All right, I think we'll get started. I'm Samantha Harris, and I am excited to be introducing the speakers for this talk. We are going to be talking about diabetes diets, and this is really going to be interactive. So save some of your questions for after the two speakers complete. And really, they're going to sit on stage and sort of answer. I'm sure there are a ton of questions for them. So our first speaker is Dr. Martin Greyjower. He's a graduate of Albert Einstein College of Medicine. He completed his endocrinology fellowship at Montefiore Medical Center in the Bronx and has been in solo practice for over 40 years. He's a clinical professor at Albert Einstein and an affiliate of Columbia University. He's a charter member of ACE and was in the first class of inductees as a fellow of the American College of Endocrinology. Our second speaker will be Amy Hess-Fischl. She is an advanced practice dietician and certified diabetes care and education specialist with 25 years of patient experience, focusing on all aspects of diabetes management. She's been working at the University of Chicago within the Department of Pediatric and Adult Endocrinology for the past 15 years. And she recently received the 2022 American Diabetes Association Outstanding Educator in Diabetes Award. Dr. Greyjower. So good afternoon. Hopefully you've digested your lunch. These are my disclosures. I'm on several speaker bureaus. So the talk was supposed to be ready in ACE's hands by April 1st. And mine was more or less on time, until three weeks ago when the New York Times had a headline, time-restricted eating doesn't work. That article was picked up by The Week magazine. It was picked up by many of the news reporters. My nutritionist in my office told me that she was getting countless patients coming and saying that we heard about this time-restricted eating doesn't work. And I realized that to leave this for the question and answer period would not be doing it justice. So the orange, or the green slides rather, are the slides that I inserted just three weeks ago after this article was published online called Calorie Restriction with or without Time-Restricted Eating and Weight Loss. And if you look at the article, and I highlighted the few things that I think are most relevant, it was a study of 139 patients. They were told to time restrict their eating to 8 AM to 4 PM. And both the placebo and the treatment arm were put on a calorie-restricted diet, 1,500 to 1,800 calories for men and 1,200 to 1,500 calories for women. And their conclusion was that a regimen of time-restricted eating was not more beneficial with regard to reduction in body weight, body fat, or metabolic risk factors than daily calorie restriction. And as I mentioned, The New York Times and other news articles carried the headline, Time-Restricted Eating Doesn't Work. So the question is, should you all just get up and leave right now? Or maybe consider, why is this paper of no relevance to this talk and of little relevance to your patients? So in order to transition into my blue slides, my real talk, let me remind you what were the learning objectives of this session. So number one is just to review what are time-restricted diets. Number two, to discuss what are some of the possible scientific mechanisms by which they might work. And number three, to review the literature on any safety and efficacy of these diets. So let's start out with the question, what exactly are we here to talk about? What are time-restricted diets? So we can divide them into intermittent fasting, which the most common ones are alternate day eating. Eat one day, you don't eat the next. Eat one day, don't eat the next. Or fasting for two non-consecutive days per week. So for example, patients don't eat on Monday and Thursday or Sunday and Wednesday. And the rest of the week, they eat. And then although many people, many patients especially, will tell me they're intermittent fasting, what they're really doing is time-restricted feeding or time-restricted eating. Really, the word feeding should be used when we're dealing with animals because you can't tell a rat in a cage, I'm going to put food down. But you can only eat it between this hour and this hour. They won't listen to you. Whereas humans, we have a kitchen full of food 24-7. We can tell the patients when they should or should not eat. So technically, we should use the word feeding for animals and eating for humans. But you'll see the terms often interchanged. And what it is is where we tell patients to restrict their food intake to less than 12 hours per day. Ideally, it should be 8 to 10 hours. And just to mention that they've looked to see if less than eight hours has any additional benefit, and it does not. So if you do have patients who are restricting themselves to six hours, they're just torturing themselves for no reason. The key point here is that if you look at the literature on time-restricted feeding, there are no restrictions on the actual food intake. We tell them when to eat, not what to eat. And the other key element here is that, and again, this is based on science, which I'll get into in a few minutes, that the time-restricted interval should begin at least one hour after waking in the morning and should end at least three hours before going to bed. So what are these time-restricted diets? All of these variations allow for non-caloric liquids during the so-called fasting period. So they're fasting from calories. They're not fasting from liquids. They allow to, in fact, sometimes should be encouraged, especially on the alternate day feeding. They should be encouraged to drink, but their drink should have no calories. So they can have black coffee, tea, diet soda, water, et cetera, but they shouldn't take in any calories. And just let me make a disclaimer, we're going to differentiate this from true or complete fasting, which are done for religious purposes, Yom Kippur, Ramadan, et cetera, or in a preoperative or a pre-procedure like a colonoscopy. And there, there are other medical considerations. So we are not going to be talking about any complete fasting. There are, of course, some similarities, but just to be on the record, we're not going to be discussing those issues. So there are, getting into the second learning objective, why might these diets work? And there are basically two theories that you need to know about, and I will tell you that this is the most exciting part of this talk. I was actually excited preparing for it because I learned certain things. Some of which I knew, but I amplified my knowledge. And some of it was new to me also. But this is the exciting part of the talk. I mean, I think I would like to say that anybody who goes into medicine, even if you're purely clinician, there's a little bit of a scientist in you. And we all like when something makes sense, right? Like, just to give an example, I would love to understand how I can take a piece of paper, put it on something called a fax machine, and it ends up in Europe exactly like it looks here. I, to this day, don't understand it. And I don't know if I ever will. But in medicine, the more I understand, the happier I am. So I think this is the exciting part. And there's two parts here to learn about. One is the circadian rhythm theory. And this applies specifically to the time-restricted eating type of restricted diet. And what it supposedly does is to improve circadian rhythm disruption from our normal Western eating lifestyles. And then there's the metabolic switch mechanism, which applies really to the alternate day or the two-day fasting type of restricted diet. And the bottom line is that switching from glucose as a fuel source to the use of fatty acids and ketone bodies. So let's go into these one at a time. So we'll start out with the circadian rhythms. So everyone learned in medical school that we all have a circadian rhythm, which we think about in terms of waking and sleeping 24-hour pattern. But we've come to learn that each organ has its own peripheral, the peripheral organs have their own circadian rhythms. Cellular function in many organs are programmed to respond to light, temperature, and nutrient availability in a circadian fashion. So that when these organs are exposed to nutrients when they shouldn't be, it disrupts the organ's internal circadian rhythm. The circadian clock directly or indirectly drives daily rhythms and the messenger RNA levels of a large number of genes across all organ systems. The master circadian clock in the hypothalamic suprachiasmatic nucleus responds to light signals and synchronizes circadian clocks in other organs via multiple signals, among them melatonin, changes in body temperature, and the autonomic nervous system, which is especially important in glucose homeostasis. Glucagon and insulin reciprocally interact with the clock components in the liver, so when your glucagon goes up, your insulin goes down, and vice versa. In adipose tissue, fasting time is associated with increased lipolysis, decreased free fatty acids, and a result of that, decreased inflammation. Now, as far back as 1989, it was shown that a late night meal produces a higher postprandial glucose compared to the same meal ingested in the morning, and the big question that nobody understood was, isn't a calorie a calorie? Why should the postprandial glucose vary depending on when you eat the meal? If I have a peanut butter and jelly sandwich, why should my postprandial glucose be higher if I eat it late at night than if I eat it for lunch? I like peanut butter and jelly. And the answer seems to be, at least part of the answer, melatonin inhibits insulin secretion. That is, I think, what's for most of you probably the novel idea to take away from today. Melatonin inhibits insulin secretion. So we now recognize that this rise in melatonin before bedtime inhibits glucose-induced insulin release from the pancreatic beta cells. Melatonin release begins three hours before bedtime and is present for one hour after waking, and therefore the instructions that we give patients not to start eating until one hour after they wake up and to end at least three hours before they go to bed. Any food ingested during these times will result in higher postprandial glucose due to impaired insulin release. And interestingly, 20% of the population in America are shift workers, which means they're up at night when their melatonin should be in sync so that they're eating in the middle of the night and therefore they're not releasing insulin properly. And 40% of the population has what's been called social jet lag, which means between 10 PM and 5 AM, they're completing work assignments, they socialize, they may care for family members, could be an elderly parent, it could be a kid, and they study. And this correlates with glucose intolerance, weight gain, liver disease, depression, and cardiovascular disease. So clearly, our lifestyle is causing a lot of medical problems. So what are some of the pivotal clinical trials with time-restricted feeding? So ten hours of feeding beginning at least one hour after awakening and at least three hours before going to bed. This study was done with patients. They were not told what to eat. They were simply told when to eat. And they were told they can eat any time during those ten hours. They chose what that ten hour interval was. So if they got up early, they could start early. If they went to bed late, they could start later. But those were the parameters. At least one hour after getting up in the morning, and it had to end at least three hours before going to sleep. And what they found was that they measured insulin sensitivity and it improved. They lost weight. Again, I wanna remind you, they were not told what to eat, only when to eat it. They lost weight, and an unexpected finding, they also slept better. So to summarize, time-restricted eating aims to avoid any caloric intake while melatonin is in the circulation with the resultant disruption in cellular and organ circadian rhythms, which is associated with decreased insulin secretion and reciprocal increased glucagon secretion, especially in the liver. So now let's transition to the second mechanism. And this has to do with ketone bodies. We all grew up thinking that ketones are bad for you, right? Diabetic ketoacidosis. Ketones, to us, are with the bad people. And there are three ketone bodies, three hydroxybutyrate, acetyl acetate, and acetone. These are produced in the liver. They are used as oxidative fuels in virtually all other tissues, in particular CNS, heart, and muscle. High levels of free fatty acids and glucagon stimulate and insulin inhibits hepatic ketogenesis. Fasting and physical exercise increase circulating ketone bodies. And what we've come to learn, three hydroxybutyrate is the most prominent of the ketone bodies under good normal physiology. And it's actually a good guy. It inhibits lipolysis, inflammation, oxidative stress, cancer growth, angiogenesis, forming new blood vessels, which we know is important for cancer growth, and atherosclerosis. It may contribute to increased longevity associated with exercise and calorie restriction. I think you're all aware that there are many people who run BMIs of 1920. They exercise like crazy, and there is some literature that they may actually live longer. During prolonged fasting, three hydroxybutyrate can replace glucose in the brain and can actually constitute more than 60% of the energy demand. It's been shown to increase cerebral blood flow by up to 30%. And this is being used clinically to reduce the incidence of seizures and epilepsy, and it's postulated to have a role in reducing dementia. SGLT2 inhibition in type 2 diabetes is associated with close to 40% reduction in cardiovascular mortality. We all know that. It's also associated with elevated levels of circulating ketone bodies. Again, we all know about the risk of DKA in patients with type 1 diabetes. It's been shown to increase myocardial blood flow and cardiac output in both in normal and in heart failure. Low carbohydrate ketogenic diets in patients with a metabolic syndrome or type 2 diabetes is associated with weight loss, decreased insulin levels, and improved cardiovascular risk profile. Ketogenesis may also prevent fatty liver injury, which we heard a lot about yesterday. So do ketone bodies play a role in the beneficial effects of intermittent fasting? So I'd like to quote two studies. One is an old study. In fact, this is when I was a fellow in endocrinology. Duke had a program. Those were the dark days of diabetes treatment, okay? When I started my fellowship, we had beef pork insulin, which many patients had allergic reactions to, so it wouldn't work so well. We had drugs called Oronase and Diabonase, which were first generation sulfonylureas. And they had a high incidence of hypoglycemia. And then there was a drug called PBI, which was taken off the market because of high incidence of lactic acidosis. PBI was the precursor of metformin. So we didn't have very many options for treating diabetes. And just to let you know how old I am, CGM didn't exist. And I remember my first year of fellowship hearing grand rounds on somebody presenting a new discovery called hemoglobin A1C. So what do we do for patients who had type 2 diabetes neurotic control? So Duke had a program, and they've published their data. You can look it up in the literature, where people would fly down to Duke for the weekends. They would completely fast them for 24 hours, give them just non-caloric liquids. And by Sunday, their blood sugars had come down dramatically. They would then go back home, wherever they lived. By Thursday, their sugars were back up. Friday, they're back on the train or the bus back to Duke. And they did this week after week after week. And they published their data that they were able to bring down their blood sugars. There was a more chronic observation. This was done by a fellow, David Horn. He's a cardiologist. When he published this study, he was in Utah, and now he's out here in California. And he published a study where he looked at the Mormon religion, the Latter-day Saints, as they like to be called. And for those of you who are not familiar, in the Latter-day Saints religion, they fast one day a month, typically a Saturday or a Sunday. They have a 24-hour fast, and they do this month after month after month. And he did a study where these were all self-reported. They asked people if they do keep the religion. And he then looked at cardiovascular outcomes. And he reported that those people who reported that they do fast one day a month actually had fewer cardiovascular outcomes. And this is being practiced, of course, over decades of time. So we had both acute and chronic data suggesting that fasting does play a positive role in health. What about studies in patients with diabetes? Now we're getting to the third learning point, what is the data? So there are actually only seven studies in the literature that were of high quality in control groups. The median duration was only 24 weeks. Of the seven, only one is a time-restricted eating. The rest were all intermittent fasting. A pooled analysis showed a non-significant decrease of only 0.11% in A1c. And a pooled analysis showed a significant decrease in body weight, but of just under two kilogram, or three and a half to four pounds. There were no changes in fasting glucose, lipid profiles, or blood pressure. So let's get back now to this New England Journal article. And again, in the yellow, I wanna highlight your attention to an otherwise busy slide. Look at the body mass index, okay? Both the time-restricted eating and the daily calorie restriction had BMIs of just under 32. Their glucoses were in the normal range. Now granted, if you look at the tertiles, 70 to 80, 80 to 90, 90 to 100, they were right at that 90 between the second and third tertile. And their A1c's were normal. In fact, if you look at the time-restricted eating group, even looking at the confidence interval, at the high, they were 5.7. So these patients, not only did they not have diabetes, they didn't even have pre-diabetes. Again, a busy slide, but these are the outcomes. And if you look at body weight at 12 months, there was a loss of 1.8 kilogram in the time-restricted eating. The body mass index went down by 0.7 in the time-restricted eating. Waist circumference went down, body fat mass went down, area of abdominal visceral fat went down, but none of these were statistically significant. Triglycerides also went down, again, not statistically significant. HDL went up, glucose levels went down, HOMA index went down, and the insulin disposition index went down. But again, none of these were statistically significant. So what is my analysis of this article? So number one, patients in this study had neither diabetes nor the metabolic syndrome. And that's why I said this article is of no relevance to this talk. Cuz this talk is on time-restricted diets in patients with diabetes. And even if we expand that to pre-diabetes, this paper still has no relevance. In addition, all patients were put on a diet. Now, I'll be honest with you, I'm a clinician like you are, okay? I see patients five days a week. I'm not a researcher. If a patient's gonna go on a diet, they're gonna lose weight, okay? The whole point of intermittent fasting, of time-restricted eating, is for those people who are not going to go on a diet. And so the concept was, let's tell these people when to eat, not what to eat. So when these people did a study putting the time-restricted eating patients on a diet, there really is no relevance to what really time-restricted eating is supposed to be. In addition, they fixed their eating pattern at 8 a.m. to 4 p.m. They did not correlate it to the time of awakening. Now I think it's fair to assume that most people did not go to bed before 7 p.m., so they may have fulfilled that end, but I would be shocked if everybody, all 139 patients, woke up before 7 a.m. So again, they did not fulfill the criteria that we usually, if you look in the literature on time-restricted eating, they didn't fulfill that either. And lastly, and I'm not a statistician and some of you could challenge me on this point, but while every parameter did not reach statistical significance, what are the odds that almost every metabolic parameter favored time-restricted eating? I showed you the data. Almost every parameter favored the time-restricted eating. So what are the odds of that happening? So my conclusion is that, number one, this paper was not relevant to this talk on time-restricted eating. In a patient without dysglycemia, they have normal glucose metabolism, who's willing to follow a calorie-restricted diet, adding time-restricted eating may have little additional benefit, but I capitalize little. I'm not convinced it has no benefit, but it may have little benefit. But I think the audience in this room are treating patients with dysglycemia. I think most of us are treating patients either with diabetes or prediabetes. So this paper really, in my opinion, has little relevance to this talk for sure and most of our patients. And again, a reminder, in true time-restricted eating, you tell the patient when to eat, not what to eat. So what about safety of the medications? So insulin sulfonylureas, as you know, have a risk of hypoglycemia. Certainly on the all-day, on the 24-hour fasting days, if patients are on insulin sulfonylureas, they have a high risk of going into hypoglycemia. And even during the 12 to 14 hours on the time-restricted eating, they also have a risk of hypoglycemia. And with SGLT2s, there's a risk of dehydration if the patient has inadequate fluid intake while fasting. So those are the real risks of these diets. And there's a real danger of inexperienced medical professionals advising intermittent fasting without adequate knowledge of diabetes and the various medications used in treatment. And just a very brief anecdote, I have a patient who was struggling with weight loss. I put her on a GLP. She did lose some weight, and then COVID hit. So she didn't leave the house. I mean, it was during that period of time where she literally did not leave the house, and she started to regain weight. And I did a telemed visit with her, and she was quite depressed. Depressed over COVID, depressed she couldn't leave the house, no social interactions. And on top of it all, she was regaining weight. We've all been through this together. So I did recommend that she speak to a therapist, and there's a therapist that I referred her to. He's a PhD in psychology, so he goes by Dr. So-and-so. She came into my office three months later, and she had lost seven pounds. And I said to her, wow, that's great. What did you do? And she said, well, Dr. So-and-so told me to go on intermittent fasting, and I've lost weight. And she did the two days a week of not eating. And I said, I'm just curious, did he ask you what medications you're on for your diabetes? And she said, no. I said, well, you know, wouldn't you have thought to ask, to say? She said, well, he's a doctor. I figure if he's recommending something, he calls himself doctor. He must know what he's doing. And I asked you a question. Even had she said to him, yes, I'm on one injection and two pills, you think he would know the difference between trulicity and lantus, or between loraglutide and tougeo? I mean, he's a psychologist. He may be very good at what he does, but you have the risk of professionals in the healthcare who are going to tell patients to fast, and she could have had a very bad outcome. She was on a GLP, and she wasn't on sulfonylurea, so it wasn't an issue. So what is my conclusion, to end my presentation? Time-restricted eating may work by not eating when melatonin is circulating in the body, and thereby prevent the disruption of the cellular circadian rhythm with its result in dysmetabolism, including insulin resistance and decreased insulin secretion. Intermittent fasting may work, at least partly, by increasing the release of the ketone body 3-hydroxybutyrate. For people with type 2 diabetes, there simply aren't adequate studies to demonstrate both efficacy and safety of either type of time-restricted diet. My personal conclusion is that time-restricted eating has little risk, has some sound scientific basis, and is therefore worth recommending with little reservation to anyone with type 2 diabetes. Intermittent fasting may work for some patients, but should only be recommended by someone knowledgeable in adjusting diabetes medications. And I want to leave you with some references. These are in your – you can get them off the slide deck. You don't have to copy them down. The first one is a review of time-restricted eating. The second one is looking at the metabolic intact of intermittent fasting in patients with type 2 diabetes. There's a review of the literature. The third one is really to tickle your scientific interest. It's a great article on ketone body, minor metabolite, major medical manifestations. I really enjoyed reading this article. It opened up my eyes, and I would strongly encourage all of you just to reawaken that scientific curiosity that you have. You don't have to get into the Krebs cycle, but it's worth reading. And lastly, for those of you who do want a hands-on primer on how to manage the actual medications, this is an article that I wrote with this David Horn on management of intermittent fasting in patients with type 2 diabetes, and it's a very hands-on article. Thank you for your attention. All right, so everyone having fun yet? Yes, yes. Now let's see if I can do this. Go back. Okay, so I don't know. I think my PowerPoint actually ate my disclosure slides. So, you know, my disclosures are, I work for, I do some consulting for Abbott Diabetes Care as well as Zaris, but my other disclosure is that I have tried the keto diet, and I just couldn't do it. So want to at least just highlight that first. So, but again, it highlights the fact, exactly what Martin was saying, is that these are options, and, you know, having multiple options for the people that we see is crucial, because we know not everyone is gonna fit in the same box, and so having some additional things to really consider is a good thing. Now before I kind of jump ahead, I know you have the, my objectives up there, a show of hands, how many of you have patients who have been asking about the keto diet? Okay, and again, keep the hands up, keep the hands up, you know, again, and then if you don't, how many of them have been successful on keto? Okay, so I just wanted to, just wanted to separate the wheat from the chaff here, because again, that's why you're all here. We want to really talk about this, because it is such a confusing concept for a lot of people, and so, you know, again, and one of these reasons why is because if you search keto on lovely Dr. Google, which I know all of you are so thrilled with, but you know, again, if you look at that, you're talking about millions of hits, and then if you just distill even further on keto diets for diabetes, we're still talking, you know, almost 27 million different hits, and lots of information and misinformation that's available. So, you know, again, that's why we see that people with diabetes are not being successful, because they don't know what to use as their end-all be-all. Now, what are some reasons why people with diabetes actually give to initiate or continue a keto diet? The top three, you know, weight loss, improved glucose control, it's an easy-to-follow diet, but there are other reasons, you know, in reducing inflammation, as well as improving mental alertness and increasing energy, but I want to start here and talk about, just give you a flavor of the myths that we do see, and then we're gonna circle back to this at the end, you know, because again, these are four things that all of my patients have said to me at one point or another, and again, just to give you a little background, as a dietician and diabetes care and education specialist, I see 95% type 1s, but again, I do see the complex type 2s that are on MDIs, pumps, as well as SGLT2s that we're going to be talking about, so what we tend to see, these that, oh, well, this is really the only way to lose weight, I have to do it, Amy, I need to do this, this diet, and this is the only way that's gonna, it's gonna help me, all right, let's talk about that, you know, it's gonna really bring my A1C down, because that's, you know, again, if I'm, you know, I really want to reduce my risk of those long-term complications. The third is, you have to eliminate all carbs, you know, again, and especially fruits and vegetables, and the final one is, you can eat as much of fat and protein as you possibly want, so, you know, again, many of you are like, I already know that, Amy, you know, but we're gonna circle back at the end and talk a little bit more, too. Again, just to give you a high level, you know, where have we come with the nutrition guidelines, you know, so, if we're talking late 1800s, very early 1900s, the Joslyn diet, 2% carbohydrate, you know, that was all we had, and the same with, you know, 1921, prior to insulin being, you know, banting at best, you know, again, still, very low, 20% of carbs, and then, as you get 1950s and onwards, 40 and up, and now, of course, is, we really don't know what is gonna be the best for each person. It is about individualization, and so, again, that's where we're seeing all of the nutrition guidelines as of now. Now, what makes it more complex, of course, when people say, I need to go on a keto diet, we need to remind ourselves of what is the current carb intake in the United States right now. Now, granted, this is NHANES data, you know, you know, a little under 44,000 adults, you know, 50% of their total calories are coming from carbohydrate. Again, we do see a decrease in the low-quality carb, but if I direct your attention to, you know, this here on the right, whoops, whoa, what just happened? Hold on, hold on, let me go back, this thing's getting touchy. There we go. The, on the right here, is that 42% of energy is still derived from low-quality carbohydrate, you know, so again, you know, it's, it's about the quality, it's not the quantity, so we do have to really keep that in mind, and that the majority of US citizens just aren't measuring up when it comes to that, and that's a bigger part of our problem. It's not just about the carbohydrate. Now, also, another sticking point here when it comes to keto diets is that the definition just depends on what you read, you know, so if we look at, you know, 2015, you know, the, when we look at keto versus very low carb, you know, 20 to 50 grams, 2019, under 30 grams is considered a keto, 2021, you know, greater than or less than 50, so, you know, again, I think that we've kind of hit our stride of, like, yeah, under 50 seems to be where we want to be, but again, a lot of people, you know, there's differing opinions of what is considered keto, and then, you know, even if we drill down even further of what's, you know, different opinions about what is low carb, you know, versus reduced carb, so again, trying to kind of get on the same page is, is difficult, you know, again, depending on, on what you read. Also, when we look at the differing opinions on macronutrient composition, so, you know, certainly the first two that you see here, that's, those are classic keto for epilepsy, you know, and again, that's between 2 and 5 percent versus modified Atkins, you know, 5 to 10, and then keto under 10, so, you know, again, when we look at all of this, it just really, again, depends on what you're reading. Also, you know, lots of pretty pictures to depict what a keto diet is, depending on where you look. Also, one thing that we desperately need is more research, so more research on the keto diet, so, you know, again, as of March 30th, there were 164, and I checked this morning on PubMed, and it was 228, so from March 30th until now, you know, again, we've seen more and more keto published articles, so why is that important? Well, the more information that we could get, the more information that we can then pass on to the people with diabetes. Now, looking at improvements in A1C in type 2 diabetes, and I want to highlight one thing here. I left this in, so this, the Bizano 2014 paper, these folks did not have diabetes. I put it in there as a comparator, and so again, I'm going to show it in the weight as well, just to kind of highlight, you know, again, the number of subjects that, as well as a percent of female, and again, really want you to kind of direct your attention to that percent of female, because, again, certainly this 2010 paper, you know, had a lot more men, you know, in there, so that'll be a very interesting kind of, you know, conversation when, even when we're looking at weight, you know, versus most of them, it was going to, it's more heavily weighted towards females. Why does that matter? You know, again, I'm not saying that men are not good at taking direction. I want to be very clear on that, but, you know, again, for the most part, we tend to see that, that more females and weight loss, you know, again, it's a, you know, it's something that is more inherently, you know, they're involved in, so, you know, again, we do tend to see this with all of the weight loss studies, as well, but certainly, what do we see with A1C? You know, again, obviously, the higher the A1C, the further the drop, but, again, even if we take a look down here, you know, some folks that were under seven A1Cs, you know, they were still having some, some nice drops, as well, so we do, we can say that, yes, the keto diet, reducing carbohydrate, of course, is going to impact glucose control. It's going to reduce A1C. We know that. Now, if we look at weight change, now, as I said, you know, again, I kept this, this 2014 paper in just as a comparator, because, again, this was not, they do not have diabetes, but, again, just to kind of look at all of this, and certainly, when we kind of look at the, the whole spectrum, you know, we're seeing, you know, again, upfront, initial weight loss, of course, is always going to be better, and that's why I also wanted to just kind of direct your attention even to the 2016 paper that, you know, at four, four months, of course, we always see such prettier numbers in a very shorter amount of time, but as time goes on, you know, 12 months, 24 months, you know, again, we're not going to necessarily be seeing as, as much, with the exception of the, the Yancey paper, you know, again, that it's going to be very similar to all the other types of diets that are available for people to use. Now, impact of keto on type 1. So, again, that's, that's what I work with the most in, in the patients that I see, you know, and so, certainly, as you saw historically, we're talking very low carbohydrates because of, of no insulin, you know, and the one problem, and that's why I'm so excited to see more and more papers coming out on, on keto, is that there's very little evidence that shows that there is any benefit to keto in type 1s. So, but again, the, the one thing is, you know, looking at quality of life as well as weight change and A1C. So, again, certainly the, the bottom line is more studies are needed, just like with intermittent fasting as well. And children. So, again, I also work with pediatrics and type 1 as well, you know, and again, so when we look at kind of the the history, you know, of course, you know, epilepsy was the, the major reason why keto diets were done, but case studies with epilepsy and type 1 in children did produce reductions in A1C, as well as postprandial glycemia and total daily dose of insulin. So, again, not that difficult to make that leap. We know that by reducing the amount of carbohydrate that a child is consuming, we're, we're going to be decreasing glucose A1C, as well as their total insulin. And interestingly enough, a paper that was published in 2018 of self-reported data, mind you. So, again, really the 300 responses, they all self-reported that these children were consuming, you know, under 50 grams of carbohydrate. And, again, their A1Cs were, were quite low. Now, again, I just had a, an appointment with a two-year-old T1D and the mother, and while she finds it very difficult that we were having that conversation, she really felt that she was giving her child a very low keto diet. And, you know, again, as we were kind of going through, she was still consuming about 80 to 100, but she was convinced that she was following keto. So, again, it's really kind of understanding and, and having that conversation of there's nothing wrong with having lower carbohydrate, but we just need to level set and understand where, you know, where they are and, and making sure that there's still adequate amount for growth. Now, this brings me to the kind of the assessment of nutrient status, because, again, that's really where the, the bigger situation lies, because most people do tend to find that on a keto diet, they want to just eliminate everything. And then we're going to be talking about there is a potential for some deficiencies. But one thing that we do have to understand is that a well-planned, very low-carb meal plan can be perfectly acceptable when it comes to micronutrients. But, again, it's about the well-planned and having that discussion with the, with the person with diabetes to really help them to make sure that they are continuing to have vegetables, that they can have some fruits, and we'll talk about that in just a few. But it is really important that we're kind of dispelling that myth of, you know, again, having a keto diet is, is not necessarily the best thing in the world, but it's a keto diet that's not necessarily well-planned could be a recipe for disaster in some of these folks, especially when it comes to their nutrient status. So the other thing that we, we do tend to find in the keto diet for long-term, you know, again, we do see that supplementation may very well be needed. And so, again, it's really important to keep that in mind. And even in that initial, you know, under 20 kind of ketosis phase, they may very well need multiple vitamin, potassium, you know, sodium, you know, again, so, you know, we can even discuss a little bit further the, the amounts of that too. But these are all the things that, while of course I'm a dietician, so of course I would say, yes, I'd love for all of your patients to be seen by a dietician, but I do understand the precarious nature of the keto diet and that there are some very strong opinions about whether it is a viable meal plan to be promoting or not, you know, but again, I am of the mindset that the person that's in front of me, you know, I work for them, you know, and again, I need to make sure that, of course, they're safe, but, you know, again, if I can help them instead of having them do some back-alley keto diet, you know, again, that's the most important thing that we have to really, you know, really convince the nutrition world as well. Quality, as I said before, we have to focus on fiber, protein, and fat quality, you know, and certainly when it comes to the fiber, we do want to make sure that we're encouraging larger amounts. Now, mind you, the recommendations are 20 to 35 grams a day for the general population. The vast majority of folks in the U.S. are eating less than 20 grams, so this does mean that they're going to be, you know, increasing their amount of fiber, especially in the vegetable world. Now, when we look at protein versus fat, now, the amount of protein that is consumed and the amount that they, that each person should consume is going to be very individualized, but in general, again, you can kind of look at this in kind of a graded fashion, you know, again, you could do the calculations, but really with protein and fat, you, there is not necessarily a limit sometimes just to get them kind of started, but, you know, the bottom line is lower saturated fat choices for, for protein itself, and when we look at fats, again, unsaturated fats, we want to limit the trans fat, the saturated fat as much as possible, and choosing, again, some, you know, a healthier choice for them to get the calories that they need. Good Lord. There we go. What just happened? I am having, oh, we'll just go next there. Yeah, that's perfect. Nutrition facts labels, everyone's favorite thing, and again, certainly taking a look at on the nutrition facts label, directing their attention to the carbohydrate area right here. And again, I want to just say, steer folks away from counting net carbs. That's kind of a fuzzy science. Again, we want to make sure that they are counting the total carbs itself, but also taking a look at the fiber, as well as the sugar alcohols that are in there. And we'll talk about that in a little while, too. Now, use of SGLT2 inhibitors with keto. So again, a paper in Diabetes Spectrum did highlight some of the protocols that are out there. And all but one was saying, do not do a keto diet on SGLT2s. Ann Peters did put her recommendations of at least 100 grams. At the University of Chicago, again, we have a protocol. It's unpublished. But we have found that greater than 70 keeps them out of the hospital. And again, as I said, we have a lot of type 1s that are using SGLT2 inhibitors off label. And initially, when I was thinking last year, there were four that they were doing 30 to 50 grams. And they all went to the ER for euglycemic DKA. And so again, once we kind of re-evaluated and just kind of bumped them up to about 70 grams, they were still having weight loss. But again, they did not have any ketones at all. So that is what we have been finding. So that is helpful, too. So let's circle back to the myths and truths. So again, we know that it's not the only way to lose weight. Again, we know it's one of many options. And that's the key. It's one of many options that are available. One thing, though, that we do have to kind of level set for folks is that it may not be as effortless as people think. Again, like Martin with the time-restricted eating, again, that is effortless. Again, you just, here, this is when you have to eat. We don't have to think about anything else. There's a little more involved here. But I'm not saying that it's not successful. But we have to choose the right people for keto. Who doesn't do well on keto? In my experience, the folks that have tried every single diet fad possible because they want to lose weight, I have found that they do not tend to be successful. Because they are looking for something quick, easy, and they want it done yesterday. And so again, I try to steer them to something else. Again, who will be a good candidate? Someone who is willing to kind of think outside the box and try new things. Because again, while there are a lot of keto recipes out there, I strongly encourage people to look at the nutrition facts label. Most of them are really, really high in saturated fats. So again, it's good to look at what other vegetables and things that we can add to some of these. But there's lots of options that people can have that are keto-friendly. Again, what have we seen from the literature that it significantly reduces A1C? We have some modest reductions. And again, I'm finding that even clinically as well, that we're really not seeing. If someone is an 8.5, sure, we can maybe get them down one. But again, if they're already 6.7, 6.8, 6.5, again, they might only go 0.2, 0.3. You can eat as much of any type of fat and protein as you want. It's about the quality. And then finally, eliminating all carbs. We want to make sure that we're including fruits and vegetables. So some final thoughts. When it comes to the best recommendations, again, we have to look at somewhere in the middle of the, if they can't follow under 50, looking at between 70 and 130. Those with SGLT2s, at least in our clinical practice, greater than 70 grams. We have to also consider that not everyone is going to be able to follow this long term. Again, but short-term games could certainly lead to increased motivation for them to keep going. And then definitely assessing that entire eating pattern and looking at, are they going to be candidates to be having some kind of supplementation? And with that, we're going to start with some questions. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. I doubt it out, you know, that's fine too. I do, and Jeff Thalman from New Jersey. Thank you for a great discussion. Two questions based on a little different topic, but melatonin, with the increased use of melatonin by our patients for sleep, has there been any evidence about melatonin raising glucose levels overnight? And number two, in my experience with my patients with diabetes and weight issues, the nighttime eating is a major issue, right, after that 7, 8 o'clock when things really fall apart. Do you think a lot of the benefits of the time-restricted eating is based on them just not eating after a certain time as opposed to any of the metabolic stuff that we hear about or the waiting until, you know, skipping breakfast and stuff like that? So as far as the melatonin pills, I wondered about that myself. I could not find anything in the literature, so I don't know. What I would suggest, if it's a question, is especially if your patient is doing finger-stick glucoses, a simple thing you can do is for that given patient, ask them to do their, let's say, fasting blood sugars for a week and then not take melatonin for a week. Don't change anything else and see what their fasting blood sugars are for the next week and just do an average of seven numbers and seven numbers. If they're within 10 points of each other, then probably it's not affecting them. But if it's more than 10 points, then the melatonin may in fact be affecting their metabolism, then maybe they should try to cut it out. But there's no literature that I'm aware of. As far as your second question, I think the whole point here is, and that was the issue about eating late at night, the observation that that same peanut butter sandwich eaten at 11 p.m. will give you a higher postprandial glucose than when eaten at lunch requires an explanation. Those are the facts. The question is, why is that? The current thinking is that melatonin may be part of the answer. I'm sure there's more than one answer, but they very nicely have shown that melatonin does cause insulin resistance. I think the issue is that we want to try to get our patients not to eat while melatonin is circulating. Go ahead. Hi. Henry Salada from University of Alabama, Birmingham. I have many patients with type 1 or type 2 diabetes who are pregnant. I've been always wondering, what's the definition of the minimal amount of carbs for them? I mean, we're talking about 130, 100, 150. I know the literature is not very strong, but what are your thoughts? Usually, 130 is a minimal, because I do have a lot. I've had six pregnant women who all had their babies at the same time. They were all on low-carb prior. Yes, we bumped them up to 130. Again, that's typical what we do for the type 1s. Great set of lectures. As you mentioned, there's a lot of data still incoming for these keto diets. As clinicians, should we be pointing patients towards diets that actually have primary and secondary prevention, like the Mediterranean diet, versus these kinds of diets that actually don't have any true efficacy? It's just potential postulation. We already have good evidence for Mediterranean diets. As clinicians, I feel we should be pointing them towards those diets, which you've already proven. Thank you. Martin, did you want to say first, or I'll go? Certainly, when we look at the nutrition recommendations, so 2019 paper, they looked at, of course, we know Mediterranean. We know DASH. Again, they weren't discounting time-restricted eating. They weren't discounting keto. They were saying that they can be considered viable options in the right person. Again, I don't think that we should discount them. I think that, again, this is an exciting time to really see long-term what can this do. I would just, the way I would answer your question is that the old saying, the best diet is the one that works. If a patient asked me, or if I was sending a patient to my nutritionist that I work with to recommend a diet, I will recommend a diet that has some scientific basis. But if the patient approached me and says, I'd like to do a keto diet, I'm not going to try to convince them to do something else just because that has the literature, because if their mind is set on the keto diet, that's the one that's going to work for them. I'd rather they follow that and lose weight. Agreed. I may not be promoting keto unsolicited, but I have so many that are asking. Again, it's about gaining trust and really having that discussion. The first question is, could you comment on SGLT2 with intermittent fasting and the risk of DKA? And then the second question, could you comment on the keto diet on a type 1 diabetes with DKA risk? As far as the SGLT2, there is no data that I'm aware of of intermittent fasting and SGLT2 causing a problem, but that could well be because nobody's really looked at it. I am very comfortable with SGLT2s and time-restricted eating. With intermittent fasting, where patients are literally fasting for two days a week, or if it's alternate day, it's even more than that, my suggestion would be to just watch them a little more carefully. You can actually measure ketones in their blood or in the urine. I would do it cautiously. What I may not have emphasized in my talk is that we always have to be aware of just global recommendations as opposed to, what do I do with my patient in my exam room? I feel that intermittent fasting should not be a global recommendation because there are too many practitioners who don't know how to manage it and it would be dangerous. I think TRE is safe that anybody can just recommend it, but for you with one patient in one exam room, I think you could use the SGLT2 with intermittent fasting as long as you're watching them and if you see them developing ketones, maybe it's time to increase their carbohydrate intake. As for the keto and type 1 and DKA, again, I think that the whole premise behind bumping that it's not keto. Again, we really do need to be recommending a little more carbohydrate and that's why even at the University of Chicago, we are recommending just greater than 70 grams, which still seems to have just as much benefit with their A1C and whatever weight loss. Again, they're still having, it's not 11 kilograms. Again, they might be having 4, 3, 4 kilograms and again, without any issues with euglycemic DKA. I think you were next. Go ahead. I know you talked about the two-day fast. I do have several patients that have wanted to extend that into up to a five-day fast. I'm very hesitant with that, almost to the point where I'm like, are we talking like psychiatry now? I just wanted to get your commentary and if there's benefit to that. To eat two days and fast five days strikes me as being a bit extreme. I could see someone doing that to get started. If somebody was really out of control, they come to their A1C as 11, 12, 13 and they need that motivation to see those blood sugars come down from 350 to 120. There, if you wanted to do something extreme like that for two weeks, their blood sugars will come down very quickly as the Duke program showed and there's nothing that motivates a patient as much as success. When they see those sugars come down by 200 points, when they see that they've lost a couple of pounds in the first two weeks, some of which is probably dehydrational, but that still motivates them. Then start to reintroduce carbohydrates, healthy carbohydrates and let them say, okay, let's go from five days of fasting, let's maybe go to every other day and let's transition you. Maybe then go to time-restricted eating. That would be my recommendation. Thank you. There have been a few studies looking at diabetics with CK, chronic kidney disease 1 and 2. What is your experience with recommending this diet in patients with chronic kidney disease at later stages? I'm asking because the ketones might be increasing the risk of an acidotic state. I'm not aware of any data, so I can't quote the literature. I can just give you my opinion. I think that as long as the patient stays hydrated, I wouldn't be concerned. My big fear would be dehydration. When you hydrate, you're going to clear the excess ketones in the urine. But my fear is always that somebody, when they're not eating, they're also not going to drink. I would tell those patients, give them a number. You need to drink 40 ounces of water a day, 50 ounces. Pick a number that you're comfortable with. Make sure you're getting that amount of liquid. If they do, I think they should be okay. Remember, you need very little insulin to keep you from going into ketoacidosis. The amount of insulin you need to control ketoacidosis is 10% of what you need to control glycemia. You need very little bit. Thank you. Thank you both so much. I had a couple questions, just two. One, are you aware of any literature on efficacy for time-restricted eating every day of the week versus maybe five days out of the week? Because some people want to take a couple days off, like the weekend or one. And then the second question, practical, do you have any smartphone apps you would recommend that you advise your patients to use to keep track of all of this? As far as the first question, no. I don't know of any literature on doing TRE for less than seven days a week. But in reality, I think that probably most patients are not keeping it seven days a week any more than they're taking their blood pressure pills 30 days a month or their Synthroid 30 days a month. Theoretically, it should make a difference. And very often you have somebody who, due to a lifestyle, for example, there may be every Friday, because a family, they get together with their family for a big meal and they can't not eat within three hours of going to bed because the family first. So I say, okay, so do it six days a week. And you know what? They do lose weight. Would they lose faster? Maybe. But if they're losing weight, it's not a race. I always tell patients it's not a rat race. You lose, I'm a happy guy. And as far as any apps, you'd have to ask my grandchildren that. The answer is I don't know. If anybody does know, please help me out here. Amy, do you have any apps? I have lots of grandchildren, but I have no apps. Because again, I mean, for time-restricted eating, I don't. But I mean, again, it's, you know, but for keto, you know, honestly, our old go-to is MyFitnessPal, Loseit. You know, those are, you know, the easy ones just for documenting. But I mean, we also have to acknowledge one really big piece here is that, and as a dietician, I'm readily admitting this, is that people don't know how to carb count. You know, and so, you know, again, that's become more evident with AID. You know, again, like, I don't know, you know, what am I supposed to put in, you know, pre-bolus? And so I think, you know, again, it's all about can we just, how much are you reducing the amount that you're having? So again, nothing keto-wise at the apps that I would recommend, though. But, yeah. Thank you. Beta blockers are known to suppress melatonin. How does that affect your patients who are on beta blockers? Do they still get the weight loss? I don't know. First of all, I wasn't aware that beta blockers suppress melatonin. I mean, are you aware of any data that people who take beta blockers don't sleep as well at night? Has that ever been shown? I mean, beta blockers have been around forever. Have you ever, were you aware of any such studies? Yeah, there's been quite a bit presented at the sleep meetings. I can't tell you when in specific, but it's pretty common knowledge. You know, fascinating question. You're going to stimulate me to look it up. And if they invite me back at ACE to speak again, I'll answer your question. But it's a great question. I will look it up. I don't know. All right. Amy, I have a question for you. Sure. There seems to be a subgroup of patients who follow a very low-carb diet who end up being these, like, hyper responders when it comes to changes in lipids, like very high total cholesterol, predominantly LDL. What is sort of your program's take on these patients? With keto itself? You know, I mean, again, certainly, you know, I'm a fan of drugs first, you know, with the endo that I work with. But, you know, again, really, really taking a good look at what their meal compositions look like, and then, you know, looking at their unsaturated fats, really taking a look at the types of protein that they're consuming, and reducing the saturated fat as well, and making sure that they've significantly limited the trans fats. But, again, this is a, you know, it's a lot of work. And so, again, I think it's, you know, that's sometimes, like, would it be easier if they went, you know, vegetarian? And so, you know, that is a conversation that we have of, you know, there might be a better option that can help with the, you know, with your cholesterol, and, you know, we don't have to go through all of this work. It seems like a lot of the leaders in the, you know, keto diet world, physicians, also seem to be anti-statin. Well, and that does, I have to say, a lot of keto, you know, it's considered natural, you know, and so then that gets into that conversation of, you know, non-nutritive sweeteners and, you know, sugar alcohols. And so that's why, for the most part, if somebody is on a keto, they don't like recommending aspartame, you know, again, they'd rather go with monk fruit or stevia, erythritol, you know, again, all of these that are a little more natural than the other non-nutritive sweeteners. So, you know, that could very well be the, some of their reasoning. But I don't want to put words in their mouth. I have another question for Dr. Greyjower. One thing I see very heavily debated in the intermittent fasting world is what is really considered fasting and what's considered breaking a fast. I know you mentioned no calories at all, but some people dispute cream, artificial sweeteners, milk in their coffee, stuff like that. Do you have a stance on those types of things? So I think the one thing that you want to really eliminate the most is the carbs because it's the carbs that's going to stop the ketosis from developing in terms of the intermittent fasting. And in terms of the melatonin, it's causing insulin resistance, which has much less of an effect on protein metabolism. So if you wanted to be really strict about it, you don't need any calories. If you want to be a little more lenient, at least try to cut out the carbs. And if the only carbs you're going to have is a little bit of milk in your coffee, like I said, if that's the diet they're going to follow, then that's the diet that's going to work. So we always start with the ideal and then we whittle it back to get our patients to comply. And if they comply with that, then great. We have three minutes. Any other questions? All right, I'll ask more questions then. Amy, I'm curious to know, so I work primarily in weight management at the Scripps Clinic. A lot of patients gain rapid amounts of weight and it's hard to often find a precipitant, a life event, a medication. A lot of times it seems like the precipitant was having gone on some type of restrictive eating plan to start with. And it seems, especially with ketogenic plans, that sort of the yo-yo effect might even be more pronounced than in other more moderate forms of restriction. Have you seen that? What's sort of your approach? In the type 1s that have gone on very significant reductions and then they go back, yes, we are seeing a much higher increase in their weight and it really upsets them. And so again, yes, I do feel that what I'm looking back at all of the folks, that yo-yo dieting is just really, really exacerbating if they just eliminate. Instead of, you know, they go from that nothing to all. And so even, so the American, if you haven't seen it, the American Diabetes Association did just come out with like a 27-page little booklet for healthcare professionals on low carb and very low carb that has some really nice practical information that, you know, again, I can't remember how much it was, like $15 or something like that. But it's worth the money to get it because, again, it does kind of show that you have to gradually increase those carbs. You can't go from 20 to 50 and then go back to 170 and, you know, go drinking with your friends, which, again, I have a lot of, you know, my young adult females that are like, well, I don't know why I'm losing weight. I have to have my three margaritas with my friends. So, you know, again, I think that it's, you know, it's important that they understand it's about that gradual and that could very well be contributing. Yeah. All right. Well, thank you guys. Excellent talks. Thanks, everyone.

time-restricted eating

TRE

diabetes management

melatonin

insulin resistance

postprandial glucose levels

intermittent fasting

circadian rhythm theory

keto diet

glycemic control

nutrient intake