Scheer Frank A J L, Hilton Michael F, Mantzoros Christos S, Shea Steven A
Division of Sleep Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4453-8. doi: 10.1073/pnas.0808180106. Epub 2009 Mar 2.
There is considerable epidemiological evidence that shift work is associated with increased risk for obesity, diabetes, and cardiovascular disease, perhaps the result of physiologic maladaptation to chronically sleeping and eating at abnormal circadian times. To begin to understand underlying mechanisms, we determined the effects of such misalignment between behavioral cycles (fasting/feeding and sleep/wake cycles) and endogenous circadian cycles on metabolic, autonomic, and endocrine predictors of obesity, diabetes, and cardiovascular risk. Ten adults (5 female) underwent a 10-day laboratory protocol, wherein subjects ate and slept at all phases of the circadian cycle-achieved by scheduling a recurring 28-h "day." Subjects ate 4 isocaloric meals each 28-h "day." For 8 days, plasma leptin, insulin, glucose, and cortisol were measured hourly, urinary catecholamines 2 hourly (totaling approximately 1,000 assays/subject), and blood pressure, heart rate, cardiac vagal modulation, oxygen consumption, respiratory exchange ratio, and polysomnographic sleep daily. Core body temperature was recorded continuously for 10 days to assess circadian phase. Circadian misalignment, when subjects ate and slept approximately 12 h out of phase from their habitual times, systematically decreased leptin (-17%, P < 0.001), increased glucose (+6%, P < 0.001) despite increased insulin (+22%, P = 0.006), completely reversed the daily cortisol rhythm (P < 0.001), increased mean arterial pressure (+3%, P = 0.001), and reduced sleep efficiency (-20%, P < 0.002). Notably, circadian misalignment caused 3 of 8 subjects (with sufficient available data) to exhibit postprandial glucose responses in the range typical of a prediabetic state. These findings demonstrate the adverse cardiometabolic implications of circadian misalignment, as occurs acutely with jet lag and chronically with shift work.
有大量流行病学证据表明，轮班工作与肥胖、糖尿病和心血管疾病风险增加有关，这可能是由于生理上对长期在异常昼夜节律时间睡眠和进食的适应不良所致。为了开始了解潜在机制，我们确定了行为周期（禁食/进食和睡眠/觉醒周期）与内源性昼夜节律周期之间的这种失调对肥胖、糖尿病和心血管疾病风险的代谢、自主神经和内分泌预测指标的影响。10名成年人（5名女性）接受了一项为期10天的实验室方案，在此期间，受试者在昼夜节律周期的所有阶段进食和睡眠，这是通过安排一个重复的28小时“一天”来实现的。受试者每28小时“一天”吃4顿等热量餐。在8天的时间里，每小时测量血浆瘦素、胰岛素、葡萄糖和皮质醇，每2小时测量尿儿茶酚胺（每位受试者总共约1000次检测），每天测量血压、心率、心脏迷走神经调节、耗氧量、呼吸交换率和多导睡眠图睡眠情况。连续记录10天的核心体温以评估昼夜节律相位。当受试者进食和睡眠时间与其习惯时间相差约12小时时，昼夜节律失调会系统性地降低瘦素水平（-17%，P<0.001），尽管胰岛素水平升高（+22%，P=0.006），但葡萄糖水平仍会升高（+6%，P<0.001），完全逆转每日皮质醇节律（P<0.001），增加平均动脉压（+3%，P=0.001），并降低睡眠效率（-20%，P<0.002）。值得注意的是，昼夜节律失调导致8名受试者中的3名（有足够的可用数据）出现了处于糖尿病前期状态典型范围内的餐后血糖反应。这些发现证明了昼夜节律失调对心脏代谢的不利影响，如在时差反应中急性发生以及在轮班工作中长期发生的情况。
