Effects of the Internal Circadian System and Circadian Misalignment on Glucose Tolerance in Chronic Shift Workers
Open accessAbstract
Context: Shift work is a risk factor for diabetes. The separate effects of the endogenous circadian system and circadian misalignment (ie, misalignment between the central circadian pacemaker and 24-hour environmental/behavioral rhythms such as the light/dark and feeding/fasting cycles) on glucose tolerance in shift workers are unknown. Objective: The objective of the study was to test the hypothesis that the endogenous circadian system and circadian misalignment separately affect glucose tolerance in shift workers, both independently from behavioral cycle effects. Design: A randomized, crossover study with two 3-day laboratory visits. Setting: Center for Clinical Investigation at Brigham and Women's Hospital. Patients: Healthy chronic shift workers. Intervention: The intervention included simulated night work comprised of 12-hour inverted behavioral and environmental cycles (circadian misalignment) or simulated day work (circadian alignment). Main Outcome Measures: Postprandial glucose and insulin responses to identical meals given at 8:00 am and 8:00 pm in both protocols. Results: Postprandial glucose was 6.5% higher at 8:00 pm than 8:00 am (circadian phase effect), independent of behavioral effects (P = .0041). Circadian misalignment increased postprandial glucose by 5.6%, independent of behavioral and circadian effects (P = .0042). These variations in glucose tolerance appeared to be explained, at least in part, by different insulin mechanisms: during the biological evening by decreased pancreatic β-cell function (18% lower early and late phase insulin; both P ≤ .011) and during circadian misalignment presumably by decreased insulin sensitivity (elevated postprandial glucose despite 10% higher late phase insulin; P = .015) without change in early-phase insulin (P = .38). Conclusions: Internal circadian time affects glucose tolerance in shift workers. Separately, circadian misalignment reduces glucose tolerance in shift workers, providing a mechanism to help explain the increased diabetes risk in shift workers.
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Long-term desynchronization of circadian rhythms is associated with adverse metabolic health effects, including weight gain, increased body fat, obesity, impaired glucose tolerance, insulin resistance, higher blood pressure, elevated cholesterol levels, and elevated risk for cardiovascular diseases, diabetes, and metabolic syndrome.
“Long-term desynchronization of circadian rhythms is associated with adverse metabolic health effects, including weight gain, increased body fat, obesity, impaired glucose tolerance, insulin resistance, higher blood pressure, and elevated cholesterol levels, as well as elevated risk for cardiovascular diseases, diabetes, and metabolic syndrome (18, 47–54).”
From Meal timing and its role in obesity and associated diseases (2024) · cites this paper as [50]
The Discussion (page not provided) reports that circadian misalignment reduced glucose tolerance in chronic shift workers and suggests decreased insulin sensitivity; it also links shift work to type 2 diabetes risk. It does not establish that long-term desynchronization is associated with the other listed outcomes, including weight gain, higher blood pressure, elevated cholesterol, cardiovascular disease, or metabolic syndrome. (LLM, conf=0.88)
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- Authors
- Morris, C. J., Purvis, T. E., Mistretta, J., & Scheer, F. A. J. L.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Morris, Christopher J.
- Scheer, Frank A. J. L.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2016-03-01
- Volume
- 101
- Issue
- 3
- Pages
- 1066-1074
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC4803172
- OpenAlex
- W2237552187
- Cited by
- 262
- References
- 39
- Citations by year
- 2026: 15 · 2025: 27 · 2024: 28 · 2023: 28 · 2022: 26 · 2021: 20 · 2020: 51 · 2019: 18 · 2018: 19 · 2017: 25 · 2016: 5
- FWCI
- 14.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL118601, R01HL094806)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK099512)
- National Center for Research Resources (UL1RR025758)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- circadian misalignment, circadian rhythm, shift work, glucose tolerance, postprandial blood glucose, insulin response, beta-cell function, insulin sensitivity, diabetes risk, circadian phase
- MeSH terms
- Adult, Blood Glucose, Circadian Rhythm, Diet, Female, Humans, Hydrocortisone, Insulin, Male, Middle Aged, Sleep, Work Schedule Tolerance, Glucose Intolerance, Cross-Over Studies, Postprandial Period, Chronobiology Disorders, Insulin-Secreting Cells, Meals
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