Although most studies explored the relationship between the TyG index and NAFLD risk, these studies focused on the general population[15, 18, 19]. Our present study focused on the associations of the TyG index, glycemic parameters, and lipid parameters with NAFLD in a T2DM population. This cross-sectional study observed a strong and positive association between the TyG index and NAFLD risk after adjustment for potential confounders. HDL-C, TG, BMI, ALT, and AST/ALT ratio were also associated with NAFLD risk but inferior to the TyG index. Further stratification analysis showed that females, patients with lesser BMI (< 25 kg/m2), younger age (< 65 years), and lower HDL-C level (< 1 mmol/L) have higher NAFLD risks when the TyG index is high. Therefore, based on the above observations, the TyG index can be used as an effective predictor of NAFLD risk in T2DM population.
NAFLD is closely associated with obesity and MS and characterized by excessive lipid accumulation in the liver tissue, which leads to hepatic IR[5, 20]. Furthermore, the hepatic IR subsequently leads to the overproduction of FBG and low-density lipoprotein. Lipotoxicity and glucotoxicity play central roles in the development and progression of NAFLD[14]. Our results showed that individuals with NAFLD had considerably higher BMI, FBG, TC, and TG levels than those without NAFLD. IR is a crucial pathophysiological mechanism of MS, which is a metabolic risk factor associated with an increased risk for T2DM and NAFLD[6, 21]. IR identification is deemed helpful to stratify and support the personalized treatment of patients with NAFLD. The TyG index combined with TG and FBG levels has been proposed as an effective substitute for IR[9]. A recent cross-sectional survey showed that the TyG index is significantly associated with hypertension, and shows the superior discriminative ability for hypertension compared with lipid parameters and glycemic parameters[22]. In line with previous study, the present study demonstrated the associations of BMI, TC, TG, HDL-C, and TyG with NAFLD risk, however, the association of the TyG index with NAFLD was stronger than those of lipid or glycemic parameters. Thus, the TyG index is a better indicator for identifying NAFLD risk compared with other lipid and glycemic parameters in patients with T2DM.
Studies on the interaction between BMI and HDL-C, sex, or age in NAFLD are limited. The interaction between HDL-C, age and TyG index might be due to the prevalence of low HDL-C in younger groups[23]. Thus, our study demonstrated that female, younger age (< 65 years), and low HDL-C level (< 1 mmol/L) are associated with higher NAFLD risks when the TyG index is higher. The potential mechanism of gender that affects the relationship between the TyG index and NAFLD is unclear, but sex-specific factors, such as hormone levels, might account for this discrepancies in different sexes and thus requires further explore[24, 25]. Although the LDL-C level was considered to be the most crucial lipid risk factor and therapeutic goal for CVDs[26], however, there was no significant association of LDL-C with the risk of NAFLD in the present study. Furthermore, when HDL-C and TC were adjusted in Model 4, the TyG index was still remarkably associated with NAFLD risk in our study.
In our present study, we examined the association of the TyG index, glycemic parameters, and lipid parameters with NAFLD. Obviously, in all participants, the OR of TyG stood out the most in comparison with the ORs of other lipid and glycemic parameters, which indicates that the TyG index might be superior to other glycemic or lipid parameters in associating NAFLD risk. The TyG index is applied in evaluating the levels of FBG and TG in T2DM population due to the two parameters are closely interrelated. High TG levels remains one of the most prevalent abnormalities in T2DM patients, and its association with increased risk of NAFLD has been fully demonstrated[27]. This study revealed that the TyG index helps to identify potential risks of NAFLD in individuals who would otherwise be neglected. Thus, clinicians should be put their attention to individuals with high FBG and TG levels.
Serum ALT level is commonly used as a surrogate indicator for evaluating liver function in various liver diseases, and ALT seems to be closely associated with steatohepatitis[28, 29]. Furthermore, ALT has high specificity for liver injury and is considered as a cardiometabolic risk factor associated with IR, MS, and CVD[30, 31]. In accordance with prior studies, our findings showed that only 18.8% of individuals with NAFLD had increased ALT levels (≥ 40 U/L)[32, 33]. This result implicated that elevated ALT is probably inadequate to evaluate the NAFLD risk of individuals with T2DM. Thus, more sensitive biomarkers for predict the risk of NAFLD are needed. Furthermore, our data demonstrated that the diagnostic accuracy of the TyG index was superior to those of ALT and AST/ALT ratio in identifying NAFLD risk in patients with T2DM.
Obesity leads to the development of MS and comorbidities, including hypertension, hyperlipidemia, IR, NAFLD, T2DM, and CVD[34, 35]. Obesity seems to play a crucial role in the initial development and progression of NAFLD[3, 36]. Previous studies found that NAFLD prevalence increases almost linearly with BMI, whereas obesity is independently related to NAFLD irrespective of other metabolic factors[37]. Another study showed that the association of TyG and NAFLD risk was significantly stronger in non-obese subjects than that in obese ones[18]. Thus, the predictive power of TyG index for NAFLD risk was partially affected by BMI of the individuals. Interestingly, our present study also demonstrated that the OR of NAFLD dramatically decreased after adjustment for BMI in Model 2 (OR, 4.24 vs. 3.02). Furthermore, subgroup analysis indicated that the relationship between the TyG index and NAFLD risk was significantly stronger in non-obese subjects than in obese ones (OR, 2.80 vs. 1.86). Therefore, these results suggested that BMI is an important factor that affects the efficacy of the TyG index in identifying individuals with NAFLD risk[38].
Nevertheless, several limitations should be noted in the present study. First, the NAFLD diagnosis was only based on ultrasonography rather than liver biopsy. The accuracy and sensitivity of NAFLD diagnosis may not be absolutely reliable. However, ultrasound examination for the diagnosis of NAFLD is a preferable and accessible imaging method in clinical practice[39]. Furthermore, our study population included only T2DM patients. The conclusion may not be applicable to the general population. Therefore, identifying the causal relationship between the TyG index and NAFLD in larger and more various population is necessary.