The Role of Fat-Free Mass in Weight-Related Complications: A Rapid Review and Meta-Analysis.

Abstract

This review synthesized evidence on the association between fat-free mass (FFM) metrics and weight-related metabolic complications in adults with overweight or obesity. A systematic search of Medline, Embase, Web of Science, and Google Scholar (inception to October 2024) identified 32 observational studies involving 138,935 participants. Random-effects meta-analyses were conducted for type 2 diabetes (T2DM, 5 studies, n = 41,235), metabolic syndrome (MetS, 3 studies, n = 2832), cardiovascular disease (CVD, 3 studies, n = 8980), and non-alcoholic fatty liver disease (NAFLD, 3 studies, n = 4570). Heterogeneity was assessed using I². Sensitivity analyses stratification by FFM metric type were performed where feasible. Low FFM metrics were significantly associated with increased risk of T2DM (pooled RR = 1.46, 95% CI 1.11-1.91), MetS (OR = 4.48, 95% CI 2.18-9.22), CVD (RR = 2.03, 95% CI 1.27-3.26), and NAFLD (RR = 2.24, 95% CI 1.52-3.32). High heterogeneity was observed for T2DM (I² = 90.9%) and MetS (I² = 79.8%); however, sex-stratified sensitivity analyses eliminated heterogeneity for T2DM (I² = 0%). Narrative synthesis of remaining studies generally supported these findings, though associations varied according to FFM metric type. Low FFM-related metrics were associated with increased risk of major weight-related metabolic complications, although the strength and consistency of associations differed by FFM metric type.