Exploring the role of nutrition in alleviating circadian disruption-related health outcomes

The human body encounters daily environmental challenges, which may take the form of fluctuating temperature, light-dark cycle, and fasting-feeding state. To cope with these challenges, a mechanism of adaptation called circadian rhythm separates numerous biochemical processes in the body into two phases that match the timing of occurrence of these external challenges. The circadian active phase occurs during the daylight, while the rest phase at night in diurnal animals. The central circadian clock, located at the suprachiasmatic nucleus (SCN) in the anterior part of the hypothalamus, received direct innervation from the eye’s retina to synchronize with the light and dark cycle.1 Apart from SCN, peripheral tissues also contain autonomous oscillators. In contrast to the central clock that depends on light as a time cue, these clocks rely on feedback loops created by clock genes and various proteins which respond to feeding rhythm.2 Activities such as eating performed during the circadian rest phase misalign the peripheral circadian clock with the central clock and may result in poor metabolic consequences, including deteriorated glucose tolerance.3 
The expression of circadian rhythmicity differs between individuals, which manifests in the spectrum between morning/early-type and evening/late-type classification called chronotype.4 Compared to their early counterparts, later chronotypes tend to have poorer diet quality as indicated by lower intake of fiber, plant protein, fruit, and vegetable intake.5 Later chronotypes are likely to have later eating behavior, such as later consumption or omission of breakfast.6,7 and late-night eating 8, which may predispose them to circadian misalignment. Furthermore, later chronotypes commonly have problems matching their physiological characteristics with the social demand to work in the early morning, a condition called social jet lag9 that describes the degree of sleep time discrepancy between weekdays and weekends. 
Studies have shown that later chronotype and social jet lag are associated with poorer glycemic control 10 and increased risk of T2DM.11 However, studies scarcely explain dietary intake factors’ contribution in the association between chronotype and social jet lag on T2DM risk. As people may have no privilege to choose their work hours and match it with their biological preference, modifying dietary intake or eating behavior could be an alternative approach to alleviate circadian disruption. Therefore, the information on how improving dietary intake or eating behavior alleviates the circadian disruption-related increased risk of T2DM needs to be investigated. 
Our study aims to evaluate if dietary intake modifies the association between social jet lag and the development of T2DM. Additionally, we seek to determine if glycemic control improves with the adoption of certain dietary patterns among people with T2DM. Lastly, the causal association between breakfast skipping and T2DM will be evaluated (using Mendelian Randomisation), as this eating behavior is commonly found in late chronotype, which indicates a shift in the timing of meals. While several studies investigated the association between breakfast skipping and T2DM, most evidence came from association studies that may not be free from confounding factors.12 Moreover, the newest study evaluating the causal association between breakfast skipping and T2DM used breakfast cereal skipping as the proxy phenotype, thus may only partially explain the exposure.13