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Differential effects of the circadian system and circadian misalignment on insulin sensitivity and insulin secretion in humans
Open accessAbstract
Glucose tolerance is lower at night and higher in the morning. Shift workers, who often eat at night and experience circadian misalignment (i.e. misalignment between the central circadian pacemaker and the environmental/behavioural cycles), have an increased risk of type 2 diabetes. To determine the separate and relative impacts of the circadian system, behavioural/environmental cycles, and their interaction (i.e. circadian misalignment) on insulin sensitivity and β‐cell function, the oral minimal model was used to quantitatively assess the major determinants of glucose control in 14 healthy adults using a randomized, cross‐over design with two 8‐day laboratory protocols. Both protocols involved 3 baseline inpatient days with habitual sleep/wake cycles, followed by 4 inpatient days with the same nocturnal bedtime (circadian alignment) or with 12‐hour inverted behavioural/environmental cycles (circadian misalignment). The data showed that circadian phase and circadian misalignment affect glucose tolerance through different mechanisms. While the circadian system reduces glucose tolerance in the biological evening compared to the biological morning mainly by decreasing both dynamic and static β‐cell responsivity, circadian misalignment reduced glucose tolerance mainly by lowering insulin sensitivity, not by affecting β‐cell function.
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“Furthermore, it has been shown that such a decrease in insulin sensitivity is mostly caused by the behavioral cycle, while the circadian system dominates the deterioration in glucose tolerance and b-cell responsivity (8,32).”
From Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [32]
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“The circadian effect appeared to be independent of melatonin signaling, because melatonin levels were low during the circadian evening ($2000-2200 h) in the previous studies (8,32).”
From Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [32]
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“longer sleep episodes correlate with an earlier intake of dinner/the last meal (83) as well as a decreased consumption of free sugars (173).”
From Meal timing and its role in obesity and associated diseases (2024) · cites this paper as [83]
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Citations
Cites
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ResultCircadian misalignment increases cardiovascular disease risk factors in humans
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Self-citationDiurnal pattern to insulin secretion and insulin action in healthy individuals
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Self-citationThe oral glucose minimal model: Estimation of insulin sensitivity from a meal test
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Self-citationGlucose metabolism during rotational shift-work in healthcare workers
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Self-citationIsn’t This Just Bedtime Snacking?
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Cited by
Sorted by citations
Circadian clocks and insulin resistance
Stenvers, D. J., Scheer, F. A. J. L., Schrauwen, P., la Fleur, S. E., & Kalsbeek, A. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0122-1 · Cited by 733
Self-citationCircadian disruption and human health
Fishbein, A. B., Knutson, K. L., & Zee, P. C. (2021) · Journal of Clinical Investigation · doi:10.1172/jci148286 · Cited by 468
The circadian regulation of food intake
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Impact of circadian disruption on glucose metabolism: implications for type 2 diabetes
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Self-citationMelatonin effects on glucose metabolism: time to unlock the controversy
Garaulet, M., Qian, J., Florez, J. C., Arendt, J., Saxena, R., & Scheer, F. A. J. L. (2020) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2019.11.011 · Cited by 193
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Metadata
- Authors
- Qian, J., Dalla Man, C., Morris, C. J., Cobelli, C., & Scheer, F. A. J. L.
- Affiliations
- Brigham and Women's Hospital (US)
- Department of Information Engineering University of Padova Padova Italy
- University of Padua (IT)
- Corresponding author
- Qian, Jingyi
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2018-07-02
- Volume
- 20
- Issue
- 10
- Pages
- 2481-2485
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- PMC
- PMC6167165
- OpenAlex
- W2807200695
- Cited by
- 170
- References
- 25
- Citations by year
- 2026: 25 · 2025: 11 · 2024: 19 · 2023: 30 · 2022: 19 · 2021: 15 · 2020: 38 · 2019: 10 · 2018: 3
- FWCI
- 9.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- National Institutes of Health (R01HL094806, R01HL118601, R01DK099512, R01DK102696, R01DK105072)
- Harvard University
- Brigham and Women's Hospital (UL1RR025758)
- American Diabetes Association (#1‐17‐PDF‐103)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- circadian misalignment, circadian system, insulin sensitivity, beta-cell function, insulin secretion, glucose tolerance, shift work, oral minimal model, type 2 diabetes risk, circadian phase
- MeSH terms
- Insulin Secretion, Adult, Blood Glucose, Circadian Rhythm, Clinical Protocols, Diabetes Mellitus, Type 2, Female, Glycated Hemoglobin, Humans, Insulin Resistance, Male, Glucose Intolerance, Cross-Over Studies, Chronobiology Disorders, Insulin-Secreting Cells
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