8127 HOMA-IR Predicts Muscle Wasting during Androgen Deprivation Therapy

Abstract Disclosure: L. Caeiro: None. L.J. Anderson: None. H. Liu: None. J.M. Garcia: None. Androgen deprivation therapy (ADT) is the primary treatment for advanced and metastatic prostate cancer. However, it induces adverse effects like reduced muscle mass and function, increased adiposity, and insulin resistance (IR). While muscle wasting is a known complication of ADT-induced hypogonadism, the extent to which other factors determine the variability in muscle loss remains unknown. In other diseases, IR is associated with muscle wasting, but its role in this setting of ADT has yet to be addressed. We hypothesized that patients with greater IR pre-ADT would display larger decreases of muscle mass and function after six months of ADT. Insulin and glucose (to calculate HOMA-IR), body composition, and physical function were assessed in patients with prostate cancer prior to and after three and six months of ADT. Body composition was assessed by dual x-ray absorptiometry and physical function by VO2 peak and 6-minute walk test (6MWT). Fasting blood samples were obtained to measure insulin and glucose in plasma. Pre-ADT, HOMA-IR was directly correlated with body mass index (BMI) (r=0.65, p<0.001, n=49), fat mass (r=0.55, p<0.001, n=49), and appendicular skeletal muscle index (ASMI) (r=0.33, p=0.021, n=49) and was inversely correlated with VO2 peak (r= -0.39, p=0.007, n=46). After three months, fat mass (p=0.015) and IR (p=0.0014) increased and VO2 peak decreased (p=0.0007), which persisted at the six-month visit. Appendicular lean mass and ASMI decreased after six months (p<0.0001). Pre HOMA-IR was negatively associated with delta BMI (r=-0.49, p<0.001, n=46), delta lean mass (r=-0.58, p<0.001, n=46), delta ASMI (r=-0.52, p<0.001, n=46), and delta 6MWT (r=-0.37, p=0.011, n=45) and positively correlated with delta VO2 peak (r=0.44, p=0.007, n=36). No associations were found with Pre-ADT HOMA-IR and changes in fat mass. In conclusion, those with greater Pre-ADT HOMA-IR lost more muscle mass, body weight, and 6MWT while unexpectedly showing less decrease in VO2 peak. This data suggests that HOMA-IR could potentially serve as a predictor of muscle mass loss in patients undergoing ADT. We propose that the significant decrease in muscle mass seen with ADT can be exacerbated by pre-existing IR. Presentation: 6/3/2024