Applied Physiology, Nutrition, and Metabolism · Jan 1, 2025
Sex modifies the association between cardiorespiratory fitness and insulin resistance in adults at risk for Alzheimer's disease
By Mamlouk G, Edmunds K, McIntyre C et al.
This study examines whether sex modifies the association between cardiorespiratory fitness (CRF) and insulin resistance in adults at risk for Alzheimer's disease (AD). This study included n = 1131 (791 females, 340 males; mean age 64.7 years) cognitively unimpaired, nondiabetic participants from the Wisconsin Registry for Alzheimer's Prevention, a longitudinal observational cohort study enriched with persons with parental history of AD dementia. CRF was estimated using a validated equation, and the homeostatic model assessment for insulin resistance (HOMA-IR) quantified insulin resistance from blood samples. Cross-sectional linear regression models were assembled in a moderation framework to test the interaction between CRF and sex on HOMA-IR scores. Finally, sex-stratified analyses were performed to test within-group associations of CRF and HOMA-IR. CRF was negatively associated with HOMA-IR (β = -0.504, SE = 0.21, p = 0.018) and the interaction of CRF and sex was likewise significant (β = -0.849, SE = 0.18, p < 0.001). Stratified models showed that the magnitude of the association between CRF and HOMA-IR was over twice as strong among males than females (males: β = -0.837, SE = 0.26, p = 0.001; females: β = -0.400, SE = 0.19, p = 0.03). Among older adults at heightened risk for AD, CRF protects against insulin resistance; however, this association may be stronger in aging males than in females.