Increased Serum Adipsin Correlates with MAFLD and Metabolic Risk Abnormalities

Figures & data

Figure 1 Flow chart of participants and enrollment time in Guangzhou Nutrition and Health Study.

Figure 2 Specific grouping characteristics of the participants in this study.

Table 1 Clinical Characteristics of Subjects in Non-MAFLD and MAFLD Groups

Variables	Non-MAFLD (n=119)	MAFLD (n=789)	P value
Age, years^b	58.92 (55.50–62.92)	60.17 (56.75–64.00)	0.020*
Male, n (%)^c	34 (28.57)	252 (31.94)	0.461
Educational level, n (%)^c
No formal education or primary school	5 (4.20)	46 (5.83)	0.453
Middle school	20 (16.81)	174 (22.05)
High school or technical secondary school	61 (51.26)	380 (48.16)
College or university	33 (27.73)	189 (23.95)
Smoking, n (%)^c	8 (6.72)	67 (8.49)	0.513
Drinking, n (%)^c	11 (9.24)	62 (7.86)	0.604
Physical activity, MET/day^b	23.68 (20.20–28.55)	23.10 (19.74–27.53)	0.151
BMI, kg/m^2b	21.57 (20.40–22.24)	25.12 (23.57–27.07)	<0.001***
Adipsin, ng/ml^b	3095.33 (2778.71–3354.77)	3543.00 (3187.94–3972.50)	<0.001***
WC, cm^b	78.15 (74.30–80.80)	88.75 (84.30–93.80)	<0.001***
HC, cm^b	89.65 (87.15–91.90)	95.00 (91.73–98.63)	<0.001***
NC, cm^b	31.70 (30.70–33.95)	34.15 (32.50–36.55)	<0.001***
WHR^a	0.87±0.06	0.94±0.06	<0.001***
Trunk fat, kg^b	8.10 (6.88–9.12)	11.23 (9.76–13.02)	<0.001***
Trunk fat percentage, %^b	32.44 (27.17–35.16)	36.80 (32.07–40.52)	<0.001***
SBP, mmHg^b	114.50 (107.00–123.50)	127.50 (117.00–140.00)	<0.001***
DBP, mmHg^b	70.50 (64.00–75.00)	78.00 (71.00–85.00)	<0.001***
TC, mmol/L^a	5.58±1.01	5.51±0.99	0.494
TG, mmol/L^b	1.03 (0.81–1.25)	1.51 (1.05–2.09)	<0.001***
LDL-C, mmol/L^a	3.64±0.92	3.64±0.91	0.987
HDL-C, mmol/L^b	1.52 (1.34–1.91)	1.24 (1.02–1.47)	<0.001***
Fasting glucose, mmol/L^b	4.49 (4.19–4.81)	4.80 (4.40–5.35)	<0.001***
Insulin, μU/mL^b	6.38 (4.38–7.90)	10.24 (7.58–14.43)	<0.001***
HOMA-IR^b	1.24 (0.88–1.57)	2.26 (1.59–3.22)	<0.001***
ALT, U/L^b	13.00 (10.00–19.00)	17.00 (13.00–22.50)	<0.001***
AST, U/L^b	19.00 (15.00–21.00)	18.00 (16.00–22.00)	0.432
AST/ALT^b	1.31 (1.11–1.56)	1.08 (0.88–1.31)	<0.001***
ALP, U/L^b	69.35 (55.59–81.54)	71.59 (60.03–84.30)	0.099
Albumin, g/L^b	45.60 (41.70–48.30)	45.60 (42.30–47.90)	0.946
UA, μmol/L^b	311.31 (277.96–346.97)	348.90 (299.74–404.73)	<0.001***
T2DM, n (%)^c	0	92 (11.66)	<0.001***
Hypertension, n (%)^c	21 (17.65)	383 (48.54)	<0.001***
Dyslipidemia, n (%)^c	62 (52.10)	563 (71.36)	<0.001***
MetS, n (%)^c	0	315 (39.92)	<0.001***

Note: *P < 0.05; ***P < 0.001. ^aIndependent samples t-test, ^bMann–Whitney U-test; ^cPearson Chi-Square test.

Abbreviations: BMI, body mass index; WC, waist circumference; HC, hip circumference; NC, neck circumference; WHR, waist-to-hip ratio; SBP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; TG, triglyceride; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; HOMA-IR, homeostasis model assessment of insulin resistance; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; UA, uric acid; T2DM, type 2 diabetes mellitus; MetS, metabolic syndrome.

Figure 3 (A) Comparison of the non-MAFLD group and MAFLD groups diagnosed by different criteria. (B) Distribution of adipsin quartile levels between the MAFLD and non-MAFLD groups. ***P < 0.001.

Table 2 Association Between Serum Adipsin Levels and MAFLD

	Model 1		Model 2		Model 3
	OR (95% CI)	P value	OR (95% CI)	P value	OR (95% CI)	P value
Adipsin (ng/mL, median [range])
Tertile 1 (2976.82 [<3237.85])	Reference		Reference		Reference
Tertile 2 (3476.33 [3237.85–3748.62])	2.54 (1.64–3.94)	<0.001***	2.08 (1.32–3.27)	0.002**	1.36 (0.81–2.27)	0.248
Tertile 3 (4113.90 [>3748.62])	10.76 (5.27–21.94)	<0.001***	7.90 (3.81–16.38)	<0.001***	3.46 (1.57–7.64)	0.002**
P for trend	<0.001***		<0.001***		0.002**

Notes: **P < 0.01; ***P < 0.001. Binary logistic regression models: model 1: crude model; model 2: adjusted for age, gender, education, smoking, drinking, physical activity, hypertension, dyslipidemia; model 3: adjusted for variables in model 2 plus TG, HDL-C, UA, HOMA-IR, AST/ALT.

Figure 4 Serum adipsin levels in MAFLD patients with or without metabolic dysregulation. **P < 0.01.

Abbreviation: MD, metabolic dysregulation.

Figure 5 (A) Relationship between the number of metabolic risk abnormalities and serum adipsin levels. The trend test was conducted by Jonckheere-Terpstra. (B) Relationship between the number of metabolic risk abnormalities and the severity of MAFLD. The trend test was conducted by linear-by-linear association chi square test.

Figure 6 Differences in serum adipsin levels among MAFLD with different severity. The trend test was conducted by Jonckheere-Terpstra.

Table 3 Spearman Correlation of Adipsin with Some Factors in MAFLD and Non-MAFLD Groups

	MAFLD		Non-MAFLD
	r	P value	r	P value
Adipsin, ng/mL
BMI, kg/m^2	0.293	<0.001***	0.251	0.006**
Physical activities, MET/day	−0.067	0.058	0.020	0.826
WC, cm	0.258	<0.001***	0.235	0.010*
HC, cm	0.191	<0.001***	0.127	0.168
NC, cm	0.214	<0.001***	0.174	0.059
WHR	0.171	<0.001***	0.203	0.027*
Trunk fat, kg	0.227	<0.001***	0.195	0.033*
SBP, mmHg	0.127	<0.001***	0.076	0.414
DBP, mmHg	0.149	<0.001***	−0.019	0.836
TC, mmol/L	−0.044	0.215	−0.076	0.412
TG, mmol/L	0.150	<0.001***	0.117	0.204
LDL-C, mmol/L	−0.040	0.265	0.043	0.640
HDL-C, mmol/L	−0.180	<0.001***	−0.214	0.020*
Fasting glucose, mmol/L	0.089	0.013*	0.050	0.592
Insulin, μU/mL	0.217	<0.001***	0.265	0.004**
HOMA-IR	0.226	<0.001***	0.266	0.003**
ALT, U/L	0.086	0.015*	0.051	0.584
AST, U/L	0.038	0.288	−0.027	0.773
AST/ALT	−0.116	0.001**	−0.106	0.251
ALP, U/L	0.026	0.465	0.057	0.542

Note: *P < 0.05; **P < 0.01; ***P < 0.001.

Abbreviations: BMI, body mass index; WC, waist circumference; HC, hip circumference; NC, neck circumference; WHR, waist-to-hip ratio; SBP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; TG, triglyceride; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; HOMA-IR, homeostasis model assessment of insulin resistance; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase.

Table 4 Subgroup Analysis of Clinical Characteristics of Patients with MAFLD Based on Severity of Fatty Liver

Variables	Mild-MAFLD (n=571)	Moderate-MAFLD (n=173)	Severe-MAFLD (n=45)	P value	P trend
Age, years^ad	60.33 (56.83–64.08)	59.58 (56.88–64.46)	58.33 (55.54–63.21)	0.426	0.684
Male, n (%)^cf	191 (33.45)	51 (29.48)	10 (22.22)	0.219	0.087
Educational level, n (%)^cf
No formal education or primary school	34 (5.95)	10 (5.78)	2 (4.44)	0.133	0.961
Middle school	115 (20.14)	47 (27.17)	12 (26.67)
High school or technical secondary school	293 (51.31)	70 (40.46)	17 (37.78)
College or university	129 (22.59)	46 (26.59)	14 (31.11)
Smoking, n (%)^cf	50 (8.76)	14 (8.09)	3 (6.67)	0.869	0.608
Drinking, n (%)^cf	46 (8.06)	15 (8.67)	1 (2.22)	0.339	0.403
Physical activities, MET/day^ad	23.18 (19.85–27.33)	23.00 (19.63–27.81)	22.70 (19.53–27.73)	0.994	0.939
BMI, kg/m^2ad	24.80 (23.39–26.41)	26.33 (24.45–28.02)	26.77 (25.21–29.59)	<0.001***	<0.001***
Adipsin, ng/ml^ad	3487.93 (3141.16–3920.39)	3631.98 (3293.55–3972.50)	4150.88 (3238.88–4524.72)	<0.001***	<0.001***
WC, cm^ad	87.80 (83.50–92.80)	90.70 (86.43–94.75)	94.10 (87.63–100.55)	<0.001***	<0.001***
HC, cm^ad	94.35 (91.35–97.70)	97.00 (92.85–100.65)	97.30 (93.73–100.23)	<0.001***	<0.001***
NC, cm^ad	34.00 (32.25–36.35)	34.75 (33.23–37.50)	35.25 (33.28–36.40)	<0.001***	<0.001***
WHR^be	0.93±0.06	0.94±0.05	0.96±0.05	0.003**	0.001**
Trunk fat, kg^ad	10.76 (9.50–12.28)	12.35 (10.92–14.07)	12.77 (11.16–15.06)	<0.001***	<0.001***
Trunk fat percentage, %^ad	36.19 (30.96–39.56)	39.21 (33.86–42.24)	38.05 (35.99–40.93)	<0.001***	<0.001***
SBP, mmHg^ad	126.50 (116.50–139.50)	130.00 (119.00–141.75)	133.50 (117.50–146.00)	0.059	0.018*
DBP, mmHg^ad	77.50 (70.50–85.00)	78.50 (71.75–86.00)	78.00 (71.50–84.25)	0.467	0.299
TC, mmol/L^be	5.49±1.02	5.56±0.91	5.56±0.90	0.669	0.400
TG, mmol/L^ad	1.36 (0.97–1.96)	1.77 (1.30–2.34)	1.73 (1.32–2.17)	<0.001***	<0.001***
LDL-C, mmol/L^be	3.63±0.92	3.65±0.89	3.78±0.91	0.581	0.370
HDL-C, mmol/L^ad	1.26 (1.06–1.52)	1.16 (0.96–1.41)	1.15 (0.96–1.40)	<0.001***	<0.001***
Fasting glucose, mmol/L^ad	4.73(4.38–5.20)	4.94 (4.60–5.51)	5.36 (4.84–6.79)	<0.001***	<0.001***
Insulin, μU/mL^ad	9.41 (6.93–12.62)	13.73(9.76–17.52)	13.86(9.99–19.08)	<0.001***	<0.001***
HOMA-IR^ad	2.04 (1.44–2.84)	2.93 (2.15–3.96)	3.35 (2.19–5.53)	<0.001***	<0.001***
ALT, U/L^ad	16.00 (12.00–21.00)	19.00 (14.00–26.50)	22.00 (16.50–32.00)	<0.001***	<0.001***
AST, U/L^ad	18.00 (16.00–21.00)	19.00 (15.00–23.00)	20.00 (16.00–24.50)	0.053	0.017*
AST/ALT^ad	1.13 (0.93–1.33)	1.00 (0.80–1.18)	0.84 (0.77–1.00)	<0.001***	<0.001***
ALP, U/L^ad	71.59 (59.60–84.12)	70.95 (61.03–85.01)	72.62 (61.81–85.69)	0.831	0.549
Albumin, g/L^ad	45.30 (41.90–47.70)	46.20 (42.80–48.15)	44.70 (42.85–48.65)	0.118	0.047*
UA, μmol/L^ad	345.58 (296.12–408.34)	352.54 (307.91–402.44)	363.33 (311.97–412.83)	0.182	0.077
T2DM, n (%)^cf	55 (9.63)	24 (13.87)	13 (28.89)	<0.001***	<0.001***
Hypertension, n (%)^cf	258 (45.18)	95 (54.91)	30 (66.67)	0.004**	0.001**
Dyslipidemia, n (%)^cf	390 (68.30)	139 (80.35)	34 (75.56)	0.007**	0.009**
MetS, n (%)^cf	191 (33.45)	97 (56.07)	27 (60.00)	<0.001***	<0.001***

Notes: *P < 0.05; **P < 0.01; ***P < 0.001. P value: ^aKruskal–Wallis test, ^bOne-Way ANOVA, and ^cPearson Chi-Square test; P trend: ^dJonckheere-Terpstra, ^eLinear contrast in one-way ANOVA and ^fLinear-by-linear association chi square test.

Abbreviations: BMI, body mass index; WC, waist circumference; HC, hip circumference; NC, neck circumference; WHR, waist-to-hip ratio; SBP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; TG, triglyceride; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; HOMA-IR, homeostasis model assessment of insulin resistance; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; UA, uric acid; T2DM, type 2 diabetes mellitus; MetS, metabolic syndrome.