Sleep Inflammation and Metabolism: Sleep-worthy Connections!

[Music] good evening thank you for braving the weather and and making another mini med school it's really a pleasure to be here and to talk about something that I'm really passionate about which I imagine will come through in this talk the importance of sleep and so I you know I will admit that I didn't choose the topic for this that I'm really excited to talk about it because it's a really important one and really fits well within the the med school framework that you guys have been going through though I was kind of struck by this sleep worthy connections and so I was thinking about that on the way here and I thought you know I guess it could be taking kind of one or two ways right like sleep worthy it's really great or like sleep worthy like we could sleep through them because it's like and I but then I was reflecting on that and thinking like either way you win right like like I got the point across like the enthusiasm about sleep and then like the importance of sleep kind of the the need to kind of take the time for sleep and and make it a value in your life and that's something that I'm I'm I've cared deeply about and one of the reasons that I really care about it is because it it has kind of dramatic significant impacts on your health and well-being including your metabolism and then kind of your immune system and we'll talk about both of those things today first lay the foundation of kind of what is sleep how do we define sleep how do we measure sleep and then kind of move into what is the the bulk of this talk so sleep and metabolism and particularly thinking in the context of if you you know if you sleep less do you way more sleep an inflammatory functioning so inflammation has become kind of what is thought to be one of the central biological pathways through which a lot of things in the world and our behaviors affect our risk for disease and sleep seems to be strongly related to that and so we'll discuss that a little bit more but not to leave on kind of a sad note about oh I'm not getting enough sleep I've got enough sleep murder in my whole life now what you know that there's kind of emerging evidence on sleep interventions and like ways in which we might be able to move sleep in a positive way to actually improve our metabolic health so first you know sleep who does it well it I'm going to guess that everyone does so we get a hundred percent of you sleep it turns out that a third of a third of your life is spent sleeping and for some that's like oh no you know that was a third of life I could have been living well it turns out that most of you don't do enough of it that's a fact and we know that but then also that that sleep that amount of sleep that one third of your life is critical to kind of make the most of the time that you're awake so it's kind of a way of optimizing your functioning and so you know it turns out if you live to 75 you typically sleep about 219,000 minutes hour hour excuse me Spanish sleep so that's that's a lot right but you know most people don't do enough and so in fact if we look at this map this is census data so you know done through the CDC to look at the variation that we see in the amount of sleep that people get and so this is percent of people who don't get seven hours of sleep per night they get less than seven hours per sleep per night and it turns out that the American Academy of Sleep Medicine and the sleep Research Society have come up with a criterion for optimal for maintaining optimal health adult health and so that's getting at least seven hours of sleep and you can see there's no place on this map and so this is at the county level where people are under around 20% so of the population and in fact if we look at San Francisco you can see that there's still the same kind of variation and you know as in most cases San Francisco is healthier as a city than many other places in the country but we still see that there are places where there's hot spots and what's interesting for me and I'm not not a focus of this talk is that these hot spots in these areas where we see were sleep kind of map on to lots of other social factors that we think dry variation and sleep and then also underlying this sleep we see the same kind of patterning for different health conditions that we know is related to not getting enough sleep like diabetes cardiovascular to see disease and the like okay so so what is sleep I mean there's you know we kind of have this on standing of what it is we do it but it is kind of magical it is something that we kind of you know I saw I see patients with insomnia so like like Ashley and I don't know she's mentioned this before we both have kind of clinics that that treat people that have sleep problems and one of the challenges with sleep and especially when it's not working correctly for you is that you really get focused on how to fix it but sleep was never something that you did it's not something you do it like comes to you right it's it's this reoccurring experience that's this altered law lack of consciousness and this inhibition of sensory activity so you kind of are kind of disengaged from the world though not completely right because you can certainly be kind of startled you can kind of have that light sleep you know that experience of having to get up early to catch a flight for instance you know it's it's not your whole system isn't offline but it is this reduce interactions with your surroundings and so that's what we use as a working definition but it does have some signatures to it so I do want to talk about this so the way that we measure it is it's certainly not a static state that happens like you're not awake or asleep it's actually very dynamic and so this is a what's called a hypno gram and what we can see is we cycle through sleep various aspects of sleep across the night and so we start at it's it's typically in kind of 90-minute cycles and what we see is that we go from awake which is at the top of that the the y-axis of this graph down all the way into deep sleep and so it goes from stage 1 to 2 to 3 stage 3 is of what's called non REM sleep as is the deeper sleep that slow-wave sleep that that type of sleep that when you wake up in the morning you feel really rested right it's that kind that you're always chasing basically and so you know you go into that and you kind of cycle up into a wakefulness it turns out that we wake up lots of times during the night most the times we don't remember it but then as you can see that red line that's another aspect of sleep that's also really critical so it's called rapid eye movement sleep so this is REM sleep this is sleep where is associated with dreaming but it's also really associate with lots of other functions so you know emotional memory memory consolidation REM sleep seems to play an incredibly important role there and so what you can see is that as you go through the night you get less deep sleep in the second half of the night and more REM sleep in the second half of the night and so this is why you know people have a tendency to wake up earlier in the morning than in the beginning of the night because their sleep is kind of lighter as it is and then it's also if true that if you wake up in the early morning of the night earlier in the morning you're more likely to remember what your dreams are because you're just more likely to be in a dreaming state when it happens right it's and so so you know it's a very dynamic process and so the way that we look at this is you know we kind of have poor people come into the lab and hook them up to lots of gear and have a really restful night's sleep you know it's like okay we're gonna study you now lights out and as you can see people do sleep but and we can kind of see these patterns in the EEG waves and so we use this to help us look at signatures of sleep but sleep is you know a process that's driven by our biology and so there are kind of two key processes that regulate whether we sleep or not and so these have been very kind of creatively named as the S&C process and so s is your homeostatic sleep drive and so this is kind of a very simple concept that kind of your need for sleep increases the longer you're awake that's the s process and so as that sleep need grows you know you begin to get closer to that feeling of sleep and so I think of it as kind of like a balloon so as you when you start the morning your balloon is really flat but as you as you are awake and you kind of go about your day it kind of builds up with the sleepiness then it gets to kind of this optimal amount you go to sleep and it lets all the sleepiness back out and you just kind of start back at kind of a flat balloon so that's one piece of it but the other is the see process and so this is your circadian rhythm so your circadian rhythm is you have rhythms in all the cells throughout your body but this one is really important it lives in your brain and it's very sensitive to environmental cues and sunlight and it's trying to always tell kind of when we should be awake and when we should be asleep and so you can think of these kind of that see process is kind of going up and and it you can think of it as kind of alerting signals and so when when people were awake during the day you know our alert signals are high our circadian rhythm is moving and then when we get towards night time if your circadian rhythm is nicely aligned with your sleep your homeostatic sleep drive that's the perfect scenario and that's what we see here so alerting signals are going down sleep need is at its highest peak and so you go to sleep and you have a nice restful night's sleep now of course our circadian rhythms are a little different we do see as we age a shifting in our circadian rhythms so as we get older we become more kind of phase advanced meaning that you tend to want to go to bed earlier and get up earlier in the morning and so that can all sometimes affect the how well aligned these types of things are and and and that's that can be a challenge for some people and so speaking of sleep and age obviously we don't sleep like we were kids anymore right and this is you know this is always kind of a challenge because you know what does this mean that we're not getting asleep you hear all this stuff about you know if you don't get enough sleep you're gonna get neurodegenerative diseases or metabolic syndrome or diabetes and you know turns out you're not sleeping as much and it turns out that like we have to recalibrate what we mean by adequate amount of sleep and so as you can see here what happens as of course we sleep more when we're younger you know when we're teenagers like everything is off and not working well and if you have teenagers at home you surely have this experience but also the amount of sleep that we get as we age changes so if you look below this light here this is a way so this is called wake after sleep onset so everything below this line is sleep and this is the number of minutes here on the the y-axis and so what you see here is is as we get older kind of the this area gets smaller and we don't really have a good understanding of why people as they age get less sleep you know we you know we had this concern like oh no this this might be something biological that that may confer risk but we actually don't have a good handle on this and this is something that I often face in the clinic that I run where folks are kind of sleeping less and they're really concerned but we're this is another instance where sleep science is kind of a new science and we're still trying to figure that out but one thing that is notable is that this slow-wave sleep this deep sleep does decrease as we get older and then kind of this lighter sleep gets you get more of this and you also get more wakening that during the night some of this is due to kind of changes in in kind of urination frequency that often kind of contributes to disturb sleep but some of it is just kind of more wakefulness during the night and so what does this mean what does this mean for our health what does this mean for everything well it turns out that sleep the amount of sleep that you get the quality of sleep that you get has been related to a whole host of biological outcomes like Ashley mentioned I do a lot of work on the immune system and we know that for instance if you don't get enough sleep every if you get say six hours of sleep per night you're at increased risk for getting the cold the common cold so we take people into laboratory and we you know we measure their sleep beforehand and then we actually inoculate them with the Rhino virus right so these are people they get paid for it but you know still not not the ideal study it's usually you know people that need the money and and graduate students things like that and so and so you know and what it turns out is time and time again we find that people who get less sleep say six or fewer hours are about four times more likely to get this cold then people get more sleep so we know that it plays a role but it also impacts a lot of biological processes that are important for chronic conditions so not infectious disease when we're talking about kind of exposures to viruses but chronic conditions and the one that comes up again and again has been in the context of weight gain and and changes in metabolisms and so I'm going to talk a little bit about that so again let's look at this map and so we see this variation one of the things that's really interesting about these maps is that as I mentioned they map on to these other by these other health outcomes and so it's not as clear in the next line I'm going to show you but a lot of the hot spots and the patterning so this is obesity in across the country and if you had them on top of each other you would see that there is this relationship and of course it isn't necessarily causal amendment you know that that wouldn't say that but it is kind of curious that we see these associations and so in fact kind of what what is the evidence that sleep is related to obesity well this has been say probably for the last 15 years we've been really interested in this question and so they've been focusing on epidemiologic data so meaning kind of population level data where they you know measure thousands of thousands of people and ask them a question about like how much sleep do you get in general and then they then they ask they get measured or they ask them about their weight and their height and get a body mass index to give them an estimate of obesity risk or whether they have obesity and so there's been so many of these studies that they can now pool them to do what's called a meta-analysis so not just looking at an individual study but kind of looking them all together to see to the extent that there is a strong effect when we look across studies that have lots of different kind of methods and and things like that and the other piece that's really important is that this is a meta-analysis a prospective study so these are studies in which the people at the beginning they didn't have obesity they weren't they weren't obese and but they had information about their sleep and then they followed him over time for a second time point to know about weight gain and whether they ended up meeting criteria for obesity and so when they pull these studies together we do see a significant effect for short sleep duration so people who sleep less are about compared to people who sleep say uh normal what what in most of these days are considered a normal amount of sleep in so this is like eight to nine hours of sleep are about 25% more likely to be meet criteria for obesity so we do have some kind of large epidemiologic data that suggests that there is this association I will say that it also seems to be true for other things like peoples just report of the quality of their sleep so it's not necessarily about the amount in some cases it's about kind of whether they kind of when they globally think about their sleep it just feels bad to them and that that's that's kind of an interesting topic in itself but we do see this kind of convergence of information and so then we're kind of left with kind of what like how how could that happen you know there's actually lots of ways that this could happen and so when we think about insufficient sleep we think about kind of a bunch of different pathways through which not getting enough sleep could impact obesity risk or weight gain and so first is these direct effects on satiety hormone so hormones that tell you whether you're should be full or should be hung and I'll talk about some of that data kind of direct effects on things like insulin and glucose regulation but beyond just biological things kind of in the brain you know sleep lives in the brain right I mean that's that's that's where it's generated that's where it's experienced and so it turns out to no surprise that effects kind of how we interact with the world and at a neural level can in fact affect how we process things that we think are rewarding right and then finally it can affect our kind of hunger or kind of our intake so in this case intake meaning you're awake longer so to keep up that energy energy you probably need to eat more and so then the question is if that's true if we can measure someone's energy expenditure do people eat more than is necessary right so it's not kind of refuting the idea that it's just about well you need to keep your body up up and awake you know that that makes sense the hunger one is an interesting one I don't know if anybody can relate to that I have two little kids and so I haven't seen like a good night's sleep and their six-year-old six years of their lives and I do find that when I don't get enough sleep I am I have like a change in like kind of my interest in certain types of foods can anyone relate to that yeah okay I hope that got picked up on the video camera so okay so we're doing it together it's not just you not just me no okay so we have all of these different pathways and then we think that you know together in some way they might impact weight gain or obesity risk and then that weight gain or obesity risk through our obesity can then impact of course kind of metabolic complications like type 2 diabetes that we know is you know closely tied to kind of weight gain but then one that I'm not going to talk about but I think is really important is it also that waking can impact your likelihood of having a sleep disorder so one of the like critical Sleep Disorders when we think about this is obstructive sleep apnea and so this is kind of obstruction of breathing during the night when you're sleeping it's often often kind of related to snoring and can cause kind of increased hyper arousal because you're kind of gasping for breath it turns out that that you know if you have that you often then experience insufficient so it kind of is like the S cycle right then you begin to experience these things again because you're you have this obstructive sleep apnoea on board the good news is very treatable right so a CPAP s' continuous pressure airway something C paps do a great job in treating sleep apnea so so in case you were wondering about that but okay so if we're gonna talk about how sleep affects our obesity risk and I met our metabolism we have to think about kind of what regulates hunger to begin with and so it turns out that this again lives in your brain and your hypothalamus an area of your brain you know is really important in making a distinction between if your body is rich or poor and energy okay so it's kind of sensing kind of the the energy balance that's going on in your body and so we have some ways in which to do this and so it turns out that to to sense fullness if if you have a lot of glucose on say you had a meal and it increased the amount of glucose this leads to elevations in insulin and insulin then binds to the hypothalamus to tell your body that you're full right that you don't need to can keep consuming this is a very tightly controlled system similarly if you consume fat or from from fat leptin is released and so leptin is a satiety hormone that also binds to the hypothalamus this comes from fat cells and it also tells you that you're full so high levels of leptin til you're full and high levels of insulin in this kind of controlled setting will tell you that you're full and then there's the one that tells you that you're hungry and so this is ghrelin this is another satiety hormone released from the stomach and binds to the hypothalamus telling you that you're hungry so high levels and ghrelin tell you that you're hungry so there's kind of a ying yang between leptin and ghrelin in that way certainly more complex than this but for the sake of this talk you'll you'll pick up what I'm what I'm laying down here all right so so how do we if we're gonna look if we're gonna look at these things how are we gonna know if sleep affects these things in the body this these aspects of metabolism is Lou whether we in the laboratories we control sleep okay and so we do this by deprivation we do have an ethics board so it's not like this but the internet if you type in sleep deprivation that is that is what it has and so we do one or two things we do either total sleep deprivation where we bring someone into the lab and we tell them okay you're gonna stay awake for the entirety of the night or for two nights and we either compare them to someone who sleeps normally or we compare them to themselves when they sleep normally in the lab the alternative would do something that's called partial sleep deprivation and this is we do this more often now because we're trying to kind of mimic what goes on in the world right we know we're kind of a sleep-deprived community and so this is something like you know taking people who sleep eight hours regularly and reducing their amount of opportunity for sleep to four hours so like a 50% reduction and so then we do that and we we measure their blood in in to look at these things and we can tell whether kind of sleep deprivation effects sleep loss affects these outcomes that we are interested in it and so if we do this I'm going to give you kind of a summary for some of these things so if we do experimental sleep loss we do see a reduction in leptin this this thing that when it's high it tells you it's you're full and this is consistent in all and all of the well controlled studies that have been done it's typically true when we look at like 24-hour sampling so rather than just kind of looking at leptin in the morning we you know we hooked someone up to an IV and we kind of measured across the night we also see increases in Grillin so this one that binds to the hypothalamus to tell you that you're hungry and not just changes in hormones we see a concomitant increase in subjective hunger so it's not just these things increasing it's actually they're increasing and then telling the body that you're hungry okay and that seems to be that that sleep loss has a direct effect on these things and so in one example of this there's a paper from 2004 where they you know because he said he's so hard to do they're always like these really small studies and they're always like really healthy often men for some reason I think you know to control for other hormonal factors that that can impact this and so these are lean individuals a crossover design meaning that these individuals were sleep deprived and they were slept they slept in the laboratory and so they went two nights of ten hours of opportunity for sleep and two nights of four hours of opportunity for sleep and so when they sample across and I apologize a little bit blurry but the bottom line is leptin so low leptin and then and you can see here that ghrelin is elevated and then the hunger is elevated across the night as well and so all the studies kind of look like this generally and so what we find is that you know it turns out that the ratio between ghrelin and leptin seems to track with this change in hunger across the night importantly not this isn't true across all study findings in part because there's often a lot of heterogeneity and the types of samples they use so if they use people that are obese or they use people you know in various ways the timing of when they collect these measures so it seems like it's really important to look at across the 24-hour cycle and then of course the important to control for dietary intakes so the studies that I'm showing you there they actually do a very controlled diets that everybody gets the same thing so that we're all kind of working with the at the same kind of baseline to understand how sleep affects these things okay so that's a tiny hormones seems to be in effect now with respect to glucose regulation and insulin sensitivity again we see this fairly consistent evidence that if you kind of do an acute sleep deprivation so kind of one night in the lab or multiple nights in the lab you get you see impaired glucose tolerance and decreased insulin sensitivity under both intravenous and oral glucose tolerance testing so kind of the standard testing for assessing insulin sensitivity you see that sleep loss impairs that and so kind of a really nice example and I and I put it here because the the first author Maduro is here at UCSF so that's that's kind of special because she's doing kind of really great work but looking at 13 healthy participants again this crossover design but in this case they had five nights of four hours in bed and they compared them to five nights and eight hours in bed and they use kind of the gold standard for looking at insulin functioning hyperinsulinemia sille anemic and you glycemic clamp and so they did this across the night on the and they did it on the last night of each of these times and again they find that whole body insulin sensitivity is lower and people that go through the sleep restriction paradigm then and when they were in the non sleep restricted paradigm okay so if you take all the studies that have done this to date you can see that it's fairly dramatic so this is insulin sensitivity in response to sleep restriction compared to a non sleep restriction comparison and you can see that you know in some cases it ranges between like a 16% reduction all the way down to a 32% reduction when they do sleep restriction and then I want to talk about sleep fragmentation because that's that's actually really interesting because sleep as I mentioned is is not just one thing it's there's a various aspects to it including REM sleep slow wave sleep all these things and we're really interested in not just what happens when people don't get sleep but is there something special about certain aspects of sleep that affect our metabolism and so only a couple studies have done this because it's really hard to do but focusing on slow-wave sleep and so I'm imagining in this case it's not just taking someone with the library and laboratory and saying you can't sleep for four hours and you can sleep for just the other four hours it's actually where you you get to slay down and sleep and then every time you go into slow-wave sleep they wake you up every time you go into that deep sleep they wake you up it sounds torturous and so what do we see so these are fragmentation studies where they actually suppress slow-wave sleep specifically and what they found and there's only again there's only been two studies that have done this they find this similar 25% reduction in insulin sensitivity and a 23 reduction in glucose tolerance when they do intravenous glucose tolerance testing and so then there's been one other study where they've actually compared slow-wave sleep suppression to REM sleep suppression right because it could just be well if you suppress slow-wave sleep that seems to be important but maybe all the all the aspects are important and when they do that they only find the effect for slow-wave sleep so another good example of kind of what is important in that richness of that of that deep sleep okay so sleep is really important but I as I mentioned kind of the homeostatic sleep drive is part of it but the circadian rhythm is really important to write that and and for those of us that have kind of ever experienced jetlag right like you just don't feel great right and if you do don't tell people because that's no one wants to hear that and so how do they do this right how do we how do we look at this experimentally and so one way in which we can do it though it's obviously not the case in doing it in humans is to actually do it in animals okay because animals have like a very clear circadian rhythm and and and mice in particular and so this is a study that was done in mice and so you can see in the red bar this is the control that's usually their sleep sleep time where it's kind of kind of a regular wake and sleep time and then you can see in this disrupted one where they've kind of continuously shift the the sleep opportunity for these animals and so it really really messes them up and and so what they find is that one that sleep disrupted animals because and at the same time they're allowed to eat whenever they want and they gain more weight compared to the control group and then if you look at their metabolism that you have higher levels of insulin higher levels of leptin and then insulin and glucose ratio a greater insulin to glucose ratio and then the increase in leptin is interesting right because that was the one that is supposed to kind of make you feel full and so we're you know where this is just an example of trying to unpack these types of things but certainly the metabolism piece it fits with with what we've seen and and this is the case when we look at in humans in shift workers is anyone ever done kind of rotating shift work yeah would you recommend it no no no no and so so it turns out that like 2 million people do this kind of shift work and it really can have some fairly dramatic effects on our health and well-being and so there have only been a couple of studies that have looked at this but so if you take this example here in a large epidemiologic cohort where kind of this is an example of different people's schedules where you know they have work days and rest days or that's kind of broken up with work nights and work days and and all these kind of things if you follow these folks you know if you look at so in this case it was 474 rotating shift workers and compared them to 800 day workers and they found that the shift workers had a higher waist-to-hip ratio so kind of maybe more central adiposity as well as kind of a worse Homa ir so evidence of insulin resistance as well as higher levels of insulin and triglycerides so you know I guess the take-home is that it's kind of this combination of sleep and circadian functioning that that seems to be important and so if we think about well okay we think about type 2 diabetes lots of things kind of contribute to your metabolism like where where does sleep fall and kind of the scheme of things right and so there have been studies that have looked at that where they've looked at kind of how does sleep stack up to these traditional risk factors like does sleep really add something new and it turns out if you look across studies and say in this case this is prospective studies again people didn't have type-2 diabetes at the beginning and then followed up at another time and and did and what we find is that people have short sleep duration have like a 48% chance more likelihood of having type 2 diabetes 21% if they had poor sleep quality and then obstructive sleep apnea as I already mentioned kind of a you know a hundred and two percent increased likelihood and so then you look at kind of the traditional risk factors and so being overweight of course it seems like sleep might contribute to being overweight so it's not necessarily fair to say that that's on its own but that is important family history of course of course family history matters and then physical inactivity and I think this is the one that's the most interesting is that we think that kind of being sedentary though that contributes to being overweight as well might have a have this impact and it's its effect is smaller than that of short sleep duration and so one of the things that I one of the questions I always get is like well if I could give up an hour of sleep to get more exercise like you know with that would that be better and you know I used to kind of think well you know I could see that because you know exercise particularly if you're sedentary you get huge benefits if you become active at all and so I guess it probably demand depends on kind of how active you are to begin with but I think the evidence is crewing that sleep getting that sleep might actually have similar or if not more benefits than exercise in certain circumstances so as a sleep researcher you know that's my new my new line so okay so we've talked about sleep and satiety hormones we talked about sleep and metabolism and so I want to get into the into the brain too right and so of course if we think about how food plays a role in our lives we like it we like food we need it and so exposure to food cues kind of engages as reward circuitry in our brain and these effects of food cues tend to be more pronounced when people are low on sleep when they're experiencing less sleep than they need and so it's similar to being under periods of stress you know there's there's a lot of evidence about kind of experiencing stress and your change in the types of foods that you want and we see the same thing with sleep loss that when people are have less sleep they tend to not only crave more food and be hungrier but the types of food differ right so they T they tend to to look for more high caloric foods more high fat high high sweet foods that we know can contribute to a negative metabolic health profile okay so what do we know about this so I think a sleepy brain is a hungry brain okay and so we go back to our sleep deprivation paradigm and in this case again it's compared to like this guy sleeping normally that was as close as I could find a picture to what I think that guy looks like when he's asleep and so they do this they they put them in this paradigm and then they put them in there in the scanner so they look at their brain functioning they look at a functional magnetic resonance imaging fMRI and while they're in there they give them these different cues right so they're like you know you're sleep-deprived here look at this pizza what happens your brain oh look at this broccoli what happens your brain and so what they find time and time again is that it engages aspects of the of your brain and so this is you know may seem like a very small thing but it's it's it's con it's the anterior cingulate cortex which is implicated in kind of your impulse control as well as kind of your emotional centers of your brain and it turns out that kind of the more that aspect increases in response to those different cues under sleep loss versus regular sleep maps on to how hungry you are for those these appetite ratings okay and so this has been done a number of different times this is another type of study like this where you know people are sleep deprived or not and they they're kind of given different variety of types of foods that they look at and then what we explain is that not only is there an increase for wanting foods in general but there's also a difference in the amount of high-calorie foods that they seem to want and then again this amount of wanting seems to go up as they feel sleepier as the the sleep deprivation the more it has an impact on their kind of subjective experience and it also seems to impact kind of emotion centers in the brain so the amygdala responds more under sleep deprivation to these food cues than an arrested brain and there's a down regulation in what's called your orbital frontal aspect of your prefrontal cortex the piece that's always trying to regulate your impulses regulate your emotions that seems to be less on line in response to sleep deprivation in these food cues than otherwise okay so what does that mean for daily life so we've done this in the lab I always talk about this study because I just think it's just genius where in this case they recruited 14 healthy non obese men again they did this crossover design and they had a baseline day than they did the sleep conditions they do both of these things they get their blood drawn in the morning and then they have a meal the meal is critical because it standardizes their hunger right so it can't just be about their hunger anymore but and then they had this supermarket task where they kind of like put together like a supermarket and gave people like a fixed amount of money and we're like okay now try to buy stuff with this right so like mimicking like what it might be in the daily world under these periods of sleep loss and what they find is that first they go crazy and just buy like tons and tons of stuff and they buy many much higher calorie dense foods than if they had their rest at night of sleep and this also mapped on to their increasing ghrelin so this this hormone that it you know hooks on to the hypothalamus to signal hunger okay and we see the same thing with sleep and soda this is work that we've done where we kind of looked at kind of national level data thousands and thousands of people to see if there's a relationship between the amount of sleep people got and kind of the amount of soda that they consumed and it turns out that people that sleep six or fewer hours per night report 11 a 21 percent more sugar sweetened beverage consumption so you know we've know that and if you've been to any of these other many minute medical school things I'm sure they talked about soda because that's kind of an issue unless a group was there so if you missed it you can look it up online but it seems like those things are linked in in an interesting way okay so why do why does this happen so well one of the leading hypotheses is that its adaptive right that that you know we eat more we eat more energy rich foods because we need to because we're awake longer we need to maintain our arousal level and so it turns out that that may be true but in a world when food is readily available people still make different decisions and so this was a study where they did look at this and they looked at both energy expenditure and they looked at kind of amount of calories consumed and what they find is that although there is a little bit of an increase in energy expenditure people did consume much more than they needed based on kind of their metabolic need from staying awake and so it's not just that okay so we have all of these different pathways that can lead to these metabolic complications another one that's of interest and was in the title of the talk so of course I'm gonna get to it was is inflammation so inflammation is another key piece of this and so inflammation is everywhere it affects everything it seems to be one of these central pathways including the type 2 diabetes but other things as well and it it often is derived from our immune cells so it comes from lots of different places and so this is a macrophage eating some bacterium it's going to begin to let out some of its inflammatory proteins that help facilitate this process and inflammation on its own is like a critical thing we need it to survive okay it plays a huge these these proteins and all the inflammatory aspects that come along with them are critical for communication within the immune system and facilitating wound healing and kind of you know orchestrating the troops your immune cell troops to kind of free you from danger but the thing is when it's elevated for a chronic amount of time is where we see this relationship with chronic disease and so when we think about biomarkers of inflammation we think about pro-inflammatory cytokines and so in this case interleukin 6 or il 6 I'll 1 beta tumour necrosis factor-alpha all 3 of those are kind of in the trifecta of inflammatory pro-inflammatory proteins and again they come from lots of sources so activated immune cells like macrophages fat cells especially visceral fat seem to be kind of this metabolically hot inflamed fat and then even muscle cells like myocytes and then beyond those proteins we have acute phase proteins the one that's really kind of of relevance and is something you can get at your doctor is C reactive protein this is released by the liver in response to increasing levels of these other pro-inflammatory meteor's mediators in particular il-6 drives the increase in C reactive protein and so just because because we have this metabolic talk I want to talk briefly about fat cells and so fat cells seem to you know there's growing more and more evidence that they are a critical source for these inflammatory proteins and it's not just that the cells themselves the adipocytes can release these proteins but they seem to be kind of magnets for these immune cells for these macrophages that become kind of necrotic in the fat cells that become super inflamed so it's it's a kind of a one-two punch of the adipocytes releasing pro-inflammatory cytokines and then these macrophages that kind of get caught inside of these adipocytes that contribute to kind of this inflamed a profile so then the question is okay to sleep the sleep really contribute to elevated levels of inflammation and so again people been really interested in this and so they've developed there's been enough studies where we can really kind of pool them to get a better estimate of kind of what is the effect because I'll of course a lot of these studies are small and so what is the overall story here and so what we see is that when we look at people that have short sleep duration we see small effects but some often significant though there are larger effects for people that sleep longer and so I haven't talked about this yet but there's a whole other literature about long sleepers and so these are people that like sleep 10 or 11 hours per night and we don't have a really good understanding of why that is do they need more sleep or is it really a marker of something like underlying illness right so when we get sick as you know you know you get a cold who sleep more you know and that's thought to be adaptive but if you have a chronic condition and you're sleeping all the time maybe that's why there's this relationship between long sleep and information another possible explanation is depression depression is often correlated with hypersomnia as well as some of these inflammatory markers so we're still trying to figure that piece out but you know there does seem to be these relationships on both ends of the continuum but then beyond that there's also evidence that sleep disturbances so symptoms of poor sleep having a diagnosis of insomnia also seems to be related to elevated levels of inflammation so if we look at this kind of this plot of all the different studies and so this is sleep disturbances and the marker that we're looking at is il-6 in particular you can see that on the right side of the line is in the realm of positive relationship and and then those like big whisker lines are kind of the the variance the kind of confidence that we can have so the shorter the smaller the lines the more confident we are in that estimate and when we pull them together we see this kind of modest effect size meaning that there is this relationship between sleep disturbances in il-6 specifically and so one of the reasons that we think that there is such a small effect is because one they come from lots of different places these these inflammatory markers and so there's lots of things that could be attributing to the the variability in them and so one way to get at this more closely is to look at the actual cell and whether it's it looks like it's going to begin to produce more of this pro-inflammatory marker and so by doing this we can look at that how much the the cells DNA we're seeing kind of gene expression of those markers so ones that are that are of importance and so we can kind of take people and have them be sleep-deprived or not and then look at their cells sometimes stimulate them and see whether those cells become up regulated for those genes that we think are going to lead to more inflammatory proteins this also helps us control the source of where those proteins are coming from so when we do this we see kind of a fairly consistent up regulation and that's the left graph there of these inflammatory genes so in this case il-6 and teens humor necrosis factor-alpha and then this this guy on the right here is a heat plot of a variety of different genes and what's interesting is we see kind of variation in kind of the up regulation in the pro-inflammatory direction and then a down regulation in ass genes and processes that we think are important for regulating inflammation so kind of this up regulation on the protein side and then that kind of a down regulation on aspects that help control inflammation but I think one of the things that's important to think about again we focused on sleep is that sleep is just a thing like sleep is it doesn't exist in isolation right and so when when sleepers users like myself or like o sleep what about sleep studies sleep and it's like we think about it like this but you know people live in world you know and they have lots of different things and so we know that a lot of the aspects that sleep affects things like stress also affect and so we become really interested in whether there's this kind of synergistic effect for this and so if we think about these recursive processes so people that are stressed during the day you know no big surprise they tend to have poor sleep at night and what has been kind of really interesting to us has been you know if you have very little sleep are you more sensitive or reactive to stressors during the day does you know if you have a really bad night of sleep does that traffic seem just a little worse like what is happening to San Francisco worse you know and so you know when we think those things all exist and so taking an example here where we do it in the laboratory this is kind of a classic way that health psychologists try to understand how stress affects the immune system is that we bring people into the lab we measure their sleep ahead of time and then we put them through with something that we think is really stressful and so in this case it's giving a speech and getting negative feedback while they do it right so you guys have been very kind with the laughter and the smiles but imagine if you were giving a similar talk like this and just got kind of like negative feedback like you know arms crossed like shaking your head like you know things like wow this person just is not living up to the billing and so you know they that we have them do that we also have them do a serial subtraction task where they have to kind of subtract by 13s and you know every time they get it wrong we like to stop start over stop start over you know it's very activating let's just say it's activating and then we at the same time have an IV in their arm and we're drawing blood the whole time right so it's like the perfect storm of things so that we can track how they're inflammatory pattern changes in response to this stressor and what do we see well we see that it really matters how much sleep they get before or how much they sleep they get globally so in this case we see this increase in il-6 in this case it's il-62 il-10 where we see an increase in this slightly people their average sleepers we see a stronger one but people that are poor sleepers have a dramatically increased one and this is particularly dramatic among people who also have higher Vissel visceral adiposity so it's not just sleep it's not just stress but it's also kind of the metabolic profile that you bring in right and so we're still trying to unpack these things but it you know they're clearly into there's intersections here that we need to understand and what the good news about that is because I don't want to give you just bad news is that means that there are lots of opportunities for intervention right sleep interventions work for some people stress interventions work for other people dietary interventions work for other people but it gives you lots of targets and so as a clinical psychologist that's really important to find something that works for the person right okay and so all that information oh my god sleep I need more sleep what can be done about this well there are things we can do and we're trying to figure that out so just hear a little bit of more data then I'm gonna go to kind of you know we're gonna wrap up here so there are lots of ways to do this in experimental settings when we deprive people of sleep we can actually give them recovery sleep to see if things improve when we give them even more sleep opportunities than their normal nights in intervention settings we can do things like sleep extension protocols these are really challenging to do because it turns out people don't sleep for lots of reasons but if we can find people that we can actually give them more opportunities to sleep and they do it we can see what happens to them among people who are in have insomnia the frontline treatment for this is something called cognitive behavioral therapy for insomnia that's been shown to be very effective in improving sleep and so we can see if that changes their biological profile and then of course there's pharmacologic interventions so like what happens if you just start taking ambien or zolpidem you know the tradename ambien like does that improve your metabolic profile so what are we so it turns out this is a very very small literature something to go through quickly if we do a sleep recovery so in this case people have four nights of regular sleep and you deprived sleep in two nights of either then 12 hours been 10 hours of opportunity you can reverse the insulin sensitivity that you you produce during the sleep restriction if you do a sleep extension in this case it's 16 healthy non obese individuals they were all reported sleeping less than seven hours on weekdays before they came into the study then they went through two weeks of habitual sleep where we just kind of they just kind of measured their sleep out in the world to make sure that in fact they were getting very little sleep and then doing an extension where they just asked them to sleep to give themself one additional opportunity hour at night and so this shows what this looks like and so it just it was just on the week' weekdays and so that's this one over here and you can see they start at week 1 week 2 where they were kind of short sleepers and then we're extended here and they were able to do it so that's really important for whether this is an actual feasible intervention and what they find is that they get as people increase their sleep time they see an increase in in glucose addi a related decrease in insulin and related improvement in in-home IR the homeostatic model of assessment of insulin resistance all improved in these patients and these weren't patients that were selected for having metabolic problems okay cognitive interval therapy for insomnia again this is not something you know we don't have a lot of studies for this but there are some kind of interesting findings for those that are not familiar with it this is a combination of sleep hygiene a sleep restriction protocol so we can increase your homeostatic sleep drive that s process as well as stimulus control meaning that you don't lay in bed when you're kind of worried and waiting you you get up and at the same time every day in the morning and then kind of cognitive strategies to help you deal with kind of these catastrophizing about not getting enough sleep those types of things if anybody is interested in you know they're like oh wow that sounds like me we do have a clinic here so I put that information there to treat people with insomnia and then as I mentioned Ashley Mason here dr. Mason has a group clinic if people want to do group therapy through the Osher Center and so what do we see in CBI there's only so it's coming here for therapy for insomnia short cbt-i they look they've looked at inflammation and so what they find is that one and in this case it was compared to a Taichi intervention also been shown to improve sleep and in a great interest and what they find is that sleep improves so this is a score on the Pittsburgh sleep quality index with a higher score meaning worse sleep and so the bottom line is the cbt-i intervention the the insomnia intervention and so as expected you see the the biggest effect there and then if you look at people that have what's considered high C reactive protein and so this is a Syriac to protein level of more than three milligrams per deciliter which is a clinical risk fact cutoff for cardiovascular risk you see that the people in the CBT eye condition remain low while the the other groups seem to creep up and so it's you know it seems like it you know you can interpret it different ways but this at least seems to keep it stable e low relative to the other interventions the SS condition was a sleep hygiene condition and so what about pharmacologic interventions wouldn't it just be easier to take a pill right no no it's not it turns out that taking pills for sleep is something that is very helpful in the short-term it becomes psychologically addictive almost immediately and so you know to keep that in mind but for science purposes yes of course we want to know if we improve sleep can we improve these these outcomes and so there has been one study of zolpidem that's been done where they did this at 10 milligrams and then they gave them an OG TT and this was in 12 men what they found is that compared to the baseline period 15 days of getting this resulted in an 86 percent increase in the area under the curve and had no real effect on insulin suggesting that when you take those things together this may be kind of pushing someone towards an impaired insulin sensitivity I will be honest they have not done very many studies of this so you know and of other sleep aids and so we don't really know but we will we will keep doing this work in some fashion so more studies are needed okay so what can you do what can you do to improve your sleep right it turns out that there are things that you've kind of always known about right that kind of the tried and true sleep hygiene things but I will say having treated lots and lots of people with sleep problems you have to do all the things right it can't just be oh you know half the time I leave my smartphone out of the room and the other eye it's like how I get to sleep at night and you know when I wake up in middle night the first thing I want to do is check my email those kind of things can certainly impact your ability to sleep soundly and so thinking about the sleep environment kind of cherishing it for sleep like setting it up to kind of be ideal for sleep is key and so keeping the bedroom quiet dark using blackout curtains keeping it cool we seem to to sleep better under cool conditions and so this can always be challenging if you have a bed partner and you have to kind of negotiate these things one thing that I always tell people is like you know it turns out that you didn't select your life partner for their sleeping habits like that that's just a roll of the dice and it changes as we get older and you you know you're like wow this is not how I thought it would play out but the rest of the time the rest of the time if you sleep well it will be better we know that from romantic relationship studies of sleep unplug from the electronics right so keeping the smartphone out of the bedroom is one start but I also would suggest kind of a wind down period kind of unplugging yourself at least one or two hours before bedtime don't consume caffeine or exercise too close to bedtime caffeine has a half-life of five to six hours right so that means if you consume a coffee at noon at 6 p.m. you still have half that caffeine in your system and that can certainly affect other people differently and you probably know if you're sensitive to caffeine or not but if you're not sure try doing it earlier and if you have sleep problems see if they improve a little bit alcohol to alcohol is great for falling asleep right it's it's soporific in that way for most people but it fragments your sleep like crazy you don't get that slow wave sleep that you love that you need so consider kind of consuming alcohol less close to bedtime then then then doing so and then avoid long naps unless you you know you you medically need them I mean everybody loves a good nap like I said I have two kids I love weekends weekends a nap time it's amazing but you want to keep them short typically what happens is people sleep more than 20 minutes they get into they started going to one of those slow-wave sleep cycles and they wake up and they feel worse than they did when they started that's called sleep inertia and so you want to try to not do that particularly if you have sleep problems already because it's this homeostatic sleep drive this balloon that I talked about in the beginning you know you're stealing some of that sleepiness it's like snacking before dinner we know that that's not a good idea and so this is the same thing and then easier said than done but it's very hard to sleep when you're worrying and oftentimes in the middle of the night when you think you can solve all these problems like you're not at your best right and so you know having a time to really focus on that kind of letting yourself you know enjoy this sleep kind of a letting yourself kind of disengage from the world and let your body do what it's always known how to do is is critical and so you know be where say like well you know if you could do two things like what would be the things that you would do so first the sleep hygiene think those are easy to do you're going to do two things and you had sleep problems the two things would be get up at the same time every day of the week because your body craves predictability and if you sleep in two hours later on the weekend it's like waking up in Colorado or or Chicago wherever to our differences that can can really make it challenging for your body to know what to do right and so that's an easy thing that you can do is kind of set a seven-day-a-week wake up you can't decide when you fall asleep that's not something that you control you don't make yourself sleep but you can't control when you wake up okay that's that's were the control we have here of course it turns out that if you wake up the same time every day you end up using the same energy every day and so you get sleepy around the same time each night so that it'll become a pattern that way but you know the focus is are like what you can control in this situation and sleep is not that thing right that's something that comes to you and then the other thing is you know you don't want to lay in bed awake so if you do that over too long that kind of begins to feed and insomnia your body starts to expect to be awakened in the middle of the night laying in bed you be it actually kind of you know people that I see you that have sleep problems they they say yeah I was feeling sleepy fro it to bed then I got in bed and I like woke up it was like a switch was flipped that is your body predicting to be awake when you're in bed you know the bed is for we say sleep in sex like it's a it's a shrine to those things okay and so you know if you find yourself unable to sleep and it's been like 15 minutes you know get out of the bed go somewhere so you begin to feel sleepy again try again that that's a good kind of you know plan for kind of staving off any kind insomnia if that's something that's about to develop and so then finally you know protect your sleep it's it's a value it's a value that I think we don't kind of put as much in as other health behaviors like nutrition and exercise but I think we're getting there and I think it's important because kind of your metabolism is counting on you to do this okay and so with that thank you and sleep well and I'll answer questions [Music] you

Channel: University of California Television (UCTV)

Views: 24,633

Rating: 4.7753778 out of 5

Keywords: metabolism, sleep, inflammation

Id: nqqxHKx30Ow

Length: 59min 17sec (3557 seconds)

Published: Tue May 15 2018

Reddit Comments

[u/civver3]

This lecture discusses the link between sleep and metabolism. Starting with an overview of sleep, the presentation then turns to the correlation between sleep deprivation and obesity. Next, the relationship between abnormal sleep and systemic inflammation is examined. The talk concludes with interventions that reverse negative effects, where sleep hygiene is superior to pharmacological solutions.

[u/DogBotherer]

All this evidence on sleep and health is really annoying for those of us who find sleep boring.

[u/ringoftruth]

I love that resistance to insulin is termed your HOMA i.r. ;) I think Homer would also approve the fine professor's ideal antidote to his "insulin resistant"waistline is not a trip to the gym but a good long NAP !!!

[u/cantstoplaughin]

Anyone else read it as Sleep Inflammation and Masturbation?