Melatonin secretion and the incidence of type 2 diabetes

JAMA. 2013 Apr 3;309(13):1388-96. doi: 10.1001/jama.2013.2710.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Case-Control Studies
  • Cohort Studies
  • Creatinine / urine
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Female
  • Humans
  • Incidence
  • Melatonin / analogs & derivatives*
  • Melatonin / metabolism*
  • Melatonin / urine
  • Middle Aged
  • Regression Analysis
  • Risk Factors
  • United States / epidemiology


  • 6-sulfatoxymelatonin
  • Creatinine
  • Melatonin