Adipokines in critically ill patients: A systematic review and meta-analysis of observational studies

Background: Critical illness is a hypermetabolic state with high mortality rates. Adipokines, including leptin, adiponectin, and resistin, regulate energy balance, inflammation, and metabolism and may influence outcomes in critically ill patients. This study evaluated changes in adipokine levels in ICU patients compared to healthy controls and explored their associations with clinical outcomes. Methods: A systematic review and meta-analysis of 34 case-control studies involving 3365 participants were conducted. Pooled weighted mean difference (WMD) of adipokine levels between critically ill patients and controls were calculated using random-effects models. Subgroup analyses were performed based on ICU type (Medical, Surgical, Mixed), septic status (septic or non-septic), and injury phase (ebb or flow). Publication bias and sensitivity analyses were also conducted. Results: Leptin (WMD: 3.22 ng/mL; 95 % CI: 0.91 to 5.53) and resistin (WMD: 19.86 ng/mL; 95 % CI: 14.78 to 24.95) levels were significantly elevated in critically ill patients, while adiponectin levels showed no significant difference (WMD: 0.37 mg/dL; 95 % CI: -1.81 to 2.55). Subgroup analyses revealed higher leptin and resistin levels in mixed-ICU and septic patients. Leptin also increased during the ebb phase, but heterogeneity remained high (I2 > 97 %). Conclusions: Leptin and resistin levels are elevated in critical illness, potentially serving as biomarkers for disease severity. However, high heterogeneity limits generalizability. Future research should standardize protocols and investigate adipokines' prognostic and therapeutic roles in critical care. (c) 2025 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.