Welcome to the late-breaking session, ACEs Clinical Practice Guideline, Use of Advanced Technology in Management of Persons with Diabetes Mellitus. My name is Sandra Weber, and in my role as chair of the ACE Clinical Practice Guideline Committee, I am honored to serve as your moderator for this inaugural presentation of ACEs newest guideline. We are excited to have the co-chairs of this guideline here today, Dr. George Grunberger and Dr. Jennifer Scherr. Dr. Grunberger is chairman of the Grunberger Diabetes Institute in Bloomfield Hills, Michigan. He is clinical professor of internal medicine and of molecular medicine and genetics at Wayne State University, professor of internal medicine at Oakland University, and visiting professor at the Charles University in Prague in the Czech Republic. Dr. Grunberger established and directed the diabetes program at the Detroit Medical Center and was medical director of Wayne State University's Comprehensive Diabetes Center. Dr. Grunberger did his fellowship and then research work at NIH. He is past president of the American Association of Clinical Endocrinologists. Dr. Grunberger has served as an educator of medical students, residents, endocrinology fellows, masters and PhD candidates, and junior faculty over his past 35 years. Dr. Jennifer Scherr is an associate professor of pediatric endocrinology at Yale University of Medicine. Dr. Scherr's passion for the care of those with type 1 diabetes is personal and began when she was diagnosed in 1987. She fulfilled her goal to become a pediatric endocrinologist, completing her undergraduate and medical school training through the accelerated Rutgers University and Robert Wood Johnson Medical School Program. She completed her residency and pediatric endocrine fellowship at Yale, then proceeded on to get her PhD. Her thesis examined the mechanisms responsible for the loss of the glucagon response to hypoglycemia and its relationship to residual beta cell function. Dr. Scherr has devoted to clinical research for the past 13 years working on a number of advanced diabetes technologies, including sensor studies and assessments of automated insulin dosing systems. On behalf of ACE, we thank you for your leadership and fortitude in this endeavor. George Grunberger, and gives me great pleasure to present today along with my co-chair, Dr. Jennifer Scherr, on behalf of the entire task force, the ACE clinical practice guideline on the use of advanced diabetes technology in management of persons with diabetes. These are disclosures for the chairs. You might ask, why do we need a clinical practice guideline in this field? Well, technology has penetrated clinical care, just like every other aspect of life. If you think about that, insulin pumps have been around in clinical use since late 1970s. Over the past decades, certainly the growth of Continuous Glucose Monitoring, or CGM, in clinical practice has been truly exponential. Integrated devices, which combine somehow both insulin pumps and CGM, have been now on the US market since 2013, so it's like eight years. The sufficient body of accumulated evidence from controlled studies and real-world data, led the ACE Diabetes Scientific Committee back in 2018 to approve creation of the first clinical practice guideline on recommendations for use of advanced diabetes technology in management of persons with diabetes. Now, ACE certainly has a history in the diabetes technology world. This was not the first time it delved into it, but until now, these have consisted of consensus and position statements over the last 10 years, not a guideline. For example, there was a consensus statement on CGM in 2010. It was followed by National Consensus Conference on Glucose Monitoring in 2015. Then ACE published its own consensus statement on glucose monitoring a year later. Then it was followed by National Consensus Conference on CGM, again, still in 2016, and on insulin pump side, the first time ACE had a consensus statement on insulin pump management was in 2010, and it was then updated in 2014 by another consensus statement. Then finally, in 2018, ACE published its position statement on integration of insulin pumps and CGM in patients with diabetes. Enough data has been accumulated then to say, fine, maybe it's time to do a clinical practice guideline, which is the highest in the hierarchy of the organization's statements. First, what do we mean by advanced diabetes technology? Let's just make sure that you're on the same page here. On the glucose monitoring side, we're addressing continuous glucose monitoring systems, also called real-time or intermittently scanned. On the insulin delivery side, we're addressing insulin pens, the smart pens, and insulin pumps. Then we are discussing the integration between the pumps and CGM with a variety of available systems on US market today, from low glucose suspend to predictive low glucose suspend to hybrid closed-loop systems and also a variety of available apps. Now, to qualify as a bona fide guideline, ACE is a very strict methodology. It's been updating its methodology for production of these guidelines. Just to go over that, so again, people realize what this is, what it's not. The latest rendition was published back in 2017. Just to give you an idea about the rigorous methodology, it involves first a literature search for high-quality primary studies and there are four formal steps, which include the evidence rating of all these studies, followed by the scientific analysis, then a variety of recommendation qualifiers, and finally creating the initial recommendation grades. If we see how this was applied to production of this specific clinical practice guideline, this comprehensive literature search was again for high-quality primary studies published in English over the last decade. By this way, 2,481 articles were identified. Then the ACE methodologists and at least two task force members screen each and every abstract. Decision then was made to either include or exclude each article, and if the recommendation was to exclude, the rationale for exclusion had to be noted. If there was any disagreement about inclusion, this was resolved by consensus with the chairs of the task force. Now, ACE staff then assign evidence levels and study type for the studies which were included. Then grade was assigned for confidence and strength of evidence, and then task force then met and discussed until it reached the consensus for recommendation of these grades. The final manuscript contains 357 citations and eight web links, each of them graded and rated, again, for the strength of evidence. In the end, again, according to the methodology accepted by the clinical practice guidelines gurus, you wind up with recommendations that are A, strong, B, intermediate, C, weak, or D, at this point, there's been no conclusive evidence that we have to rely on expert opinion. Now, so just to get an idea, not to belabor, but it is included in the appendix of the manuscript, what do we mean by strong and intermediate evidence? So strong evidence would be, you know, level one, such a randomized control trial or meta-analysis of variety of randomized control trials. For the intermediate or level two, we're discussing the network meta-analysis, retrospective case control study, cross-sectional study, and some studies of that sort. On the weak or no evidence side, on the evidence rating for level three, we're talking about single-case reports, consecutive case theories, preclinical studies, feasibility studies, or safety studies. And finally, so level four is basically pieces where there's no evidence right now. It might be a theory or opinion or consensus or review of the subject, but right now there's no evidence. And again, details are included in an appendix to the manuscript. Now, the format, as we'll go through right now, is the usual format ACE has followed in the past for its clinical practice guidelines. That is, you ask and then hopefully answer clinically relevant questions for management of persons with diabetes using advanced technology. And I will hand it off now to my co-chair, Dr. Jennifer Sherr, to start with the glucose metrics for clinical practice and recommendations for treatment goals. Thank you, Dr. Grunberger, and thank you everyone for joining us virtually today. I'm very honored to present the guidelines with Dr. Grunberger on behalf of our co-authors. So as we begin, the first question we felt that was important to address is what glucose metrics should be used in clinical practice to assess glycemic status. To further delve down into this, we wanted to describe what the priority metrics for clinical decision-making are in regards to the use of diabetes technologies. For assessment of success, we believe that CGM is the preferred glucose monitoring method with 14 days of data and at least 70% of the data captured over this time period. Metrics that should be considered for all persons with diabetes would include the coefficient of variation, which should ideally be less than 36%, as well as the mean glucose and the glucose management indicator, which should both be individualized according to treatment goals. Then we also know assessment of time and target range is important. Time and target range can be subdivided into time in range, defined as 70 to 180, time below range, classified as less than 70 or less than 54, and time above range of greater than 180. The evidence here is grade C, with the best level of evidence being 2. And as you can see in the table, the targets set vary by diabetes type and if a woman with diabetes is pregnant. When thinking about the data that is available, we recommended starting clinical decision-making assessment with percent time and target range and percent time below range, which will allow us to assess glycemia and provide the basis for therapy adjustment. Here, emphasis should be placed on reduction of time below range. For this, the grade is B and the best evidence level is 1. Now that we have a method to interpret the data, let's talk about glucose monitoring technologies. In section two, we frame questions regarding who would benefit from diabetes technologies. Notably, this is a departure from description of an appropriate candidate, placing the focus instead on who would benefit from the technology. We'll start this section by exploring CGM. CGM is strongly recommended for all individuals with diabetes treated with intensive insulin therapy, defined as three or more injections of insulin per day or use of an insulin pump. It is important to note that we did not define intensive insulin therapy as being basal bolus. So if somebody is using NPH and takes at least three injections a day, we would still strongly recommend the use of CGM. This is grade A with the best level of evidence 1. Structured self-monitoring of blood glucose is recommended for individuals on insulin therapy who have limited success with or are unable or unwilling to use CGM. Grade A, best evidence level 1. CGM is recommended for all individuals with problematic hypoglycemia. And here we define problematic hypoglycemia, meaning frequent or severe hypoglycemia, nocturnal hypoglycemia, or hypoglycemia unawareness. This is grade A, best evidence level 1. Finally, CGM is recommended for children and adolescents with type 1 diabetes. Grade A, best evidence level 1. When further exploring who could benefit from CGM, CGM is recommended for pregnant women with type 1 and type 2 treated with intensive insulin therapy. Again, grade A, best evidence level 1. And a similar recommendation is made for women with gestational diabetes who are treated with insulin therapy. We also felt CGM should be recommended for women with gestational diabetes who are not on insulin therapy. Here, it is grade B with best evidence level 1. Finally, CGM may be recommended for individuals with type 2 who are treated with less intensive insulin therapy, again, meaning less than three injections of insulin a day. This is grade B with best evidence level 1. For our next question, we wanted to determine what an efficient approach to interpreting CGM data was. The ambulatory glucose profile may be utilized to assess glycemic status in persons with diabetes. This is grade B with best evidence level 1. What is an efficient approach to interpreting CGM data? When using the AGP, a systemic approach is recommended. As noted previously, you'd want to make sure you have sufficient data, ideally 14 days with at least 70% of the data captured. Then you would review the overall glycemic status, looking at the glucose management indicator and average glucose. Next, you can check their time and ranges, the targets of which we discussed a few moments ago. For example, for a person with type 1, our goal may be to spend less than 4% time under 70 and less than 1% time under 54. If time below range is acceptable, we can then focus on time in range and time above range. This is grade B with best evidence level 1. Continuing with our interpretation of the AGP report, we will then review the 24-hour glucose profile to identify the times and magnitude of the problem identified. Notably, the daily profiles that make up the 24-hour report are also available to review. We can then review the treatment regimen and adjust as needed. This also is grade B with best evidence level 1. Next, we want to determine when one method of continuous glucose monitoring would be preferred over the other. Here, it was determined real-time CGM should be recommended over intermittently scanned CGM to persons with diabetes with problematic hypoglycemia and can require predictive alarms or alerts. However, it is important to note that the lifestyle of the person with diabetes and other factors should also be considered. In the end, the best device is the one someone will choose to wear. This is grade B with best evidence level 1. Intermittently scanned CGM should be considered for persons with diabetes who meet one or more of the following criteria. Someone who's newly diagnosed with type 2 diabetes, somebody who's treated with non-ensotropic therapies, someone who is motivated to scan the device several times a day, and someone who is at low risk for hypoglycemia but desires more data than self-monitoring of blood glucose provides. This is grade D with the best evidence level being 4. Then we turn to considering when should diagnostic or professional CGM be considered. We felt diagnostic professional CGM should be used in the management of persons with diabetes who meet one or more of the following criteria. Those newly diagnosed with diabetes, those not using CGM on a regular basis, those who may have problematic hypoglycemia but no access to personal CGM, persons with type 2 diabetes treated with non-insulin therapies who would benefit from episodic use of CGM as an educational tool, and persons who would like to learn more about CGM before committing to its daily use. Importantly, in those using masked or blinded diagnostic professional CGM, They must have adjunctive self-monitoring of blood glucose to assist in daily diabetes self-care. This is grade B with a best evidence level of one. Finally, when should intermittent or occasional use of CGM be considered? Here, it may be recommended for the management of persons with diabetes who are reluctant or unable to commit to routine CGM use. This is grade C with the best evidence level of one. Now we'll transition to insulin delivery modalities and I'll hand it back off to Dr. Grunderber. Thank you so much, Dr. Sher for that part. And so to pick it up where you left it off, we'll be discussing the insulin delivery side. So next question asked was who would benefit from use of these smart connected pens? And your recommendation was that connected pens may be recommended for all persons with diabetes who are treated with intensive insulin management, again defined as three or more injections per day, who are not on insulin pump therapy, in whom assessment of insulin dosing may help the person with diabetes and the clinician to further optimize insulin regimen and avoid stacking of rapid acting insulin doses that could lead to hypoglycemia. And this was assigned this point, grade C, the best evidence level two. Next question asked was how about people who are benefiting from use of insulin pump without CGM? And your recommendation was that use of insulin pump without continuous glucose monitoring could be used to manage persons with diabetes who are achieving glycemic targets with minimal time below range or who report infrequent episodes of symptomatic hypoglycemia, but who are using self-monitoring blood glucose on a regular basis, which may be defined as at least four times per day for a person with type 1 diabetes. And the recommendation here was grade B, the best evidence level one. To advance the questions then, who would benefit from use of insulin pump with continuous glucose monitoring, as separate devices or a sensor-augmented pump? The recommendation was that insulin pump with CGM or sensor-augmented pump, or SAP, is recommended to manage all persons with diabetes treated with intensive insulin management who prefer not to use automated insulin suspension or dosing systems or who have no access to them. The grade A and best evidence level one. Next, the question was posed, who would benefit from use of more advanced insulin pump technologies, such as the low-glucose suspend, predictive low-glucose suspend, or hybrid closed loop? Here, the recommendation was that LGS, or low-glucose suspend, is strongly recommended for all persons with type 1 diabetes to reduce the severity and duration of hypoglycemia, while PLGS, or the predictive low-glucose suspend, is strongly recommended for all persons with type 1 diabetes to mitigate hypoglycemia. Both systems do not lead to a rise in mean glucose and lead to increased confidence and trust in technology, more flexibility around mealtimes, and reduce diabetes distress for both patients and caregivers. Thus, anyone with frequent hypoglycemia, impaired hypoglycemia awareness, and those who fear hypoglycemia leading to permissive hyperglycemia should be considered for this method of insulin delivery, grade A, best evidence level one. To follow up with the next recommendation in this category about the more advanced technologies, the recommendation was that automated insulin dosing, or AID systems, are strongly recommended for persons with type 1 diabetes, as their use has been shown to increase time and range, especially in the overnight period, without causing an increased risk of hypoglycemia. And given the improvement in time and range and reduction of hyperglycemia with AID systems, this method of insulin delivery is preferred above other modalities. For persons with diabetes with suboptimal glycemia, significant glycemic variability, impaired hypoglycemia awareness, or who allow for permissive hyperglycemia due to fear of hypoglycemia, such AID systems should be considered, grade A, best level evidence one. Now, there are special situations we also addressed in this guideline. So, let's move to that section. In what settings or special situations is use of diabetes technologies beneficial? Here, the recommendation was that continuation of either CGM and or the pump should be considered in hospitalized persons with diabetes without cognitive impairment, and ideally with the presence of a family member who is knowledgeable and educated in the use of these devices or with a specialized inpatient diabetes team available for advice and support. This was graded A, best level evidence one. To continue on the special situations, the next recommendation was that the real-time CGM is recommended for persons of 65 years or older with insulin-requiring diabetes to achieve improved glycemic control, reduce episodes of severe hypoglycemia, and improve quality of life. However, glycemic goals should be individualized due to increased comorbidities and reduced capacity to detect and counterregulate against severe hypoglycemia in this older population. Grade A, best evidence level one. Next special situation was for clinicians prescribing CGM as a tool to track glucose before, during, and after exercise in person with diabetes, monitor glycemic response to exercise, and help direct insulin and carbohydrate consumption in order to avoid hypo- and hyperglycemia. When this technology is utilized as part of AID systems, it can reduce glycemic excursions during exercise. And this was, again, grade A, best evidence level one. What about telemedicine? Obviously, it became a popular topic during this pandemic time. Here, the question was, what is the role of telemedicine in implementation and ongoing use of this advanced diabetes technology? The recommendation from the task force was that telemedicine, including periodic phone calls, smartphone web interactions, and periodic supervision by healthcare professional interactions, is strongly recommended to treat persons with diabetes, provide diabetes education, monitor glucose, and or insulin data remotely to indicate the need for therapy adjustments, and improve diabetes-related outcomes and control with better engagement. Again, grade A, best level evidence one. And then we asked about, what about smartphone apps? A very popular, obviously, topic. And the question, again, was posed, do smartphone apps have utility in management of diabetes? And here, recommendation basically said for clinically validated smartphone apps that they should be recommended to persons with diabetes to teach and reinforce diabetes self-management skills, encourage engagement, such as coaching, and support and encourage desired health behaviors, for example, healthy eating instruction or physical exercise tracking. Again, we're discussing clinically validated apps. And here, the grade B, the best evidence level one. And then I will pass it on to my co-chair, Dr. Sherd, for the safety considerations for advanced diabetes technologies. Take it away. Thank you, Dr. Brunberger. So, let's start by considering continuous glucose monitoring. With the use of CGM, clinicians should make a reasonable effort to ascertain that a person with diabetes is not inadvertently ingesting a substance or medication that will cause the CGM to deliver false or misleading information. Furthermore, clinicians should make a reasonable effort to make persons with diabetes aware of the theoretical risk of radiation exposure to diabetes technologies. This is grade C, best evidence level three. Furthermore, persons with diabetes who have a care provider, such as a spouse, adult child of a geriatric person with diabetes, or a parent of a child with diabetes, could remotely monitor glucose data, should be cautioned that remote glucose monitoring is dependent upon server functionality and that data interruption can result. Backup plans of having persons with diabetes revert to self-monitoring of blood glucose or methods to communicate CGM data to those who remotely follow will be needed until functionality can be restored. This is grade D, with the best evidence level of four. What about safety issues with insulin delivery devices? All persons with diabetes using an insulin delivery technology should receive comprehensive training in all aspects of its proper use and care. This is grade A, with best evidence level of two. Use of FDA-cleared and clinically validated smartphone bolus calculators in the absence of pump therapy is strongly recommended to decrease the frequency of hypoglycemia or severe postprandial hyperglycemia. Grade A, best evidence level one. Clinicians should also ensure that persons with diabetes using an insulin delivery technology are aware of the frequency and relative risk of pump malfunction. Receive instruction for identifying signs of pump malfunction. Know who to contact in the event of a pump malfunction and have a defined plan for emergency measures. For example, reverting to an insulin pen until there's remediation of the situation. And this can happen commonly with people having an infusion set failure or like a patient of mine last week on vacation who walked into a pool with his pump still attached. This is grade A and best evidence level two. What about non-physician prescribed integrated devices such as do-it-yourself, open artificial pancreas system, looping and other automated non-US FDA approved systems? Are they safe and effective in management of persons with diabetes? Clinicians should caution persons with diabetes who are using do-it-yourself systems that these devices have not undergone rigorous review by the FDA for safety and efficacy. This is grade B with best evidence level four and expert opinion. Importantly, we know Tidepool has submitted for regulatory review of the loop algorithm in January, 2021. But at this time, no DIY algorithm is FDA approved. Finally, what are the criteria for discontinuing the use of continuous glucose monitors and or insulin pumps in persons with diabetes? Clinicians should strongly consider discontinuation of insulin pump therapy based on an individual's ability to use it effectively and safely or based on the personal preference of a person with diabetes to discontinue this insulin delivery modality. This is grade A with best evidence level one. Again, the cornerstone of all these technologies is the desire of the person with diabetes to use a device and ensuring there is appropriate education on how to safely use these devices. Now let's finish by reviewing recommendations for implementing advanced diabetes technologies in practice. Who should prescribe, direct, supervise, and implement implementation of diabetes technologies? Initiation and use of diabetes technologies should be implemented by healthcare professionals who are trained, committed, and experienced to prescribe and direct the use of these tools. Clinicians should have the infrastructure to support the needs of persons with diabetes using the technologies. This is grade B with the best evidence level of one. How should patient education programs be structured? Training of persons with diabetes should utilize a structured, comprehensive training program that covers all aspects of safe and effective use of diabetes technologies. Grade C, best evidence level of two. Additionally, diabetes self-management education and support program specialists should assess knowledge base, review data with persons with diabetes, and provide individualized feedback for initiating therapy, adjustments, and or behavioral modifications as needed to support the attainment of individualized glycemic goals. This is grade B, an expert opinion, and best evidence level of one. With a rapidly evolving world of diabetes technologies, we also recognize that there are areas that remain to be addressed. These include, but are not limited to, further assessment of connected pens in the real world setting, continued safety assessment of diabetes technologies with particular attention on infusion set failures that can impact all pump systems, assessment of technologies in those who may be cognitively impaired or have hearing or vision impairment with the ability to remotely monitor data. And with some systems that allow for a patch pump to automate insulin delivery, it would seem use of such technologies could help those with cognitive impairments. Methods to allow remote monitoring of data and deliver care more strategically are also needed. As data is being streamed to the cloud and clinics can access this, how do we develop tools and strategies to flag those who need earlier intervention and optimization of therapy? And can this be done by using dose algorithms to help optimize treatment, like in the case of the DreamMed Advisor Pro, which can assess a wealth of data and recommend titrations that a clinician must approve. Additional future directions include continuing to conduct clinical trials with particular focus on outcomes like time and ranges, quality of life metrics and cost effectiveness. The importance of miniaturization of diabetes technologies will be critical as this will likely help with device acceptance and persistence. Extended duration infusion sets will also help so that we can change the sensor and the insulin infusion set at a similar frequency or even the development of a dual glucose sensor and insulin infusion catheter. And finally, the development of a full closed loop system could further reduce the burden for persons with diabetes. To conclude, I would like to share that the complete clinical practice guidelines are to be published in endocrine practice shortly. Throughout construction of these guidelines, the task force recognize with the rapidity of technological advancements, a living document with regular updates would be prudent. And most importantly, diabetes technologies may afford persons with diabetes a wealth of benefits. This education on devices available, setting realistic expectations of what devices can do and ensuring access for persons with diabetes will be essential. While Dr. Grenberger and I had the pleasure of sharing the task force recommendations, we want to recognize all the members of the task force who worked on this document in guidance for almost two years. Thank you for your time and we'd be happy to answer any questions. I didn't know. What is an efficient approach to interpreting CGM data? Hello, everybody. Hello, everybody. Thank you so much for that great presentation, Drs. Grenberger and Sher. We'll now go on to question and answer. And thank you. Please continue to place your questions in there. So the first question, are you recommending that time and range or GMI replace the use of A1C for overall glycemia assessment? So I'll go ahead and answer this one. Thank you so much. And thank you for the opportunity to be part of the consensus practice guideline development. It really was an amazing endeavor and we really hope this will be impactful for people's practice. As we think about time and range, I think currently we're not in a position where we can completely replace A1C with time and range. However, I'm hopeful that in future years we'll see further data gathered in order to allow for that recommendation to occur. Right now, what we know and really what we wanted to hone in on in the guidelines is that time and range and use of continuous glucose monitors truly allow clinicians to better understand how to optimize care for their persons with diabetes. It gives us a better picture. It's not just a number of whether we're hitting target. It tells us whether we need to attack time above range or time below range. And so we really think it's critical for clinical care. Great, Dr. Grunberg in particular, could you address what the guidelines really are and what they aren't? Because it certainly can be confusing as to what guidelines really are trying to drive home. Yeah, well, thank you again, Sandy, for moderating it. Obviously, I'm incredibly grateful to my co-chair, Dr. Sher and everybody on the task force and we had a pleasure presenting this. But I think it's very important to answer that question because I don't think people understand what is the purpose or difference between guidelines and rest of the stuff an organization publishes. And I think I tried to sort of address it in very beginning, if anybody actually listened, because ACE has been involved in position statements, drafting consensus statements, consensus conferences in this field for more than a decade. But there's never really been until now hardcore evidence, peer-reviewed quality trials published in sort of review literature to go after the hardcore evidence, which is required for a guideline. There is a very strict structure to guideline development. And as you know, ACE has been very strict about it. And the point is that we are looking at published, peer-reviewed, high-level evidence. So even though all of us are practicing endocrinologists, all of us would like to chime in with our own opinions. This is not an opinion piece. This is not a position statement. We had to stick to what actually has been published. And it's been frustrating in a way to all of us because we do this for a living. We know what's coming down the pike. We know it's going to be presented ATTD next week and ADL later this month and so on, but we can't put it in the guideline because it has not been published yet. So before people start sort of criticizing this, we are not aware. Yes, we are aware of what's going on, but again, remember to be a bona fide guideline. You have to rely on published, peer-reviewed evidence. And that's why all the 357 references in this paper have been graded. And so you can see both the level of basically the grading level, the qualities, but also what is the best level of evidence. So we don't have time to go into details of this, but it's a very rigorous methodology. And in order for this to be listed as a guideline, it has to follow the structure. Great, thank you. What are the medications that interfere with CGM? So I'll go ahead and answer this one. Some of the medications that are known to interfere with CGM, and again, it's really going to depend on the CGM type, but we would be thinking about acetaminophen and certain CGM, vitamin C that's greater than 500 international units, and then also hydroxyurea. Again, I don't think that's commonly used, but it is listed on the potential interfering substances. Great, thank you. Another question, do you have a list of apps that you find useful and would recommend to patients? Well, one of the problems in this field, again, remember, we had to rely on high quality peer-reviewed evidence. And as we know, I mean, there are tons of apps out there and patients are using these apps. The problem is that very few of them have been actually validated in clinical trials and published peer-reviewed trials. So most of these don't rise to the level which would actually allow us to list it as a strong recommendation. But we say a well-validated app, yes, if the patients know what they're doing, can be useful. I think one of the helpful things for people who look for specifics to start with, last year, I believe it was a January 2020 issue of Diabetes Care, actually American Diabetes Association and the European Association for the Study of Diabetes published their position statement on apps. So I think it'd be a good place to start. But again, there's such a proliferation, but again, remember in a guideline, we were stuck with going only with those which have been FDA approved clinical validated. Great, do either of you wanna tackle more or any information on the theoretical radiation risk? So I think that what we can say there is that it is absolutely theoretical. I think that it is related to the fact that it has not been tested. It is listed on the label, the manufacturers are going to need to claim that, but it's due to lack of evidence. And so we can't go beyond what we have in terms of what's currently published. Excellent in there. As far as can comment on the next question, can you comment on the accuracy of CGM in chronic kidney disease patients? One of the problems is when you talk about accuracy is that again, what do you use as a standard? And I'm not really aware of any data yet, unless Jen knows, which have been looking at this kind of question specifically to answer that. We do know that CGM is very valuable in people who have chronic kidney disease because I would say more prone to hypoglycemia. And when people sort of start pooh-poohing maybe the accuracy of CGM, I remind them, look at the accuracy of your finger sticks or how reliable A1C is, okay? So again, yes, we know, and it's not perfect, but somebody needs to do studies, very careful design studies to guide us in, okay, how do we evaluate someone's EGFR versus accuracy of CGM? And so I don't know if Jen knows anything more about it, but again, that really didn't rise to the level of a recommendation from the task force at this point. And I can't add anything. I don't know anything off the top of my head as a pediatric endocrinologist. We don't have many patients with CKD, thankfully. There was a question regarding, is there a list of clinically validated technologies for diabetes management? And then probably to tag onto that, if you want to do that at the same time, what about a process for clinical validation? So both comments on that. Yeah, one of the things is that, and that's important, I already alluded to that when we talk about apps, is that for clinical validation, remember all the medications and devices have to be approved by the FDA in the U.S. And to meet the FDA's approval is a pretty high hurdle. I happened to sit actually on the advisory committee of the FDA on devices. And I'll tell you, this is not an easy task. So for this to rise to a level, you're looking at usually at least two independent, prospective, randomized, ideal double-blinded trials, which have enough people, have hard core endpoints, and the methodology has to be very rigorous. The issue in this field is that number one, it's been incredibly rapidly evolving. Number two is that it's very difficult to do a double-blinded study, right? I mean, so again, you can do it with medications. So to get enough people in a high quality, randomized, controlled, prospective, long-term trial with hardcore endpoints in this field has been incredibly challenging. So I'm not the pessimist here, but I think people have realized how difficult this has been. That's of course one of the reasons why this guideline was being delayed, because we didn't feel, at least at ACE, there has been enough hardcore evidence in this ongoing field. And just as a reminder to everyone, for that exact reasoning, we did invite the FDA to our meeting this year for that exact reason, to be able to have their input as to what products are there, what was approved in this past year, and their thinking behind it. I found that very useful, and I'm hoping that we have that again next year. Yeah, I like it. And let me just point something out, because one encouraging thing was several years ago, actually FDA convened a consensus panel, and I represented ACE at that panel, in which the question was asked, will FDA move and try to accept time and range, all these metrics from CGM and quality of life measures, as a primary endpoint in the trials? Because as you know, until now, only A1C lowering has been used, for example, to evaluate drugs for diabetes. And at least back then, FDA was very encouraging, and they actually encouraged industry to start designing trials in which time and range, quality of life, and amount of time in hypoglycemia, would become the primary endpoints. Well, let me switch gears, and address the question about pregnancy. And there were two related to that. What are some of the issues that you run into when using CGMs in pregnancy, and then your opinions on whether this is something you use in your practice? So I can start out, again, as a pediatric endocrinologist, I often don't see this. We do a lot of counseling. But I would suggest that use of CGM in pregnancy is definitely rapidly expanding. We have indicated this in the way that we graded the evidence in our guidelines. And I think we are gonna see continued evidence to be built. I know that there are some randomized control trials going on currently to assess this. So if anything, I think we will be able to answer this question with stronger evidence. And I think that the importance of attaining targeted glycemia, both for the mother, neonatal outcomes, and imprinting is so evident. And so it's great that these trials are being done so that we can determine true glycemic variability, and tailor therapies to optimize the care of both the mother and the child. And if I can add, it's important, and we actually addressed it in the guideline, because some of the studies already have been done in pregnancy, that people realize that, of course, the time and range and all the glucose metrics are different, right? So if you actually look at the consensus from which we borrowed when we recommended the metrics, that there are different times in range, below range, obviously, for pregnancy. So it's also important when people start looking, remember that the time and range has been defined for general non-pregnant population, 70 to 180. But I don't think anyone taking care of pregnant ladies would tolerate a glucose of 179, for example. So I just saw a patient last week who is very, very meticulous about her control. And so she said herself, the time and range, 60 to 90. Okay, and because when we actually download devices, it's set at default 70 to 180, it looked horrible. I mean, she had like 26% time and range. And then actually I looked at what her device said, she was like 95% time and range, because she said it's 60 to 90. So I think it's important in pregnancy that we realize that, number one. Number two, as Jen pointed out, several studies are ongoing, because again, it's very difficult to, for example, rely on A1C during pregnancy. So to have CGM metrics to both protect against hypoglycemia is incredibly important. Wonderful, I'm just gonna briefly ask you to comment. Approval from insurance for these devices can be really a significant administrative burden. And although this isn't what was addressed in these guidelines, certainly anything that you want to comment on about addressing the problem. So if you don't mind if I can jump in. Again, I do this every day, and it's been interesting, obviously, this whole process. Remember from the very beginning, when people would deny insulin pumps because they were experimental, 35 years after being on the market. Then the same thing with CGM, it's all experimental. It's been getting better, obviously, much better. And one of the things which was sort of encouraging, I mean, not there was that much encouraging stuff about the pandemic, was that Medicare actually suspended some of these crazy guidelines they had for patients to be on CGM. Remember that, at least where I am, most commercial carriers are covering CGM if you are on any insulin treatment, no questions asked. But Medicare had this crazy thing, you had to be injecting at least three insulin injections a day and do at least four finger sticks a day. But remember, they only cover three finger sticks a day, but that's a different story, in order to qualify for technology for which you don't need any finger sticks. So that's been incredibly difficult. The older patients who needed actually more because of the dangers of hypoglycemia, hypoglycemia unawareness, what have you, were being denied. So during the pandemic, actually, Medicare suspended this. And so it's gonna be now up to regional carriers to make sure they actually carry out the Medicare policy. But that's been one encouraging thing, and hopefully the CGMs will be more routinely approved now. And just to piggyback on that, I do wanna say, I think that I am very hopeful that these guidelines will also encourage payers to change their stance. And I think that we as a community can continue to advocate and inform them of these guidelines so that they can appropriately change their coverage practices, because we can make it happen. And I'm gonna go on to the next question. So I can paraphrase it a little bit, the GMI, which is an individual average, and then the A1C, which is a surrogate marker that is usually looked at as a population average. The specific question then was that 30% of the time, it's about a 0.4% difference or even more, that if you had a patient that has a GMI of seven, which is a mean blood glucose of 154 and a measured A1C of 8.2, which would you base your intervention? Yeah, one of the things, and I would refer whoever asked that because it's a complicated question, I would ask whoever answered the question, is that we actually did that. And if you remember the diabetes care paper, which actually described what GMI is, addresses them. There are actually two clinical scenarios in that paper. And we basically say, if there's a discrepancy, if a GMI is sort of always lower than A1C, this is what you do. If GMI is always higher than A1C, this is what you do in an individual patient. Actually, there are two patient scenarios in there, if you can look it up. Because clearly, as you said, A1C is really not that helpful in an individual patient. But GMI, which is derived from that person's CGM, is. And it's very important that targets for that patient are based on the CGM, not the population A1C. And a follow-up to you, Dr. Sher, the vitamin C, is it a false low or a false high? False high. False high, great. And for our last two minutes, I'd like to take the privilege of giving each of you a chance to say, a lot of questions have come up about what we would like to see done in the future in this, and that there are still a large amount of gaps. For each of you, how would you prioritize the needed studies and which ones should be done sooner or later, so that if anyone in the audience is looking for their next project, they know what we need next? Jen, do you wanna start? Oh gosh, those are great questions. I think that we are a large enough community, we can tackle all of this. And I think that the excitement and meeting people through ACE and finding collaborators, we can go ahead and come at this all together. But I think that the biggest issue I could see right now is ensuring coverage of devices, because we know they help. And so I think that is a major advocacy issue to undertake. I think continued improvement of AID, automated insulin delivery, and smaller devices, and getting more individuals with diabetes on them will be of great importance, so testing in broader populations. That was a little all over the place, but thanks. No, I think it's incredibly important, as you said, we have to start looking at this special situation, because thankfully in 2021, I don't think anybody's questioning that CGM in type 1 diabetes, or anybody on intense insulin regimen is a standard of care. We're not debating that anymore. So I think we need to start addressing questions in broader population. What do we do with type 2 diabetes? What do we do with people who are not on insulin? And then where is the pregnancy? Where is the little kids? Where is the older adults? Where is people on dialysis? What are the special situations we are only alluding to, for which we said we don't have enough data? So hopefully industry will take the lead on coming up with new and fancier devices, but I think we are the ones as clinicians to hopefully carry out those studies, and we collectively, as you said, have enough patience and expertise to make it happen. Well, thank you for all the excellent questions. Thank you, Dr. Grunberger and Dr. Sher for leading this committee. Thank you to the entire committee for tackling this really timely and well-needed guideline. Appreciate it, and everyone, enjoy the rest of the conference.

ACE Clinical Practice Guideline

advanced technology

diabetes mellitus

continuous glucose monitoring

insulin pumps

glycemic status

intensive insulin therapy

special situations

safety considerations