Age at menarche and type 2 diabetes risk: the EPIC-InterAct study.
Elks CE., Ong KK., Scott RA., van der Schouw YT., Brand JS., Wark PA., Amiano P., Balkau B., Barricarte A., Boeing H., Fonseca-Nunes A., Franks PW., Grioni S., Halkjaer J., Kaaks R., Key TJ., Khaw KT., Mattiello A., Nilsson PM., Overvad K., Palli D., Quirós JR., Rinaldi S., Rolandsson O., Romieu I., Sacerdote C., Sánchez MJ., Spijkerman AM., Tjonneland A., Tormo MJ., Tumino R., van der A DL., Forouhi NG., Sharp SJ., Langenberg C., Riboli E., Wareham NJ., InterAct Consortium None.
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.