Abstract
Coronary Heart Disease (CETO) is one of the most common causes of mortality in industrialised societies, and it has been demonstrated elsewhere that shift workers have an increased risk of developing CHD compared to day-workers. One possible explanation for this increased risk is that a shift worker may show inappropriate postprandial responses to a night-time meal, when their biological clock is not adapted to the night shift. This could lead to an elevation in the circulating levels of certain hormones and metabolites, such as triacylglycerol (TAG) and insulin, which are known to be risk factors for CHD. This thesis investigated the relationships between meal times and postprandial hormone and metabolic responses in simulated and real-life shift-workers. The work is presented as three major clinical trials. In the first of these, a combination of timed bright light and darkness/sleep was used to induce a gradual 9-hour phase advance in 12 healthy subjects, who then underwent a rapid 9-hour phase delay. Three meal study days were arranged, to occur during the baseline condition, immediately after the rapid phase delay, so that the subjects effectively had "simulated jet lag", and two days later. Blood parameters measured included plasma glucose, insulin, proinsulin, C-peptide, non-esterified fatty acids (NEFA), TAG and glucose- dependent insulinotropic polypeptide (GIP). Substantial differences in plasma TAG and NEFA were observed in the postprandial responses when the subjects consumed an identical meal immediately after the rapid phase delay, compared with during the baseline conditions. Two days after the rapid phase delay, subjects showed inteimediate hormone and metabolite levels, suggesting that the biological clock had a major effect on these postprandial responses. In the second study, day and night-time postprandial responses were compared in a simulated shift work environment, and the effectiveness of a number of potentially beneficial procedures was investigated. These included alterations to the content of the meal consiraied prior to the night shift, bright light exposure during the night shift, and a daytime rest period prior to the night shift. As in the first study, significant differences were seen in a number of hormones and metabolites on the night shift. compared with during the day. The content of the previous meal, bright light exposure and a daytime rest period prior to the night shift all had significant effects on the night-time postprandial responses. The most exciting discovery made was that a single 8-hour night-time bright light exposure significantly lowered the TAG postprandial responses on the simulated night shift. As all the work conducted up until this point had utilised simulated conditions, it was important to illustrate that similar differences in postprandial responses at night-time could be demonstrated in "real-life shift workers". Thus, nine midwives were recruited from the Royal Surrey County Hospital, and studied on four occasions. This allowed comparison of postprandial responses on both day and night shifts, and also allowed further investigation of the effect of altering the content of the previous meal. Significant differences were again found in a number of blood parameters when the night-time and day-time responses to the test meal were compared, with the most striking being a delayed NEFA rise on the night shift, compared with during the day. In conclusion, this series of studies have illustrated that the human body responds differently to a meal consumed at night-time, compared with during the day, both in a simulated and a real-life environment. This results in variations in the levels of a number of known CHD risk factors, and may be linked with the elevated CHD risk reported in shift workers. Alteration to the meal prior to the night shift, exposure to bright light during the night shift, and instituting a rest period prior to the night shift, were all shown to be potentially beneficial in reducing the variation between day and night-time responses.