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Melatonin Secretion and the Incidence of Type 2 Diabetes
Open accessAbstract
IMPORTANCE: Loss-of-function mutations in the melatonin receptor are associated with insulin resistance and type 2 diabetes. Additionally, in a cross-sectional analysis of persons without diabetes, lower nocturnal melatonin secretion was associated with increased insulin resistance. OBJECTIVE: To study the association between melatonin secretion and the risk of developing type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: Case-control study nested within the Nurses' Health Study cohort. Among participants without diabetes who provided urine and blood samples at baseline in 2000, we identified 370 women who developed type 2 diabetes from 2000-2012 and matched 370 controls using risk-set sampling. MAIN OUTCOME MEASURES: Associations between melatonin secretion at baseline and incidence of type 2 diabetes were evaluated with multivariable conditional logistic regression controlling for demographic characteristics, lifestyle habits, measures of sleep quality, and biomarkers of inflammation and endothelial dysfunction. RESULTS: The median urinary ratios of 6-sulfatoxymelatonin to creatinine were 28.2 ng/mg (5%-95% range, 5.5-84.2 ng/mg) among cases and 36.3 ng/mg (5%-95% range, 6.9-110.8 ng/mg) among controls. Women with lower ratios of 6-sulfatoxymelatonin to creatinine had increased risk of diabetes (multivariable odds ratio, 1.48 [95% CI, 1.11-1.98] per unit decrease in the estimated log ratio of 6-sulfatoxymelatonin to creatinine). Compared with women in the highest ratio category of 6-sulfatoxymelatonin to creatinine, those in the lowest category had a multivariable odds ratio of 2.17 (95% CI, 1.18-3.98) of developing type 2 diabetes. Women in the highest category of melatonin secretion had an estimated diabetes incidence rate of 4.27 cases/1000 person-years compared with 9.27 cases/1000 person-years in the lowest category. CONCLUSIONS AND RELEVANCE: Lower melatonin secretion was independently associated with a higher risk of developing type 2 diabetes. Further research is warranted to assess if melatonin secretion is a modifiable risk factor for diabetes within the general population.
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“While some studies show that elevated melatonin concentrations are associated with improved glucose control (15)(16)(17)”
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 [16]
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“In addition to potential increased cancer risk, lower melatonin secretion is associated with a higher risk for type 2 diabetes (McMullan et al. 2013).”
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Metadata
- Authors
- McMullan, C. J., Schernhammer, E. S., Rimm, E. B., Hu, F. B., & Forman, J. P.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- McMullan, Ciaran J.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2013-04-03
- Volume
- 309
- Issue
- 13
- Pages
- 1388
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC3804914
- OpenAlex
- W2086677877
- Cited by
- 369
- References
- 54
- Citations by year
- 2026: 15 · 2025: 21 · 2024: 18 · 2023: 30 · 2022: 29 · 2021: 26 · 2020: 36 · 2019: 25 · 2018: 43 · 2017: 24 · 2016: 28 · 2015: 39 · 2014: 28 · 2013: 6
- FWCI
- 18.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Heart, Lung, and Blood Institute (R01HL103607, HL103607)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058845, DK58845)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- melatonin secretion, type 2 diabetes, 6-sulfatoxymelatonin, urinary melatonin metabolites, insulin resistance, diabetes risk, women, sleep quality, inflammation, endothelial dysfunction
- MeSH terms
- Aged, Creatinine, Diabetes Mellitus, Type 2, Female, Humans, Melatonin, Middle Aged, Regression Analysis, Risk Factors, United States, Cohort Studies, Incidence, Case-Control Studies
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