Abstract

Abstract Context Early age at menarche (AAM) is a risk factor for type 2 diabetes later in life, but the pathogenic pathways that confer increased risk remain unknown. Objective We examined the associations between AAM and inflammatory and glucose metabolism biomarkers among US adult women who were free of diabetes. Methods Using the National Health and Nutrition Examination Survey (NHANES) 1999-2018, 19 228 women over 20 years old who were free of self-reported cancer and diabetes were included in this cross-sectional analysis. AAM was the self-reported age at first menstruation. C-reactive protein (CRP), fasting glucose, fasting insulin, and ferritin levels were measured as biomarkers of inflammation and glucose metabolism in adult blood samples using latex-enhanced nephelometry, enzymatic, and immunoassay methods. Multiple linear regression was used to relate AAM to the biomarkers. Results The median age at the time of blood sample collection was 44 years (interquartile range, 33-62). After age adjustment, there was an association between a lower AAM and higher CRP (P-trend = .006), fasting glucose (P-trend < .0001), fasting insulin (P-trend < .0001), and ferritin (P-trend < .0001). These remained significant after additional adjustment for demographic, reproductive, lifestyle, and adiposity variables, except for ferritin. Smoking modified the effect of AAM on CRP (P-interaction = .014), fasting insulin (P-interaction < .001), and fasting glucose (P-interaction < .001). In stratified analysis, the observed associations became more pronounced in nonsmokers, while they were attenuated to nonsignificance in active smokers. Conclusion Earlier age at menarche is associated with an unfavorable inflammatory and glucose metabolic biomarker profile in a nationally representative sample of adult women free of diabetes, especially among nonsmokers.