Serum Metrnl is Decreased in Metabolic Dysfunction-Associated Fatty Liver Disease: A Case-Control Study

Figures & data

Table 1 General Clinical and Laboratory Parameter in Participants with and without MAFLD

Variable	Controls	MAFLD	P
N	176	176
Sex(M/F)	88/88	88/88	1.000
^#Age(years)	40(31−54)	44(35−56)	0.103
^#BMI(kg/m2)	23(21−24)	26(24−28)	<0.001
^#WC(cm)	83(75−88)	93(88−99)	<0.001
*HC (cm)	98.29±6.32	102.40±6.32	<0.001
^#SBP (mmHg)	120(109−133)	132(121−142)	<0.001
^#DBP (mmHg)	77(72−87)	85(80−90)	<0.001
^#FBG(mmol/L)	4.96(4.60−5.33)	5.32(4.95−5.83)	<0.001
^#TG(mmol/L)	1.03(0.76−1.39)	1.07(1.21−2.14)	<0.001
*TC (mmol/L)	4.76±0.83	5.17±0.98	<0.001
^#UA(μmol/L)	332.40(271.45−377.87)	342.40(299.60−409.70)	0.006
^#Creatinine(μmol/L)	68(57−81)	66(57−77)	0.126
^#ALT(U/L)	15(12−20)	22(16−35)	<0.001
^#AST(U/L)	21(18−25)	23(20−28)	<0.001
^#γ-GGT(mmol/L)	18.50(14.30−24.07)	26.80(20.40−40.90)	<0.001
*LDL-C(mmol/L)	2.94±0.63	3.30±0.74	0.231
*HDL-C(mmol/L)	1.36±0.25	1.24±0.27	<0.001
^#WBC(×10^9/L)	5.90(5.10−7.00)	6.50(5.50−7.33)	0.007
^#Metrnl(pg/mL)	379.06(248.81−504.70)	240.40(176.28−305.75)	<0.001

Notes: *Data normally distributed are shown as mean ± SD. Independent Sample t test was performed. ^#Data with skewed distribution are shown as median (25^th−75^th). Mann–Whitney U-test was performed.

Abbreviations: BMI, body mass index; WC, waist circumference; HC, hip circumference; SBP, systolic blood pressure; DBP, diastolic blood pressure; FBG, fasting blood glucose; TG, Triglyceride; TC, Total cholesterol; UA, uric acid; ALT, alanine aminotransferase; AST, aspartate aminotransferase; γ-GGT, γ-gamma glutamyl transferase; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; WBC, white blood cell.

Figure 1 Serum Metrnl levels (median (IQR) marked) in MAFLD and control group. ** P<0.01.

Figure 2 Gender differences of serum Metrnl (median (IQR) marked) in MAFLD and control group. ** P<0.01.

Table 2 Correlation Between Serum Metrnl and Other Variables

Metrnl	Univariate Correlations		Multivariate Regression Analysis
	r	P	Standardβ	P
Age	0.010	0.900	−	−
BMI	−0.027	0.730	−	−
WC	−0.122	0.142	−	−
SBP	−0.169	0.036	−0.177	0.027
DBP	−0.215	0.008	−	−
FBG	−0.024	0.750	−	−
ALT	−0.127	0.093	−	−
AST	0.019	0.798	−	−
γ-GGT	−0.162	0.032
UA	−0.138	0.071	−	−
Creatinine	−0.284	<0.001	−0.213	0.008
TG	−0.004	0.961	−	−
TC	−0.140	0.066	−	−
LDL-C	−0.028	0.718	−	−
HDL-C	0.079	0.302	−	−
WBC	−0.054	0.479	−	−

Note: Data with statistical differences have been bolded.

Abbreviations: BMI, body mass index; WC, waist circumference; SBP, systolic blood pressure; DBP, diastolic blood pressure; FBG, fasting blood glucose; ALT, alanine aminotransferase; AST, aspartate aminotransferase; γ-GGT, γ-gamma glutamyl transferase; UA, uric acid; TG, Triglyceride; TC, Total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; WBC, white blood cell.

Table 3 Independent Factors Associated with MAFLD in Binary Logistic Regression Models

Variables	Univariate	Multivariate
	P	β±SE	Wald	OR (95% CI)	P
Sex	0.010	2.318±0.662	12.268	10.156(2.766–37.158)	<0.001
Age	0.125
BMI	0.166
WC	0.006	0.114±0.028	16.588	1.121(1.061–1.184)	<0.001
SBP	0.166
DBP	0.044	0.013±0.021	0.409	1.013(0.973–1.056)	0.523
FBG	0.017	0.330±0230	2.057	1.391(0.886–2.183)	0.152
TG	0.085	0.808±0.291	7.718	2.244 (1.269–3.969)	0.005
TC	0.236
LDL-C	0.105
HDL-C	0.277
Creatinine	0.046	−0.031±0.017	3.132	0.097(0.937–1.003)	0.077
UC	0.219
WBC	0.759
ALT	0.707
AST	0.400
γ-GGT	0.008	0.058±0.017	12.317	1.060(1.026–1.095)	<0.001
Metrnl	<0.001	−0.010±0.002	29.915	0.990(0.987–0.994)	<0.001

Note: Data with statistical differences have been bolded.

Abbreviations: β, Regression coefficient; SE, standard error; BMI, body mass index; WC, waist circumference; SBP, systolic blood pressure; DBP, diastolic blood pressure; FBG, fasting blood glucose; TG, Triglyceride; TC, Total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; UA, uric acid; WBC, white blood cell; ALT, alanine aminotransferase; AST, aspartate aminotransferase; γ-GGT, γ-gamma glutamyl transferase.

Table 4 General Clinical and Laboratory Parameter of All Subjects According to Serum Metrnl

Variable	T1	T2	T3	P
Serum Metrnl (pg/mL)	<233.65	233.65–346.24	≥346.24	−
N	117	118	117	−
Percentage of MAFLD (%)	67.52	66.95	15.38	<0.001
Sex(M/F)	99/18	58/60	12/105	<0.001
^#Age(years)	40(32−55)	46(33−58)	41(32−51)	0.103
^#BMI(kg/m^2)	26(24−27)	25(23−27)	23(21−24)	<0.001
^#WC(cm)	91(86−98)	89(84−95)	82(74−88)	<0.001
*HC (cm)	101.76±6.36	100.10±5.81	98.71±7.27	0.003
^#SBP (mmHg)	131(120−142)	128(117−139)	114(106−133)	<0.001
^#DBP (mmHg)	84(78−90)	83(78−88)	75(71−85)	<0.001
^#FBG(mmol/L)	5.23(4.87−5.89)	5.25(4.88−5.59)	4.92(4.58−5.23)	<0.001
^#TG(mmol/L)	1.44(1.04−1.95)	1.50(1.08−2.06)	1.01(0.71−1.42)	<0.001
*TC (mmol/L)	5.11±0.87	5.09±1.02	4.68±0.83	<0.001
*LDL-C(mmol/L)	3.17±0.67	3.24±0.79	2.94±0.63	0.003
*HDL-C(mmol/L)	1.27±0.29	1.27±0.28	1.35±0.25	0.027
^#UC(μmol/L)	363.20(307.35−423.50)	342.00(298.70−395.80)	299.40(260.75−347.45)	<0.001
^#ALT(U/L)	22.60(17.40−33.68)	17.90(14.57−26.95)	15.20(10.90−20.40)	<0.001
^#AST(U/L)	23.10(20.10−27.80)	22.40(19.70−26.70)	20.50(18.00−24.60)	<0.001
^#γ-GGT(U/L)	26.50(20.15−38.05)	22.60(19.05−31.30)	15.90 (13.30−22.65)	<0.001
^#Creatinine(μmol/L)	77(65−83)	67(59−80)	59.30(51.90−68.10)	<0.001
^#WBC(×10^9/L)	6.50(5.45−7.35)	6.30(5.50−7.30)	5.60(4.90−6.80)	0.005

Notes: *Data normally distributed are shown as mean ± SD. One-way ANOVA test was performed. ^#Data with skewed distribution are shown as median (25^th−75^th). Kruskal–Wallis test was performed.

Abbreviations: BMI, body mass index; WC, waist circumference; HC, hip circumference; SBP, systolic blood pressure; DBP, diastolic blood pressure; FBG, fasting blood glucose; TG, Triglyceride; TC, Total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; UA, uric acid; ALT, alanine aminotransferase; AST, aspartate aminotransferase; γ-GGT, γ-gamma glutamyl transferase; WBC, white blood cell.

Figure 3 Prevalence of MAFLD according to serum Metrnl tertiles. T1–T3: 67.52%, 66.95%, and 15.38%. P<0.001.

Table 5 MAFLD Risk According to Metrnl Tertiles in Multinomial Logistic Regression Models

OR (95% CI)
	T1(Reference)	T2	T3	P for Trend
Model 1	1	0.794(0.565–1.680)	0.087(0.046–0.165)	<0.001
Model 2	1	0.539(0.259–1.121)	0.022(0.007–0.069)	<0.001
Model 3	1	0.592(0.270–1.296)	0.030(0.009–0.098)	<0.001
Model 4	1	0.580(0.244–1.380)	0.023(0.006–0.086)	<0.001

Notes: Model 1: crude; Model 2: adjusted for age, sex, BMI, WC, HC; Model 3: adjusted for age, sex, BMI, WC, HC, SBP, DBP, FBG. Model 4: adjusted for age, sex, BMI, WC, HC, SBP, DBP, FBG, TG, TC, HDL-C, LDL-C, γ-GGT, AST, ALT, Creatinine, UA, WBC.

Figure 4 ROC curves of Metrnl values for MAFLD diagnosis. AUC= 0.755 (95% CI 0.7047–0.8054), P<0.001.