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

Cathy E Elks et al. Diabetes Care. 2013 Nov.

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.

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Figures

Figure 1
Figure 1
HRs for type 2 diabetes by category of age at menarche in the EPIC-InterAct study. Results presented are HRs for diabetes in each group compared with the reference category (13 years, representing the median age at menarche). Results are from Prentice-weighted Cox regression models performed within each country participating in InterAct and pooled using the random-effects meta-analysis. Models are adjusted for age at recruitment, date of birth, center, and lifestyle and reproductive factors (●), and with additional adjustment for adult BMI (○).
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