Association between triglyceride-glucose related indices and mortality among individuals with non-alcoholic fatty liver disease or metabolic dysfunction-associated steatotic liver disease

Abstract

Background: The prognostic value of triglyceride-glucose (TyG) related indices in non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is still unclear. This study aimed to determine the associations between TyG-related indices and long-term mortality in this population.

Methods: The data came from the National Health and Nutrition Examination Survey (NHANES III) and National Death Index (NDI). Baseline TyG, TyG combining with body mass index (TyG-BMI), and TyG combining with waist circumference (TyG-WC) indices were calculated, and mortality status was determined through 31 December 2019. Multivariate Cox and restricted cubic spline (RCS) regression models were performed to evaluate the relationship between TyG-related indices and long-term mortality among participants with NAFLD/MASLD. In addition, we examined the association between TyG-related indices and all-cause mortality within subgroups defined by age, sex, race/ethnicity, and fibrosis-4 index (FIB-4).

Results: There were 10,390 participants with completed ultrasonography and laboratory data included in this study. NAFLD was diagnosed in 3672/10,390 (35.3%) participants, while MASLD in 3556/10,390 (34.2%) amongst the overall population. The multivariate Cox regression analyses showed high levels of TyG-related indices, particularly in TyG-BMI and TyG-WC indices were significantly associated with the all-cause mortality, cardiovascular mortality, and diabetes mortality in either NAFLD or MASLD. The RCS curves showed a nonlinear trend between three TyG-related indices with all-cause mortality in either NAFLD or MASLD. Subgroup analyses showed that TyG-BMI and TyG-WC indices were more suitable for predicting all-cause mortality in patients without advanced fibrosis.

Conclusion: Our study highlights the clinical value of TyG-related indices in predicting the survival of the NAFLD/MASLD population. TyG-BMI and TyG-WC indices would be the surrogate biomarkers for the follow-up of the population without advanced fibrosis.

Keywords: Metabolic dysfunction-associated steatotic liver disease; Mortality; NHANES III; Non-alcoholic fatty liver disease; TyG index; TyG-BMI index; TyG-WC index.

Fig. 1

Nonlinear relationship between TyG-related indices and all-cause mortality among NAFLD/MASLD. The relationship was evaluated by RCS after adjustment for age, sex, race, income, marital status, education, smoking, sedentary lifestyle, diabetes, hypertension, plasma HDL-C, and FIB-4 (model 2). The solid lines in the figure represents HRs, and the shaded regions represents the 95% CIs. (A) TyG index in NAFLD; (B) TyG-BMI index in NAFLD; (C) TyG-WC index in NAFLD; (D) TyG index in MASLD; (E) TyG-BMI index in MASLD; (F) TyG-WC index in MASLD. BMI, Body mass index; CI, confidence intervals; FIB-4, Fibrosis-4 index; HDL-C, high-density lipoprotein cholesterol; HR, hazard ratios; MASLD, metabolic dysfunction-associated steatotic liver disease; NAFLD, non-alcoholic fatty liver disease; RCS, restricted cubic spline; TyG, triglyceride-glucose; WC, waist circumference

Fig. 2

Subgroup analyses of association between TyG-related indices and all-cause mortality among NAFLD/MASLD. Green box means HR value, and the bars on both sides of box mean 95% CI of HR. The adjusted model 2 (age, sex, race, income, marital status, education, smoking, sedentary lifestyle, diabetes, hypertension, plasma HDL-C, and FIB-4) was used in this analysis. (A) TyG index in NAFLD; (B) TyG-BMI index in NAFLD; (C) TyG-WC index in NAFLD; (D) TyG index in MASLD; (E) TyG-BMI index in MASLD; (F) TyG-WC index in MASLD. BMI, body mass index; CI, confidence intervals; FIB-4, Fibrosis-4 index; HDL-C, high-density lipoprotein cholesterol; HR, hazard ratios; MASLD, metabolic dysfunction-associated steatotic liver disease; NAFLD, non-alcoholic fatty liver disease; TyG, triglyceride-glucose; WC, waist circumference .