Countermeasures to metabolic impairment during circadian misalignment

Abstract

People who work evening, night or rotating shifts (i.e. "nonstandard" work hours) represent one in five U.S. employees and are at a 44% increased risk for developing Type 2 diabetes (T2D) compared to people who work standard day shifts. Shift workers experience acute, repeated bouts of misalignment between their endogenous circadian system and external behavior/environmental factors such as sleep, energy intake, activity, and light. Circadian misalignment is one mechanism suggested to increases the risk of T2D in shift-working populations. To date, there have been limited attempts at identifying strategies or countermeasures to prevent the impact of such circadian misalignment on T2D risk in a sizeable proportion of the population. The following thesis aims to test a nutritional countermeasure known as time-restricted eating (TRE). TRE has previously shown metabolic benefits in people with obesity. The overall aims of the two studies compiled within this thesis are to determine the impact of TRE on (1) circulating and muscle lipid accumulation and (2) insulin sensitivity and glycemic homeostasis. Both studies follow a randomized crossover design with a rigorous inpatient diet-, activity and light-controlled protocol in 32 healthy men and women. In these studies, participants underwent a 6d randomized crossover inpatient study with at least 1 month between conditions. In one condition, participants ate during the biological night as typically done during night shift work (circadian misalignment). In the other condition, participants consumed meals only in the biological daytime (circadian misalignment + time restricted eating), while keeping sleep times and diet consistent. Consolidating food intake to the biological daytime, particularly in night shift work, was hypothesized to reduce the risk of T2D by reducing the mismatch between the endogenous circadian system and external behaviors. Findings from this study represent a critical advancement in the fields of translational circadian and metabolic physiology by identifying and testing a countermeasure to circadian misalignment. Achievement of our proposed aims could lead to the development of new intervention strategies for chronic disease prevention and management. The knowledge to be gained offers the potential to support cost-effective programs that may inform our healthcare approach to metabolic disease prevention in populations at risk for these diseases such as shift workers, individuals with sleep disorders and anyone who eats outside of daytime hours.