Clinical baseline characteristics

A total of 4,634 patients with prediabetes or diabetes who had completed ultrasonography data were identified from the NHANES III database. Among these participants, 50.1% were men, 75.6% were Non-Hispanic White, and 46.5% were diagnosed with MASLD. Compared to non-MASLD participants, those with MASLD showed higher levels of BMI, WC, FBG, HbA1c, ALT, AST, systolic blood pressure (SBP), diastolic blood pressure (DBP), and TG. They were more likely to have a history of using antihypertensive, lipid-lowering, and glucose-lowering medications, as well as a history of heart attacks. Additionally, they had higher incidences of hypertriglyceridemia, diabetes, high blood pressure, low HDL-c, and were more often overweight or obesity. Notably, all TyG-related indices were elevated in MASLD patients. However, there was no significant difference between the MASLD and Non-MASLD groups regarding the prevalence of significant liver fibrosis (FIB-4 > 1.3), platelet count, or creatinine levels (Table 1).

Table 1 Baseline characteristics among individuals with prediabetes or diabetes

We then compared the baseline characteristics between the alive and deceased groups among MASLD patients with prediabetes or diabetes. The deceased group was predominantly composed of Non-Hispanic Whites and characterized by older age. They also exhibited higher levels of SBP, WC, HbA1c, TG, creatinine, PLT, ALT, and FIB-4, along with lower education levels. Moreover, the TyG, TyG-WHtR, TyG-WC, and TyG-WWI indices were significantly elevated in the deceased group, which was also associated with higher rates of comorbidities, such as high blood pressure, diabetes, and a history of heart attacks, as well as greater use of antihypertensive and glucose-lowering medications compared to non-MASLD patients (Table 2).

Table 2 Baseline characteristics among MASLD individuals with prediabetes or diabetes by mortality statusAssociation between TyG-related indices and mortality in MASLD participants with diabetes or prediabetes

During a median follow-up period of 25.4 years, 2,157 individuals with MASLD combined with prediabetes or diabetes were identified. Among them, 1,163 individuals (53.9%) died, with 329 deaths (15.3%) attributed to cardiovascular cause and 78 (3.6%) to diabetes. In unadjusted model, higher TyG index, TyG-WC index, TyG-WHtR index, and TyG-WWI index were associated with an increased risk of all-cause mortality. The associations remained stable even after adjusting for covariates in model 1, model 2, and model 3 (TyG index, adjusted hazard ratio (aHR): 1.215, p = 0.007; TyG-WC index, aHR: 1.001, p < 0.001; TyG-WHtR index, aHR: 1.265, p < 0.001; TyG-WWI index, aHR: 1.021, p < 0.001). The relationship between TyG-BMI index and all-cause mortality was not significant only in unadjusted model (HR: 1.001, p = 0.308). Similar results were found between TyG-related indices and cardiovascular mortality. When examing the link between TyG-related indices and diabetes mortality, higher TyG-WC, TyG-BMI, TyG-WHtR, and TyG-WWI index were all associated with an increased risk of diabetes mortality (TyG-WC index, aHR: 1.006, p < 0.001; TyG-BMI index, aHR: 1.015, p < 0.001; TyG-WHtR index, aHR: 2.719, p < 0.001; TyG-WWI index, aHR: 1.057, p < 0.001). However, the relationship between TyG index and diabetes mortality was not significant in model 3 (HR: 1.573, p = 0.058) (Table 3).

Table 3 HRs of TyG-related indices for all-cause and cause specific mortality among individuals with MASLD and prediabetes or diabetesRCS analysis

In our study, we further investigated the potential nonlinear relationship between TyG-related indices and all-cause mortality in MASLD patients with prediabetes or diabetes using restricted cubic splines (RCS). After adjusting for age, sex, ethnicity, family income ratio, marital status, education level, smoking status, and FIB-4, We observed positive linear relationships between TyG and TyG-WWI with all-cause mortality (p for nonlinear = 0.920; p = 0.525, respectively). In contrast, TyG-BMI, TyG-WHtR, and TyG-WC demonstrated positive nonlinear relationships with all-cause mortality (p for nonlinear = 0.003; p = 0.007; p = 0.001, respectively) (Fig. 2).

Fig. 2

RCS curves were employed to illustrate the correlation between TyG-related indices and all-cause mortality in MASLD patients with prediabetes or diabetes, adjusting for factors such as age, sex, ethnicity, family income ratio, marital status, education level, smoking, and FIB-4. A TyG index; B TyG-BMI index; C TyG-WHtR index; D TyG-WWI index; E TyG-WC index. Abbreviations: MASLD, Metabolic Dysfunction-Associated Steatotic Liver Disease; TyG, Triglyceride-glucose; BMI, Body mass index; WHtR, Waist-height ratio; WWI, Weight-adjusted waist index; WC, waist circumference; RCS, Restricted cubic spline; FIB-4, Fibrosis-4 index.

Predictive power of TyG-related indices for all-cause and cause-specific mortality in MASLD participants with prediabetes or diabetes

Time-dependent AUC curves indicated that TyG-WWI demonstrated the strongest predictive ability for all-cause and cardiovascular mortality across various time intervals compared to other indices. However, it was less effective in predicting diabetes-related mortality (Fig. 3).

Fig. 3

Time-dependent AUC curves assessing the predictive power of the TyG correlation index for all-cause and cause-specific mortality in MASLD patients with prediabetes or diabetes. A All-cause mortality; B Cardiovascular mortality; C Diabetes mortality. Abbreviations: MASLD, Metabolic Dysfunction-Associated Steatotic Liver Disease; AUC, Area under the curve; TyG, Triglyceride-glucose; BMI, Body mass index; WHtR, Waist-height ratio; WWI, Weight-adjusted waist index; WC, waist circumference.

Subgroup analysis

To assess the applicability of these metrics across diverse populations, we performed subgroup analyses. The correlation between TyG, TyG-BMI, TyG-WHtR, TyG-WC, and TyG-WWI and all-cause mortality was consistent across various subgroups, including age, sex, smoking status, levels of liver fibrosis, and diabetes status (p for interaction > 0.01) (Fig. 4). Furthermore, we performed subgroup analyses focusing on MASLD women with diabetes or prediabetes. The results showed that the effect of TyG indices on all-cause mortality was consistent across pre-menopausal and menopausal subgroups (Table S1).

Fig. 4

Subgroup analysis of the correlation between TyG-related indices and all-cause mortality in MASLD patients with prediabetes or diabetes. A TyG index; B TyG-BMI index; C TyG-WHtR index; D TyG-WWI index; E TyG-WC index. Abbreviations: MASLD, Metabolic Dysfunction-Associated Steatotic Liver Disease; TyG, Triglyceride-glucose; BMI, Body mass index; WHtR, Waist-height ratio; WWI, Weight-adjusted waist index; WC, waist circumference.