Well thank you for that introduction. So we're going to talk about a very important topic because you do a lot of it. You spend about a third of your life sleeping so you need to know a little bit about it and so do your patients and if you're a child or adolescent you're spending about half of your life sleeping. So what I'm going to talk about is a little bit about physiology of sleep because not many people are aware of how sleep works. Think about its impact on health a little bit and its impact on obesity and talk about a little bit about sleep optimisation. So in the old days people believed that when you go to sleep you actually die. Hypnos is the god of sleep for the brother of Thanatos the god of death. So here's Hamlet saying to die to sleep no more, to die to sleep, to sleep perchance a dream, for in that sleep of death what dreams may come. So people believed that you just die and then you wake up again. And then there's different attitudes towards sleep and that sleep is a waste of time. So Thomas Edison you're aware of it, the founder of our 24-7 society, electricity and light, sleep is an acquired habit, cells don't sleep, fish swim in the water at night, all night, even a horse doesn't sleep, a man doesn't need any sleep. And Isaac Asimov also said a similar thing, a science fiction writer. But actually Thomas Edison is wrong on all accounts. Sleep is a very highly conserved physiological function across multiple species. Cells have rest and activity cycles, fish do sleep, in fact some of the models of sleep are fish, horses do sleep, a man needs sleep and in fact Edison lost his first job because he slept on the job. And he used to have a corner in the lab where he used to go and sleep and nobody knew about it so he was pretending to be like that. So there are people like Alan Rechshofen who's a sleep researcher in the 70s saying if sleep does not serve an absolute vital function that's the biggest mistake the evolutionary process made. And he wanted to test this so he developed this model called the totally sleep deprived rat. And the way it works is the totally sleep deprived rat is basically, is the EEG connected here while the control rat is here. So every time this totally sleep deprived rat goes to sleep the wheel turns and it lands in the water so it has to wake up. It's a very terrible experiment to do, causing this total sleep deprivation. And what he observed was these rats lived about 21 days when they were totally sleep deprived. When they looked at them at necropsy they could see over time they had this temperature decline, they had oedema after pause, they had motor weakness and ataxia, they couldn't generate enough EEG amplitude showing that their brain was dying and they had enlarged adrenals showing high stress and had hardly any body fat. So sleep is absolutely important. Here it's showing it's related to mortality and the data showing the shorter sleep is also associated with higher mortality rates. But how is sleep regulated? It's regulated by the hypothalamus, which you know is a three cubic centimetre area sitting at the base of your brain and it's an abnormal hypothalamus and the MRI scan showing inflammation and the patient was sleepy all the time. So as you know the hypothalamus manages everything, your hormones, water balance, thirst, temperature regulation, appetite, circadian rhythms, emotions, reproduction, memory and sleep. And this was first observed by Van Economo because in the 1920s you had the encephalitis lethargica epidemic, which resulted in a lot of people being sleepy and a lot of people being awake. And the ones who were affected had the hypothalamus affected. You may have seen the film Awakenings with Robin Williams, some of them developed Parkinson's disease and that's what the early days of L-DOPA, but some of them were really sleepy and they had damaged the lateral hypothalamus, which is the wakefulness centre. And the way your sleep is regulated is regulated by two factors. One is your process S, which is your appetite. So the more awake you are, the more sleep debt you develop. As you can see the process S going up. But this means that in the afternoon you're going to be sleepy, so you have a circadian signal coming through saying you can't sleep now. So there's another process called process C, which is circadian system. When the process S is high and process C is low, that's when you go to sleep. But what happens when you have jet lag or shift work is there's this misalignment of the two. So your circadian system says it's time to be awake, while your process S says you need sleep. So when the two are misaligned, that's when you get these problems. So how do you evaluate sleep? You can take a sleep history, but usually it may not be as helpful. It could be questionnaires and people very bad at telling you how sleepy they are. It could be sleep diaries where they write what time they went to bed, what time they wake up, what the quality of sleep was. You can use accelerometry. Many of you have got Fitbits and Apple Watches that do that. Or you can do polysomnography, which is looking into the brain. And polysomnography means basically polymany, somnosleep, graphy means writings. So it involves EEG, electroocularogram, looking at your eye movements, EMG, respiratory effort, oxygen saturation, sleep position, microphone in case you say something funny and video in case you do something funny. But polysomnography is expensive, it's really hard to do, and you need people like this to do it. So I have no hair because it gets tangled up. So it's very difficult to do for women. But this says look at eye movements, look at nasal airflow, looking at the microphone, and also look at the brain activity. And this is somebody who's awake. And you go through different stages when you're awake. So you go through stage one sleep where the EEG slows down, and then stage two which has these big waves called K-complexes. And then you go to stage three, which is deeper sleep. You can see it's very slow waves, 75 microvolts. And deeper stage, stages of sleep have got this very high voltage, slow waves, what we call slow wave sleep. But then you retrace all that and you get to something crazy called rapid eye movement sleep where the eyes flick from one side to the other. And what's important about rapid eye movement sleep is related to your dreaming. And at that time your muscle tone is completely paralyzed. So apart from your eye muscles and your diaphragm, all your muscles are paralyzed. That's because if you're dreaming you'd be running down the street chasing people and doing some stupid things that you wouldn't want to do during your dreaming. And it's of course REM behavior disorder where people have early signs of Parkinson's or dementia where they enact out their dreams during sleep. So you go through these cycles of sleep from awake all the way to REM sleep and you create six or seven cycles of these between about 60 to 90 minutes overnight. Are our sleeps synchronized? You can see Mr. and Mrs. sleeping next to each other. The sleep is completely different. So you don't have synchronized sleeping at night in the same bed. Many people don't realize how sleepy they are. So this is motorway driving at night. You can see that actually there are drops into sleep episodes. It's called micro-sleep that happen. And if you chew gum you can reduce all this, reduce the risk of accidents. But many of you miss sleep problems in your clinic and that's what your patient ends up doing, causing a severe accident. So they have sleep disorder like sleep apnea or they're sleep deprived or they have environmental consequences such as the exon valdez. In your clinic asking about sleep is really important because it tells you if somebody is depressed or not. You can see there's a lot of wakefulness at the top and when you get peroxetine within three days you can see that wakefulness is reduced. So you can even see the response to the treatment. So this is a normal hypnogram. How are hormones related to this? So non-REM sleep, which is slow wave sleep, is associated with parasympathetic activity and REM sleep is associated with sympathetic activity. So one of the first hormones that's related to blood pressure is renin. So renin is low when there's high REM activity. The other hormones that's related to sleep is growth hormones. So growth hormones are incredibly related to slow wave sleep. And you can see it occurs early in the sleep night and mainly during sleep and so does prolactin. And you can check this by getting people to sleep at the wrong time. So if they sleep at the wrong time, such as in the afternoon here, you still get the growth secretions. It's not circadian hormone. It mainly occurs during sleep. And if you give a drug called gamma hydroxybutyrate that increases slow wave sleep, you can see there's a higher, with increasing doses, you can see higher levels of growth hormone secretion. And as we age, our slow wave sleep goes down and so does our growth hormone, nocturnal growth hormone. The other hormone that's important is what's circadian but it's also ultradian. It's released by minute pulses. Of course, there's changes also in glucose. You become insulin resistant during sleep and glucose levels tend to go up. What about the sleep and obesity relationship? Let's go back to the total sleep deprived rat. You can see the total sleep deprived rat was eating like crazy. It was eating as much as it could but it couldn't eat enough to keep its weight going because its energy expenditure was so high. It was burning everything but it couldn't stay awake enough. So that's the result in weight loss in the total sleep deprived rat. So sleep deprivation is associated with increased appetite in the rat due to increased energy expenditure. But what about humans? As we go through time, you can see the adults, both men and women different ages, sleeping less than six hours increased over time between 1985 and 2004 and this coincided very nicely with the obesity epidemic in the US. So data from the US shows this relationship and one of the first studies to show this relationship was from Daniel Kripke of 1.1 million individuals. As you can first see, if you go up the BMI ladder, the BMI ladder goes up as the sleep duration goes down and also there's increased mortality. And in young children, there's a Japanese study showing the odds of having obesity based on sleep duration. So if your reference is 11 hours, the shorter the sleep, the higher the risk of having obesity in children, which is confirmed in another data set here from New Zealand looking at seven-year-olds. So if baseline is more than nine hours, less than nine hours, you can see nearly four-fold increase and three-fold in the adjusted model. One of the studies that really put this on the map was the children of the 90s studies in Bristol, which I collaborated with. It's a study of 13,000 pregnant women and their children who've been followed up. They're now 30 years old, all the children. And I looked at all the different factors, 25 different factors that are important in terms of obesity prediction from age 30 months to age seven. And one of the factors that came up was sleep at 30 months. And this was an even greater effect in diet or physical activity. So the aspects of the children of the 90s studies, you can see 12 hours, more than 12 hours, you reference. As you go to less than 10.5 hours, you see a 45% increase in risk of obesity developing at age seven. This is a longitudinal study of adults. I just want to point out that ones sleeping in five hours are getting more obesity as things go along. And in fact, it appears that the relationship between obesity and sleep duration is much stronger in children than adolescents and adults, because as you get older, it doesn't seem to have the same effect. So if you look at the odds ratio, it's with less than four hours of sleep or 3.21 in the younger age group or 1.71 in the older age group. Adolescents are notorious because their circadian system is different. Circadian system of adolescence says go to bed late, wake up late. What do we do? We let them stay up all night and wake up really early. So they're very sleep deprived and using the gadgets of the time or the technology. So we did a study in the UK of eight secondary schools. And what we noticed again, sleep duration was associated with obesity, with shorter sleep duration associated with higher BMI and also technology contributed to the higher BMI as well as disruption of sleep. So can we replicate this in Qatar? So we did this in Qatar called Qatar Obesity Reduction Study in Primary School Children. I just want to point out in this grouping, if you look at the weekday sleep duration, it's 7.6 hours. This grouping should be getting about 12 to 13 hours of sleep and again, it's 7.6 hours. And what we noticed that for each hour of sleep, increased the sleep duration, there was a 45% decrease in overweight and obesity. And in terms of body composition, you can see there's a relationship, negative relationship between BMI, waist circumference, fat mass and fat percentage with duration of sleep. So here we have this region, you can see Qatar is winning, but Kuwait is there, Dr. Ebba, and so are all the other Gulf countries in terms of sleep. And let me compare sleep in Qatar compared to sleep in UK. So sleep in UK, you can see the pink area, pink green area, it's very regimented sleep, it's very regular. But look at sleep in Qatar, it's completely dysregulated. There's no pattern to it. And this is happening in children. So our interest emanated from seeing how does this work? Does sleep work through leptin or ghrelin? As you know, leptin is important, it's released by your fat cells. And it's basically, we know about a mutation, a human mutation that has obesity, leptin is much more important, starvation. So low leptin is telling you you're hungry all the time, that you need to replace your fat cells. And then ghrelin is released by your stomach to tell you you're hungry. So if you look in the sleep gastrectomy here, ghrelin levels are low and this is one of the reasons that gastric bypass and sleep gastrectomy work. So we looked at a group of individuals in Wisconsin where we had lots of information about them and we noticed that short sleep duration was associated with higher BMI, reduced leptin and increasing ghrelin. And this is equivalent to about a 900 calorie deficit a day. Your body is telling you you're losing 900 calories and that's what happens. At the same time, a group in Chicago brought young individuals and they sleep deprived them. They brought them to four hours of sleep for two days compared to 10 hours of sleep. You can see the leptin levels are lower with two hours of sleep, ghrelin levels are higher. They're increasing reporting hunger and increased appetite. Similarly, cortisol levels are also higher with sleep deprivation. So four hours of sleep compared to eight hours of sleep, the cortisol levels are much higher. But interestingly, the cortisol levels are higher at a time when your cortisol levels should be lowest. So that's when they have the highest impact. Additionally, looking at salivary cortisol, you can see four hours of sleep associated with higher cortisol levels. What about glucose and insulin? Let's just concentrate on the HOMA, homeostatic model assessment for insulin resistance. You can see four hours of sleep is a much higher HOMA compared to 12 hours of sleep. And this level of HOMA, these are young individuals, 20 year olds who are brought in and sleep deprived in the lab. And if you look at a 60 year old HOMA, it's equivalent to sleep deprivation. So these individuals develop accelerated aging. They're having the HOMA levels of a 60 year old. So I hope I've convinced you that there's a relationship between sleep loss and obesity. There are many different factors involved. They're still being worked out. And it's not the most sort of established relationship. And it's been established across multiple countries, multiple populations. But what about if you take short sleepers and we sleep extend them? So this was a study published in JAMA Internal Medicine where they randomized people to their usual sleep compared to sleep extension. And you can see in the baseline, they have similar sleep of about six hours. The sleep extension group managed to increase their sleep. So it's possible to extend sleep. And you can see that in terms of energy intake, you can see the ones who are sleeping more, their energy intake is lower. And if you look at it this way, energy intake was much lower when you increased sleep in these individuals who had short sleep duration. And this is about, you're looking at about 270 calories here. Now, let me put this into context for you. A chocolate biscuit is about 100 calories. If you have 100 calories extra a day, that's equivalent to five kilos a year and 25 kilos in five years. The other thing to note that in these individuals, the sleep extension actually improved a lot of the quality of their life. They felt more alert during the day. They could function more. So sleep and circadian rhythms are absolutely essential, and we need to pay more attention to it. And we increasingly understand the relationship with cardiometabolic risk and obesity. Now, I'm going to change tack a little bit and talk to you about sleep apnea, which is a repetitive episode of upper airway obstruction. So if you look at this individual, you can see in the bottom right-hand corner, you can see the airway being completely shut on the MRI scan. And this is what it looks like diagrammatically. You can see from simple snoring when the air sort of flaps the upper airway to complete obstruction where there's movement of the chest and the abdomen, but there's no air flowing. And this is what results in reflux esophagitis that many of your patients complain about in the clinic. While you ignore it, you're happy to give them a PPI, but you're not happy to address the underlying problem of sleep apnea and obesity. And this is what it looks like. So there's no air flow. There's thoracic and abdominal movement. In your clinic, you can really assess it using the stop-bang questionnaire. It's a very good questionnaire to use. About 80% of your group with type 2 diabetes will have a sleep apnea, and the scoring is like the high risk of sleep apnea. But if anybody reports that they've been noted to be stopping breathing while asleep, then that's a really good sign of sleep apnea. In fact, I had a patient who came in with a herniated lung, and he had broken ribs. And nobody knew why this has happened until we spoke to the wife. And the wife said, I noticed he was stopping breathing. So I elbowed him in the chest and broke his ribs. So he developed a hernia because of that. Of course, it affects neurocognitive functions, got cardiovascular effects, sleep apnea, headache, early morning headache, heartburn, the sexual dysfunction. We're happy to give Viagra in our diabetes clinic, but we don't go and talk about problems with sleep apnea that might actually help. The prevalence depends on which population you study. So in the general population, it's about 15%. And as obesity goes up, the prevalence goes up. And it's about 80% in your diabetes population. And it's associated with weight gain and obesity. So weight gain triggers sleep apnea, but it's not the whole story. Because if you look here, it's sleep apnea here. The black part is the part that's attributable to overweight. And it's about 50%. So craniofacial abnormalities that contribute to this. And there's also ethnic factors. The South Asians have got different, more propensity to sleep apnea. And there are many other factors coming to it. You're acromegaly with a large tongue, the short jaw, drugs, alcohol can trigger sleep apnea as you get older. And also if you're male, gender. Smoking also affects it. And if you look at sleep apnea, from just simple snoring to regular snoring, the risk of diabetes goes up, just snoring without thinking about sleep apnea. But this is a sleep heart health study where they look at respiratory disturbance index, hypoxemia, and time spent below 90%. And each of these, you can see higher fasting blood glucose and two-hour glucose with greater degree of hypoxemia and sleep apnea. And this we know from animals, because if you take animals and you put them in the hypoxic chamber, they develop diabetes-type phenotype. And even if you expose a pregnant rat to hypoxemia, the newborn end up developing high fasting insulin. And if you go up altitude, your glucose levels go up because of hypoxemia. And if somebody's sick, they come into the clinic, you will see that they might have a chest infection, for example. And they also have insulin resistance. Diabetes is more common in COPD. So hypoxemia is the key. How do we treat it? If it's snoring, it might be allergy-related. That can be treated on mandibular advancement devices. In children, adenoid and tonsils is really important. No child should be snoring unless they have a cold. If they continue to snore, then that's a problem because it affects their cognitive function and school performance. Other treatment, the main thing is obesity management. That's absolutely essential. And then bariatric surgery comes in, then surgery of the palate. CPAP treatment is basically, we're talking a little bit about that, medications. And lifestyle works really well. You can see improvement in sleep apnea. And you might have seen the latest Surmount OSA, which has appetite, with improvement in sleep apnea, which has appetite. This is how you treat CPAP. This was the first CPAP machine. It's a reverse vacuum cleaner that blows air that keeps the airway open. But things have improved over the years. And they've got better interfaces. And you can see with CPAP, you can see opening of the airway. So it's very easy to treat. You can stop many of the problems for your patient in terms of driving and workplace accidents. But of course, you need to understand the underlying problem. Obesity as well as airway vulnerability. So to conclude, sleep is not a passive state. You don't die. You're fully awake. Many things happen in your sleep. People ask me, why do you sleep? I say, why are you awake? Why are you awake? Sleep is important for your multiple homeostatic functions. It's not a unitary state. Many things are happening at the same time. It's not yes or no. It's important in obesity management. And rarely do we talk about it in terms of diabetes and obesity management. Thank you for listening.

sleep deprivation

obesity

hormones

sleep apnea

CPAP

healthcare