MON-166 - Association of Circulating SIRT6 and IGFBP2 with Menopausal Status and Obesity in Women

Background: Menopause is accompanied by metabolic aging and a higher cardiometabolic burden, yet the contribution of newer metabolic regulators such as sirtuin-6 (SIRT6) and insulin-like growth factor binding protein-2 (IGFBP2) to this transition is not well defined. Both proteins have been linked to insulin sensitivity, aging processes, and endocrine function, but how they relate to menopausal status in the context of obesity remains uncertain.

Methods: This cross-sectional study measured circulating SIRT6 and IGFBP2 in 88 women (48 premenopausal and 40 postmenopausal), with additional stratification by obesity status. Multivariable linear regression was used to test the independent and joint effects of menopausal status and obesity on SIRT6 and IGFBP2, with age and body mass index (BMI) included a priori as covariates; SIRT6 values were log-transformed to address skewed distribution. Sensitivity models incorporated indices of insulin resistance (HOMA-IR) and markers of the GH–IGF-1 axis, and the relationship between SIRT6 and IGFBP2 was assessed using Pearson and Spearman correlations as well as adjusted regression.

Results: In models adjusted for age and BMI, there was evidence of a menopause-by-obesity interaction for circulating SIRT6 (interaction p = 0.078). Among non-obese women, postmenopausal status was associated with higher SIRT6 levels than premenopausal status (adjusted difference on the log scale = 0.36 ± 0.15, corresponding to a 43% higher SIRT6 concentration, p = 0.018), whereas no such difference was apparent in obese women (p = 0.79). IGFBP2 concentrations did not differ by menopausal status or obesity after adjustment (all p > 0.20). Across the full sample, SIRT6 and IGFBP2 were positively correlated (Pearson r = 0.57, p = 5.6 × 10⁻⁹; Spearman ρ = 0.49, p < 1 × 10⁻⁶), and this association persisted after adjusting for menopausal status, adiposity, insulin resistance, and IGF-1.

Conclusions: Circulating SIRT6 shows a menopause-related increase that is most evident in non-obese women, suggesting that adiposity modifies the link between menopause and SIRT6. In contrast, IGFBP2 appears largely unrelated to menopausal and obesity status in this cohort, yet remains strongly and positively associated with SIRT6, consistent with coordinated regulation within metabolic aging pathways. These findings support SIRT6 as a potential biomarker of menopausal metabolic remodeling and underscore the influence of adiposity on endocrine and metabolic adaptation in female aging.

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