Adverse metabolic and cardiovascular consequences of circadian misalignment

被引:1569
作者
Scheer, Frank A. J. L. [1 ,2 ]
Hilton, Michael F. [1 ]
Mantzoros, Christos S. [2 ,3 ]
Shea, Steven A. [1 ,2 ]
机构
[1] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
[3] Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA
关键词
autonomic nervous system; diabetes; glucose metabolism; leptin; obesity; DORSOMEDIAL HYPOTHALAMIC NUCLEUS; BODY-MASS INDEX; SLEEP DURATION; POSTPRANDIAL HORMONE; SHIFT WORK; LEPTIN; CORTISOL; GLUCOSE; EXPRESSION; RESPONSES;
D O I
10.1073/pnas.0808180106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:4453 / 4458
页数:6
相关论文
共 50 条
[1]   A clinical trial of the effects of dietary patterns on blood pressure [J].
Appel, LJ ;
Moore, TJ ;
Obarzanek, E ;
Vollmer, WM ;
Svetkey, LP ;
Sacks, FM ;
Bray, GA ;
Vogt, TM ;
Cutler, JA ;
Windhauser, MM ;
Lin, PH ;
Karanja, N .
NEW ENGLAND JOURNAL OF MEDICINE, 1997, 336 (16) :1117-1124
[2]  
Borbely A A, 1982, Hum Neurobiol, V1, P195
[3]   Drug Insight: the role of leptin in human physiology and pathophysiology - emerging clinical applications [J].
Brennan, Aoife M. ;
Mantzoros, Christos S. .
NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM, 2006, 2 (06) :318-327
[4]   Organization of circadian functions: interaction with the body [J].
Buijs, Ruud M. ;
Scheer, Frank A. ;
Kreier, Felix ;
Yi, Chunxia ;
Bos, Nico ;
Goncharuk, Valeri D. ;
Kalsbeek, Andries .
HYPOTHALAMIC INTEGRATION OF ENERGY METABOLISM, 2006, 153 :341-360
[5]  
Camm AJ, 1996, CIRCULATION, V93, P1043
[6]   The pancreatic β cell is a key site for mediating the effects of leptin on glucose homeostasis [J].
Covey, Scott D. ;
Wideman, Rhonda D. ;
McDonald, Christine ;
Unniappan, Suraj ;
Huynh, Frank ;
Asadi, Ali ;
Speck, Madeleine ;
Webber, Travis ;
Chua, Streamson C. ;
Kieffer, Timothy J. .
CELL METABOLISM, 2006, 4 (04) :291-302
[7]  
CZEISLER CA, 1999, SCIENCE, V284, P2177, DOI [10.1126/science.284.5423.2177, DOI 10.1126/SCIENCE.284.5423.2177]
[8]   METABOLIC EFFECTS OF THE NOCTURNAL RISE IN CORTISOL ON CARBOHYDRATE-METABOLISM IN NORMAL HUMANS [J].
DINNEEN, S ;
ALZAID, A ;
MILES, J ;
RIZZA, R .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (05) :2283-2290
[9]   Differential rescue of light- and food-entrainable circadian rhythms [J].
Fuller, Patrick M. ;
Lu, Jun ;
Saper, Clifford B. .
SCIENCE, 2008, 320 (5879) :1074-1077
[10]   Short sleep duration as a risk factor for hypertension - Analyses of the first national health and nutrition examination survey [J].
Gangwisch, JE ;
Heymsfield, SB ;
Boden-Albala, B ;
Buijs, RM ;
Kreier, F ;
Pickering, TG ;
Rundle, AG ;
Zammit, GK ;
Malaspina, D .
HYPERTENSION, 2006, 47 (05) :833-839