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第五届肥胖症年度研讨会 Fifth Annual Obesity Symposium
睡眠 压力和肥胖 Sleep, Stress and Obesity
一个沉重的问题 A Weighty Issue
睡眠紊乱 肥胖和II型糖尿病 Sleep Disturbances, Obesity and Type 2 Diabetes
流行病的相互作用 Interacting Epidemics
我是托马斯内兰 I'm Thomas Neylan
我来自加州大学旧金山分校的老兵医院 I'm at UCSF's VA
研究睡眠和创伤后精神压力问题 I'm a sleep and PTSD researcher
我很荣幸向大家介绍冯考特博士 And it's a real privilege to introduce Dr. Van Cauter
她是芝加哥大学的医学教授 who is a professor of medicine at University of Chicago
冯考特博士发表了大量的著作 获得了无数奖 Dr. Van Cauter has many grand publications and awards
她所得到的成就 but she has accomplished something
让很多学术界的同行羡慕不已 that most people in academia only dream of
都是一些具有很强冲击力的发现 That is real high impact discovery
她通过严谨的试验设计 And she has really shown through elegant experimental designs
证明了睡眠缺失对代谢 高血糖 the impact of sleep loss on metabolism, hyperglycemia
胰岛素抗性等产生的影响 insulin resistance
她开创了一个新的领域 and she's really helped to create a field
今天的研讨会内容大都在她的研究领域之内 Much of the symposium today is actually Eve's field
所以能向大家介绍冯考特博士我感到十分荣幸 So it's a real privilege to introduce Dr. Van Cauter
谢谢 你讲得太好了 Thank you for the kind words
当然有一些夸张 be exaggerated of course
但我还是接受你的评价 but I'll take it as they are
很高兴今天能为大家做报告 I'm delighted to be speaking to you today
我给大家提供一个视角 I give my perspective
一个我们实验室的视角 which is that of laboratory
在我们的大多数试验中 Most of our work
我们选择的样本都是瘦且健康的年轻成年人 we've taken young healthy lean adults
他们的睡眠很好 who were good sleepers
基线测试显示他们的各方面都很好 and perfectly fine on baseline
然后我们对他们的睡眠进行操作 and we manipulated their sleep
要么改变睡眠长度 要么改变睡眠质量 either the duration or the quality
然后观察会产生什么结果 and we observed the consequences
我不打算给大家讲解这些工作之间的联系 So I'm not discussing associations in most of these works
只讲这些精心控制的条件 We are discussing the consequences
产生了什么后果 of the well-controlled intervention
首先我要让大家回顾一下我们今天讨论的问题 So just to remind you of the scope of the problem that we discuss today
这几张图来自于美国疾病控制中心 These are the maps from the CDC
它们很能说明问题 They are wonderfully illustrative
最上面的显示的是肥胖症的流行情况 The obesity epidemic is on top
下面显示的是糖尿病的流行情况 The diabetes epidemic is at the bottom
两者有着相同的发展趋势 They go hand in hand
从1990到2000年 So from 1990 to 2000
大家可以看到蓝色的部位 you see that the blue had to...
深蓝色的部位扩散了 the dark blue spread
出现了红色的部位 and the red color had to be introduced
这里显示的是近年来的变化情况 These are now the more recent years
2004年 深色部位表示流行程度很高 2004, the darker color represented a higher prevalence
然后是2005年 2005
大家看到2006和2007年扩散得比较厉害
and you see how it's spread in 2006 and 2007
所以很多研究都在进行中 and you see how it's spread in 2006 and 2007
希望搞清楚这种巨大的变化 So there's a lot of work going on
在如此短的时间里如何得以实现 to try to understand how these enormous changes
显然遗传因素无法解释这些疾病的流行趋势 occurred over such a short period of time
人们提出了两个主要原因 其一是 a genetic factor obviously cannot alone explain these epidemics
食品营销方式的转变 And the two major explanations that have been given
人们能够以更低的价格获取大量的食物 are the changes in food marketing practices
而不需要付出太多的努力 where ever larger amounts of food are available at the low costs
另一个原因是体力活动的减少 and without much effort
但大多数专家还是认为这些理由是不充分的 and reduction in physical activity
除了研究关于本地区的非传统因素之外 But most experts believe that these are non-sufficient
人们还研究了 And amongst the ultra-native, non-traditional explanations
睡眠时间缩短和睡眠质量下降所产生的影响 that are being investigated is the possibility
我确实相信 that we have the reduced sleep duration and quality
前面的报告人所提出的各种问题 I do believe that the problems that the previous speakers
非常值得我们进一步探索 brought to our attention
因为这也是在短期内出现的主要变化 is something very well worth exploring
下面给大家看看这场讲座的提纲 because it is also a major change over a short period of time
正因为我认为睡眠很重要 So the overview of my talk
如果你们想打一个小盹 since I believe in the importance of sleep
那么你们可以订好醒来的时间 if you need to take a nap
我首先要讲解睡眠不足和肥胖风险 you can time yourself
然后是糖尿病的风险 I will discuss first insufficient sleep and the risk of obesity
然后讲解睡眠质量不高所产生的影响 then the risk of diabetes
以及睡眠呼吸障碍 then the impact of poor sleep quality
这是可能导致糖尿病的另一种流行病 and obstructive sleep apnea
最后我会简单的讲讲 another epidemic on the risk of diabetes
我会给大家看一些数据 And lastly, just very very briefly
证明睡眠失调 I'll show you some data
会对其他健康问题产生重大影响 that suggest that the presence of the sleep disorder
这张图片是我刚开始研究睡眠问题时制作的 can have a major impact on the severity of another medical condition
所以比较早了 So this is a slide from when I started working in this sleep field
这是一张课堂教学用到的幻灯片 so it's an old slide
睡眠研究学会对其进行了发布 You know, it was a class slide
这是教学第一年所使用的图片 that Sleep Research Society distributed
睡眠行为定义 and it was the year first slide for teaching
大家知道 睡眠是一种低强度的生理活动 Behavioral definition of sleep
有固定的姿势 you know, reduced physical activity
大家可以从这张图上看出 stereotypic posture, etc.
每个物种都有固定的睡眠姿势 and then you have those slide
包括这个美丽的妇人 showing the stereotypic posture for various species
但现在我们有了另一种固定的睡眠姿势 including the lovely woman
大家看到到处都是睡得死沉死沉的健康年轻人 but now we have another stereotypic posture
你们知道 经常你早上11点登机的时候 in that you see young healthy people just deadly asleep anywhere
发现飞机上有半数人在起飞前已经睡着了 You know, it's very common to board a plane at 11 a.m.
因此 似乎我们已经养成了一种奇特的 and half of the cabin is sleeping even before takeoff
睡得很少的睡眠行为 So it seems that we have developed
遗憾的是 a novel behavior of sleeping less
我们关于普通人群中睡眠时间的信息 Unfortunately
都来自于抽样对象的自述报告 a lot of what we know about sleep duration
经常不太准确 in the general population is based on self-report
其次 我们知道有很多人睡眠时间都很短 which is not very accurate often
我们不知道为什么他们的睡眠时间这么短 And secondly, we know that there are a lot of short sleeper
是因为他们严重失眠吗? We don't necessarily know why they are short sleepers
入睡存在困难吗? Are people...do people have more insomnia?
还是因为他们参与了竞争性的活动 More difficulty in achieving sleep
现在有了高科技 电力供应充足 or is it really the competition with all the activities
24小时不间断的生活方式 that are available now thanks to all the technology, the electricity
这些因素都产生了很大的影响 the 24-hour life
这里有一张从一篇评论文章中摘下来的有趣图表 probably plays a major role
我应该把出处标出来 So here is an interesting slide that comes from a review
我认为这张图表很有意思 I should have the reference on there
和今天前面一位报告人的演讲内容有关 but I thought it was interesting
如果大家看看一般人群中 and it connects to the talk of the last speaker of the day
睡眠时间短的人所占的比例 which is that if you look at the prevalence of short sleepers
你会发现不同种族和不同民族显示出了差异 in the general population
这是95年到99年的变化情况 and you look across difference races, ethnic groups
95年用蓝色表示 99年用红色表示 and this is showing the changes from 95 to 99
大家可以看到 95 is in blue and 99 is in red
非洲裔美国人和西班牙裔美国人中 What you can see is that
睡眠时间过短的人的增长比例超过了白人 in African Americans and in Hispanics
而这些人群已经属于 the number of short sleepers has increased more than in whites
某些疾病的高风险人群 And these are populations that are already
特别是心脏代谢类疾病 at a higher risk for variety of diseases
糖尿病 高血压 and particularly cardiometabolic disease
这些疾病都受到了睡眠的严重影响 diabetes, hypertension
因此美国和全世界其他地方 that are majorly impacted as I will show by sleep
这些常见的慢性病之所以存在差异 So there is a possibility
可能与睡眠长短存在差异有关 that health disparities in some of the most common chronic conditions
也许还与人们的社会经济压力有关 in this country and elsewhere could be related to
因为社会经济能力决定了 differences in the sleep duration
他们是否有能力获得充足的睡眠 and perhaps the socioeconomic burden
首先 我要讲第一个问题 on the ability to achieve sufficient sleep
也就是睡眠缺失对肥胖风险的影响 so starting with my first topic
我先要回顾一下我们的实验室研究成果 which is really the impact of sleep loss on the risk of obesity
一开始 第一批研究 I want to review laboratory studies
主要关注的是能量的摄入 And initially, the first studies
但在过去几年当中 were mostly focusing on energy intake
有一些研究开始关注 but in the past few years
天平的另一边 there were a number of studies
即能量的消耗问题 that have looked at energy expenditure
我在此要感谢我的高级合作人 on the other side of the balance
斯彼格博士 And so I want you to pay attribute to my senior collaborator
她是法国国家健康研究所的高级科学家 Dr. Spiegel
她主持了睡眠负债的研究 who is now a senior scientist in the equivalent of the French NIH
睡眠负债会产生很大的影响 She conducted the sleep debt study
在她的帮助下 一个新的研究领域被建立起来 that indeed has had a very high impact
在她主持的研究项目中 and sort of helped to create that field of inquiry
实验室招募了16到19名志愿者 She directed a study where the volunteers...
我刚才已经提到 where 16, 19 were enrolled in the laboratory
这些都是健康的年轻男性 As I mentioned
精瘦 健康 完全没有任何疾病 they were healthy young men
头三天晚上 他们按照推荐的睡眠量睡了8小时 lean, fit, absolutely free of any disease
然后在接下来的6天 The first three nights where they were recommended 8 hours in bed
我们将他们的睡眠时间降到了每晚4小时 And then we reduced their sleep duration
当我们设计这个实验时 to only 4 hours in bed for six nights
我们并不知道 And then, really we didn't know at the time
要还完前6天的睡眠负债 when we designed this experiment
需要多长的时间 how long it would take to pay the sleep debt
因此我们决定连续6天晚上让他们多睡4小时 accumulated over the six nights
然后最后计算睡眠恢复的情况 So we decided to give them back the 4 hours for 6 nights
她在试验开始前和结束时 and evaluated them at the end of that sleep recovery
都对试验参与者进行了血样测试 So she conducted...she did blood sampling
通过葡萄糖耐受力测试 at the beginning and at the end
对他们的葡萄糖耐受力进行了评估 and she also evaluated glucose tolerance
这里是关于瘦素的变化情况 with intervene of glucose tolerance test
大家知道 And here are the findings on the hormone leptin
就在我们开展这项试验的几年前 As you know
瘦素刚刚被发现 leptin was born about a few years
瘦素颠覆了我们对脂肪的认识 before this study was conducted
因为脂肪不再是一种神经元 Leptin revolutionized our view of fat
而是一种内分泌器官 because fat rather than being a nerve dipole
释放出瘦素 was then recognized as an endocrine organ
瘦素由贮脂细胞释放出来 releasing this hormone
和大脑交换信息 And the hormone leptin is released by the lipocyte
大脑中心负责控制饥饿和胃口 and communicates to the brain
以及全身其他各处的能量平衡 brain center that controls hunger and appetite
当瘦素水平很高时 the energy balance of the rest of the body
它传递出饱腹感的信息 When leptin levels are high
不需要更多的热量了 it is communicating a message of satiety
而当瘦素水平变低时 no more calories are needed
传递出的信息是需要摄入热量 When leptin levels are low
而这能够强烈的刺激饥饿感 it is communicating a message of caloric need
因此每晚只睡4小时的志愿者 and it is a powerful stimulator of hunger
他们24小时的瘦素检测显示 So the 24-hour profiles of leptin in the volunteers
他们的瘦素水平很低 with 4 hours in bed indicated
这意味着他们的饥饿感增加 胃口变好 that leptin levels were lower
处在热量不足的状况之下 and that suggested that a state of increased hunger and appetite
我们分析了他们到底是否饥饿 a state of caloric deprivation
他们常常抱怨医院的饭菜不好吃 We had analyzed whether they are hungry or not
无论如何 you know, usually they complained about the food in the hospital
我们不知道他们是否因此感到更饿 in any case, and rightly
但现实情况是 so we don't know whether they were in fact more hungry
他们的瘦素水平出现了很大的差异 But the real problem was this
瘦素水平低转化过来的情况就是 which is a huge difference in leptin
接下来3天他们每天热量的缺口高达1000卡 and translates into of an impression of having been underfed
因此这个影响力是很大的 by about 1000 calories for three days
问题在于他们 So it's a very big impact
两种条件下他们得到的食物完全一样 The problem of this is that they were receiving
因此瘦素在他们睡觉的时候 the exactly same food on the both conditions
就已经在传递信息了 so the leptin levels were screaming
这说明在控制试验中剥夺人们的睡眠 for mean in the mist of blanket
可能提高他们暴饮暴食和增加体重的风险 So that suggested that sleep deprivation in this controlled experiment
我们当然等不及开展进一步的试验 might represent a risk factor for overeating and eventually weight gain
接下来在第二个试验中 We of course were eager to further examine that
我们不光检测了脂肪细胞释放出的瘦素水平 and to follow up with a second study
而且还检测了饥饿素 where not only we measured leptin as the product of fat cells
饥饿素和瘦素正好相反 but we also measured ghrelin
饥饿素越高 人感到越饿 which is the opposite of leptin
饥饿素主要由胃细胞释放 It is that the higher the ghrelin, the more hunger
也主要作用于掌管胃口的下丘脑中心 And ghrelin is released by stomach cells primarily
有时我们把瘦素和饥饿素 and also acts on the same hypothalamic centers that control appetite
比喻为调节胃口的"阴"和"阳" Sometimes leptin and ghrelin are described
因此在这项研究中 as the Ying and Yang of appetite regulation
因为有人对前面的研究提出了批评 So in this study
因此为了答复他们的质疑 我们设计了这个试验 which was partly designed in response
短期的睡眠剥夺 to the criticism of the previous study
随机性的横向设计以及顺序效应 a short period of sleep deprivation
很重要的是 a randomized cross-over design or order effect
我们组织了问卷调查 And then importantly
每个小时了解试验参与者的饥饿和胃口情况 we administered questionnaires
这样我们便知道他们想说什么 about hunger and appetite every hour
以及他们的感受是什么 so that we would know what the volunteers were saying
这里是他们的瘦素水平 were feeling
当试验参与者的睡眠受到限制时 And here are the findings in that the leptin levels
在这张图上 睡眠限制 when the subjects were sleep restricted
风险用红色表示 so in these slides, sleep restriction
他们的瘦素水平便下降了 dangers are always in red
这和我们之前的结论一样 The leptin levels were decreased
但令人吃惊的是 that confirmed what we had seen previously
他们的饥饿水平却上升了 But surprisingly
因此饥饿因素变高了 the ghrelin levels were increased
而饱腹感降低了 so the hunger factor was higher
和这个结果相一致的是 the satire factor was lower
当我们通过问卷调查他们的情况时 And consistent with that
发现他们全天的饥饿感都很强 胃口很好 hunger and appetite were higher at all times of day
我可以告诉大家 when we measured them with these questionnaire
志愿者最想吃的食物是高碳水化合物的食物 I can tell you that the foods that the volunteers
包括糖 咸的食物 were craving mostly were carbohydrates-rich foods
包括椒盐饼 等等 以及高淀粉食物 including the sweets, the salty snacks
我们仍然对这些问题很感兴趣 which include pretzels, etc., and starchy foods
但我们现在能以另一个角度 And so this is a...we are still of course interested in these issue
来看待这些问题 and we are now looking at these issues
这项研究是由塔莎莉主持的 with yet a different protocol
她也是我的主要高级合作者之一 which is led by Dr. Tasali
她制定了随机交叉的试验模式 who was one of my main and most senior collaborator
让这些健康的年轻成年人在实验室呆了5天 And her protocol compares in a randomized crossover design again
要求他们分别睡8.5小时和4.5小时 of young healthy adults for 5 days in the laboratory
在每种条件下的头四天 either with 8.5 hours in bed or 4.5 hours in bed
志愿者得到的食物完全一样 During the first 4 days of each condition
热量摄入也完全一样 the volunteers received exactly the same food
但最后一天 exactly the same caloric intake
就是最后一晚 But the last day
我们给他们安排了即兴自助餐 just before they get their last night here
所以他们突然面对着 they get an ad lib buffet
研究中心厨房能做出的最好的食物 So they are all of a sudden faced with
也就是呈现在这里的 the best the kitchen of the clinical research center can produce
他们在参加营养师研究之前 which is represented here
就已经接受过访问 So they had an interview
所以我们没有将西兰花拿出来 before even starting the study with the dietician
因为有人不喜欢西兰花 so that we are not putting out broccoli out there
那里放置的所有食物 for personal hate broccoli
都是他们通常愿意吃的食物 Everything that is out there is food
我们让他们自己进餐 that they would normally be willing to eat
进餐过程是隐私的 We let them eat by themselves
他们自助午餐吃了1个小时 you know, in privacy
然后得到了额外的一盘小吃 They have an hour to eat lunch buffet
他们有整整一个小时来享受即兴自助的食物 and then there is an additional tray of snacks that is there
当然 They have a full hour time with ad lib food
我们对他们吃的所有东西都进行了测量 And of course
这是测量结果 we measured absolutely everything that they eat
第一批11个试验参与者摄入的热量 And so here are the findings
睡眠剥夺的情况下摄入的热量 The difference in caloric intake in the first 11 subjects in this study
比充分休息时摄入的热量高出430卡 was +430 calories when they were sleep-deprived
主要是通过摄入 as opposed to fully rested
更多的碳水化合物食物实现的 And it was mostly under the form of
我们的这项试验继承了阿金斯博士的研究 increased intake of carbohydrate-rich foods
阿金斯博士认为 如果你的睡眠不足 So we are here partly, as the legacy of Dr. Akins
那么你就会出现进食困难 where it looks as if you are sleep-deprived
如果吃的是阿金斯的食物 那么就更困难了 knew you have trouble following any diet
这是另一些实验室的研究结果 but probably with the Akin's diet even worse
我给大家看的这项试验 Now this kind of work is being going on in other laboratories
是在纽约开展的 and I'd like to show here a study that was conducted at...
试验的主持人是玛丽皮埃尔昂奇 I think it's in New York
这是一个非常类似的随机交叉研究 I think led by Marie-Pierre St-Onge
试验参与者也是健康的年轻人 And it's a very similar randomized crossover design
他们的睡眠时间要么很短 要么正常 of healthy young volunteers
试验也选择了即兴自助 either short sleep or normal sleep
这是肥胖症研究中的标准程序 they also used the ad lib buffet
测试不同药物产生的厌食影响 which is a standard protocol of obesity research to measure
都是通过即兴自助实现的 you know, the anorexic impact of different drugs
所以他们也选择了即兴自助 this ad lib buffet
记录试验参与人的热量摄入增加了300卡 So they used that buffet as well
和我们的结果非常相似 and they recorded an increase of 300 calories
重要的是 这项研究还测量了能量消耗情况 very similar to what we had recorded
使用二重标识水法 Importantly, this study also measured energy expenditure
这是在正常条件下 using the double labeled water method
测量能量消耗的标准方法 which is kind of the gold standard for measuring energy expenditure
然后他们发现没有显著的变化 under normal living condition
这就意味着 热量的摄入有所增加 Then they found no significant differences
但热量消耗却没有增加 And that was so suggesting there is an increased caloric intake
因此有可能出现体重增加 but there is not an increased energy expenditure
这个研究结论和芝加哥大学的一项研究不谋而合 therefore the risk of weight gain
芝加哥大学的研究由佩内夫主持 That was consistent with a study from University of Chicago
他也使用了随机交叉设计 led by Dr. Peneve
在研究中心开展了为期2周的试验 where he used also randomized cross-over design
试验对象分别处于8.5小时 comparing two weeks in the clinic research centers
和5.5小时的睡眠条件之下 either with 8.5 hours in bed
他的试验设计很周到 or 5.5 hours in bed
因为他以"家庭方式" And he was diabolical
向试验参与者提供食物 because what he did is to serve the food
也就是进餐前不会对食物进行测量 in so-called "family style" way
你可以想吃多少吃多少 such that there is no pre-measure serving
其次 since you can help yourself as much as you want
他为志愿者的卧室配备了迷你吧台 And second
当然不提供酒水 he installed mini bars without alcohol of course
志愿者可以自助进餐 in the bedrooms of the volunteers
他们对所有摄入的食物进行了测量 where they could help themselves to as much as they wanted
这项研究的假定前提是 And again, everything was measured
睡眠不足的试验参与人 So the hypothesis of this study was that
比长时间睡眠时吃得多 the subject would eat more under sleep restriction
情况确实如此 than under sleep extension
多余的能量主要从零食中摄入 And that was actually the case
大约也是300卡 but was primarily more from energy intake from snacks
在这个研究中 And it was about 300 calories as well
佩内夫博士及其同事 And here in this study
也用二重标识水法 Dr. Peneve and coworkers
测量了能量的消耗情况 also measured energy expenditures
尽管这种方法非常精确 by the double labeled water method
但他们也没能证明 And even though that method is very precise
两种控制环境下能量消耗存在什么差异 they were unable to show a difference in energy expenditure
因此 能量消耗的问题 between the two conditions
最近得到了人们越来越多的重视 So this issue of, you know, the energy expenditure
因为显然人们这样说 has been more in the limelight lately
如果你长时间保持苏醒状态 because obviously, people are saying
那么哪怕是静止的状态 well, if you are keeping yourself awake a longer time
其实也在消耗能量 even under a sedentary condition
是热量测定实验室进行的一项研究 it has to use some energy
志愿者躺在同样的床上 比较了一夜不睡觉 So there was a study that was done in a calorimetric room
和安睡一夜之间的差别 comparing a full night of sleep deprivation
也就是躺在床上一动不动 versus a full night of sleep in the same bed
这项研究的主持者是 recumbent, etc.
科罗拉多州立大学的卡农斯怀特 showing that this is a study by...
他们的研究证明 Canons Wright at the University of Colarado
一夜不睡觉所消耗的能量 And what they are showing is
一晚上不睡觉所消耗的能量 that the energy cost of a night of sleep loss
消耗的平均能量为143卡 a night without any sleep, is...
少于因睡眠缺乏而摄入的能量 averages 143 calories
另一个问题是 which is less than the stimulation of energy intake
疲劳的试验参与人会从事运动 And the other question is
还是会减少他们的体力活动 whether the tired subject is more likely to exercise
我们希望在实验室找到答案 or to reduce the physical activity
而且我们也确实找到了 We try to do this in the laboratory
但最近 and we were successful
佩内夫博士所领导的研究团队 but recently
他们首先对48名试验参与者 the team of Dr. Peneve was able to show
进行了横断面研究 first in the cross-sectional study
这些招募来的试验参与人 that amongst of a group of 48 individuals
都有II型糖尿病的家族病史 who were recruited
通过活动记录仪对他们的睡眠进行测量 because they were at familial risk for Type 2 diabetes
而他们的能量消耗则通过加速度测定法来测定 And then their sleep was measured by actigraphy
因此那些睡眠时间较短的人 and their energy expenditure was measured by accelerometry
也就是每晚睡眠时间 that in fact, those who were short sleepers
不足6小时 where short sleep was considered
对他们睡眠长度的评判依据不再是自述报告 as less than 6 hours per night
而是测量的结果 not by self-report
他们每天的活动量要少27% by measurement
花在体力活动上的时间也更少 They had 27% of fewer daily activity counts
而且更多的从事静态活动 less time in physical activity
所有这些都是实验室测量的 and remained more sedentary
接下来 去年发表了一项研究显示 And all of these were in the laboratory
这是一项干预性研究 Then in the subsequent study just published last year
对有患II型糖尿病的 it's an intervention study
健康成年人来说 where again, in the healthy adults
研究人员在随机交叉试验中 but at risk for Type 2 diabetes
对睡眠限制和睡眠延时进行了比较 they compared sleep restriction to sleep extension
结果显示 in a randomized cross-over design
睡眠限制与活动水平的降低有关 and showed that in fact
因此 尽管保持苏醒状态 sleep restriction was associated with reduced levels of activity
会消耗能量 So even though the maintenance of wakefulness
但胃口调动起来后 has an energy cost
人们摄入的能量要高于所消耗的能量 this stimulation of appetite is greater
因此白天的时候 than the energy cost
睡眠不足的个体 and then during the daytime
倾向于消耗较少的能量 there's a tendency for the sleep-deprived individuals
这是艾伊恩教授留下的研究数据 to expend less energy
我把它放在这里 So that is kind of a Professor Iyon left
我想他会感到高兴的 so I'm just gonna put that out there
这个变化图说明了 I think he would like this slide
肥胖症和睡眠时间减少的变化趋势 But the shift's illustrating the epidemic of obesity
我刚刚给大家讲到了实验室的研究数据 and the reduction in sleep duration
数据从某种程度上支持这种联系的存在 and I just reviewed with you the laboratory evidence
还提到这些都属于干预性研究 that kind of supports that link in the course of relationship
有大量证据 或大量流行病学证据证明 where those were all interventions studies
我想我们今天已经听过了很多这方面的研究成果 There are large body of evidence or epidemiological evidence
我不想就这个问题继续讲解 that I think we hear more about it today
下面我要讲讲II型糖尿病的风险 but that's not what I want to continue to discuss now
我想提醒大家的是 在第一项研究中 so now I want to discuss the risk of Type 2 diabetes
斯彼格博士实施了静脉内葡萄糖耐受性测试 And to just remind you that in this first study
我再给大家讲讲II型糖尿病是如何发展的 Dr. Spiegel performed this intravenous glucose tolerance test
不是每个人都会出现这个变化 And just to remind the...how Type 2 diabetes evolves
但大多数试验参与人都有 not in everybody
需要胰岛素去利用葡萄糖的器官 but in the majority of the subjects
变得对胰岛素不再敏感 The tissues that need insulin to utilize glucose
这也被称为"胰岛素抗性" become less sensitive to insulin
因此为了达到相同的葡萄糖代谢 also called "insulin resistant"
胰腺中的β细胞就需要释放出更多的胰岛素 So in order to achieve the same glucose metabolism
当到达了某一个临界点时 the beta cells of the pancreas have to release more insulin
β细胞无法释放出足够的胰岛素 If at some point
去控制葡萄糖水平时 the beta cells fail to release enough insulin
糖尿病就发生了 to control glucose levels
我们称之为"前糖尿病" that's the beginning of diabetes
它可能发展成为糖尿病 called pre-diabetes
所以事实上 and then it evolves to diabetes
胰岛素敏感性和β细胞的反应 And so in fact
是互补的 insulin sensitivity and the beta cell response
而作为两者平衡的结果 have to be compensating for each other
就是葡萄糖稳态指数应该保持恒定 and remain...and the product of the two
如果出于某种原因 which is the disposition index has to remain constant
你的胰岛素敏感性降低了 So if for some reason
比如怀孕妇女 you become less insulin sensitive
或者你正在服用某种药物 like a women becomes pregnant
或者你的体重增加了 or you are taking a drug
那么只要你的β细胞 or you put on some weight
能够向上调整胰岛素的分泌水平 as long as your beta cells are able
那么你患糖尿病的风险将不会出现变化 to upregulate the production of insulin
但如果事实上 your diabetes risk will not change
你的β细胞不堪重负 But if in fact
那么这条抛物线将会回到最初的位置 your beta cells cannot accommodate that extra load
你患糖尿病的风险便增加了 then this hyperbola will move to the origin
在斯彼格博士的第一项研究中 and your diabetes risk will be increased
她注意到睡眠缺失会造成胰岛素敏感度的下降 So in this first study of Dr. Spiegel
也就是连续5天 每天只睡4个小时 she noticed a decrease of insulin sensitivity with sleep loss
然而 β细胞不仅没有释放出更多的胰岛素 5 days of 4 hours in bed
去进行弥补 However, the beta cells instead of compensating
释放出的胰岛素反而大幅度减少了 and releasing more
因此 葡萄糖稳态指数 they actually release significantly less
也就是糖尿病风险的标识 And therefore, the disposition index
与糖尿病风险成反比 this marker of diabetes risk
葡萄糖稳态指数越低 inversely related to diabetes risk
糖尿病风险越大 So the lower the disposition index
因此这些人的葡萄糖稳态指数发生了显著变化 the higher the diabetes risk
三年之后 was significantly changed
内德尔查韦研究团队开展了另一项研究 Three years after that
研究对象是体重超重的中年人 Nedeltchava team did another study
比较他们在连续14天每晚只睡5.5个小时的状态 where those were overweight, mid-age individuals
和充分休息的状态 14 nights of 5.5 hours in bed is compared
发现他们的胰岛素敏感性也降低了 to a full rested condition
而β细胞也没有进行弥补 decreased insulin sensitivity
因此他们的葡萄糖稳态指数也下降了 beta cells failing again to compensate
两年前 and therefore, decrease in disposition index
现任哈佛大学教授的巴克斯顿博士 Two years ago
发表了另一项研究 Dr. Buxton now at Harvard
他让健康的年轻人连续6夜每晚只睡5个小时 published this other study
结果他们的胰岛素敏感度也下降了 6 nights of 5-hour bedtimes in healthy young individuals
而β细胞没有做出弥补 decrease of insulin sensitivity
因此他们的糖尿病风险增加了 no compensation by the beta cells
我还可以列举出很多类似的研究 and therefore, decrease in diabetes risk
我只是想向大家说明 And that could put few more of these studies on this slide
实验室研究结论是一致的 just to show you that
也就是说 there is a good consistency in these laboratory studies
原本葡萄糖耐受力正常的人 that all two people who were totally
睡眠受到干扰后 都出现了前糖尿病症状 with normal glucose tolerance at baseline
我想和大家分享这个信息 and who became pre-diabetic after the sleep manipulation
我们很想搞清楚胰岛素敏感度是多少 Now this is to share with you
胰岛素敏感度下降了多少 We were interested to figure out this insulin sensitivity
是否可以在分子层面对其进行测试 this decline in insulin sensitivity
健康人体中最容易获得的样本 Can we measure it at the molecular level
就是脂肪组织了 So one tissue that can be easily sampled
从肚脐周围取一些脂肪组织进行活检并不困难 in healthy humans is adipose tissue
我们问志愿者 It's not difficult to take a biopsy of fat around the umbilicum
是否接受这个小手术 And we asked the volunteers
在正常睡眠情况下做一次 whether they would accept this procedure
然后在一个月的睡眠限制后在做一次 and have it both with normal sleep
这项工作的领导者是 and then a month later with restricted sleep
脂肪细胞生物学家爱尔曼格拉迪 this was really a collaboration led
我们测量了什么呢 by the adipocyte biologist Ehrmann Grady
我们将脂肪细胞进行分离 and what we measured...
我们在脂肪细胞中的测量内容 then the fat cells are isolated
就是胰岛素发出信号过程的第一步 and what we measured in the fat cells
这是细胞膜 is one of the first steps of insulin signaling
这是脂肪细胞内部 So insulin...this is the cell membrane
胰岛素和胰岛素受体联系在一起 this is the inside of adipocyte
形成了胰岛素受体基质 insulin binds to its receptor
下一步就是苏氨酸蛋白激酶的氧化磷酸化过程 It forms this insulin receptor substrates
最重要的一步是 And the next step is phosphorylation of AKT
将葡萄糖运转体放在靠近细胞膜的位置 which is a crucial step
然后把葡萄糖运送到细胞内部 in bringing glucose transporters near the membrane
所以我们这里测量AKT的氧化磷酸化情况 and helping bring glucose inside the cell
这是免疫墨点法得出的结果 So what we measure here is the phosphorylation of AKT
这里是胰岛素 These are immunoblots
所有脂肪细胞 This is the insulin
都面对胰岛素浓度的升高 that every and all the adipocytes
AKT总量是控制 are exposed to increasing insulin concentration
例如 在最上面的部分 Total AKT is the control
第一个墨点显然就表现出了异常 And you see, for example, on top here
胰岛素浓度为0.5纳摩尔 that the first blot that is clearly aberrant
我不打算就这个指标多讲 is at the concentration of 0.5 nanomolar of insulin
但大家可以看出 And then, I'm not going to blabber that
当试验参与者的睡眠被剥夺时 but you can see that
他们需要更多的胰岛素 it takes a larger amount of insulin
才能对等量的AKT进行氧化磷酸化 to phosphorylate the same amount of AKT
这种情况出现在每个试验参与者身上 when the subject is sleep deprived
实际有7名志愿者参与了这项试验 And this was observed in each and every subject
试验将会在两周后结束 There were actually 7 subjects in this experiment
大家到时候可以看到胰岛素的剂量反应曲线 which is coming out next...in two weeks from now
AKT的氧化磷酸化的剂量反应曲线 where you see that the dose response curve of insulin...
胰岛素浓度曲线显然会向右边偏移 of phosphorylation of AKT
因此脂肪细胞出现了胰岛素抗性 to insulin concentration is clearly shifted to the right
这种变化是巨大的 so the adopocyte has become insulin resistance
因为半全反应的胰岛素浓度 And the change is enormous
基本上翻了一番 because the insulin concentration for half maximum response
你需要两倍的胰岛素 is basically doubled
才能对等量的AKT进行氧化磷酸化处理 You need twice as much as insulin
这是一点 to phosphorylate the same amount of AKT
很说明问题 So that is one thing
显示了睡眠剥夺对脂肪细胞的重大影响 It's really demonstrative
我所感兴趣的是 an important impact of sleep deprivation on the adipocyte
睡眠不仅对大脑十分重要 My interest in this, it really is
对身体也同样重要 sleep is not only for the brain
对全身的细胞都很重要 it's also for the body
脂肪需要睡眠来保持正常功能 It's for peripheral cells of the body
如果脂肪需要睡眠 Fat needs sleep in order to function normally
那么肌肉凭什么不需要? If fat needs sleep
凭什么其他部位不需要睡眠? why those muscle needs sleep?
因此这打开了一种可能性 why those...ect
即全身的所有细胞 So it quite opens up the possibility
不仅是脑细胞 that each peripheral cell in the body
都需要睡眠才能保持正常的功能 not only the brain cells
这就是我要讲的内容 really need sleep to function normally
我还想讲讲流行病学方面的内容 So that is...that's the story
因为卡普奇亚博士开展了这项 I want to just...a tiny bit of epidemiology
关注睡眠长短与II型糖尿病发生几率的 because Dr. Capuccia performed
前瞻性元分析研究 these meta-analysis of prospective studies
在这些研究中 relating sleep duration and the incidence of Type 2 diabetes
他们对睡眠长短的基线进行了测量 So these were studies
测量方法是自述报告 where sleep duration was assessed at baseline
然后研究了他们患糖尿病的几率 usually by self-report
研究人员在接下来的一段时间内 and then the incidence of diabetes
对糖尿病的病例进行了统计 the number of diabetes cases was counted
他计算出他们的相对风险为28% in the follow-up period
所以如果你的睡眠时间太短 And he calculated the relative risk of 28%
那么你患II型糖尿病的可能性要高28% so you are 28% more likely to develop Type 2 diabetes
28%的比例在男性身上表现出100%的显著性 if you are short sleeper
在女性身上并不显著 This 28% was actually 100% in men
我有我自己的研究方法 and not significant in women
我密切关注了所有新出来的研究成果 And then I have my own method
这些研究都属于纵向研究 I kind of keep track of all the new studies
因为纵向研究可以说明因果关系的发展方向 that come out looking only at longitudinal studies
然后我将相对风险进行了排序 which because they give some idea as to the direction of causality
黑点处表示不显著 And then I probe the relative risk on the scale
也就是统计数据上不显著 I put black dots when it's not significant
这里表示的是试验参与者的人数 statistically significant
大家可以看到 大多数研究 and here is the number of subjects
都发现睡眠时间短的人 and you see that the majority of studies
患糖尿病的风险更大 have found indeed an increased risk of developing diabetes
下面我想讲一讲睡眠质量低所带来的影响 in short sleepers
这没有考虑睡眠时间长短的因素 So it brings me now to the impact of poor sleep quality
我很荣幸给大家展示 independent of sleep duration
我的同事塔莎莉博士的研究 and gives me pleasure again to showcase
她认为随着年龄的增长 the work of my collaborator Dr. Tasali
人的睡眠质量就会下降 She had thought that poor sleep quality
患糖尿病的风险也会增加 as typical of aging
那么两者之间是否存在风险呢 and the increase of diabetes risk is typical of aging
她想到了一个办法 and could the two be related
也就是将17岁青少年的低质量睡眠 And so she had the idea of
加到20多岁的健康年轻人身上 giving the poor sleep quality of 17-year-old
她在床的两边 to young healthy people in their 20s
各安装了一个扩音器 And so she did that by installing
然后她呆在控制室里 on each side of the bed amplifiers
每当志愿者进入深度睡眠时 and then she was in the control room
也就是慢波睡眠阶段时 And each time the volunteer would enter the deep sleep
她会发出尖锐的强度较大的声音 also called slow-wave sleep
并对声音进行校正 she would send a sound of pitch and intensity
这样志愿者虽然没有醒来 calibrator so that the volunteer
但马上又回到了浅睡状态 would not wake up
她这样连续干了三个夜晚 but would immediately revert to shallow sleep
她其实是个好人 and she did that for 3 nights in a row
这是一个难度很大的试验 She's normally a very nice person
她成功了 And so...this is a very difficult experiment
因为她把慢波睡眠的时间从80分钟 She was very successful
健康年轻人的正常慢波睡眠时间就是80分钟 in that she was able to reduce slow-wave sleep from 80 minutes
降到了10分钟以下 which is the normal amount in young healthy subjects
连续三个晚上 to less than 10 minutes
但没有改变睡眠的整体时间 3 nights in a row
因此试验参与者并没有完全醒来 without changing total sleep time
他们的快速眼动期睡眠时间并没有改变 so the subjects did not fully aroused
她观察到 and without changing REM sleep time
试验参与人的胰岛素敏感性降低了 and then what she observed
你们记得这个内容吧 is a decrease of insulin sensitivity
而β细胞产生的胰岛素却没有变化 You remember that already
也就是没有增加胰岛素的量 No change in beta cell function
没有对此进行补充 no increased release of insulin
因此他们的葡萄糖稳态指数出现了下降 no compensation
显示出糖尿病的风险上升 and therefore, a decrease in disposition index
他们的葡萄糖耐受力也降低了 indicating an increase in diabetes risk
如果我们从流行病学的角度去看 and the glucose tolerance was decreased
抱怨难以安睡的人 And if we look at epidemiology again
这又是自述报告 是通过问卷调查完成的 people who complain about difficulty in maintaining sleep
他们患糖尿病的风险更高 this is self-report again, this is questionnaires
我用简单的方法对各种研究文献进行了总结 are indeed also more likely to develop diabetes
这些都是严格的前瞻性研究 And this is my little way to summarize the literature
研究人员询问试验参与人的睡眠质量 in strictly prospective studies
并以此作为基线 where individuals at baseline
然后估计偶发性糖尿病的病例数量 were asked about their sleep quality
这就引出了我的下一个主题 And then the number of cases of incident diabetes was estimated
也就是所谓的"糖尿肥胖症" So this brings me to the next topic
是由"肥胖"和"糖尿病"两个词组成的 which is of course the epidemic of the so-called "diabesity"
这个状况与另一个流行病有关 the combination of "obesity" and "diabetes"
也就是睡眠呼吸障碍 is associated with another epidemic
睡眠呼吸障碍是一种睡眠紊乱 the epidemic of obstructive sleep apnea
其特征是反复的 Obstructive sleep apnea is a sleep disorder
上呼吸道完全或部分堵塞 characterized by recurrent episodes
据报告 这一疾病的发病率为 of complete or partial upper airway obstruction
男性24% 女性9% The prevalence used to be
这个里程碑性质的论文作者是特里杨 reported as 24% in men and 9% in women
我想发表于1993年 This was a landmark paper by Terry Young
但是今天 由于肥胖症 I think it was in 93
睡眠呼吸障碍的发生率 But today, because the epidemic of obesity
有了很大的提高 the prevalence of obstructive sleep apnea
特别是女性 has increased enormously
女性过去受到了很好的保护 And particularly in women
但现在50%的肥胖女性 who used to really be very protected
都存在睡眠呼吸障碍 but now we have up to 50% of obese women
这是一种复杂的睡眠紊乱 who have obstructive sleep apnea
因为它具有各种不良的要素 It's a complex sleep disorder
它通常会导致睡眠时间缩短 in that it has all the bad ingredients
我们刚才已经谈到这个问题了 So it's generally associated with reduced total sleep time
会造成睡眠不连贯 and we have talked about that already
这是我一会儿要讨论的问题 It's associated with sleep fragmentation
慢波活动的降低 I will discuss that in a minute
这是塔莎莉博士的试验结论 Low slow-wave activity
她在卧室里发出了讨厌的声音 This was Dr. Tasali's experiment
然后是间歇性缺氧 with diabolic sounds coming into the room
而这又会损害葡萄糖耐受力 And then it has intermittent hypoxia
在这个图表中 which in itself is also deleterious to glucose tolerance
我对三个不同实验室的研究结论 And in this slide
进行了总结 I'm just summarizing the findings
其中两项试验是约翰霍普金斯大学 of three different laboratory studies
以及塔莎莉博士的研究 two from John Hopkins
他们在实验室中 and Dr. Tasali's study
对健康的年轻人模拟了各种睡眠呼吸障碍的情况 where different components of obstructive sleep apnea
在这项研究中 were mimicked in the laboratory in healthy young subjects
庞加比和斯坦马塔奇斯 So in this study
将睡眠的各个阶段都考虑了进来 Punjabi and Stamatakis
不仅仅是慢波睡眠 induced all stage sleep fragmentation
发现他们的胰岛素敏感性都出现了下降 not specific the slow-wave sleep
然后 庞加比和其他人 and also showed the reduction of insulin sensitivity
对苏醒的试验参与人进行了研究 And then, Punjabi and others
对5个小时的间歇性缺氧和常氧状态进行了比较 did a study in the wake subjects
发现他们的胰岛素敏感性出现了下降 but 5 hours of intermittent hypoxia is compared to normoxia
我给大家看看... and showing again a decrease of insulin sensitivity
变化程度为 I want to just give you a little...
胰岛素敏感性通常降低了25% you know, these changes
所以对于正常的健康的瘦型成年人来说 are typical 25% decrease in insulin sensitivity
胰岛素敏感性每降低25% So for normal healthy lean person
会让他们的体重增加10公斤 a 25% decrease of insulin sensitivity
所以这是个不小的变化 will occur with about a 10-kilo weight gain
是个很大的变化 So it's not a small change
霍普金斯大学的同样的研究团队 It's a big change
对住院病人进行了测试 The same team at Hopkins
这些病人都不是糖尿病患者 examined then inpatients
研究人员用静脉内葡萄糖耐受力测试方法 non-diabetic patients
研究了睡眠障碍对胰岛素敏感性的影响 using this intravenous glucose tolerance test
这些属于实验室进行的横断面研究 the impact of obstructive sleep apnea on insulin sensitivity
很多人参与了这项评估活动 So these are cross-sectional laboratory studies
研究人员对试验参与人进行了分类 A large number of people for this kind of assessment
分类依据是呼吸障碍-呼吸浅慢指数 and people were stratified
该指数可以对睡眠呼吸障碍的严重程度进行量化 according to the apnea-hypopnea index
如果你每小时出现5次以下的呼吸障碍 which quantifies the severity of obstructive sleep apnea
那么你就不算患有睡眠性呼吸障碍 This is considered...if you have less than 5 events per hour
5到15次 可能患有 you are considered not to have sleep apnea
15到30次 中度障碍 5 to 15 might
超过30次 严重障碍 15 to 30 moderate
可以看到睡眠性呼吸障碍和胰岛素敏感性之间 and over 30 severe
存在分级化的联系 And you can see the graded relationship
对睡眠性呼吸障碍的个体进行前瞻性研究显示 between the severity of obstructive sleep apnea and insulin sensitivity
他们患糖尿病的风险很高 Prospective studies of individuals with obstructive sleep apnea
最后我想简单讲讲 are suggestive of an increased risk of developing diabetes
如果你已经得了糖尿病 Lastly, I want to say two words about
而你又同时患有睡眠性呼吸障碍 what happens
情况会怎么样 if you are already diabetic
首先 and you have obstructive sleep apnea
从过去几年发表的数据来看 So the first thing is that
有证据证明 II型糖尿病患者 from data published over the last few years
出现睡眠性呼吸障碍的比例特别的高 it has emerged that Type 2 diabetes
从这5项研究可以看出 is associated with exceptionally high prevalence of sleep apnea
加权平均值为68% From these 5 studies
也就是说每3名II型糖尿病患者中 the weighted average is 68%
有2个人同时存在这两种疾病 meaning that 2 out of 3 patients with Type 2 diabetes
大多数时候 who go to see their doctors, actually have this comorbidity
他们自己和他们的医生对此并不知情 and most of the time
这张图表 neither them or their doctors knows about it
对不同疾病患者中 So this is the...this is a slide
睡眠性呼吸障碍的发病率进行了总结 that kind of has tried to summarize the prevalence
大家可以看出 of obstructive sleep apnea in different disease states
II型糖尿病患者中 And you will see that it seems
睡眠性呼吸障碍的比例最高 that Type 2 diabetes may
这里很重要的一点是 be associated with the highest degree of OSA
为了控制葡萄糖 and then what's important here
如果II型糖尿病患者要控制糖尿病 is this analysis where glucose control which is really
他们需要服用1种 2种3种药物 you know, how well the diabetes is controlled in patients
那么睡眠性呼吸障碍有哪些影响呢 who have Type 2 diabetes and take 1, 2, 3 drugs
因此我们将其与没有睡眠性呼吸障碍 what is the impact of having OSA
中度睡眠性呼吸障碍进行了比较 So it is compared to not having OSA
他们的血红蛋白A1c会增加1% having even mild OSA
如果你患有糖尿病 is associated with an increase in hemoglobin A1c of 1%
如果想让血红蛋白Aic降低1% I can tell you to get a decrease of 1% in your hemoglobin A1c
你至少要服用一种药物 if you are diabetic
然后严重的睡眠性呼吸障碍的对象 you have to take at least one drug
与无睡眠性呼吸障碍的对象进行了比较 And having severe OSA
发现他们的血红蛋白A1c升高了2% is compared to no OSA
那么需要服用2到3种药物才能达到这个效果 is associated with an increase in hemoglobin A1c by 2%
这也是一个横断面研究 which is really the equivalent of 2 to 3 drugs
并没有告诉我们 Now this is a cross-sectional analysis
因果关系的发展方向 It doesn't have...doesn't tell us about
显然 主要的问题是 the direction of causality
对睡眠性呼吸障碍的有效治疗 And clearly the major questions are
能够改变II型糖尿病患者的血糖 whether effective treatment of OSA
目前的数据显示 can improve glycemic control in patients with Type 2 diabetes
尽管有很多研究团队致力于这个问题的研究 The data so far
但这个问题的答案还不确定 even though quite a number of groups are working on this
而且也不是那么鼓舞人心 remain somewhat inconclusive
当然其中一个问题是 not terribly encouraging
患者的依从性还比较低 One issue of course is compliance
第二个问题是 which is generally low
对睡眠性呼吸障碍的有效治疗 and the second question would be
如果我们确实有治疗方法 does effective treatment of OSA
而且试验对象也比较依从 if we had a treatment
那么这种方法能否减缓II型糖尿病的发展 to which the subject would be really compliant
或是减轻其严重程度? would it delay the development of Type 2 diabetes
我把这些问题留给大家 or reduce the severity
我想感谢在这个领域 And with these thoughts
和我共事的这些研究人员 I will thank the numerous people
他们给了我很多支持 who are working in this area with me
当然还要感谢我们的研究经费的来源机构 I'm in debt to their efforts
我们会不断的打交道 and also of course, the funding agencies
谢谢大家认真听我的报告 whom we are battering nonstop
这是个很好的问题 很重要 And so l'd like to thank you for your attention
我们的研究很少有女性参与进来 It's a good and important question
除了塔莎莉博士对睡眠质量下降的研究之外 We have very few women in our studies
她的研究中一半试验参与者为女性 excepting Dr. Tasali's study of reduced sleep quality
我们没有发现性别差异 It was about half women
在睡眠限制的研究中 and we did not see a sex difference
大多数研究只招募男性志愿者 In the studies of sleep restriction
原因是 most of our studies have enrolled a majority of men
你们知道 and the reason for that is that
葡萄糖的耐受力会受到月经周期的影响 as you know
所以如果招募女性参与这些随机交叉试验 glucose tolerance is influenced by the phase of the menstrual cycle
她们必须在两种条件下都恰好处于卵泡期 So when you enroll women in these randomized cross-over design
也就是说她们的月经周期必须规律 they have to be in the follicular phase in both conditions
这意味着她们不能这样 只能那样 等等 which means they have to have regular cycles
所以情况会变得比较困难 which means they don't...they have and so on
我一直觉得我们付给女性的费用 And so it becomes very difficult
应该是男性的三倍 I always think we should pay women
但我们的老板不同意 three times as many...as much as men...
第一项研究的顺序效应 but our RB doesn't think so
当然遭到了一些批评 So the order effect of the first study
他们认为我们制造了睡眠负债 was of course a criticism that came up
然后我们让试验参与人补回来 that we had built a sleep debt
所以这并没有真正对 and then the subject we cover the sleep
正常睡眠和限制睡眠进行比较 so it was not really comparing
这就是为什么我们开展了第二次试验 normal sleep to sleep restriction
也就是针对短期睡眠和长期睡眠 which is why we did the second study
制定的随机交叉试验 which was a randomized cross-over design
我们在任何条件下 of short sleep versus long sleep
都没有再次得到有关瘦素的研究结论 the leptin findings have not been reproduced
因为只要身体质量发生变化 even by ourselves under all conditions
体内的脂肪比例发生变化 As soon as there is a change in body mass
瘦素水平就会相应的调整 change in percentage of fat
因此很难证明睡眠长短会造成什么影响 leptin levels are very reactive to that
有一些流行病学的研究 And it's difficult then to show an impact of sleep duration
发现对其他辅助因素进行了控制之后 There have been epidemiology studies
睡眠时间短的人 瘦素水平也低 who have found reduced leptin levels in those with short sleep
听不清 after controlling for a number of cofactors
这是一个重要而有趣的问题 Inaudible
我刚才没有讲 That's a very important and interesting question
我想我可以给大家分享一个经验 and it has not been addressed
这是另一套知识 I think I can share the one experience that there was a novel...
制药公司已经发现 set a different knowledge and development
那些被随机分配到活性药物小组的人 that pharmaceutical company had noticed
和分配到无效对照剂小组的人 that there was a small decrease in BMI
前者的身体质量指数更高 in those randomized to the active drug
所以他们叫我过去开发一个测试程序 as compared to the placebo
结果高级领导层 And so they called me in to develop a protocol to examine that
决定不将这项研究继续下去 and then the upper management
我的项目就被扔进了垃圾桶 decided not to continue the development
感谢你带给我们的这场令人惊叹的演讲 And my project was in the trash can
你的研究非常的重要 Thank you for that amazing talk
我想请你评价一下 Your work is so important
三种持续时间不同的压力 I was wondering if you could comment a little bit
短期压力 长期压力和抑郁 on any of these three periods of stress
它们之间可能有怎样的交叉... So acute stress, chronic stress and depression
听不清 How they might interact...
压力的问题 Inaudible
谢谢你 爱丽莎 The issue of stress...
谢谢你的评论和问题 thank you Elisa
关于压力的问题 for the comments and for the question
在这样的讨论环节当中 The issue of stress comes up...
经常有人提出这个问题 this question comes up a lot
在一些研究中 in the discussion periods like this one
我们测量了试验参与者在睡眠受限的情况下 In a number of studies
24小时的皮质醇变化情况 we've measured the 24-hour profile of cortisol
我们看到他们的皮质醇水平出现了升高 and with sleep restriction
这可能会影响到 we observed the increase even in cortisol levels
试验参与人胰岛素抗性的升高 that is likely to have played
然而 当我们要求试验参与人 a role in the increased insulin resistance of the subject
对实验室每天感受到的压力 However, when we asked the subjects
做一个分级式评分时 to score their stress on the scale day to day
他们给自己的分数显示 他们并不感到压力 after in the laboratory
他们感觉自己很累 they do not score themselves as being more stressed
情绪不高 等等 They scored themselves as being tired
但是全方位分析来看 as having a lower mood, and things like that
专门针对压力的评分 but in the pan analysis
他们并没有在压力那一项打很高的分数 objective that's specifically address stress
我感觉我们的研究在这方面是不完美的 they are not...they don't have increased scores
因为志愿者来到实验室之后 And I really think that our studies are flawed in this respect
他们只需按照要求做事 because the volunteers come into the lab
他们吃饭 and they just have to follow these instructions
在电视前玩耍 they receive their meals
每当我们发现他们有一点累了 they play in front of the television
研究助理就会过来 and as soon as we see them a little bit tired
带来更多的游戏 新的游戏 a research assistant comes in
新的电影 新的影片 with some more games, new games
他们不需要自己去应对任何事情 new films, new video
现实生活中睡眠缺失的人 They don't have a thing to deal with
必须自己去做事情 The real life of a person who is sleep deprived
情况是完全不同的 and has to get things done
我们一直梦想开发一个实验室设计 is completely different
志愿者需要完成一些任务 and that it is a dream of developing a lab protocol
如果完不成 他们就会受到一些惩罚 where there would be tasks to do
这是难以实现的 And you know, some sort of punishment if they don't get done
但毫无疑问 some sort of...you know, it would be difficult
我想我们的条件是一种理想条件 but certainly
实验室很舒适 I think that the...we have the ideal condition
房间就像假日酒店一样 the lab is nice
食物不算最好 但也凑合 the rooms are like a nice holiday inn
而且工作人员也很好 非常愿意帮助他们 the food is not great, but it's quite ok
他们随时都在说 The people are very nice, very supportive
别睡 你做得很好 你做得很好 they are plod you all the time
这不是真实的生活 stay awake. You did great, you did great
所以我认为 That's not real life
现实生活中睡眠缺失 So I think that
长期的部分睡眠缺失所造成的影响 the impact of sleep deprivation
要比我们在实验室测量到的结果更大 chronic partial sleep deprivation in real life is greater
所以我们看到的只是一部分 than what we are measuring here in the lab
提到失眠 So that's one part
我对艾丽沙刚萨斯的研究很感兴趣 Regarding insomnia
他考察了失眠人群的 I think that I'm fascinated with the work from Elise Gansas
皮质醇水平 where he examined the cortisol profile
通过睡眠多项生理检查发现 of people with insomnia
那些自认为失眠的人 which...who based on polysomnography
在实验室其实睡得很正常 have insomnia complaints
或者自认为失眠的人 but normal sleep time in the lab
在实验室睡觉时 睡眠时间也很短 or the insomnia complaints
他指出 那些在实验室睡眠时间很短的人 and short sleep time in the lab
他们的皮质醇水平出现了升高 And he showed that those with short sleep time in the lab
而那些在实验室正常睡觉的人 really had elevated even in cortisol levels
他们的皮质醇水平也正常 And those with normal sleep time in the lab
我认为这个现象很有趣 had normal cortisol levels
因为我认为睡眠时间长短 And I think this is really interesting
比睡眠质量 because sleep duration I think
更能影响促肾上腺皮质的分泌 is more important for the corticotropic access
当我们在试验参与人正常睡眠的时间里 than sleep quality
对他们的睡眠进行限制时 So when we restrict sleep during the hours
我们会把灯光调暗 that the subjects would normally be sleeping
但不会全关 we dimmed the lights
因为如果把灯全部关掉 but not to extremes
试验参与人就很难保持苏醒状况了 because if we go to extremes
所以房间的灯光强度是设定了级别的 it would be very hard for them to stay awake
在正常的夜间时期 So there is a gradation in the light intensity in the room
我们会调低灯光的强度 where during the normal nocturnal period
但我觉得你的问题非常重要 we reduced light intensity
因为GMY联系研究 but your question I think is an important one
得出的数据显示 because there is new data that have emerged
夜间褪黑素水平的升高 from GMY Association studies
会增加糖尿病的风险 indicating that the nocturnal elevation of melatonin
特别是改变β细胞的功能 could play a role in the risk of diabetes
因此 哪怕是一点点灯光 beta cell function particularly
也能够抑制褪黑素的分泌 And so if...even a small amount of light
从而影响到 can inhibit melatonin release
葡萄糖耐受力的降低 and could have contributed to
所以这个问题提得很好 our observation of reduced glucose tolerance