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, Maria José Sanchez, 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

Research output: Contribution to journalArticlepeer-review


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 confirmthis association and to examine whether it is explained by adiposity. RESEARCH DESIGN AND METHODSdThe prospective European Prospective Investigation into Cancer andNutrition (EPIC)-InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 individuals from26 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 latermenarche 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 earlymenarche 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)3526-3534
Number of pages9
JournalDiabetes Care
Issue number11
Publication statusPublished - Nov 2013

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialised Nursing
  • Medicine(all)


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