Age at menarche and metabolic markers for type 2 diabetes in premenopausal women: The BioCycle study

Context: Early age at menarche has been linked to an elevated risk of type 2 diabetes. However, the underlying mechanism is unclear. Objective: Our objective was to examine associations between age at menarche and type 2 diabetes risk factors. Design, Participants, and Setting: The BioCycle Study followed 253 healthy premenopausal women from the general population (Buffalo, NY) for one to two menstrual cycles. Main Outcome Measures: Age at menarche was self-reported. Body mass index and waist circumference were measured by trained personnel. Total body and trunk fat were measured by dualenergy x-ray absorptiometry. Fasting glucose, insulin, highly sensitive C-reactive protein, and SHBG levels were measured up to eight times per cycle. Insulin resistance (IR) and β-cell function were evaluated using the homeostasis model assessment (HOMA)-IR and HOMA-β. Results: The mean age at menarche was 12.5 ± 1.2 yr. After adjustment for age, race, education, and physical activity, early menarche (≤12 yr) was significantly associated with an increase of 1.35 kg/m² in body mass index (P = 0.01), 2.52% in percent total body fat (P = 0.004), 3.02% in percent trunk fat (P = 0.004), 0.15 μIU/ml in (log)insulin (P = 0.02), 0.15 U in (log)HOMA-IR (P = 0.03), and 0.16 U in (log)HOMA-β (P = 0.01) compared with average menarche (12-14 yr). No associations were found for SHBG or highly sensitive C-reactive protein. Conclusions: Early onset of menarche is associated with unfavorable metabolic phenotypes compared with average onset of menarche in healthy premenopausal women, including reduced insulin sensitivity and β-cell function and greater total and trunk fat.