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On the origin and the consequences of circadian abnormalities in patients with cirrhosis.

Montagnese, S, Middleton, B, Mani, AR, Skene, DJ and Morgan, MY (2010) On the origin and the consequences of circadian abnormalities in patients with cirrhosis. Am J Gastroenterol, 105 (8). pp. 1773-1781.

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Abstract

OBJECTIVES: Plasma melatonin profile abnormalities have been described in patients with cirrhosis and generally attributed to impaired hepatic melatonin metabolism. The possibility that they might reflect circadian clock dysfunction has not been explored. In addition, the relationship between plasma melatonin profiles and the sleep disturbances observed in these patients remains unclear. The aims of this study were: (i) to evaluate circadian clock function and hepatic melatonin metabolism in cirrhotic patients, and (ii) to study the relationship between plasma melatonin profiles and sleep-wake behavior. METHODS: The study population comprised 20 patients with cirrhosis (mean (range) age, 59 (39-77) years) and 9 healthy volunteers (60 (38-84) years). Plasma melatonin/cortisol concentrations were measured hourly, for 24 h, in light/posture-controlled conditions. Urinary 6-sulfatoxymelatonin, the main melatonin metabolite, was measured simultaneously to determine clearance. The ability of light to suppress nocturnal melatonin synthesis was assessed. Habitual sleep quality/timing was evaluated using a questionnaire, actigraphy, and sleep diaries. RESULTS: There was evidence of central circadian disruption in patients compared with healthy controls: peak plasma melatonin/cortisol times were delayed (04:48+/-02:36 vs. 02:48+/-00:54, P=0.01; 10:18+/-02:54 vs. 08:54+/-01:24, P=0.06) and the plasma melatonin response to light was reduced (12%+/-19% vs. 24%+/-15%, P=0.09). However, the mean 24 h plasma melatonin clearance did not differ significantly between patients and healthy volunteers (0.22+/-0.10 vs. 0.28+/-0.17 l/kg per h, P=0.36). Finally, although patients showed a degree of misalignment between sleep and circadian timings, there was no association between circadian abnormalities and impaired sleep quality. CONCLUSIONS: Plasma melatonin profile abnormalities, predominantly central in origin, are observed in patients with mild to moderately decompensated cirrhosis. However, they are substantially unrelated to the sleep disturbances prevalent in this population.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Biochemical Sciences
Authors :
AuthorsEmailORCID
Montagnese, SUNSPECIFIEDUNSPECIFIED
Middleton, BUNSPECIFIEDUNSPECIFIED
Mani, ARUNSPECIFIEDUNSPECIFIED
Skene, DJUNSPECIFIEDUNSPECIFIED
Morgan, MYUNSPECIFIEDUNSPECIFIED
Date : August 2010
Identification Number : 10.1038/ajg.2010.86
Uncontrolled Keywords : Actigraphy, Adult, Aged, Aged, 80 and over, Case-Control Studies, Circadian Rhythm, Female, Humans, Hydrocortisone, Likelihood Functions, Liver Cirrhosis, Male, Melatonin, Middle Aged, Sleep Disorders, Statistics, Nonparametric
Additional Information : This is an electronic version of an article published in Am J Gastroenterol, 105 (8) 2011, DOI:10.1038/ajg.2010.86 Link to the published version: http://dx.doi.org/10.1038/ajg.2010.86.
Depositing User : Symplectic Elements
Date Deposited : 01 Feb 2013 12:54
Last Modified : 23 Sep 2013 19:58
URI: http://epubs.surrey.ac.uk/id/eprint/745531

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