Factors Associated with Liver Fibrosis in Chinese Patients with Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease

Figures & data

Table 1 Comparison of Clinical Parameters Between Patients with and without Liver Fibrosis

Variable	All Patients	Non-Liver Fibrosis Group (FIB-4 <1.30)	Liver Fibrosis Group (FIB-4 ≥1.30)
N	565	336	229
Age (year)	57.00(48.00, 66.00)	55.00(45.25, 61.00)	62.00(53.50, 69.00)**
Male (%)	59.12	61.31	56.77
SBP (mmHg)	134.00(123.00, 148.50)	133.00(123.00, 144.00)	137.00(124.00, 154.00)*
DBP (mmHg)	83.00(76.00, 91.00)	83.00(76.00, 91.00)	83.00(75.00, 91.50)
BMI (kg/m^2)	27.31(25.22, 29.41)	27.13(24.81, 29.37)	27.43(25.53, 29.52)
Duration (year)	8.00(3.00, 13.00)	8.00(3.00, 12.00)	8.00(3.00, 15.00)
TP (g/L)	68.52±5.93	68.63±5.93	68.37±5.94
ALB (g/L)	42.20(40.00.44.45)	42.38(40.20, 44.48)	41.90(40.00, 44.45)
GLB (g/L)	25.90(23.10, 29.30)	26.20(23.40, 29.39)	25.55(22.87, 29.15)
ALT (U/L)	19.90(14.90, 29.95)	17.35(13.65, 22.90)	25.80(17.45, 41.65)**
AST (U/L)	19.70(16.30, 24.55)	17.60(15.10, 20.96)	24.20(19.60, 35.45)**
GGT (U/L)	27.00(19.25, 39.65)	25.75(18.75, 36.55)	30.40(20.15, 47.55)**
ALP (U/L)	80.80(66.35, 96.55)	79.20(66.00, 95.68)	82.80(66.70, 97.15)
BUN (mmol/L)	5.25(4.40, 6.40)	5.29(4.40, 6.58)	5.23(4.42, 6.00)
Scr (μmol/L)	66.50(57.30, 77.10)	66.50(57.83, 76.15)	66.20(56.00, 78.25)
SUA (μmol/L)	316.80(261.75, 377.41)	314.75(262.10, 373.88)	323.75(260.90, 383.60)
GFR (mL/min)	97.80(88.05, 107.33)	100.66(90.94, 108.95)	94.46(86.07, 103.40)**
TC (mmol/L)	4.88(4.02, 5.66)	4.98(4.13, 5.70)	4.69(3.95, 5.65)
TG (mmol/L)	1.62(1.18, 2.44)	1.58(1.14, 2.39)	1.66(1.22, 2.53)
HDL (mmol/L)	1.04(0.90, 1.22)	1.03(0.90, 1.22)	1.04(0.89, 1.22)
LDL (mmol/L)	3.14(2.56, 3.74)	3.21(2.65, 3.75)	3.00(2.47, 3.66)*
FPG (mmol/L)	8.20(6.74, 10.44)	8.35(6.76, 10.74)	8.01(6.66, 10.08)
HbA1c (%)	8.60(7.50, 10.20)	8.75(7.50, 10.48)	8.40(7.40, 9.90)*
HOMA-IR	3.46(2.02, 6.03)	3.42(2.02, 6.21)	3.65(2.02, 5.47)
HGB (g/L)	144.00(132.50, 156.00)	145.00(133.00, 156.00)	143.00(132.00, 154.40)
PLT (×10^9/L)	226.00(192.00, 265.00)	245.50(211.00, 279.00)	201.00(173.50, 238.00)**
APRI	0.25(0.20, 0.35)	0.21(0.17, 0.25)	0.36(0.27, 0.49)**
NFS	−0.68(−1.34, 0.04)	−0.95(−1.78,-2.28)	−0.14(−0.89, 0.46)**

Notes: Date was presented as mean ± SD, median (P25, P75) or percentage. *P < 0.05; **P < 0.01.

Abbreviations: FIB-4, fibrosis-4 index; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, body mass index; TP, total protein; ALB, albumin; GLB, globulin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, γ-glutamyl transpeptidase; ALP, alkaline phosphatase; BUN, blood urea nitrogen; Scr, serum creatinine; SUA, serum uric acid; GFR, glomerular filtration rate; TC, total cholesterol; TG, triglyceride; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; FPG, fasting plasma glucose; HbA1c, glycosylated hemoglobin; HOMA-IR, homeostasis assessment of insulin resistance; HGB, hemoglobin; PLT, platelets; APRI, aspartate aminotransferase-to-platelets ratio index; NFS, nonalcoholic fatty liver disease fibrosis score.

Figure 1 Comparison of prevalence of hypertension, hyperlipidemia, and obesity between NLF group and LF group. (A) Comparison of prevalence of hypertension, between NLF group and LF group; (B) Comparison of prevalence of hyperlipidemia between NLF group and LF group; (C) Comparison of prevalence of obesity between NLF group and LF group. **P < 0.01.

Table 2 Comparison of Clinical Parameters in Patients with Different Degrees of Liver Fibrosis

Variable	F1-2 (1.3 ≤ FIB-4 <2.67)	F3-4 (FIB-4 ≥2.67)
N	185	44
Age (year)	62.00(53.00, 69.00)	62.50(54.00, 70.75)
Male (%)	104	24
SBP (mmHg)	136.00(124.50, 154.00)	141.00(121.25, 154.75)
DBP (mmHg)	83.00(74.50, 92.00)	83.50(75.50, 90.75)
BMI (kg/m^2)	27.64(25.53, 29.60)	27.23(25.35, 29.32)
Duration (year)	9.00(3.00, 14.50)	6.00(2.00, 15.75)
TP (g/L)	68.13±5.76	69.38±6.63
ALB (g/L)	41.86(39.95, 44.16)	42.70(40.05, 45.18)
GLB (g/L)	25.5(22.79, 29.15)	26.80(23.43, 29.32)
ALT (U/L)	23.90(16.25, 34.05)	41.60(29.75, 69.25)**
AST (U/L)	23.10(19.10, 31.60)	39.40(28.48, 51.68)**
GGT (U/L)	28.30(19.65, 42.00)	36.95(23.80, 74.35)*
ALP (U/L)	83.60(67.15, 97.80)	79.40(61.08, 94.40)
BUN (mmol/L)	5.30(4.50, 6.05)	5.10(4.33, 5.75)
Scr (μmol/L)	66.60(55.90, 79.95)	64.69(56.05, 73.78)
SUA (μmol/L)	323.75(258.35, 381.83)	323.95(278.33, 384.08)
GFR (mL/min)	94.56(86.16, 102.97)	93.61(85.01, 105.21)
TC (mmol/L)	4.68(3.95, 5.56)	4.83(3.97, 6.39)
TG (mmol/L)	1.64(1.20, 2.51)	1.75(1.30, 2.58)
HDL (mmol/L)	1.03(0.88, 1.20)	1.11(0.94, 1.32)
LDL (mmol/L)	3.00(2.47, 3.61)	3.02(2.47, 4.21)
FPG (mmol/L)	8.31(6.69, 10.08)	7.61(6.54, 10.14)
HbA1c (%)	8.40(7.50, 9.90)	8.35(7.25, 9.95)
HOMA-IR	3.54(2.15, 5.67)	4.13(1.62, 5.44)
HGB (g/L)	143.00(133.50, 154.50)	142.50(130.25, 154.25)
PLT (×10^9/L)	211.00(179.00, 250.00)	183.50(164.25, 204.25)**

Notes: Date was presented as mean ± SD, median (P25, P75) or percentage. *P < 0.05; **P < 0.01.

Abbreviations: FIB-4, fibrosis-4 index; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, body mass index; TP, total protein; ALB, albumin; GLB, globulin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, γ-glutamyl transpeptidase; ALP, alkaline phosphatase; BUN, blood urea nitrogen; Scr, serum creatinine; SUA, serum uric acid; GFR, glomerular filtration rate; TC, total cholesterol; TG, triglyceride; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; FPG, fasting plasma glucose; HbA1c, glycosylated hemoglobin; HOMA-IR, homeostasis assessment of insulin resistance; HGB, hemoglobin; PLT, platelets.

Table 3 Correlation Between FIB-4 and Other Indicators

Variable	r	Variable	r
Age (year)	0.338**	SUA (μmol/L)	0.069
SBP (mmHg)	0.125**	GFR (mL/min)	−0.231**
DBP (mmHg)	−0.044	TC (mmol/L)	−0.091*
BMI (kg/m^2)	0.056	TG (mmol/L)	−0.010
Duration (year)	0.111**	HDL (mmol/L)	0.005
TP (g/L)	−0.026	LDL (mmol/L)	−0.096*
ALB (g/L)	−0.036	FPG (mmol/L)	−0.076
GLB (g/L)	−0.026	HbA1c (%)	−0.102*
ALT (U/L)	0.409**	HOMA-IR	0.027
AST (U/L)	0.582**	HGB (g/L)	−0.022
GGT (U/L)	0.116**	PLT (×10^9/L)	−0.464**
ALP (U/L)	0.050	APRI	0.754**
BUN (mmol/L)	−0.032	NFS	0.454**
Scr (μmol/L)	0.026

Notes: Spearman correlation analysis was applied in this part. *P < 0.05; **P < 0.01.

Abbreviations: FIB-4, fibrosis-4 index; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, body mass index; TP, total protein; ALB, albumin; GLB, globulin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, γ-glutamyl transpeptidase; ALP, alkaline phosphatase; BUN, blood urea nitrogen; Scr, serum creatinine; SUA, serum uric acid; GFR, glomerular filtration rate; TC, total cholesterol; TG, triglyceride; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; FPG, fasting plasma glucose; HbA1c, glycosylated hemoglobin; HOMA-IR, homeostasis assessment of insulin resistance; HGB, hemoglobin; PLT, platelets; APRI, aspartate aminotransferase-to-platelets ratio index; NFS, nonalcoholic fatty liver disease fibrosis score.

Table 4 Logistic Regression Analysis of Liver Fibrosis in Type 2 Diabetes Mellitus Patients Combined with Non-Alcoholic Fatty Liver Disease

Variable		OR	95% CI
Age (year)	< 50
	≥50	4.315**	2.252–8.266
SBP (mmHg)		1.012*	1.001–1.024
ALT (U/L)	< 40
	≥40	11.686**	2.881–47.400
AST (U/L)	< 50
	≥50	1.296	0.1880–8.916
GGT (U/L)		1.010*	1.002–1.018
GFR (mL/min)		0.990	0.976–1.004
LDL (mmol/L)		0.761*	0.599–0.967
HbA1c (%)		0.954	0.852–1.068
PLT (×10^9/L)	< 260
	≥260	0.252**	0.165–0.384

Notes: Liver fibrosis was used as the dependent variable, and age, SBP, ALT, AST, GGT, eGFR, LDL, HbAlc, and PLT were used as independent variables. *P < 0.05; **P < 0.01.

Abbreviations: SBP, systolic blood pressure; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, γ-glutamyl transpeptidase; GFR, glomerular filtration rate; LDL, low-density lipoprotein cholesterol; HbA1c, glycosylated hemoglobin; PLT, platelets.