Adverse metabolic and cardiovascular consequences of circadian misalignment

TLDR

Shift work is linked to higher obesity, diabetes, and cardiovascular disease risk, likely due to maladaptation from chronically sleeping and eating at abnormal circadian times. The study aimed to elucidate how misalignment between behavioral cycles and endogenous circadian rhythms affects metabolic, autonomic, and endocrine risk factors for obesity, diabetes, and cardiovascular disease. Ten adults underwent a 10‑day protocol with a 28‑hour day, eating four isocaloric meals and sleeping at all circadian phases while hourly plasma leptin, insulin, glucose, cortisol, urinary catecholamines, and daily cardiovascular and sleep metrics were recorded, with core body temperature logged continuously. Circadian misalignment reduced leptin, increased glucose and insulin, reversed the cortisol rhythm, raised mean arterial pressure, lowered sleep efficiency, and caused prediabetic‑range postprandial glucose in 3 of 8 subjects, underscoring its adverse cardiometabolic impact.

Abstract

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.