THU512 Elevated Insulin Like Growth Factor Binding Protein 2 Levels Are Associated With Muscle Wasting And Increased Insulin Sensitivity In Cancer Patients

Abstract

Abstract Disclosure: L. Caeiro: None. L.J. Anderson: None. H. Liu: None. K. Krumm: None. J.M. Garcia: None. Cancer-associated weight loss is a complex metabolic syndrome characterized by a loss of skeletal muscle mass and function. Insulin resistance is present in cancer but its role in cancer-related muscle wasting is poorly understood. Recent data from in vitro and animal models show that tumor-derived insulin-like growth factor binding protein (IGFBP)-2 can lead to skeletal muscle wasting and insulin resistance in cancer. We hypothesized that muscle mass and function would be inversely associated with IGFBP-2 levels and insulin resistance in circulation. IGFBP-2, physical function, body composition, insulin and glucose (to calculate HOMA-IR), quality of life (QOL), and cytokines were assessed in male cancer patients with (CWL, n=25) or without (CWS, n=47) weight loss. Physical Function was assessed by hand grip strength (HGS), stair climb power (SCP), and one repetition maximum (1RM) tests of the major muscle groups. Body composition was measured by bioimpedance (BIA) and CT scans and QOL by Karnofsky and ECOG scores. Blood samples were obtained after an overnight fast to measure IGFBP-2, insulin, glucose, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in plasma. CWL had higher plasma IGFBP2 levels (p = 0.01) and lower skeletal muscle index (SMI) (p = 0.03) and body mass index (BMI) (p = 0.007) when compared to CWS, but no differences were found with SCP, HGS, 1RM tests, or with HOMA-IR. IGFBP2 was negatively correlated with SMI (N = 65, R² = -.58, P = <0.001), BMI (N=73, R² = -.54, P = <0.001), CT-derived muscle mass (N = 48, R² = -.56, P = <0.001), BIA fat percent, (N = 25, R² = -.56, P = 0.005), 6 month weight change (N = 73, R² = -.27, P = 0.020), 12 month weight change (N = 73, R² = -.24, P = 0.044), insulin (N = 53, R² = -.48, P = <0.001) ,and HOMA IR (N = 53, R² = -.51, P = <0.001) and positively correlated with IL-6 (N = 72, R² = .33, P = 0.005) and TNF-α (N = 72, R² = .27, P = 0.021) in cancer patients. HOMA-IR was positively correlated with SMI (N = 31, R² = .39, P = 0.029), CT-derived muscle mass (N = 31, R² = .38, P = 0.036), and BIA fat percent (N = 21, R² = .62, P = 0.003). No association was found with IGFBP2 and QOL, SCP, HGS or the other functional parameters with exception of Knee Extension (N = 26, R² = .39, P = 0.049). In conclusion, cancer weight losing patients have increased IGFBP2 levels that were associated with muscle wasting, decreased fat mass, weight loss, and elevated IL-6 and TNF-α. HOMA-IR was negatively correlated with IGFBP2 and positively correlated with muscle mass. We postulate that a decrease in fat mass seen in weight-losing cancer patients leads to an increase in insulin sensitivity. More studies are needed to test this hypothesis and establish the role of IGFBP-2 as a mediator of muscle wasting in cancer. Presentation: Thursday, June 15, 2023