Revisiting insulin resistance in human cancer cachexia - a systematic review and meta-analysis

BACKGROUND: In patients with cancer, unintentional weight loss and cancer-associated cachexia (CAC) reduce overall survival and impair the quality of life. Because of insulin's anabolic effects, insulin resistance could contribute to CAC progression. However, the role of insulin resistance in CAC remains unclear, and this study aimed to investigate the association between insulin resistance and CAC. Addressing this knowledge gap may help identify treatable targets to improve patient outcomes.

METHODS: We performed a systematic review and meta-analysis. By including studies reporting both fasting levels of circulating insulin and glucose in patients with cancer and CAC according to the internationally accepted CAC definition, we calculated the HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) index to estimate the level of insulin resistance (defined as HOMA-IR above 2.0) in patients with CAC. A subgroup analysis was conducted from studies reporting a HOMA-IR index both from a group of patients with CAC and a group without CAC (nonCAC).

RESULTS: Seventeen studies were included, with a total of 197 patients. The mean HOMA-IR of all studies was 1.84 (95% confidence interval [CI]: 1.77-1.91). Twelve studies found HOMA-IR below 2.0. Five of the 17 studies also reported HOMA-IR from a group of patients with cancer without CAC. We observed a mean difference of -0.42 (95% CI: -2.24 to 1.40) in favour of a lower HOMA-IR in patients with CAC compared to nonCAC, and thus no statistically significant difference between the groups.

INTERPRETATION: This systematic review suggests no clear association between insulin resistance and CAC. However, the limited sample sizes and study heterogeneity highlight the need for larger, longitudinal investigations.