Main characteristics of the study population by NAFLD
A total of 2280 patients with T2DM were included. Among which, 67% were male, and 1543 (67.7%) had NAFLD. Compared with the non-NAFLD group, participants in the NAFLD group were younger and had a higher BMI, higher frequency of smoking or drinking, higher mean systolic and diastolic BP, shorter diabetes duration, less favorable metabolic profile (FBG, UA, AST, ALT, GGT, TC, and TG), lower HDL-C level and AST/ALT ratio, and higher TyG index (Table 1).
Table 1
Characteristics of the participants according to presence of NAFLD
| Non‒NAFLD N = 737 (32.3%) | NAFLD N = 1543 (67.7%) | P value |
Male (%) | 445 (60.4%) | 1100 (71.3%) | <0.001 |
Age, years | 53 (46‒60) | 49.5 (40‒57) | <0.001 |
DD, years | 6 (2‒12) | 4 (0.5‒10) | <0.001 |
Hypertension (%) | 316 (42.9%) | 695 (45.0%) | 0.33 |
Drinking (%) | 168 (22.8%) | 411 (26.6%) | 0.049 |
Smoking (%) | 127 (17.2%) | 358 (23.2%) | 0.001 |
BMI, kg/m2 | 23.7 (21.5‒25.8) | 26.7 (24.5‒29.4) | <0.001 |
HbA1C, % | 8.4 (7.1‒10.4) | 8.7 (7.3‒10.4) | 0.072 |
FBG, mmol/L | 7.3 (5.8‒9.7) | 7.9 (6.3‒10.5) | 0.002 |
UA, µmol/L | 268 (216‒329) | 303 (254‒367) | <0.001 |
ALT, U/L | 16 (12‒23) | 21 (15‒32) | <0.001 |
AST, U/L | 17 (14‒21) | 19 (15‒24) | <0.001 |
GGT, U/L | 17 (13‒27) | 27 (18‒45) | <0.001 |
AST/ALT ratio | 1.05 (0.82‒1.33) | 0.86 (0.69‒1.08) | <0.001 |
SBP, mmHg | 131 (121‒143) | 133 (124‒144) | 0.043 |
DBP, mmHg | 81 (75‒89) | 83.5 (77‒90) | <0.001 |
TC, mmol/L | 4.15 (3.53‒4.96) | 4.44 (3.76‒5.21) | <0.001 |
TG, mmol/L | 1.21 (0.86‒1.80) | 1.9 (1.3‒3.03) | <0.001 |
HDL-C, mmol/L | 1.14 (0.93‒1.39) | 1.0 (0.82‒1.19) | <0.001 |
LDL-C, mmol/L | 2.5 (1.96‒3.20) | 2.6 (1.96‒3.27) | 0.117 |
TyG index | 8.89 (8.44‒9.44) | 9.42 (8.93‒9.98) | <0.001 |
Data are presented as median (interquartile range) or percentage |
ALT: alanine transferase; AST: aspartate transferase; BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; DD: Diabetes Duration; FBG: fasting blood glucose; GGT: gamma-glutamyl transferase; HbA1c: glycosylated hemoglobin; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; NAFLD: nonalcoholic fatty liver disease; TC: high cholesterol; TG: triglyceride; TyG: triglycerides and glucose index; UA: uric acid |
Associations between the TyG index and NAFLD risk
The prevalence of NAFLD remarkably increased with the increase in TyG level. Binary logistic regression was performed to examine whether TyG index is independently associated with NAFLD in patients with T2DM within four different models. The NAFLD risk significantly increased with the increasing TyG level, the OR were 5.0 in the highest TyG quartile (95% CI, 3.79–6.60; P < 0.001; Model 0). As presented in Table 2, the OR for NAFLD were higher with increasing TyG quartiles after adjusting for age, gender (4.24, 95% CI 3.20–5.63, P < 0.001 for trend; Model 1). In the highest TyG quartile, the OR were 3.02 (95% CI, 2.22–4.11; P < 0.001 for trend) for NAFLD after further adjustment for BMI (Model 2), and the OR were 2.90 (95% CI, 2.12–3.98; P < 0.001) for NAFLD after adjustment for Model 3. The associations persisted after additional adjustment in Model 4 (OR, 3.27; 95% CI, 2.03–5.27; P < 0.001). In addition, the prevalence of NAFLD in individuals with the highest TyG quartile was 86.3%, which showed a 1.73-fold increase compared with the prevalence in the lowest quartile (50%, Fig. 1).
Table 2
Odds ratios for NAFLD in different quartiles of TyG index
| Q1 (Reference) | Q2 OR (95% CI) | Q3 OR (95% CI) | Q4 OR (95% CI) | P value |
TyG index | <8.76 | 8.76‒9.28 | 9.28‒9.85 | ≥ 9.85 | ‒ |
Unadjusted | 1 | 1.76 (1.38‒2.23) | 2.99 (2.32‒3.85) | 5.00 (3.79‒6.60) | <0.001 |
Model 1 | 1 | 1.74 (1.36‒2.21) | 2.93 (2.27‒3.79) | 4.24 (3.20‒5.63) | <0.001 |
Model 2 | 1 | 1.42 (1.09‒1.85) | 2.45 (1.85‒3.24) | 3.02 (2.22‒4.11) | <0.001 |
Model 3 | 1 | 1.37 (1.05‒1.79) | 2.54 (1.91‒3.39) | 2.90 (2.12‒3.98) | <0.001 |
Model 4 | 1 | 1.46 (1.08‒1.97) | 2.76 (1.93‒3.96) | 3.27 (2.03‒5.27) | <0.001 |
Model 0 was unadjusted |
Model 1 was adjusted for age, sex |
Model 2 was adjusted for age, sex and BMI |
Model 3 was adjusted for all variables in model 2 plus hypertension, smoking status, drinking habits, duration of diabetes mellitus, and AST and ALT levels |
Model 4 was adjusted for all variables in model 3 plus HbA1C, FBG, UA, TC, and HDL-C levels |
Association of the TyG index, glycemic parameters, and lipid parameters with NAFLD
Binary logistic regression models that separately consider each glycemic and lipid parameters as predictors of NAFLD were performed. Table 3 shows the OR and 95% CI of NAFLD with FBG, HbA1c, BMI, TC, TG, HDL-C, LDL-C, TyG index, TG/HDL-C ratio, and AST/ALT ratio in the total population within Model 3. As shown in Table 3, BMI (OR, 1.31; 95% CI, 1.26–1.35; P < 0.001), TC (OR, 1.13; 95% CI, 1.03–1.23; P = 0.009), TG (OR, 1.25; 95% CI, 1.15–1.34; P < 0.001), HDL-C (OR, 0.41; 95% CI, 0.29–0.57; P < 0.001), TyG index (OR, 1.82; 95% CI, 1.58–2.10; P < 0.001), TG/HDL-C (OR, 1.14; 95% CI, 1.08–1.20; P < 0.001), and AST/ALT ratio (OR, 0.68; 95% CI, 0.55–0.85; P < 0.001) were associated with NAFLD. However, FBG, HbA1C, and LDL-C levels had no association with NAFLD risk as observed in Model 3. Although the OR of HDL-C for NAFLD risk is higher in Model 3, the OR dramatically decreased after further adjustment in Model 4 (OR, 0.52; 95% CI, 0.32–0.84; P = 0.008). The OR of TyG stood out the most in comparison with the ORs of lipid and glycemic parameters, which indicates that TyG index can be a better discriminator of NAFLD.
Table 3
Association of the TyG index, glycemic, lipid parameters with NAFLD in total subjects
| OR (95% CI) | P value |
TyG index | 1.82 (1.58‒2.10) | <0.001 |
BMI, kg/m2 | 1.31 (1.26‒1.35) | <0.001 |
FBG, mmol/L | 1.03 (0.99‒1.06) | 0.1 |
HbA1c, % | 1.05 (0.99‒1.10) | 0.06 |
ALT, U/L | 1.02 (1.01‒1.04) | <0.001 |
AST/ALT ratio | 0.68 (0.55‒0.85) | <0.001 |
TC, mmol/L | 1.13 (1.03‒1.23) | 0.009 |
TG, mmol/L | 1.25 (1.15‒1.34) | <0.001 |
HDL-C, mmol/L | 0.41 (0.29‒0.57) | <0.001 |
LDL-C, mmol/L | 1.04 (0.93‒1.15) | 0.519 |
TG/HDL-C ratio | 1.14 (1.08‒1.20) | <0.001 |
ALT: alanine transferase; AST: aspartate transferase; BMI: body mass index; FBG: fasting blood glucose; HbA1c: glycosylated hemoglobin; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; TG: triglyceride; TC: high cholesterol; TyG: triglycerides and glucose index |
Adjusted for age, sex, BMI, hypertension, smoking status, drinking habits, duration of diabetes mellitus, AST, and ALT levels. |
Associations between the TyG index and NAFLD in subgroups of age, sex, BMI, HDL-C, and AST/ALT ratio
Stratified analyses were conducted in different subgroups (age, sex, BMI, HDL-C, and AST/ALT ratio) to further validate the above results after adjustment for Model 4 as shown in Table 4. The results suggested that compared with participants with lower TyG, higher TyG levels were more remarkably associated with the risk of NAFLD in younger age (< 65 years; OR, 2.35; 95% CI, 1.83–3.02; P < 0.001), female (OR, 2.69; 95% CI, 1.67–4.32; P < 0.001), lower BMI (< 25 kg/m2; OR, 2.80; 95% CI, 2.01–3.91; P < 0.001), lower HDL-C (< 1 mmol/L; OR, 2.76; 95% CI, 1.98–3.83; P < 0.001), and higher AST/ALT ratio (≥ 0.9; OR, 2.63; 95% CI, 1.91–3.62; P < 0.001). However, no association between TyG index and NAFLD was observed in the older age subgroups (≥ 65 years; OR, 1.49; 95% CI, 0.65–3.39; P = 0.343). Additionally, in the subgroup analysis, the TyG index had interaction effects with age (P value for interaction = 0.043), BMI (P value for interaction < 0.001), HDL-C (P value for interaction < 0.001), and AST/ALT (P for interaction = 0.011) on NAFLD risk after adjusting for potential confounders (Model 4). The result indicates an excess risk due to the additive interaction.
Table 4
Subgroup analysis of the association between TyG index and NAFLD
| Stratified Group | OR (95% CI) | P value | P for interaction |
Age, years | <65 | 2.35 (1.83‒3.02) | <0.001 | 0.043 |
≥ 65 | 1.49 (0.65‒3.39) | 0.343 |
Sex | Female | 2.69 (1.67‒4.32) | <0.001 | 0.486 |
Male | 2.09 (1.59‒2.76) | <0.001 |
BMI, kg/m2 | <25 | 2.80 (2.01‒3.91) | <0.001 | <0.001 |
≥ 25 | 1.86 (1.33‒2.60) | <0.001 |
HDL-C, mmol/L | <1 | 2.76 (1.98‒3.83) | <0.001 | <0.001 |
≥ 1 | 2.26 (1.65‒3.11) | <0.001 |
AST/ALT ratio | <0.9 | 1.63 (1.13‒2.34) | 0.009 | 0.011 |
≥ 0.9 | 2.63 (1.91‒3.62) | <0.001 |
BMI: body mass index; ALT: alanine transferase; AST: aspartate transferase; HDL-C: high-density lipoprotein cholesterol; TyG: triglycerides and glucose index |
Adjusted for age, sex, BMI, hypertension, smoking status, drinking habits, duration of diabetes mellitus, AST and ALT levels, HbA1C, FBG, UA, TC, and HDL-C levels. |