients have, you know, nausea and diarrhea are the most common side effects. And when you look at the nausea, it's about 44.2 percent of participants. Diarrhea was 31.5 percent. And then the more, the scarier ones with the gallbladder and cholecystis, it's very rare. It's, you know, less than three percent. When you look all the way down, pancreatitis is 0.2 percent. So you would wonder, why would people stay on it if they have 40 percent nausea? Well, patients actually stay because they like the effects and the effects actually get better over time. So the nausea subsides, the diarrhea subsides, the vomiting and the constipation seems to subside. So educating the patient is key, that it may take them a few weeks, it may even take a month. And you may want to treat them for nausea with antianemics. You may want to treat them for constipation, for acid reflux. The tolerability is quite high. Most patients actually stay on it. This is a paper by Wilding as well. A small number of patients discontinued. So you could see it was less than 10 percent that actually discontinued on GLP therapy and the patients actually continue on the medications. This is an excellent paper by Sean Wharton's group looking at how we can really minimize the discontinuation rate and try to keep our patients on it, not just for glycemic control, not just for weight, but for all its benefits for the heart and for the kidneys. We educate patients. We tell them to escalate the dose slowly and effective management of those GI sites. That's like I said, PPI, H2 blockers, a little antianemic. Now, obviously, if I have to give a patient Zofran or PPI for a long duration just to stay on the drug, we're going to have a conversation with the patient. That might not be the best drug for them because they're getting very sick. But education is key. So for this patient, she did great on this. So we're going to this is her what she looks like now. And you could see that she has this is before I add the GLP. She just has episodes that she's just getting high sugars with food. So she just really was scared to try anything. And I said, let's try a different one. Let's try trizepatite. So we did this is GLP, GIP, dual agonist. And we did a small dose of 2.5 starting dose. And I titrated her up to 5 milligrams. She met with a dietician. She was on insulin, but we started lowering the doses. She was on a carb count. And we started adjusting that. And you could see that her time and range has now jumped from 46% all the way to 87%. If you're looking at the last 28 days, if you last look at the last 14 days, 90% doing great. And this is only after a few weeks of being on a five milligram dose. So patient did great. She actually self lowered her insulin upon my instructions. I told her to educate her that if you see that you're getting low, go ahead and reduce the basal and cranial insulin by a certain amount. She did a great job on that. And she then began to see improvement in her glucose control. And she presented a clinic for further titration of her trizepatite. So we did that. We lowered the insulin again, both cranial and basal. She didn't need to take her H2 blocker after a while, her promotedine. She actually tolerated as we saw in those studies that after a while they get better and she didn't get a rash or any of those really scary side effects she had with the other medications of GLP that she had been on before. So the clinical pearls for this is that if the patient cannot tolerate one drug in class, try a different one or try for in this case a dual agonist. I've had patient on the dual agonist who just didn't tolerate and went back to a receptor agonist. Every patient is different. Now, would this patient benefit with an SGLT2 inhibitor? She had a really traumatizing experience with mechanical sclerosin. So, you know, it's something that I could possibly add later. We have to educate the patient as well. And also make sure you're educating the patient in terms of when you're trying to adjust insulin as you titrate the GLP or the GLP and GIP that they need to lower their insulin levels and to notify you if they don't know how. Education is key. All right. So we're going to finish with a few cases of the not-so-usual cases of type 2 diabetes. So this is something that many of you might see in your practice. I see a lot of it. 77-year-old female with a type 2 diabetes history, osteoporosis, and dementia. She was diagnosed in 2012. She was started early on that hormone that her A1C started climbing. She had in recent years lost weight. So this woman already doesn't have weight to lose. She lost weight. And her A1C still remained high at 7.3%. She was diagnosed with type 2 diabetes just because of her age. She started out metformin. She tried to maintain a carb-controlled diet and exercise. She dropped even more weight. And yes, the A1C did drop. Then she went back to her homeland. She went off her diet and her usual exercise routine. And she gained seven pounds. And the A1C went back up. Her primaries increased from metformin dose to twice daily. And then of 750, she continued to lose weight. This is getting really scary. This woman does not have enough weight to lose. And the glucose readings started to escalate. Now the A1C is eight. So the primary is like, well, flip a side. Obviously, you don't want to do a GLP-1 receptor agonist. This lady is already losing a lot of weight. And then of course, she developed hypoglycemia and that was discontinued. So that's when she was referred to me. And this is when she was just on the metformin. At that time, I thought maybe she's a late onset diabetes or LADA type 1. So I drew GAD-65 antibodies. It was undetectable. I prescribed sitagliptin because of the history that she had of hypoglycemia and weight loss. I did not want to give her anything that could cause either of those. It's for A1C and it was very expensive. The DPP-4 inhibitors, even though they've been around for a while, especially for our patients with Medicare, very expensive. Cost of drug is so high. So it was discontinued. And then she's actually got dementia. So she's cared for by caregivers that are not nurses or, and are not trained to give insulin. So the family was very concerned about starting insulin. So we tried a short-acting secretagogue, nitiglinide, before meals. She actually did okay. Education to the caregivers, make sure she is eating her first few bites, then go ahead and have her take it. She did well on this dose for a while. And then she had a major stressor. Her husband died. And so of course her eating habits changed. She wasn't sleeping. She was very stressed. A1C went up to 9.1. Her BMI is still low. She's on metformin and nitiglinide. So GAD-65, I reordered it again, and this time it's high. So you're going to see in these patients, this is LADA, latent onset autoimmune diabetes of adulthood, that you may not see that presentation of that antibody quite yet. You could also draw the other antibodies. She still makes insulin. Her C-peptide is not undetectable. She has frequent episodes of hypoglycemia on the nitiglinide. So when you discontinue it and you don't have her take it at all, her sugars are very high. So at that point, we're trying to add a little bit of perennial insulin, a little bit of basal insulin for her, but she's very erratic. One regimen might work and you could see that her sugars, then her shoots up, her A1C shoots up, and then you remove something and it comes down. So this is a very unstable and she doesn't really change very much in terms of her lifestyle. So it is just showing how erratic LADA is in our patients. They're not quite type one, they're not quite type two. Finally, she settles down and she is just on a little bit of Degludef, nine units daily, and a touch of Metformin, 500 milligrams daily. You could see that she's doing really well, education in terms of her diet was key. So this is latent onset autoimmune diabetes of adulthood, progressing to type one diabetes. It is not type two, it is misdiagnosed often for type two. It's a slow progression to type one diabetes in adults. Beta cell function declines, tends to be slower than type one. And in our case, she would have episodes that were erratic that she was taking insulin at large amounts and then not. Insulin requirement happens within five to six years of onset. So that's about how long it took from when she was diagnosed to when we started insulin, about five years. So pre-cuts can be used and you could use a sugar actin, a teflonide, but they must be used in care, especially in the elderly. And it's important to maybe even consider CTM in these patients and antibody testing. You can actually use all those antibody tests. Zinc transporters might actually come out positive first, but GAT65 antibody is the most commonly seen in a lot of patients. So this is just a table for you to kind of review on your own, but I think it's important to see that the onset is about five to six years from when you see them, where they're a little pre-diabetic, they're usually thin. Yes, GAT65 titers are the most sensitive, but they're not going to necessarily come up right away. So if you have suspicion, they're not actually testing positive, monitor them a little more closely as I did for this patient. And this patient is a little bit different. This is what our S-endos live for. This is a 46-year-old patient with a history of type 2 diabetes and hypertension. She comes to the clinic with a 50-pound sudden weight gain over a year. Now, how many of our patients will tell us, I gained 50 pounds in the past year. Did they really, right? Meaning they didn't do anything, meaning they didn't do anything, but I actually believe this woman, she came in for a diet drug or bariatric surgery consultation. She was really, really concerned. She used to weigh 110, and now she weighs 160 pounds. What I want to see is 7.1. She is on metformin. She eats 1,000 to 1,200 calories per day. So she restricts her diet. She's exercising one and a half hours per night, treadmill exercise. It's intense. She's lost some weight, about 20 pounds, but it was due to intense exercise. She's got the round puffy face, fat pads, stretch marks on her abdomen, and dark skin, acanthosis microcancer on her neck. She's got hypertension. She's got tachycardia. So what does she have? So S-endos live for this. This is Cushing's. We tested a lot. Patients have pseudo Cushing's, but this woman actually had Cushing's, and she actually had adrenal Cushing's. Her AM cortisol and BCH are high, high urinary cortisol, high salivary. Her one milligram overnight dexamethasone suppression test did not suppress. We did her scan. We found a 2.1 centimeter right adrenal lesion. She saw one of my endocrine surgeons and got a right adrenalectomy, and she did require hydrocortisone for the first six months. It was difficult to wean her off. This has been going on for a while, but we finally were able to wean her off. She came off that form in, and her blood pressure normalized. Her A1c actually started getting better and better over time, and she lost 40 pounds and came down to 120 pounds. And you can see that, yes, when patients say, I have Cushing's, once in a while you'll get one. This is the final case, and I think this is a really good one because we forget to ask this question. So this is a patient who was a 62-year-old male with a history of hypertension. Not on this. He goes to the UCLA emergency department with blurred vision, intermittent eye drainage for three weeks, worsening bilateral eye pain. He presents first to an outside hospital who got very shocked in the community and said, go to the UCLA. So he did for higher level of care. He says that his cat sneezed in his face two weeks before, and he started getting these symptoms. So he thought he was just allergic, and he didn't think anything of it until he started getting eye pain. No follow-up with the primary care provider for a while. He has not seen a doctor for 10 years. He did know that he had hypertension at age 40, so it's been over 20 years he's had hypertension. He just ignored it. And they did an A1c in their emergency department, found it was 8.1%. His sugar was actually a little bit high, but, you know, point of care wasn't too bad. Not aware that he had diabetes. Blood pressure was high. Heart rate was only a little high. BMI is high. So definitely eye symptoms, pain, drainage, redness, visual disturbances. Left eye pressure was very high. This is an emergency for our ophthalmologist. They did some imaging, a CT and MRI. He was diagnosed with neovascular glaucoma to the left eye, and he had undiagnosed bilateral diabetic retinopathy. Really poorly controlled diabetes as well as hypertension. He was given drops to lower the pressure and he was sent to retinal clinic and glaucoma clinic. He was actually seen very quickly within the next one to two days. He was quickly prescribed and received injections of anti-VEGF, Bevacizumab, to the left eye by the retinal team. The left eye, because of the high pressure, they put a drainage valve to lower that pressure. His eye symptoms stabilized, but he continued these anti-VEGF injections to treat both the retinopathy and the glaucoma, and everything else he denies. He says, I don't have a history of diabetes in my family or hypertension or CD, and no neuropathy. So he saw me in clinic, and, you know, at first he declined any medical intervention for his diabetes. He agreed to see our dietician. He started exercising a little bit more, but his blood pressure remained high. But even with lifestyle modification, he did great. Again, his blood pressure was still very high. We did a little bit of metformin. He did agree to that. It was on Losartan and Atorvastatin. Small cardiology that diagnosed with mild CHF, but the story doesn't end there. He's got those eye problems. He's getting those injections. So you could see that his A1C is falling down. It's doing well. And I mean, I only have this guy on metformin initially, but then with the heart failure and now proteinuria, we added Amboglycloflozin, which of course will help the glycemic control. It's supposed to help the proteinuria, but you can kind of look down the list and see that despite me increasing the Amboglycloflozin, he is still having issues. His retinopathy is getting worse. He continues to get these injections. So this is the question we have to ask our patients is, are you getting shots in the eye? Because anti-VEGF actually induces hypertension proteinuria. So if you have a patient that you say, yes, perfectly well controlled, all of a sudden, why is there so much protein in the urine? Why is the blood pressure high? A1C seems fine. You need to ask them about that. And if you're not in an integrated system where your patient's seeing an outside ophthalmologist, a lot of times the patient will forget to tell you. I don't know if they just kind of blank it out and just don't want to tell you they're getting shots in their eye, but that's why it's so important to ask this question. So these are his actual numbers and you can see that it, you know, despite his sugars being fine, he's got proteinuria when he's getting these shots and you know, it's, it's persistent. And then he was actually changed from a systemic form, which is Bevacizumab to Ranibizumab, which actually was better in terms of the proteinuria, but then it got worse again. So it was stopped and it does take a few months for it to wear off. So you're not going to see that proteinuria go away immediately. So that is very important. And you might want to have a question of what about SGLT2 inhibitors? Do they help the retina itself? We actually think that there might be some improvement in terms of macular edema in these patients that there may be expressed in the retina parasites. There needs to be more studies. So there may be even benefits from being on SGLT2 inhibitors, not just for the proteinuria for a retinopathy patients who are getting these injections, but also direct effects on the eyes. So clinical pearls for this one is to consider anti-VEG and induced proteinuria. If you're a patient's A1c is improved and it's fine, but the proteinuria is getting worse and the blood pressure is going off. Anti-VEGF agents are nephrotoxic to the podocytes. That's the reason why. It's also a duration effect and a dose effect. And it could also be based on the medications that they're on. And that is because Bevacizumab is much more systemic versus Ranibizumab. Cost also goes in this order, cheapest to the most expensive. So you want to work with your ophthalmologist and you may have to work with them and say, can you hold it for a while? Let me deal with the proteinuria and the hypertension and restart. So communication is key. And I do that all the time in my practice. So you want to monitor the blood pressure and really need to look at both the microvascular and macrovascular complications for our patients. Be aware of any diuretics they could be also receiving if they've got glaucoma, because if you add an SGLT2 inhibitor, you need to adjust that to avoid hypotension. Work with ophthalmology, cardiology, and nephrology. All right. So finally, the take-home points of this talk is, again, to individualize care. Lifestyle changes with and without metformin may be all you need. You saw that in several cases. Benefit of new therapies for not just diabetes, but cardio-renal benefits. You go to multiple conferences, that's what everyone's talking about now, cardio-renal metabolic. Staying on the same regimen a patient has been on to keep an A1C at full or close to full, like the patient that wanted refills, may be not enough and may be dangerous, right? The patient gets hypoglycemic, for instance. A1C may not be the best indicator, so think about time and range. Knowing the side effects of new therapies and counseling the patients is key to avoid the side effects. So that is the end of my talk, and I notice there's some questions in the Q&A. So for case three, yes, I agree. The postprandial blood pressure spikes at CARBOS could help. That is definitely something that you can use. Of course, it's cheap, but I don't know what your experience with the CARBOS is. A lot of my patients get a lot of GI side effects from CARBOS, but I have used CARBOS for the postprandial blood pressure spikes. And in the future, if you're looking at studies, they're looking at perhaps effects of, for our type 2 diabetics, maybe an SGLT1 receptors that are in the intestine, if you're into that research, where it helps with the postprandial hyperglycemia spikes. That might be something in the pipeline in the future as an alternative to CARBOS, but I agree with that. So why was there, it was not that high. That's a great question. It was a little high. I think it was mainly that the cortisol itself was very high. So I recognize that I kind of misspoke there. The question is why is her ACTH high when she had adrenal hypercortisol? It was slightly, it was kind of right on the edge, but the cortisol, and I did do a pituitary MRI. I didn't mention that, that was negative, but it was actually because she also had adrenal veins. Are you, yeah, so yes, it wasn't high. I'm sorry, I missed a book on that ACTH. It was the same question there. It wasn't really suppressed. It was kind of right on the edge of normal. So that's why it was kind of a difficult case for me to look at. There was more to that case. I think we were just kind of trying to illustrate to you that for a patient, a lot of our patients will say that they think they have Cushing's, and in that case, that what was curative for her in terms of her diabetes, her control, and her obesity was getting the adrenal activity. And thank you. Thank you. So, and thanks for pointing out the ACTH. It wasn't that high. So definitely not to the level of Cushing's from the pituitary. All right. So thank you so much, everyone. I hope you enjoyed this lecture. Thank you. Have a wonderful evening. Okay. Thank you.

type 2 diabetes

individualized care

complications

comorbidities

guidelines

barriers to treatment

SGLT2 inhibitors

GLP1 receptor agonists

diabetes technology

lifestyle modifications