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Fatigued Patients with Chronic Liver Disease Have Subtle Aberrations of Sleep, Melatonin and Cortisol Circadian Rhythms.

ABSTRACT: Aims:We sought to examine whether disturbances in central and peripheral circadian rhythms were related to the experience of fatigue in patients with chronic liver disease (CLD). Methods:Fatigued and non-fatigued patients with compensated CLD were enrolled in a prospective pilot study. Patients underwent a one week evaluation of free-living sleep and physical activity patterns, followed by a 24-hour admission, during which they underwent serial blood sampling, polysomnography, a 6-minute walk test and continuous core temperature measurements under standardized conditions. Blood samples were analyzed for liver tests, melatonin levels, lipids, and cortisol. Circadian rhythms were analyzed using single cosinor analyses. Results:Six fatigued and six non-fatigued patients were studied; five participants had cirrhosis. Fatigue severity was positively associated higher peak melatonin levels (rho=0.59, p=0.04) and a delay in night-time melatonin peak and inversely associated with sleep efficiency (rho=-0.63, p=0.04). Polysomnography, 6-minute walk test, and core temperature measurements did not differ significantly between the fatigued and non-fatigued patients. Although liver enzymes, bilirubin and albumin demonstrated a circadian pattern, it was not associated with fatigue. Fatigued patients showed a blunted and delayed cortisol rhythm and fatigue was strongly correlated with cortisol amplitude (rho=-0.77, p=0.004) and phase (r=-0.66, p=0.02). Conclusion:Subtle aberrations in melatonin and adrenal circadian rhythms, as well as reduced sleep efficiency, likely contribute to fatigue in patients with CLD. These abnormalities may ultimately be a therapeutic target to improve quality of life for fatigued patients with CLD.

SUBMITTER: Tana MM

PROVIDER: S-EPMC6287634 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Fatigued Patients with Chronic Liver Disease Have Subtle Aberrations of Sleep, Melatonin and Cortisol Circadian Rhythms.

Tana Michele M MM Alao Hawwa H Morris Nevitt N Bernstein Shanna S Hattenbach Jacob J Rehman Rahiya B RB Brychta Robert R Sarkar Souvik S Zhao Xiongce X Walter Mary M Buckley Ashura A Chen Kong K Rotman Yaron Y

Fatigue : biomedicine, health & behavior 20171203 1

<h4>Aims</h4>We sought to examine whether disturbances in central and peripheral circadian rhythms were related to the experience of fatigue in patients with chronic liver disease (CLD).<h4>Methods</h4>Fatigued and non-fatigued patients with compensated CLD were enrolled in a prospective pilot study. Patients underwent a one week evaluation of free-living sleep and physical activity patterns, followed by a 24-hour admission, during which they underwent serial blood sampling, polysomnography, a 6 ...[more]

PMID: 30546968

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Project description:BACKGROUND:The phase and amplitude of rhythms in physiology and behavior are generated by circadian oscillators and entrained to the 24-h day by exposure to the light-dark cycle and feedback from the sleep-wake cycle. The extent to which the phase and amplitude of multiple rhythms are similarly affected during altered timing of light exposure and the sleep-wake cycle has not been fully characterized. METHODOLOGY/PRINCIPAL FINDINGS:We assessed the phase and amplitude of the rhythms of melatonin, core body temperature, cortisol, alertness, performance and sleep after a perturbation of entrainment by a gradual advance of the sleep-wake schedule (10 h in 5 days) and associated light-dark cycle in 14 healthy men. The light-dark cycle consisted either of moderate intensity 'room' light (?90-150 lux) or moderate light supplemented with bright light (?10,000 lux) for 5 to 8 hours following sleep. After the advance of the sleep-wake schedule in moderate light, no significant advance of the melatonin rhythm was observed whereas, after bright light supplementation the phase advance was 8.1 h (SEM 0.7 h). Individual differences in phase shifts correlated across variables. The amplitude of the melatonin rhythm assessed under constant conditions was reduced after moderate light by 54% (17-94%) and after bright light by 52% (range 12-84%), as compared to the amplitude at baseline in the presence of a sleep-wake cycle. Individual differences in amplitude reduction of the melatonin rhythm correlated with the amplitude of body temperature, cortisol and alertness. CONCLUSIONS/SIGNIFICANCE:Alterations in the timing of the sleep-wake cycle and associated bright or moderate light exposure can lead to changes in phase and reduction of circadian amplitude which are consistent across multiple variables but differ between individuals. These data have implications for our understanding of circadian organization and the negative health outcomes associated with shift-work, jet-lag and exposure to artificial light.

Dataset Information

Fatigued Patients with Chronic Liver Disease Have Subtle Aberrations of Sleep, Melatonin and Cortisol Circadian Rhythms.

Publications

Fatigued Patients with Chronic Liver Disease Have Subtle Aberrations of Sleep, Melatonin and Cortisol Circadian Rhythms.

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