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Cited by 180Circadian rhythm and melatoninPancreatic function and diabetesSleep and related disorders

Acute melatonin administration in humans impairs glucose tolerance in both the morning and evening

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Rubio-Sastre, Patricia, Scheer, Frank A.J.L., Gómez-Abellán, Purificación, Madrid, Juan A., Garaulet, Marta·2014·SLEEP
DOI 10.5665/sleep.4088PMC PMC4173928
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Abstract

STUDY OBJECTIVES: To study the effect of melatonin administration on glucose metabolism in humans in the morning and evening. DESIGN: Placebo-controlled, single-blind design. SETTING: Laboratory assessments. PARTICIPANTS: 21 healthy women (24 ± 6 y; body mass index: 23.0 ± 3.3 kg/m(2)). INTERVENTIONS: Glucose tolerance was assessed by oral glucose tolerance tests (OGTT; 75 g glucose) on 4 occasions: in the morning (9 AM), and evening (9 PM); each occurring 15 minutes after melatonin (5 mg) and placebo administration on 4 non-consecutive days. MEASUREMENTS AND RESULTS: Melatonin administration impaired glucose tolerance. When administered in the morning, melatonin significantly increased the incremental area under the curve (AUC) and maximum concentration (Cmax) of plasma glucose following OGTT by 186% and 21%, respectively, as compared to placebo; while in the evening, melatonin significantly increased glucose AUC and Cmax by 54% and 27%, respectively. The effect of melatonin on the insulin response to the OGTT depended on the time of day (P < 0.05). In the morning, melatonin decreased glucose tolerance primarily by decreasing insulin release, while in the evening, by decreasing insulin sensitivity. CONCLUSIONS: Acute melatonin administration in humans impairs glucose tolerance in both the morning and evening. When administering melatonin, the proximity to meal timing may need to be considered, particularly in those at risk for glucose intolerance.

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  • The sample size was based on prior work (14) with an effect size of 1.24 for the difference in 2-h glucose AUC after morning OGTT between heterozygous carriers and noncarriers.

    “The sample size was based on our prior work (14), with an effect size of 1.24 for the difference in 2-h glucose area under the curve (AUC) following a morning oral glucose tolerance test (OGTT) after melatonin administration as compared with placebo between heterozygous carriers and noncarriers of the MTNR1B common variant.”

    From Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With <i>MTNR1B</i> Diabetes Risk Variant (2026) · cites this paper as [14]

    The Calculations and Statistical Analysis section describes 120-minute glucose AUC after OGTT, and Table 1 reports a morning melatonin-versus-placebo difference. Neither passage reports an effect size of 1.24 or a comparison between heterozygous carriers and noncarriers of the MTNR1B variant; searches for those terms found no such analysis. Page numbers were not available in our copy. (LLM, conf=0.86)

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  • Earlier work shows that elevated melatonin-whether from exogenous administration or due to the endogenous evening rise-acutely impairs glucose tolerance, with stronger effects in MTNR1B risk allele carriers.

    “The present results align with and extend our earlier work showing that elevated melatonin—whether from exogenous administration or due to the endogenous evening rise—acutely impairs glucose tolerance, with stronger effects in MTNR1B risk allele carriers (11–14).”

    From Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With <i>MTNR1B</i> Diabetes Risk Variant (2026) · cites this paper as [14]

    The Results (page not provided) show that a 5 mg dose of exogenous melatonin impaired glucose tolerance in 21 healthy young women, both in the morning and evening. The paper did not test the endogenous evening rise or compare effects by MTNR1B risk-allele status; its Introduction mentions MTNR1B only in connection with diabetes risk. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Other studies show that elevated melatonin concentrations are associated with impaired glucose control.

    “others show associations with impaired glucose control (18)(19)(20).”

    From Interplay of Dinner Timing and <i>MTNR1B</i> Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [18]

  • The impairment of glucose tolerance and decrease in insulin secretion during late dinner timing might be partly due to the 3.5-fold higher melatonin concentrations.

    “This difference might be partly due to the 3.5-fold higher melatonin concentrations, as supported by our earlier trial in which acute melatonin administration impaired glucose tolerance and in vitro b-cell experiments showing decreased insulin secretion due to melatonin (10,11,18,28).”

    From Interplay of Dinner Timing and <i>MTNR1B</i> Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [18]

  • The mechanisms underlying the association between melatonin administration and glycemic control remain unclear.

    “While a few other studies (9–14) have examined the effects of melatonin administration on glycemic control, the mechanisms underlying such association remain unclear (7).”

    From Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With <i>MTNR1B</i> Diabetes Risk Variant (2026) · cites this paper as [14]

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Authors
Rubio-Sastre, P., Scheer, F. A. J. L., Gómez-Abellán, P., Madrid, J. A., & Garaulet, M.
Affiliations
  • Instituto Murciano de Investigación Biosanitaria (ES)
  • Brigham and Women's Hospital (US)
Corresponding author
Garaulet, Marta
ORCID
Venue
SLEEP
Publisher
Oxford University Press (OUP)
Published
2014-10-01
Volume
37
Issue
10
Pages
1715-1719
ISSN
  • 0161-8105 (ISSN-L)
  • 1550-9109
DOI
10.5665/sleep.4088
PMC
PMC4173928
OpenAlex
W2082407123
Cited by
180
References
27
Citations by year
2026: 11 · 2025: 12 · 2024: 16 · 2023: 13 · 2022: 16 · 2021: 16 · 2020: 17 · 2019: 15 · 2018: 19 · 2017: 17 · 2016: 17 · 2015: 10
FWCI
7.15
Type
journal article
Language
en
Open access
Locations
  • SLEEP (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (R01HL094806)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
Keywords
melatonin, glucose tolerance, glucose metabolism, insulin secretion, insulin sensitivity, time of day, oral glucose tolerance test, plasma glucose, meal timing, impaired glucose tolerance
MeSH terms
Insulin Secretion, Adult, Blood Glucose, Female, Glucose Tolerance Test, Humans, Insulin, Insulin Resistance, Melatonin, Time Factors, Body Mass Index, Single-Blind Method, Glucose Intolerance, Area Under Curve, Young Adult

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