Age at menarche and risk of type 2 diabetes: results from 2 large prospective cohort studies

Abstract

The authors investigated the association between age at menarche and risk of type 2 diabetes mellitus (T2DM) among 101,415 women from the Nurses' Health Study (NHS) aged 34-59 years (1980-2006) and 100,547 women from Nurses' Health Study II (NHS II) aged 26-46 years (1991-2005). During 2,430,274 and 1,373,875 person-years of follow-up, respectively, 7,963 and 2,739 incident cases of T2DM were documented. Young age at menarche was associated with increased risk of T2DM after adjustment for potential confounders, including body figure at age 10 years and body mass index (BMI; weight (kg)/height (m)(2)) at age 18 years. Relative risks of T2DM across age-at-menarche categories (< or =11, 12, 13, 14, and > or =15 years) were 1.18 (95% confidence interval (CI): 1.10, 1.27), 1.09 (95% CI: 1.02, 1.17), 1.00 (referent), 0.92 (95% CI: 0.83, 1.01), and 0.95 (95% CI: 0.84, 1.06), respectively, in the NHS (P for trend < 0.0001) and 1.40 (95% CI: 1.24, 1.57), 1.13 (95% CI: 1.00, 1.27), 1.00 (referent), 0.98 (95% CI: 0.82, 1.18), and 0.96 (95% CI: 0.78, 1.19), respectively, in NHS II (P for trend < 0.0001). Associations were substantially attenuated after additional control for updated time-varying BMI. These data suggest that early menarche is associated with increased risk of T2DM in adulthood. The association may be largely mediated through excessive adult adiposity. The association was stronger among younger women, supporting a role for sex hormones in younger onset of T2DM, in addition to BMI.

Figure 1.

Relative risk of type 2 diabetes mellitus (T2DM) by age at menarche in A) the Nurses’ Health Study (1980–2006) (P for trend < 0.0001) and B) Nurses’ Health Study II (1991–2005) (P for trend < 0.0001), after adjustment for age, birth weight, having been breastfed, childhood socioeconomic status, race/ethnicity, family history of diabetes, perceived body figure at age 10 years, physical activity, quintile of dietary score, alcohol consumption, smoking status, baseline hypertension, baseline hypercholesterolemia, menopause status, use of hormone replacement therapy, adult socioeconomic status, parity, oral contraceptive use, regularity of menstrual cycles between ages 18 and 22 years, and body mass index at age 18 years (model 3). Bars, 95% confidence interval.

Figure 2.

Relative risks of A) adult obesity at baseline and B) excessive weight gain since age 18 years by age at menarche in the Nurses’ Health Study (NHS; 1980–2006) and Nurses’ Health Study II (NHS II; 1991–2005), after adjustment for baseline age, socioeconomic status in childhood and adulthood, smoking status, physical activity, quintile of dietary score, menopause status, use of hormone replacement therapy, alcohol intake, parity, perceived body figure at age 10 years, and body mass index at age 18 years (all P’s for trend < 0.0001). Bars, 95% confidence interval.