title: Age at menarche and type 2 diabetes risk: the EPIC-InterAct study.
abstract: OBJECTIVE
  Younger age at menarche, a marker of pubertal timing in girls, is associated with higher risk of later type 2 diabetes. We aimed to confirm this association and to examine whether it is explained by adiposity.
  
  
  METHODS
  The prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 individuals from 26 research centers across eight European countries. We tested the association between age at menarche and incident type 2 diabetes using Prentice-weighted Cox regression in 15,168 women (n = 5,995 cases). Models were adjusted in a sequential manner for potential confounding and mediating factors, including adult BMI.
  
  
  RESULTS
  Mean menarcheal age ranged from 12.6 to 13.6 years across InterAct countries. Each year later menarche was associated with 0.32 kg/m2 lower adult BMI. Women in the earliest menarche quintile (8-11 years, n = 2,418) had 70% higher incidence of type 2 diabetes compared with those in the middle quintile (13 years, n = 3,634), adjusting for age at recruitment, research center, and a range of lifestyle and reproductive factors (hazard ratio [HR], 1.70; 95% CI, 1.49-1.94; P < 0.001). Adjustment for BMI partially attenuated this association (HR, 1.42; 95% CI, 1.18-1.71; P < 0.001). Later menarche beyond the median age was not protective against type 2 diabetes.
  
  
  CONCLUSIONS
  Women with history of early menarche have higher risk of type 2 diabetes in adulthood. Less than half of this association appears to be mediated by higher adult BMI, suggesting that early pubertal development also may directly increase type 2 diabetes risk.
authors.affiliation: Corresponding author: Cathy E. Elks, cathy.elks@mrc-epid.cam.ac.uk.
authors.forename: Cathy E
authors.initials: CE
authors.lastname: Elks
authors.forename: Ken K
authors.initials: KK
authors.lastname: Ong
authors.forename: Robert A
authors.initials: RA
authors.lastname: Scott
authors.forename: Yvonne T
authors.initials: YT
authors.lastname: van der Schouw
authors.forename: Judith S
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authors.forename: Beverley
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authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.forename: Heiner
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authors.lastname: Boeing
authors.forename: Ana
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authors.lastname: Fonseca-Nunes
authors.forename: Paul W
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authors.lastname: Franks
authors.forename: Sara
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authors.lastname: Grioni
authors.forename: Jytte
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authors.lastname: Halkjaer
authors.forename: Rudolf
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authors.forename: Timothy J
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authors.forename: Kay Tee
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authors.forename: Amalia
authors.initials: A
authors.lastname: Mattiello
authors.forename: Peter M
authors.initials: PM
authors.lastname: Nilsson
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Domenico
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authors.lastname: Palli
authors.forename: J Ramón
authors.initials: JR
authors.lastname: Quirós
authors.forename: Sabina
authors.initials: S
authors.lastname: Rinaldi
authors.forename: Olov
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authors.lastname: Rolandsson
authors.forename: Isabelle
authors.initials: I
authors.lastname: Romieu
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.forename: María-José
authors.initials: MJ
authors.lastname: Sánchez
authors.forename: Annemieke M W
authors.initials: AM
authors.lastname: Spijkerman
authors.forename: Anne
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authors.lastname: Tjonneland
authors.forename: Maria-Jose
authors.initials: MJ
authors.lastname: Tormo
authors.forename: Rosario
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authors.lastname: Tumino
authors.forename: Daphne L
authors.initials: DL
authors.lastname: van der A
authors.forename: Nita G
authors.initials: NG
authors.lastname: Forouhi
authors.forename: Stephen J
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authors.lastname: Sharp
authors.forename: Claudia
authors.initials: C
authors.lastname: Langenberg
authors.forename: Elio
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authors.lastname: Riboli
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
mesh_terms: D050154:Adiposity; D000328:Adult; D000367:Age Factors; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology*; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D008019:Life Style; D008137:Longitudinal Studies; D008572:Menarche / Q000502:physiology*; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications; D009765:Obesity / Q000453:epidemiology; D011446:Prospective Studies; D012306:Risk; D012307:Risk Factors