title: Circulating estrone levels are associated prospectively with diabetes risk in men of the Framingham Heart Study.
abstract: OBJECTIVE
  In postmenopausal women and preclinical murine models, estrogen administration reduces diabetes risk; however, the relationship of estradiol and estrone to diabetes in men is poorly understood. We determined the relationship between circulating estradiol and estrone levels and diabetes risk in community-dwelling men of the Framingham Heart Study (FHS).
  
  
  METHODS
  Cross-sectional relationships of estradiol and estrone levels with diabetes were assessed at examination 7 (1998-2001) in FHS generation 2 men (n = 1,458); prospective associations between hormone levels at examination 7 and incident diabetes were assessed 6.8 years later at examination 8. Type 2 diabetes mellitus was defined as fasting glucose >125 mg/dL, medication use, or both. Estradiol, estrone, and testosterone levels were measured with liquid chromatography-tandem mass spectrometry, and free estradiol and estrone were calculated.
  
  
  RESULTS
  In cross-sectional models, men with elevated estrone and estradiol had 40% and 62% increased likelihoods of existing diabetes per cross-sectional doubling of estrone and estradiol levels, respectively. Free estrone (cross-sectional odds ratio 1.28 [95% CI 1.02-1.62], P = 0.04) was associated with impaired fasting glucose at examination 7. There was an increase in risk of existing diabetes with increasing quartiles of total and free estrone and estradiol and an increase in risk of incident diabetes with increasing quartiles of estrone levels. In multivariate longitudinal analyses, a twofold increase in total or free estrone levels at examination 7 was associated with 77 and 93% increases, respectively, in odds of incident diabetes at examination 8.
  
  
  CONCLUSIONS
  Although both estradiol and estrone exhibit cross-sectional associations with diabetes in men, in longitudinal analyses estrone is a more sensitive marker of diabetes risk than is estradiol.
authors.affiliation: Department of Mathematics, Boston University, Boston, Massachusetts, USA. guneetk@bu.edu
authors.forename: Guneet Kaur
authors.initials: GK
authors.lastname: Jasuja
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Travison
authors.forename: Maithili
authors.initials: M
authors.lastname: Davda
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Rose
authors.forename: Anqi
authors.initials: A
authors.lastname: Zhang
authors.forename: Mark M
authors.initials: MM
authors.lastname: Kushnir
authors.forename: Alan L
authors.initials: AL
authors.lastname: Rockwood
authors.forename: Wayne
authors.initials: W
authors.lastname: Meikle
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Coviello
authors.forename: Ralph
authors.initials: R
authors.lastname: D'Agostino
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
mesh_terms: D000368:Aged; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000473:pathology; D004958:Estradiol / Q000097:blood; D004970:Estrone / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013739:Testosterone / Q000097:blood
chemical_list: D004970:Estrone; D013739:Testosterone; D004958:Estradiol