Sex modifies the relationship between cardiorespiratory fitness and insulin resistance

Abstract

AbstractBackgroundCardiorespiratory fitness (CRF) is a protective lifestyle factor against age‐related changes in insulin resistance in adults at‐risk for Alzheimer’s disease (AD); however, this association may differ between males and females. While sex‐dimorphic mechanisms of neurodegeneration and peripheral insulin have been proposed in aging models, it is still unclear whether sex differences exist in the influence of CRF. This study examines whether sex modifies the association between CRF and insulin resistance in a participant sample enriched with risk for AD.MethodThis study included n = 1,131 cognitively unimpaired, nondiabetic participants, where CRF was estimated using a validated equation that incorporates age, sex, BMI, resting heart rate, and self‐reported physical activity. The Homeostatic Model Assessment for Insulin Resistance (HOMA‐IR) quantified insulin resistance using measured plasma glucose levels in mg/dL and insulin in µIU/mL following a 12‐hour fast. Cross‐sectional linear regression models were assembled in a moderation framework to test the interaction between CRF and sex on HOMA‐IR scores using the IBM SPSS PROCESS Macro v3.4. All models controlled for age, education, Apolipoprotein E4 (APOE4) carriage, body mass index (BMI), and familial history of AD. Finally, sex‐stratified analyses were performed to test within‐group associations of CRF and HOMA‐IR.Result71.8% of participants had family history of AD and 38.8% were APOE4 carriers. Participants had a mean age of 64.5 ± 7 years and a mean of 16 ± 3 years of education. CRF was negatively associated with HOMA‐IR (β = ‐0.064, SE = 0.03, p = 0.04) and the interaction of CRF and sex was likewise significant (β = ‐0.114, SE = 0.03, p<.001). Stratified models showed that the magnitude of the association between CRF and HOMA‐IR was almost three times as strong among men than women (males: β = ‐0.178, SE = 0.03, p<.001; females: β = ‐0.06, SE = 0.03, p = 0.04).ConclusionAmong older adults at heightened risk for AD, CRF protects against insulin resistance; however, this association may be stronger in aging males than in females.