SAT-318 Insulin Resistance in Prostate Cancer Patients on Androgen Deprivation Therapy

Abstract Disclosure: J.R. Fredrick: None. L. Caeiro: None. L.J. Anderson: None. N. Acosta: None. J.M. Garcia: None. Introduction: Prostate Cancer (PCa) is the leading cause of cancer in men and androgen deprivation therapy (ADT) is a common treatment in cases of locally advanced and metastatic disease. ADT is associated with insulin resistance (IR), increased adiposity and decreased muscle mass. However, the relationship between IR and these outcomes is not well-characterized. Our hypothesis was that patients with higher IR would have excess loss of muscle mass, physical function, worsening mitochondrial respiration and poor patient reported outcomes after six months of starting ADT. Methods: This longitudinal, 6-month, observational study recruited PCa men starting ADT (n=59). After excluding patients with pre-existing diabetes, the sample size was reduced to 39. Fasting plasma insulin and glucose levels were used to calculate HOMA_IR, a validated tool for IR. We assessed body composition, physical function, mitochondrial respiration, and patient-reported outcomes (PROs) before and after 6 months of ADT. Body composition was assessed by dual-energy x-ray absorptiometry, physical function by VO2 (aerobic capacity), hand grip strength, 6-minute walk test (6MWT), and stair climb power and actical data was used to check for daily moderate to vigorous activity. Also, we measured mitochondrial respiration from muscle biopsies and PROs with validated questionnaires including Functional Assessment of Cancer Therapy - Prostate (FACT-P) and European Organisation for Research and Treatment of Cancer Core Quality of Life (EORTC QLQ-C30). Results: Before ADT, HOMA_IR was directly correlated with higher BMI and fat mass and PROs. After 6 months of ADT, baseline HOMA_IR was negatively correlated with changes in weight and appendicular lean mass (ALM), 6MWT, and PROs. Surprisingly, there was a positive correlation between baseline HOMA_IR and change in peak VO2; however, this correlation was no longer significant after adjusting for body fat mass. After 6 months on ADT, there was a significant increase in HOMA_IR and there was a positive correlation between changes in IR and changes in fat mass, and appetite. There was no correlation between changes in IR and changes in 6MWT, VO2, mitochondrial respiration or PROs. Conclusion: In PCa men initiating ADT, baseline IR measured by HOMA_IR predicted greater declines in muscle mass, body weight, physical performance and quality of life after 6 months of treatment. Six months of ADT lead to increases in IR, fat mass and appetite. More studies are needed to understand the interplay between IR, body composition, physical function and PROs in men with PCa starting before and during ADT and whether therapies targeting IR will benefit these patients. Presentation: Saturday, July 12, 2025