Serum Albumin to Globulin Ratio is Associated with the Presence and Severity of Inflammatory Bowel Disease

Figures & data

Table 1 Characteristics of Patients with IBD and Non-IBD Cohorts

	UC (n = 179)	Non-UC (n = 123)	CD (n = 210)	Non-CD (n = 88)
Sex (Male/Female)	95/84	63/60	149/61	56/32
Age (yr)	49.20 ± 15.20	46.20 ± 13.80	31.40 ± 10.46	33.28 ± 9.51
BMI (kg/m^2)	20.80 (19.20,22.80)^a	22.20 (20.00,24.20)	19.10 (17.30,21.40)^b	21.60 (19.50,24.50)
Current smoking (n,%)	25 (14.0%)	26 (21.1%)	19 (9.0%)^b	17 (19.3%)
Duration years (yr)	1.00 (0.30,4.00)		1.00 (0.50;4.00)
ESR (mm/h)	18.00 (6.00,26.00)^a	7.00 (3.00,15.00)	19.00 (9.00,34.00)^b	5.50 (2.00,12.00)
CRP (mg/L)	5.45 (2.89,18.34)^a	3.13 (2.11,8.91)	9.79 (3.16,28.63)^b	3.13 (2.12,9.60)
WBC (10^9/L)	6.94 (5.53,8.61)^a	6.23 (5.10,7.83)	6.50 (5.11,8.37)^b	6.26 (5.30,7.98)
Albumin (g/L)	36.99 ± 6.14^a	40.25 ± 4.67	38.26 ± 5.53^b	41.31 ± 4.40
Globulin (g/L)	30.42 ± 4.51^a	28.27 ± 4.06	31.54 ± 5.26^b	27.93 ± 4.07
AGR	1.24 ± 0.27^a	1.45 ± 0.27	1.25 ± 0.30^b	1.51 ± 0.27
Ca^2+ (mmol/L)	2.17 (2.10,2.26)^a	2.25 (2.16,2.32)	2.21 ± 0.13^b	2.25 ± 0.13
Clinical score (n, %)
Remission	9 (5.0%)		78 (37.1%)
Active disease	170 (95.0%)		132 (62.9%)
Endoscopic score (%)	0/1/2/3 5.0/19.0/48.1/27.9		0/1/2/3 17.1/22.9/42.4/17.6
Age at diagnosis (%)			A1/A2/A3 2.9/84.2/12.9
Disease Location (%)	E1/E2/E3 24.0/33.0/43.0		L1/L2/L3/L4 25.7/33.3/39.5/1.5
Disease behavior (%)			B1/B2/B3/P 51.4/20.5/4.8/23.3
Medications (n, %)
5-ASA	162 (90.5%)		64 (30.48%)
Antibiotics	46 (25.7%)		1 (0.48%)
Steroids	53 (29.6%)		26 (12.38%)
Immunosuppression	18 (10.1%)		49 (23.33%)
Biological therapy	8 (4.5%)		106 (50.48%)
Disease categories (n, %)
Acute gastroenteritis		25 (20.3%)		21 (23.9%)
Enterocolitis		32 (26.0%)		28 (31.8%)
Gastrointestinal dysfunction		48 (39%)		34 (38.6%)
Ischemic enteritis		11 (8.9%)		1 (1.1%)
Diverticulitis		7 (5.7%)		4 (4.5%)

Note: ^ap < 0.05 compared with non-UC; ^bp < 0.05 compared with non-CD. Endoscopic score: Mayo endoscopic score (UC): 0- inactive, 1- mild, 2- moderate, 3- severe disease; SES-CD score (CD): 0- inactive- ≤2, 1- mild- 3–6, 2- moderate- 7–15, 3- severe- ≥16. Age at diagnosis, disease location, and behavior were categorized using the Montreal classification: A (age at diagnosis): A1- ≤16, A2- 17–40, A3- >40; L (location): L1- ileal disease, L2- colonic disease, L3- ileocolonic disease, L4- isolated upper disease; B (behavior): B1- nonstructuring/ penetrating phenotype, B2- structuring phenotype, B3- penetrating phenotype, P- perianal phenotype. E (extension): E1- ulcerative proctitis, E2- left-side colitis, E3- extensive colitis. The chi-square test was used to compare categorical variables. Student’s t-test and the Mann–Whitney U-test were used accordingly. Data were shown as Mean ± standard deviation or medians (interquartile ranges).

Abbreviations: UC, ulcerative colitis; CD, Crohn’s disease; BMI, body mass index; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; WBC, white blood cell; AGR, albumin to globulin ratio; SES-CD, Simplified endoscopic activity score for Crohn’s disease.

Figure 1 The difference in serum AGR between UC patients and non-UC patients, CD patients, and non-CD patients.

Note: **p < 0.01, Student’s t-test.

Table 2 Correlation Between BMI, Serum Biomarkers, and Disease Activity in UC Patients

Parameters	AGR		CRP		ESR			WBC
	r	p-value	r	p-value	r	p-value		r		p-value
AGR	–	–	–	–	–	–		–		–
CRP	−0.549	< 0.001	–	–	–	–		–		–
ESR	−0.657	< 0.001	0.621	< 0.001	–	–		–		–
WBC	−0.283	< 0.001	0.336	< 0.001	0.286	< 0.001		–		–
Mayo score	−0.413	< 0.001	0.342	< 0.001	0.352	< 0.001		0.243		0.001
BMI	0.153	0.041	0.028	0.710	−0.076	0.314		−0.045		0.549

Note: Spearman correlation analysis was used.

Abbreviations: UC, ulcerative colitis; AGR, albumin to globulin ratio; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; WBC, white blood cell; BMI, body mass index.

Table 3 Correlation Between Serum Biomarkers and Disease Activity in CD Patients

Parameters	AGR		CRP		ESR		WBC
	r	p-value	r	p-value	r	p-value	r	p-value
AGR	–	–	–	–	–	–	–	–
CRP	−0.584	< 0.001	–	–	–	–	–	–
ESR	−0.700	< 0.001	0.677	< 0.001	–	–	–	–
WBC	−0.231	0.001	0.381	< 0.001	0.329	< 0.001	–	–
HBI score	−0.471	< 0.001	0.696	< 0.001	0.479	< 0.001	0.307	< 0.001
BMI	0.192	< 0.001	−0.069	0.323	−0.111	0.109	−0.061	0.383

Note: Spearman correlation analysis was used.

Abbreviations: CD, Crohn’s disease; AGR, albumin to globulin ratio; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; WBC, white blood cell; BMI, body mass index. Spearman correlation analysis was used.

Figure 2 The correlation between serum AGR and BMI, other inflammation markers. (A) BMI, (B) ESR level, (C) CRP level, (D) WBC level of UC patients were shown by scatter plot; the correlation between serum AGR and (E) BMI, (F) ESR level, (G) CRP level, (H) WBC level of CD patients were shown by scatter plot.

Note: Spearman correlation analysis was used.

Table 4 Linear Regression Analysis of Serum AGR with Disease Activity in UC Patients

	Model 1^a	p-value	Model 2^b	p-value
	Standardized Coefficients β (95% CI)		Standardized Coefficients β (95% CI)
AGR	−0.411 (−5.083, −2.568)	< 0.001	− 0.244 (−4.119, −0.414)	0.017
AGR≤1.28	−0.352 (−2.485, −1.078)	< 0.001	− 0.196 (−1.865, −0.119)	0.026
CRP	0.267 (0.010, 0.033)	< 0.001	0.030 (−0.011, 0.016)	0.727
ESR	0.335 (0.029, 0.072)	< 0.001	0.132 (−0.007, 0.047)	0.139
WBC	0.220 (0.056, 0.273)	0.003	0.073 (−0.061, 0.170)	0.351
Ca^2+	−0.284 (−7.868, −2.611)	< 0.001	− 0.144 (−5.537, 0.214)	0.069

Note: Model 1^a: unadjusted. Model 2^b: adjusted for age, gender, BMI, current smoking, disease duration, disease extension, CRP, ESR, WBC, Ca²⁺.

Abbreviations: UC, ulcerative colitis; CI, confidence interval; BMI, body mass index; AGR, albumin to globulin ratio; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; WBC, white blood cell.

Table 5 Linear Regression Analysis of Serum AGR with Disease Activity in CD Patients

	Model 1^a	p-value	Model 2^b	p-value
	Standardized Coefficients β (95% CI)		Standardized Coefficients β (95% CI)
AGR	−0.430 (−5.772, −3.196)	< 0.001	−0.204 (−3.674, −0.581)	0.007
AGR≤1.24	−0.396 (−3.210, −1.666)	< 0.001	−0.162 (−1.844, −0.145)	0.022
CRP	0.523 (0.042, 0.066)	< 0.001	0.356 (0.022, 0.051)	< 0.001
ESR	0.431 (0.054, 0.097)	< 0.001	0.083 (−0.013, 0.042)	0.296
WBC	0.282 (0.210, 0.573)	< 0.001	0.040 (−0.114, 0.225)	0.517
Ca^2+	−0.186 (−7.852, −1.271)	0.007	−0.010 (−3.233, 2.756)	0.875

Note: Model 1^a: unadjusted. Model 2^b: adjusted for age, gender, BMI, current smoking, disease duration, disease localization, disease behavior, CRP, ESR, WBC, Ca²⁺.

Abbreviations: CD, Crohn’s disease; CI, confidence interval; BMI, body mass index; AGR, albumin to globulin ratio; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; WBC, white blood cell.

Figure 3 Distributions between serum AGR and endoscopic score in IBD patients. (A) Mayo endoscopic score in UC patients (0 or 1, n = 43; 2 or 3, n = 136), (B) SES-CD score in CD patients (0 or 1, n = 84; 2 or 3, n = 126). AGR was shown by binary ordered endoscopic disease activity, using a composite IBD endoscopy score (0 or 1 indicating inactive or mild disease and 2 or 3 indicating moderate or severe disease, respectively).

Note: **p < 0.01, ***p < 0.001. Student’s t-test.

Figure 4 Correlation between serum AGR and Mayo score in UC patients (A), HBI score in CD patients (B) by using a scatter plot.

Note: Spearman correlation analysis was used.

Figure 5 Receiver operator characteristic analysis of albumin to globulin ratio for distinguishing UC from non-UC (A) and CD from non-CD (B).

Figure 6 Multivariate adjusted odds ratios for distinguishing inflammatory bowel disease (UC and CD) from non-inflammatory bowel disease. Unadjusted^a: unadjusted model. Model 1^b: adjusted for age, sex. Model 2^c: adjusted for covariates from Model 1 and adjusted for BMI, current smoking, ESR, CRP, WBC, Ca²⁺.