Association of frailty index with sarcopenia: Mediation analysis of triglyceride-glucose-related indices: a cross-sectional study

Frailty and sarcopenia are closely related geriatric syndromes that share overlapping pathophysiological mechanisms. However, the metabolic pathways linking frailty burden to sarcopenia remain unclear. The triglyceride-glucose (TyG) index and its derivatives, which serve as surrogate markers of Insulin resistance (IR), may help explain this association. This study aimed to examine the association between frailty index (FI) and sarcopenia and evaluate the potential mediating role of TyG and its derivatives (TyG-BMI, TyG-WC, TyG-WHtR, and TyG-ABSI). This cross-sectional study included 2152 adults aged 20 to 59 years from the 2011-2014 National Health and Nutrition Examination Survey. FI was calculated using a 49-item deficit accumulation model. Sarcopenia was defined according to the for the National Institutes of Health criteria, and muscle quality index (MQI) was additionally analyzed as a continuous indicator of muscle quality. Weighted logistic and linear regression models were used to assess the associations of FI with sarcopenia and MQI. Mediation analyses were further performed to evaluate the role of TyG-related indices. Higher FI scores were associated with increased prevalence of sarcopenia and lower MQI. These associations varied by age (interaction P = .0191) and sex (interaction P = .0261), with stronger associations observed in individuals aged <40 years and in females. Mediation analyses showed that TyG and its related indices significantly mediated the association between FI and sarcopenia. Among these indicators, TyG-WHtR showed the strongest mediation effect, accounting for 28.26% of the total effect. FI was significantly associated with sarcopenia, and this relationship was partially mediated by TyG-related indices. These findings suggest that IR-related metabolic dysfunction may contribute to the observed association between FI and muscle health and provide new insight into the metabolic pathways underlying sarcopenia. Given the cross-sectional design, causal directionality cannot be inferred.