Epidemiological studies have shown that shift work is associated with an increased risk for the development of diabetes, obesity, and cardiovascular disease. Recent animal studies and acute human studies suggest that this association may be due to the misalignment between the fasting/feeding and sleep/wake cycles relative to the cycle of the endogenous circadian timing system. That is, activity and food intake during the 'biological night'or sleep loss during the 'biological day'may result in metabolic, autonomic and endocrine changes that pre-dispose to diabetes, obesity, and cardiovascular disease. For instance, we recently found that acute experimental misalignment between the sleep/wake and fasting/feeding cycle-typical of shift work-can lead to significantly decreased plasma leptin, increased plasma glucose and increased mean arterial pressure. We also found reduced sleep efficiency during circadian misalignment to an extent that has been shown to significantly decrease circulating leptin, increase appetite and increase sympatho-vagal balance in other acute studies. Building on these new findings, and overcoming a number of limitations in the prior work, we aim to determine the progressive physiological changes across a work week of realistic simulated shift work focusing on those metabolic, endocrine, inflammatory, and cardiovascular variables that are biomarkers of susceptibility to the development of diabetes, obesity, and cardiovascular disease. Also, since the effect of shift work is most clinically relevant in actual shift workers, we will determine whether the potential maladaptive physiological effects are observed also in chronic shift workers or that this population has adapted. We will use a 14 day/night laboratory protocol involving a within-subject, randomized, cross-over design including a simulated night shift and day shift schedule using a formal battery of scheduled behaviors and light exposures in healthy day workers and shift workers. The principal dependent variables are derived from circulating adipocyte hormones (leptin, adiponectin, resistin, ghrelin), measures of insulin resistance (mixed meal response and intravenous glucose tolerance test), inflammatory markers (CRP, IL-6, TNF-alpha, MCP-1), peripheral vascular endothelial function, and autonomic control (catecholamines, sympatho-vagal balance, baroreceptor sensitivity and systemic blood pressure). Changes in these variables will be monitored across numerous days and nights of shift work, compared between day and night shift schedules, and compared between non-shift workers and chronic shift workers. Following on from the convincing epidemiological studies and recent acute physiology studies, the proposed intense physiological study utilizing realistic shift work-schedules over a number of days are now needed to determine the specific underlying metabolic, endocrine, inflammatory, autonomic and cardiovascular mechanisms that explain the adverse health consequences of chronic shift work. We anticipate that this work will lay the groundwork for the development of targeted and timed therapies to counteract the public health burden of shift work.

Public Health Relevance

Shift work is associated with an increased risk for diabetes, obesity, and cardiovascular disease. This research will determine whether simulated night work increases metabolic, hormonal, neuronal, heart and blood vessel risk factors in shift workers and non-shift workers. This research will provide a possible mechanistic explanation for the increased risk for diabetes, obesity, and cardiovascular disease in shift workers.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Clinical and Integrative Diabetes and Obesity Study Section (CIDO)
Program Officer
Kaufmann, Peter G
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Brigham and Women's Hospital
United States
Zip Code
Tucker, Matthew A; Morris, Christopher J; Morgan, Alexandra et al. (2017) The Relative Impact of Sleep and Circadian Drive on Motor Skill Acquisition and Memory Consolidation. Sleep 40:
Morris, Christopher J; Purvis, Taylor E; Mistretta, Joseph et al. (2016) Effects of the Internal Circadian System and Circadian Misalignment on Glucose Tolerance in Chronic Shift Workers. J Clin Endocrinol Metab 101:1066-74
Lane, Jacqueline M; Chang, Anne-Marie; Bjonnes, Andrew C et al. (2016) Impact of Common Diabetes Risk Variant in MTNR1B on Sleep, Circadian, and Melatonin Physiology. Diabetes 65:1741-51
Dashti, Hassan S; Zuurbier, Lisette A; de Jonge, Ester et al. (2016) Actigraphic sleep fragmentation, efficiency and duration associate with dietary intake in the Rotterdam Study. J Sleep Res 25:404-11
Morris, Christopher J; Purvis, Taylor E; Hu, Kun et al. (2016) Circadian misalignment increases cardiovascular disease risk factors in humans. Proc Natl Acad Sci U S A 113:E1402-11
Dashti, Hassan S; Follis, Jack L; Smith, Caren E et al. (2015) Habitual sleep duration is associated with BMI and macronutrient intake and may be modified by CLOCK genetic variants. Am J Clin Nutr 101:135-43
Bandín, C; Scheer, F A J L; Luque, A J et al. (2015) Meal timing affects glucose tolerance, substrate oxidation and circadian-related variables: A randomized, crossover trial. Int J Obes (Lond) 39:828-33
Morris, Christopher J; Garcia, Joanna I; Myers, Samantha et al. (2015) The Human Circadian System Has a Dominating Role in Causing the Morning/Evening Difference in Diet-Induced Thermogenesis. Obesity (Silver Spring) 23:2053-8
Gu, Changgui; Coomans, Claudia P; Hu, Kun et al. (2015) Lack of exercise leads to significant and reversible loss of scale invariance in both aged and young mice. Proc Natl Acad Sci U S A 112:2320-4
Dashti, Hassan S; Scheer, Frank Ajl; Jacques, Paul F et al. (2015) Short sleep duration and dietary intake: epidemiologic evidence, mechanisms, and health implications. Adv Nutr 6:648-59

Showing the most recent 10 out of 28 publications