Age at menarche and type 2 diabetes risk: the EPIC-InterAct study

Cathy E Elks, Ken K Ong, Robert A Scott, Yvonne T van der Schouw, Judith S Brand, Petra A Wark, Pilar Amiano, Beverley Balkau, Aurelio Barricarte, Heiner Boeing, Ana Fonseca-Nunes, Paul W Franks, Sara Grioni, Jytte Halkjaer, Rudolf Kaaks, Timothy J Key, Kay Tee Khaw, Amalia Mattiello, Peter M Nilsson, Kim OvervadDomenico Palli, J Ramón Quirós, Sabina Rinaldi, Olov Rolandsson, Isabelle Romieu, Carlotta Sacerdote, María-José Sánchez, Annemieke M W Spijkerman, Anne Tjonneland, Maria-Jose Tormo, Rosario Tumino, Daphne L van der A, Nita G Forouhi, Stephen J Sharp, Claudia Langenberg, Elio Riboli, Nicholas J Wareham, InterAct Consortium

Research output: Contribution to journalArticle (Academic Journal)peer-review

126 Citations (Scopus)


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.

RESEARCH DESIGN AND 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.

Original languageEnglish
Pages (from-to)3526-34
Number of pages9
JournalDiabetes Care
Issue number11
Publication statusPublished - Nov 2013


  • Adiposity
  • Adult
  • Age Factors
  • Diabetes Mellitus, Type 2
  • Europe
  • Female
  • Humans
  • Incidence
  • Life Style
  • Longitudinal Studies
  • Menarche
  • Middle Aged
  • Neoplasms
  • Obesity
  • Prospective Studies
  • Risk
  • Risk Factors
  • Journal Article
  • Research Support, Non-U.S. Gov't


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