title: Melatonin secretion and the incidence of type 2 diabetes.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: Renal Division, Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA. cmcmullan1@partners.org
authors.forename: Ciaran J
authors.initials: CJ
authors.lastname: McMullan
authors.forename: Eva S
authors.initials: ES
authors.lastname: Schernhammer
authors.forename: Eric B
authors.initials: EB
authors.lastname: Rimm
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: John P
authors.initials: JP
authors.lastname: Forman
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D008550:Melatonin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000652:urine; D008875:Middle Aged; D012044:Regression Analysis; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: C054513:6-sulfatoxymelatonin; D003404:Creatinine; D008550:Melatonin
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