Abstract: Circadian rhythm disorders have been classically associated with disorders of abnormal timing of the sleep-wake cycle, however circadian dysfunction can play a role in a wide range of pathology, ranging from the increased risk for cardiometabolic disease and malignancy in shift workers, prompting the need for a new field focused on the larger concept of circadian medicine. The relationship between circadian disruption and human health is bidirectional, with changes in circadian amplitude often preceding the classical symptoms of neurodegenerative disorders. As our understanding of the importance of circadian dysfunction in disease grows, we need to develop better clinical techniques for identifying circadian rhythms and also develop circadian based strategies for disease management. Overall this review highlights the need to bring the concept of time to all aspects of medicine, emphasizing circadian medicine as a prime example of both personalized and precision medicine.

Abstract: Insulin resistance is a main determinant in the development of type 2 diabetes mellitus and a major cause of morbidity and mortality. The circadian timing system consists of a central brain clock in the hypothalamic suprachiasmatic nucleus and various peripheral tissue clocks. The circadian timing system is responsible for the coordination of many daily processes, including the daily rhythm in human glucose metabolism. The central clock regulates food intake, energy expenditure and whole-body insulin sensitivity, and these actions are further fine-tuned by local peripheral clocks. For instance, the peripheral clock in the gut regulates glucose absorption, peripheral clocks in muscle, adipose tissue and liver regulate local insulin sensitivity, and the peripheral clock in the pancreas regulates insulin secretion. Misalignment between different components of the circadian timing system and daily rhythms of sleep-wake behaviour or food intake as a result of genetic, environmental or behavioural factors might be an important contributor to the development of insulin resistance. Specifically, clock gene mutations, exposure to artificial light-dark cycles, disturbed sleep, shift work and social jet lag are factors that might contribute to circadian disruption. Here, we review the physiological links between circadian clocks, glucose metabolism and insulin sensitivity, and present current evidence for a relationship between circadian disruption and insulin resistance. We conclude by proposing several strategies that aim to use chronobiological knowledge to improve human metabolic health.

Abstract: Underground workplaces are an important element in modern urban planning. As a result, an increasing but unquantified proportion of the population is being regularly exposed to them. We narratively reviewed the literature on the range of possible environmental exposures, and the possible health effects, to identify future research directions. There is a large but mainly observational research literature on likely underground exposures, including effects of artificial lighting, shift working and light at night on circadian disruptions and associated health effects. There are five studies comparing underground and aboveground environments. Shift working, artificial lighting and poor sleep quality leading to circadian disruption is one physiologic pathway. Working underground may increase exposure to these risks, and may also be associated with vitamin D deficiency, sick building syndrome, excessive noise, radon exposure, and negative psychological effects. In order to plan appropriate interventions, we need to expand our knowledge of the health effects of underground environments. Larger and longer-term studies are required to measure a range of human factors, environmental exposures and confounders. Controlled trials with health economic analyses of new lighting technologies are also required.