Adverse metabolic and cardiovascular consequences of circadian misalignment
Adverse metabolic and cardiovascular consequences of circadian misalignment
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DOI：
10.1073/pnas.0808180106
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发表时间：
2009-03-17
影响因子：
11.1
通讯作者：
Shea, Steven A.
中科院分区：
文献类型：
--
作者：
Scheer, Frank A. J. L.;Hilton, Michael F.;Shea, Steven A.
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的风险增加有关，这可能是生理上对在异常的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因子的影响。10名成年人（5名女性）接受了一项为期10天的实验室方案，在该方案中，受试者在昼夜节律周期的各个阶段进食和睡眠——通过安排一个重复的28小时“一天”来实现。受试者在每个28小时“一天”中进食4顿等热量的餐食。在8天时间里，每小时测量一次血浆瘦素、胰岛素、葡萄糖和皮质醇，每两小时测量一次尿儿茶酚胺（每个受试者总计约1000次检测），并且每天测量血压、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10天记录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（-17%，P<0.001），尽管胰岛素增加（+22%，P = 0.006）但仍会使葡萄糖升高（+6%，P<0.001），完全逆转每日皮质醇节律（P<0.001），使平均动脉压升高（+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名受试者中有3名（有足够可用数据）在餐后出现处于糖尿病前期典型范围的血糖反应。这些发现表明了昼夜节律失调对心脏代谢的不良影响，就像时差反应时急性发生以及轮班工作时慢性发生的情况一样。
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 approximate to 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 approximate to 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.