Adverse metabolic and cardiovascular consequences of circadian misalignment – Source: Proceedings of the National Academy of Sciences, Mar 2, 2009

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-hour “day.” Subjects ate 4 isocaloric meals each 28-hour “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 hours out of phase from their habitual times:

• Systematically decreased leptin (down 17%, P < 0.001) [leptin is a hormone that regulates body weight, metabolism and reproductive function], • Increased glucose [blood sugar] (up 6%, P < 0.001) despite increased insulin (up 22%, P = 0.006), • Completely reversed the daily cortisol rhythm (P < 0.001) [cortisol is known as the 'stress response' or energy/wakefulness hormone, and is normally highest in the morning, lowest at night],

• Increased mean arterial pressure (up 3%, P = 0.001),

• And reduced sleep efficiency (down 20%, P < 0.002). Notably, circadian misalignment caused 3 of 8 subjects (with sufficient available data) to exhibit postprandial [after meal] 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. Source: Proceedings of the National Academy of Sciences, Mar 2, 2009. [Online before print] PMIDPMID: 19255424, by Scheer FAJL, Hilton MF, Mantzoros CS, Shea SA. Division of Sleep Medicine, Brigham and Women’s Hospital; Harvard Medical School, Harvard University; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. [E-mail:]

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