Diabetes Research and Clinical Practice · Feb 6, 2026

Reproductive factors, insulin resistance surrogate indices, and circadian syndrome among middle-aged and elderly women a mediation analysis using two-national cohorts

By Liu L, Lin J, Li L et al.

AIMS: We investigated the mediation effects of seven insulin resistance(IR) indices: triglyceride glucose (TyG), triglyceride glucose-waist to height ratio (TyG-WHtR), triglyceride glucose-waist circumference (TyG-WC), estimated glucose disposal rate (eGDR), metabolic score for IR, lipid accumulation product (LAP), and Chinese visceral adiposity index (CVAI) on the associations between reproductive factors and circadian syndrome (CircS) in middle-aged and elderly women. METHODS: This study was conducted using the China Health and Retirement Longitudinal Study (CHARLS) as training set and the English Longitudinal Study on Aging (ELSA) as validation set, with baseline non-CircS individuals. Regression models established causal relationships between reproductive factors and incident CircS. Mediation analysis quantified IR mediation effects. Receiver operating characteristic curves evaluated IR indices' predictive capacity. RESULTS: The incidence of new-onset CircS was 465 (15.94%) in CHARLS and 291 (11.89%) in ELSA, respectively. The CircS incidence was higher in earlier age at menarche or menopause. Mediation analyses revealed that TyG, TyG-WHtR, TyG-WC, LAP, CVAI, and eGDR mediated the menarche-CircS association, with TyG-WHtR accounting for 14.3% of the mediating effect. The TyG-WHtR cutoff value for predicting CircS was identified 4.507 for early menarche. CONCLUSION: Significant inverse relationships were observed between early age at menarche/menopause and increased CircS risk, with IR largely mediating these associations.

doi.org/10.1016/j.diabres.2026.113141PubMed 41655796Populations