Cited by 369Circadian rhythm and melatoninSleep and related disordersAdipokines, Inflammation, and Metabolic Diseases

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Melatonin Secretion and the Incidence of Type 2 Diabetes

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McMullan, Ciaran J., Schernhammer, Eva S., Rimm, Eric B., Hu, Frank B., Forman, John P.·2013·JAMA

DOI 10.1001/jama.2013.2710PMC PMC3804914

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Abstract

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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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.
ORCID: McMullan, Ciaran J.
Schernhammer, Eva S.
Rimm, Eric B.
Hu, Frank B.
Venue: JAMA
Publisher: American Medical Association (AMA)
Published: 2013-04-03
Volume: 309
Issue: 13
Pages: 1388
ISSN: 0002-9955 (ISSN-L)
0098-7484
DOI: 10.1001/jama.2013.2710
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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Melatonin Secretion and the Incidence of Type 2 Diabetes

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