Adverse metabolic and cardiovascular consequences of circadian misalignment

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 11; pp. 4453 - 4458
• Main Authors: Scheer, Frank A.J.L, Hilton, Michael F, Mantzoros, Christos S, Shea, Steven A
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 17.03.2009; National Acad Sciences
• Series: From the Cover
• Subjects: Adult; adults; Biological Sciences; Blood pressure; Body temperature; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - etiology; catecholamines; Chronobiology Disorders - complications; Chronobiology Disorders - metabolism; Circadian rhythm; Circadian Rhythm - physiology; Circadian rhythms; cortisol; Diabetes; Eating; Effects; Fasting; Female; females; glucose; Health risks; Heart rate; Humans; ingestion; Insulin; leptin; Male; Metabolic diseases; Metabolic Diseases - etiology; Metabolism; Norepinephrine; Obesity; Oxygen consumption; Postprandial Period; Prediabetic State - etiology; risk; Risk factors; Shift work; Sleep; Type 2 diabetes mellitus; Wakefulness; work schedules
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.0808180106

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 [almost equal 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 [almost equal 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.