Age at Menarche and Type 2 Diabetes Risk

The EPIC-InterAct study

  1. The InterAct Consortium
  1. 1Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, U.K.
  2. 2Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
  3. 3Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St. Mary’s Campus, Norfolk Place, London, U.K.
  4. 4Public Health Division of Gipuzkoa, Basque Government, San Sebastian, Spain
  5. 5Instituto BIO-Donostia, Basque Government, San Sebastian, Spain
  6. 6Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública), Madrid, Spain
  7. 7INSERM, CESP Centre for Research in Epidemiology and Population Health, U1018: Epidemiology of Diabetes, Obesity, and Chronic Kidney Disease Over the Life Course, Villejuif Cedex, France
  8. 8Université Paris-Sud, UMRS 1018, Villejuif, France
  9. 9Navarre Public Health Institute, Pamplona, Navarra, Spain
  10. 10Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany
  11. 11Department of Epidemiology, Nutrition, Environment, and Cancer Unit, Catalan Institute of Oncology, L'Hospitalet de Lolgbregat, Barcelona, Spain
  12. 12Department of Clinical Sciences, Clinical Research Center, Skåne University Hospital, Lund University, Malmö, Sweden
  13. 13Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
  14. 14Fondazione IRCCS Istituto Nazionale Tumori Milan, Via Venezian, Milan, Italy
  15. 15Danish Cancer Society Research Center, Copenhagen, Denmark
  16. 16Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany
  17. 17Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, U.K.
  18. 18Department of Public Health and Primary Care, University of Cambridge, Addenbrooke's Hospital, Cambridge, U.K.
  19. 19Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
  20. 20Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark
  21. 21Department of Cardiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark
  22. 22Molecular and Nutritional Epidemiology Unit, ISPO Ponte Nuovo, Florence, Italy
  23. 23Consejería de Sanidad, Public Health Directorate, Oviedo-Asturias, Spain
  24. 24International Agency for Research on Cancer, Lyon Cedex, France
  25. 25Department of Public Health and Clinical Medicine, Umeå University, Family Medicine, Umeå University, Umeå, Sweden
  26. 26Center for Cancer Prevention (CPO-Piemonte), Turin, Italy
  27. 27Human Genetics Foundation, Turin, Italy
  28. 28Andalusian School of Public Health, Granada, Spain
  29. 29National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
  30. 30Department of Epidemiology, Murcia Regional Health Council, Ronda de Levante, Murcia, Spain
  31. 31Department of Health and Social Sciences, Universidad de Murcia, Campus de Espinardo, Spain
  32. 32Cancer Registry and Histopathology Unit, “Civile–M.P. Arezzo” Hospital, Ragusa, Italy
  33. 33Associazone Iblea per la Ricerca Epidemiologica–Onlus, Ragusa, Italy
  1. Corresponding author: Cathy E. Elks, cathy.elks{at}mrc-epid.cam.ac.uk.

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.

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.

Footnotes

  • Received February 22, 2013.
  • Accepted May 23, 2013.

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