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The circadian rhythms of many night-shift workers are maladapted to their imposed behavioural schedule, and this factor may be implicated in the increased occurrence of cardiovascular disease (CVD) reported in shift workers. One way in which CVD risk could be mediated is through inappropriate hormonal and metabolic responses to meals. This study investigated the responses to standard meals at different circadian times in a group of night-shift workers on a British Antarctic Survey station at Halley Bay (75 S) in Antarctica.Twelve healthy subjects (ten men and two women) were recruited. Their postprandial hormone and metabolic responses to an identical mixed test meal of 3330 kJ were measured on three occasions: (i) during daytime on a normal working day, (ii) during night-time at the beginning of a period of night-shift work, and (iii) during the daytime on return from nightworking to daytime working. Venous blood was taken for 9 h after the meal for the measurement of glucose, insulin, triacylglycerol (TAG) and non-esterified fatty acids. Urine was collected 4-hourly (longer during sleep) on each test day for assessment of the circadian phase via 6-sulphatoxymelatonin (aMT6s) assay.During normal daytime working, aMT6s acrophase was delayed (7·7 1·0 h (...)) compared with that previously found in temperate zones in a comparable age-group. During the night shift a further delay was evident (11·8 1·9 h) and subjects' acrophases remained delayed 2 days after return to daytime working (12·4 1·8 h). Integrated postprandial glucose, insulin and TAG responses were significantly elevated during the night shift compared with normal daytime working. Two days after their return to daytime working, subjects' postprandial glucose and insulin responses had returned to pre-shift levels; however, integrated TAG levels remained significantly elevated.These results are very similar to those previously found in simulated night-shift conditions; it is the first time such changes have been reported in real shift workers in field conditions. They provide evidence that the abnormal metabolic responses to meals taken at night during unadapted night shifts are due, at least in part, to a relative insulin resistance, which could contribute to the documented cardiovascular morbidity associated with shift work. When applied to the 20% of the UK workforce currently employed on shift work, these findings have major significance from an occupational health perspective.

SUMMARY Mutations in clock genes are associated with abnormal circadian parameters, including sleep. An association has been reported previously between a polymorphism (3111C), situated in the 3′‐untranslated region (3′‐UTR) of the circadian gene Clock and evening preference. In the present study, this polymorphism was assessed in: (1) 105 control subjects with defined diurnal preference, (2) 26 blind subjects with free‐running circadian rhythms and characterized with regard to circadian period (τ) and (3) 16 delayed sleep phase syndrome patients. The control group was chosen from a larger population (n = 484) by Horne‐Östberg questionnaire analysis, from which three subgroups were selected (evening, intermediate and morning preference). Data from sleep diaries completed by 90% of these subjects showed a strong correlation between preferred and estimated timings of sleep and wake. The mean timings of activities for the evening group were at least 2 h later than the morning group. Genetic analysis showed that, in contrast with the previously published finding, there was no association between 3111C and eveningness. Neither was there an association between 3111C and τ, nor a significant difference in 3111C frequency between the normal and delayed sleep phase syndrome groups. To assess the effect of this polymorphism on messenger RNA (mRNA) translatability, luciferase reporter gene constructs containing the two Clock polymorphic variants in their 3′‐UTR were transfected into COS‐1 cells and luciferase activity measured. No significant difference was observed between the two variants. These results do not support Clock 3111C as a marker for diurnal preference, τ, or delayed sleep phase syndrome in humans.

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Seventeen healthy volunteers (10 women and 7 men, aged 29-68) were flown from London to San Francisco between 20 November 1985 and 25 January 1986 and remained there for 14 days prior to flight home. Subjects took melatonin (N= 8, 5 women, 3 men) or placebo in a double-blind design, at 18.00h local time for three days before the return flight and at bedtime (22.00-24.0011) in Great Britain for four days. For three days before departure and on days 1-7,14,15,21 and 22 after their retum subjects collected 6-hourly sequential urine samples and kept a daily sleep log. 'They recorded mood and oral temperature 2 hourly and performed logical reasoning and letter cancellation tests 4 hourly from 08.00h (or wake up time) to 24,OOh (or bedtime) whichever was the earlier. Urine was also collected for 48 h prior to departure from the U.S.A.. On day 7 after their return subjects rated 'jet lag' (IOcm visual analogue scale-VAS) from 0 (insignificant) to 100 (very bad). Melatonin significantly improved 'jet lag' (p=0.009). Comparisons by ANOVA between jet-lagged placebo subjects (N = 7) and melatonin (N = 8) showed decreased sleep latency with melatonin (p=0.0397) which correlated positively with jet lag ratings, p < 0.001. Sleep quality was significantly improved in the melatonin group and correlated negatively with jet-lag ratings (p<0.001). No important differences were found in temperature, or performance data. Baseline differences were present in some pcrformancc ratings but no othcr variables. Mclatonin treated subjects tended to be more alert than placebo subjects, especially at bedtime. They were also less depressed. Endogenous melatonin and cortisol rhythms resynchronized more rapidly in melatonin subjects (p=0.0216 and p=0.0299 respectively, absolute acrophase shifts). Cortisol rhythms indicated adaptation to U.S.A. time in 14 days. These data suggest that MT can alleviate jet-lag after Eastward flight over eight time zones. Presumably its affects are primarily on sleep latency, quality, and directly or indirectly on some hormonal rhythms.