Association Between Thyroid Hormone Levels and Advanced Liver Fibrosis in Patients with Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease

Figures & data

Table 1 Characteristics of T2DM Cases with and without NAFLD

	Without NAFLD Group (n=586)	With NAFLD Group (n=836)	P
Age (years)	57.28±14.13	53.07±13.32	<0.001
Male (%)	358(61.09)	528(63.16)	0.429
SBP (mmHg)	134.56±17.88	133.53±16.30	0.259
DBP (mmHg)	79.88±11.48	79.41±10.12	0.415
WC (cm)	90.68±10.26	94.95±9.06	<0.001
BMI (kg/m2)	25.38±4.04	26.32±3.68	<0.001
HbA1c (%)	8.44±2.09	8.77±2.00	<0.001
FPG (mmol/L)	8.72±3.92	9.31±3.69	0.004
FINS (µIU/mL)	14.27±34.38	15.93±26.27	0.348
HOMA-IR	2.81(1.75, 4.99)	4.54(2.77, 7.05)	0.004
PLT (×10^9/L)	220.06±61.75	219.70±56.10	0.912
ALB (g/L)	40.60±4.10	40.53±3.68	0.765
TC (mmol/L)	4.27±1.12	4.45±1.25	0.011
TG (mmol/L)	1.70±1.36	2.56±2.58	<0.001
HDL-C (mmol/L)	1.03±0.34	0.93±0.28	<0.001
LDL-C (mmol/L)	2.55±0.89	2.62±0.92	0.104
ALT (U/L)	16(12, 23)	23(16, 35)	<0.001
AST (U/L)	17(14, 21)	20(16, 27)	<0.001
GGT (U/L)	21(16, 34)	32(22, 48)	<0.001
Scr (µmol/L)	76.29±45.57	78.06±24.09	0.162
FT3 (pmol/L)	4.50±1.01	4.21±1.50	<0.001
FT4 (pmol/L)	16.69±10.95	16.42±7.46	0.585
TSH (mU/L)	2.01(1.34, 2.97)	2.05(1.29, 2.87)	0.648
FIB-4	1.068(0.774, 1.465)	1.162(0.857, 1.590)	0.002
APRI	0.212(0.162, 0.287)	0.244(0.182, 0.332)	0.000

Abbreviations: SBP, systolic blood pressure; DBP, diastolic blood pressure; WC, waist circumference; BMI, body mass index; HbA1c, glycosylated hemoglobin; FPG, fasting plasma glucose; FINS, fasting insulin; HOMA-IR, homeostatic model assessment for insulin resistance; PLT, platelet; ALB, albumin; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, γ-glutamyl transferase; Scr, serum creatinine; FT3, free triiodothyronine; FT4, free thyroxine; TSH, thyroid stimulating hormone; FIB-4, fibrosis-4 score= age (years) × AST (U/L)/[platelet (×10⁹/L) ×(√ALT(U/L)]; APRI, aspartate aminotransferase-to-platelet ratio Index=  [AST (U/L)/ULN/platelet (×10⁹/L)]×100; ULN, upper limit of normal.

Table 2 Characteristics of T2DM Cases with and without NAFLD-Related Advanced Fibrosis Estimated by NFS

	Without Advanced Fibrosis Group (n=174)	With Advanced Fibrosis Group (n=81)	P
Age (years)	37.74±8.76	64.73±10.10	<0.001
Male (%)	114(65.2)	61(75.31)	0.012
SBP (mmHg)	133.87±11.28	144.49±26.10	<0.001
DBP (mmHg)	79.96±7.11	85.85±16.79	<0.001
WC (cm)	90.51±7.22	105.41±9.51	<0.001
BMI (kg/m2)	25.67±2.57	30.33±5.26	<0.001
HbA1c (%)	9.25±2.06	8.47±1.76	0.005
FPG (mmol/L)	9.76±3.96	8.95±3.39	0.537
FINS (µIU/mL)	15.43±13.55	22.60±26.27	0.073
HOMA-IR	4.92(3.07, 7.37)	4.09(2.52, 6.22)	0.160
PLT (×10^9/L)	259.81±59.12	159.47±39.62	0.000
ALB (g/L)	44.82±3.03	37.94±3.64	0.000
TC (mmol/L)	4.85±1.46	4.36±0.97	0.005
TG (mmol/L)	3.10±2.66	1.97±1.29	<0.001
HDL-C (mmol/L)	0.89±0.21	0.93±0.34	0.211
LDL-C (mmol/L)	2.88±1.08	2.67±0.89	0.084
ALT (U/L)	36(21, 52)	17(12, 25)	<0.001
AST (U/L)	23(17, 52)	21(16, 28)	0.093
GGT (U/L)	36(27, 52)	27(18, 42)	<0.001
Scr (µmol/L)	65.11±14.09	73.69±26.36	0.009
FT3 (pmol/L)	4.79±0.89	4.28±1.19	<0.001
FT4 (pmol/L)	16.73±2.49	15.28±3.99	0.150
TSH (mU/L)	1.86(1.28, 2.70)	2.05(1.35, 3.45)	0.070

Abbreviations: SBP, systolic blood pressure; DBP, diastolic blood pressure; WC, waist circumference; BMI, body mass index; HbA1c, glycosylated hemoglobin; FPG, fasting plasma glucose; FINS, fasting insulin; HOMA-IR, homeostatic model assessment for insulin resistance; PLT, platelet; ALB, albumin; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, γ-glutamyl transferase; Scr, serum creatinine; FT3, free triiodothyronine; FT4, free thyroxine; TSH, thyroid stimulating hormone.

Table 3 Prevalence of Advanced Fibrosis in Cases with Different TH Levels

	n	Advanced Fibrosis, n (%)	OR (95% CI)	P trend
FT3 (pmol/L)				<0.001
< 4.0	174	29(16.67)	–
4.0~	201	20(9.95)	0.273(0.138, 0.542)
4.4~	210	19(9.05)	0.494(0.240, 1.020)
4.8~	251	13(5.18)	0.549(0.264, 1.140)
FT4 (pmol/L)				0.370
<14.6	206	26(12.62)	–
14.6~	202	16(7.92)	0.738(0.401, 1.358)
16.1~	210	18(8.57)	1.239(0.627, 2.447)
17.7~	218	21(9.63)	1.137(0.588, 2.200)
TSH (mU/L)				0.295
<1.33	207	19(9.18)	–
1.33~	208	19(9.13)	1.468(0.789, 2.732)
2.01~	212	16(7.55)	1.476(0.793, 2.747)
2.94~	209	27(12.92)	1.817(0.948, 3.483)

Abbreviations: FT3, free triiodothyronine; FT4, free thyroxine; TSH, thyroid stimulating hormone.

Table 4 Association of TH Levels with the Incidence of Advanced Fibrosis

	Model 1		Model 2		Model 3
	OR (95% CI)	P	OR (95% CI)	P	OR (95% CI)	P
FT3	0.693(0.582, 0.852)	<0.001	0.676(0.565, 0.808)	<0.001	0.492(0.384, 0.631)	<0.001
FT4	0.990(0.972, 1.008)	0.286	0.991(0.972, 1.009)	0.313	0.991(0.968, 1.014)	0.435
TSH	1.036(0.996, 1.079)	0.081	1.039(0.997, 1.082)	0.069	1.040(0.997, 1.085)	0.057

Notes: Model 1: none (univariate); Model 2: adjusted for sex; Model 3: adjusted for sex, WC, SBP, TC, TG, HOMA-IR and Scr.

Abbreviations: FT3, free triiodothyronine; FT4, free thyroxine; TSH, thyroid stimulating hormone.