Association between triglyceride-glucose-frailty index and metabolic dysfunction-associated fatty liver disease: Mediation analysis involving obesity indicators in the NHANES

The triglyceride-glucose frailty index (TyGFI), integrating metabolic dysfunction and physiological decline, has been proposed as a novel marker of cardiometabolic risk. Its association with metabolic dysfunction-associated steatotic liver disease (MASLD), however, remains unclear. Our objective was to assess TyGFI's predictive value for MASLD risk and to explore the mediating role of obesity indices in the relationships among insulin resistance, aging, and MASLD. Using data from 988 participants aged ≥45 years in the 2017-2018 National Health and Nutrition Examination Survey, we examined the relationship between TyGFI and MASLD. MASLD was defined by controlled attenuation parameter (CAP ≥ 278 dB/m) and at least 1 cardiometabolic risk factor. Multivariable logistic regression, restricted cubic spline, subgroup, and receiver operating characteristic analyses were conducted. Mediation analysis was applied to assess the role of obesity indicators, including body mass index, waist circumference, lipid accumulation product, and visceral adiposity index. Elevated TyGFI was independently associated with an increased prevalence of MASLD, with a significant dose-response relationship across quartiles. The association was consistent across demographic and clinical subgroups. receiver operating characteristic analysis indicated modest predictive ability (AUC = 0.62). All 4 obesity indicators correlated strongly with TyGFI and MASLD; mediation analyses showed that body mass index, waist circumference, and lipid accumulation product significantly mediated the TyGFI-MASLD association, whereas visceral adiposity index did not. TyGFI is independently associated with MASLD risk in middle-aged and older adults, with much of its effect mediated through obesity-related pathways. These findings highlight the potential of TyGFI as a risk assessment tool and underscore the importance of obesity control in MASLD prevention.