Association Between Triglyceride-Glucose Index and Risk of Metabolic Dysfunction-Associated Fatty Liver Disease: A Cohort Study

Figures & data

Table 1 Baseline Characteristics of Participants According to Quartiles of TyG Index (N = 2056)

Variables	Quartiles of TyG Index				P for Trend
	Q1 (<7.93)	Q2 (≥7.93 to <8.23)	Q3 (≥8.23 to <8.58)	Q4 (≥8.58)
Sex					<0.001^a
Male	255 (51.1)	331 (64.1)	348 (66.0)	364 (70.8)
Female	244 (48.9)	185 (35.9)	179 (34.0)	150 (29.2)
Age (years)	35.02±8.64	37.73±9.79	38.55±10.43	38.30±11.04	<0.001^b
BMI (kg/m^2)	21.45±1.73	21.88±1.80	22.09±1.82	22.38±1.74	<0.001^b
SBP (mmHg)	118.61±11.39	120.45±12.91	122.50±13.46	122.88±13.55	<0.001^b
DBP (mmHg)	71.02±7.85	72.55±8.52	73.94±8.56	74.14±9.19	<0.001^b
GGT (U/L)	15.55 (11.00, 21.65)	17.10 (13.00, 22.76)	18.24 (13.85, 23.62)	21.00 (15.65, 27.00)	<0.001^c
ALT (U/L)	16.00 (12.00, 21.00)	17.00 (13.00, 21.02)	18.00 (14.00, 22.06)	19.77 (15.00, 25.00)	<0.001^c
AST (U/L)	17.41 (15.00, 20.00)	18.00 (16.00, 20.00)	18.29 (16.00, 20.05)	19.00 (17.00, 21.01)	<0.001^c
LDL-C (mmol/L)	2.34±0.49	2.51±0.54	2.61±0.55	2.63±0.54	<0.001^b
HDL-C (mmol/L)	1.49±0.28	1.41±0.24	1.33±0.24	1.28±0.24	<0.001^b
TC (mmol/L)	4.19±0.56	4.35±0.60	4.45±0.61	4.56±0.62	<0.001^b
TG (mmol/L)	0.60 (0.52, 0.68)	0.85 (0.78, 0.92)	1.13 (1.03, 1.24)	1.71 (1.47, 2.07)	<0.001^b
FPG (mmol/L)	4.67±0.41	4.80±0.44	4.89±0.47	5.16±0.99	<0.001^b
SUA (µmol/L)	294.18±74.86	306.39±69.55	312.12±74.92	324.96±79.98	<0.001^b

Notes: Data were present as mean±SD, median (interquartile range) or n (%). ^aThe variables were tested by χ²-test for linear trend; ^bmean±standard deviation, and the variables were tested by one-way analysis of variance for linear trend; ^cMedian (interquartile range), and the variables were tested by Kruskal–Wallis test.

Abbreviations: BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; GGT, γ-glutamyl transpeptidase; ALT, alanine aminotransferase; AST, aspartate transaminase; ALP, alkaline phosphatase; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; TC, total cholesterol; TG, triglyceride; FPG, fasting plasma glucose; SUA, serum Uric Acid.

Figure 1 Cumulative incidence of MAFLD according to quartiles of TyG at baseline (average follow-up years=2.5±0.5). (A) Incidence of MAFLD in total population. (B) Incidence of MAFLD in male. (C) Incidence of MAFLD in female. The variables were tested by χ²-test for linear trend and multiple comparisons. Bonferroni correction was applied in all multiple comparisons (P_Bonferroni =0.05/6=0.008).

Table 2 Univariate Analysis of Potential Predictive Factors for MAFLD

Variables	Overall Statistics, n (%)	HR (95% CI)	P
Sex
Female	758 (36.9)	ref
Male	1298 (63.1)	3.514 (2.473, 4.995)	<0.001
Age (years)	37.42±10.12	1.037 (1.025, 1.048)	<0.001
<30	529 (25.7)	ref
30–39	715 (34.8)	0.949 (0.679, 1.325)	0.757
≥40	812 (39.5)	2.248 (1.638, 3.085)	<0.001
BMI (kg/m^2)	21.95±1.80	1.298(1.238, 1.360)	<0.001
<23	1390 (67.6)	ref
≥23	666 (32.4)	2.650 (2.078, 3.380)	<0.001
SBP (mmHg)	121.14±12.97	1.025 (1.016, 1.034)	<0.001
DBP (mmHg)	72.93±8.63	1.031 (1.017, 1.046)	<0.001
Hypertension
No	1733 (84.3)	ref
Yes	323 (15.7)	1.721 (1.285, 2.304)	<0.001
GGT (U/L)	20.94±17.10	1.008 (1.005, 1.011)	<0.001
≤50	1991 (96.8)	ref
>50	65 (3.2)	1.892 (1.141, 3.138)	0.013
ALT (U/L)	19.93±13.66	1.008 (1.004, 1.011)	<0.001
≤40	1970 (95.8)	ref
>40	86 (4.2)	1.698 (1.097, 2.630)	0.018
AST (U/L)	19.03±6.20	1.016 (1.006, 1.025)	0.001
≤40	2034 (98.9)	ref
>40	22 (1.1)	1.000 (0.320, 3.121)	1.000
LDL-C (mmol/L)	2.53±0.54	1.782 (1.466, 2.165)	<0.001
<3.4	1911 (92.9)	ref
≥3.4	145 (7.1)	1.987 (1.332, 2.964)	0.001
HDL-C (mmol/L)	1.38±0.26	0.132 (0.079, 0.220)	<0.001
Low HDL-C
No	1899 (92.4)	ref
Yes	157 (7.6)	1.712 (1.170, 2.504)	0.006
TC (mmol/L)	4.39±0.61	1.526 (1.276, 1.825)	<0.001
<5.2	1860 (90.5)	ref
≥5.2	196 (9.5)	1.557 (1.063, 2.280)	0.023
TG (mmol/L)	0.15±0.36	1.442 (1.260, 1.605)	<0.001
Hypertriglyceridemia
No	1752 (85.2)	ref
Yes	304 (14.8)	1.964 (1.481, 2.604)	<0.001
FPG (mmol/L)	4.88±0.65	1.272 (1.146, 1.413)	<0.001
Hyperglycemia
No	1910 (92.9)	ref
Yes	146 (7.1)	1.781 (1.195, 2.653)	0.005
SUA (µmol/L)	309.54±75.66	1.006 (1.005, 1.008)	<0.001
Hyperuricemia
No	1880 (91.4)	ref
Yes	176 (8.6)	1.938 (1.397, 2.688)	<0.001

Note: Data were present as mean±SD or n (%).

Abbreviations: BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; GGT, γ-glutamyl transpeptidase; ALT, alanine aminotransferase; AST, aspartate transaminase; ALP, alkaline phosphatase; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; TC, total cholesterol; TG, triglyceride; FPG, fasting plasma glucose; SUA, serum Uric Acid; TyG, triglyceride-glucose index.

Figure 2 Kaplan-Meier analysis of MAFLD risk according to TyG index quartiles (Log rank test P < 0.001). TyG index Q1: <7.93, Q2: ≥7.93 to <8.23, Q3: ≥8.23 to <8.58, Q4: ≥8.58.

Table 3 Association of TyG Index with MAFLD Risk in Cox Proportional Hazard Models

Variables	Crude Model^a		Model 1^b		Model 2^c
	HR (95% CI)	P	HR (95% CI)	P	HR (95% CI)	P
TyG index	2.190 (1.755, 2.732)	<0.001	1.864 (1.471, 2.363)	<0.001	1.784 (1.383, 2.302)	<0.001
Q1 (<7.93)	ref		ref		ref
Q2 (≥7.93 to <8.23)	1.557 (1.013, 2.395)	0.044	1.229 (0.798, 1.893)	0.350	1.235 (0.801, 1.904)	0.340
Q3 (≥8.23 to <8.58)	2.475 (1.664, 3.681)	<0.001	1.858 (1.245, 2.772)	0.002	1.785 (1.192, 2.673)	0.005
Q4 (≥8.58)	3.038 (2.063, 4.474)	<0.001	2.146 (1.450, 3.175)	<0.001	2.000 (1.377, 2.992)	0.001
P for trend		<0.001		<0.001		<0.001

Notes: ^aAdjusted for none; ^bAdjusted for sex, age and BMI at baseline; ^cAdjusted for sex, age, BMI, hypertension, GGT, ALT, AST, LDL-C, low HDL-C, TC and SUA at baseline. All covariates were brought into the model in the form of categorical variables.

Figure 3 A nonlinear relationship of TyG index with risk of MAFLD. (A) male and female (total population). (B) male. (C) female. Data were fitted using a Cox regression model of the restricted cubic spline with 3 knots at 10th, 50th and 90th percentiles of baseline TyG index. The reference point was the 50th percentile of the TyG index (8.23). The solid red line represented point estimation on the association of TyG index with MAFLD, and the shaded portion represented 95% CI estimation. In crude model, adjusted for none. In model 1, adjusted for sex, age and BMI at baseline. In model 2, adjusted for sex, age, BMI, hypertension, GGT, ALT, AST, LDL-C, low HDL-C, TC and SUA at baseline. All covariates were brought into the model in the form of categorical variables.

Table 4 Subgroup Analysis of Association Between TyG Index and MAFLD Risk

Variables	Incidence of MAFLD, n (%)	HR (95% CI)^a	P^a	P for Interaction^b
Sex				0.414
Male	228 (86.4)	1.744 (1.319, 2.305)	<0.001
Female	36 (13.6)	2.120 (1.091, 4.121)	0.027
Age (years)				0.034
<30	60 (22.7)	1.371 (0.794, 2.368)	0.257
30–39	81 (30.7)	1.484 (0.925, 2.381)	0.102
≥40	123 (46.6)	2.258 (1.550, 3.289)	<0.001
BMI (kg/m^2)				0.452
<23	115 (43.6)	1.826 (1.281, 2.601)	0.001
≥23	149 (56.4)	1.745 (1.201, 2.535)	0.004
Hypertension				0.501
No	206 (78.0)	1.779 (1.342, 2.358)	<0.001
Yes	58 (22.0)	1.876 (0.987, 3.566)	0.055
GGT (U/L)				0.780
≤50	248 (93.9)	1.830 (1.404, 2.386)	<0.001
>50	16 (6.1)	1.780 (0.449, 7.061)	0.412
ALT (U/L)				0.703
≤40	242 (91.7)	1.820 (1.394, 2.376)	<0.001
>40	22 (11.0)	1.650 (0.579, 4.699)	0.348
LDL-C (mmol/L)				0.410
<3.4	237 (89.8)	1.801 (1.385, 2.341)	<0.001
≥3.4	27 (18.6)	1.850 (0.533, 6.424)	0.333
Low HDL-C				0.565
No	234 (88.6)	1.720 (1.309, 2.261)	<0.001
Yes	30 (11.4)	2.183 (1.029, 4.633)	0.042
TC (mmol/L)				0.253
<5.2	234 (88.6)	1.876 (1.435, 2.452)	<0.001
≥5.2	30 (11.4)	1.298 (0.529, 3.185)	0.569
Hyperuricemia				0.453
No	221 (83.7)	1.733 (1.310, 2.292)	<0.001
Yes	43 (16.3)	2.124 (1.041, 4.334)	0.039

Notes: ^aAdjusted for sex, age, BMI, Hypertension, GGT, ALT, AST, LDL-C, Low HDL-C, TC and SUA at baseline (except the corresponding stratification variable). ^bAdjusted for sex, age, BMI, Hypertension, GGT, ALT, AST, LDL-C, Low HDL-C, TC and SUA at baseline. All covariates were brought into the model in the form of categorical variables.

Abbreviations: BMI, body mass index; GGT, γ-glutamyl transpeptidase; ALT, alanine aminotransferase; AST, aspartate transaminase; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; TC, total cholesterol.

Figure 4 Time-dependent ROC of TyG index in predicting 2-, 3-, and 4-year risk of incident MAFLD.

Abbreviations: ROC receiver operating characteristic curves, SE sensitivity, SP specificity, YD Youden index, AUC area under curve.