Factors influencing diagnostic delays in celiac disease

Table 1 Baseline characteristics of patients with celiac disease, n (%)

Measures	Diagnosed within 2 years (n = 93)	Delayed diagnosis group
		Diagnosed within 2-5 years (n = 42)	Diagnosed over 5 years (n = 31)	P value
Gender				0.485
Female	66 (71.0)	31 (73.8)	19 (61.3)
Male	27 (29.0)	11 (26.2)	12 (38.7)
Ethnicity				0.241
Han	17 (18.3)	12 (28.6)	5 (16.1)
Uygur	30 (32.3)	17 (40.5)	13 (41.9)
Kazak	41 (44.1)	10 (23.8)	13 (41.9)
Other ethnic	5 (5.4)	3 (7.1)	0 (0.0)
tTG (CU), M (P25, P75)	928.1 (45.4, 2279.2)	243.4 (32.1, 1254.6)	1082.5 (82.7, 1988.5)	0.745
BMI (kg/m2), M (P25, P75)	20.6 (18.7, 24.7)	22.3 (20.2, 25.1)	22.7 (19.1, 25.3)	0.874
First onset of symptoms to visit (months), M (P25, P75)	1 (0.6, 15)	12.3 (2, 36)	12 (1, 21)	< 0.001
First visit to diagnosis (months), M (P25, P75)	0 (0, 0)	20.6 (0, 24)	96 (60, 114)	< 0.001
Patients with comorbidities	15 (16.1)	5 (11.9)	2 (6.5)	0.371
Patients without comorbidities	78 (83.9)	37 (88.1)	29 (93.5)
Non-classical CeD	15 (16.1)	9 (21.4)	4 (12.9)	0.605
Classical CeD	78 (83.9)	33 (78.6)	27 (87.1)
Number of hospitalizations ≤ 3	85 (91.4)	33 (78.6)	19 (61.3)	< 0.001
Number of hospitalizations > 3	8 (8.6)	9 (21.4)	12 (38.7)
Age at diagnosis				0.046
≤ 45 years old	48 (51.6)	14 (33.3)	9 (29.0)
45-60 years old	37 (39.8)	23 (54.8)	21 (67.7)
> 60 years old	8 (8.6)	5 (11.9)	1 (3.2)
Age of onset				0.308
≤ 45 years old	33 (35.5)	11 (26.2)	9 (29.0)
45-55	37 (39.8)	13 (31.0)	13 (41.9)
> 55 years old	23 (24.7)	18 (42.9)	9 (29.0)
Education	31 (33.3)	13 (31.0)	10 (32.3)	0.826
Below junior high school
High school	37 (39.8)	21 (50.0)	13 (41.9)
Bachelor's degree or above	25 (26.9)	8 (19.0)	8 (25.8)
Job	44 (47.3)	18 (42.9)	14 (45.2)	0.888
Freelance
Contract	49 (52.7)	24 (57.1)	17 (54.8)
Pathology	51 (54.8)	25 (59.5)	18 (58.1)	0.865
Marsh II
Marsh III	42 (45.2)	17 (40.5)	13 (41.9)

tTG: The anti-tissue transglutaminase; BMI: Body mass index; CeD: Celiac disease.

Table 2 Univariate and multivariate regression analyses of diagnostic delays in patients with celiac disease, mean ± SD

Measures	Diagnosed within 2 years	Delayed diagnosis group		Univariate regression analysis, OR (95%CI), P value	Multivariate regression analysis, OR (95%CI), P value
		Diagnosed within 2-5 years	Diagnosed over 5 years
Age at diagnosis	46.8 ± 13.1	51.3 ± 14.2	49.6 ± 10.3	1.02 (1.00-1.05), P = 0.063	1.01 (0.98-1.04), P = 0.554
Leukocytes	6.4 ± 1.9	5.6 ± 1.6	6.1 ± 1.8	0.83 (0.70-0.99), P = 0.042	0.83 (0.68-1.00), P = 0.051
Hemoglobin	119.6 ± 23.6	121.8 ± 23.1	118.2 ± 28.4	1.00 (0.99-1.01), P = 0.856
Total protein	68.7 ± 10.5	68.1 ± 9.9	65.8 ± 9.5	0.98 (0.95-1.01), P = 0.307
Serum calcium	2.1 ± 0.2	2.2 ± 0.2	2.2 ± 0.2	3.85 (0.76-19.45), P = 0.103	1.44 (0.23-8.80), P = 0.696
Thyroid stimulating hormone	4.0 ± 5.0	3.1 ± 2.4	3.5 ± 4.6	0.96 (0.89-1.04), P = 0.295
Blood urea nitrogen	4.0 ± 1.4	4.7 ± 1.7	4.9 ± 2.1	1.37 (1.10-1.71), P = 0.005	1.29 (1.01-1.65), P = 0.038
Serum iron	8.2 ± 3.1	10.5 ± 5.5	10.4 ± 9.3	1.10 (1.02-1.19), P = 0.016	1.07 (1.00-1.15), P = 0.063

Table 3 Association between blood urea nitrogen levels and delayed diagnosis of celiac disease

Model	OR	95%CI	P value
1	1.37	1.12-1.73	0.005
2	1.34	1.07-1.72	0.015
3	1.37	1.09-1.78	0.013
4	1.42	1.09-1.91	0.015

Model 1: Unadjusted covariates. Model 2: Adjusted for age, sex, and body mass index. Model 3: Adjusted for age, sex, body mass index, presence or absence of vitamin D deficiency, presence or absence of anemia, and presence or absence of thyroid disease. Model 4: Age, sex, body mass index, presence or absence of vitamin D deficiency, presence or absence of anemia, and presence or absence of thyroid disease. Model 4: Adjusted for age, sex, body mass index, presence or absence of vitamin D deficiency, presence or absence of anemia, presence or absence of thyroid disease, white blood cells, creatinine, albumin, and serum iron.

Table 4 Characteristics of patients with celiac disease based on blood urea nitrogen tertiles, mean ± SD/M (P₂₅, P₇₅)/n (%)

Indicators	Q1	Q2	Q3	P value
Gender				0.004
Female	48 (84.2)	38 (69.1)	30 (55.6)
Male	9 (15.8)	17 (30.9)	24 (44.4)
Ethnicity				0.001
Han	5 (8.8)	13 (23.6)	16 (29.6)
Uygur	17 (29.8)	18 (32.7)	25 (46.3)
Kazak	30 (52.6)	24 (43.6)	10 (18.5)
Other ethnic	5 (8.8)	0 (0.0)	3 (5.6)
tTG (CU)	769.3 (29, 1896.5)	967.4 (71.7, 2673.4)	263.2 (38.8, 1660)	0.639
BMI (kg/m2)	20.1 (18.4, 24.2)	21.9 (19, 24.1)	22.5 (20, 25.9)	0.705
First onset of symptoms to visit (months)	1 (0.5, 12)	3 (1, 12)	6 (1, 12.3)	0.514
First visit to diagnosis (months)	0 (0, 1)	0 (0, 18)	14 (0, 48)	0.002
Patients with comorbidities (%)	11 (19.3)	7 (12.7)	4 (7.4)	0.18
Patients without comorbidities	46 (80.7)	48 (87.3)	50 (92.6)
Non-classical CeD	5 (8.8)	10 (18.2)	13 (24.1)	0.094
Classical CeD	52 (91.2)	45 (81.8)	41 (75.9)
Number of hospitalizations ≤ 3	48 (84.2)	49 (89.1)	40 (74.1)	0.109
Number of hospitalizations > 3	9 (15.8)	6 (10.9)	14 (25.9)
Age at diagnosis	43.89 ± 11.78	47.67 ± 12.79	54.02 ± 12.67	< 0.001
Age of onset	42.85 ± 12.74	46.95 ± 12.87	52.70 ± 13.52	0.001
Education				0.636
Below junior high school	19 (33.3)	15 (27.3)	20 (37.0)
High school	22 (38.6)	28 (50.9)	21 (38.9)
Bachelor's degree or above	16 (28.1)	12 (21.8)	13 (24.1)
Job				0.031
Freelance	19 (33.3)	32 (58.2)	25 (46.3)
Contract	38 (66.7)	23 (41.8)	29 (53.7)
Pathology				0.438
Marsh II	29 (50.9)	31 (56.4)	34 (63.0)
Marsh III	28 (49.1)	24 (43.6)	20 (37.0)

tTG: The anti-tissue transglutaminase; BMI: Body mass index; CeD: Celiac disease.

Table 5 Two-stage analysis of the association between blood urea nitrogen levels and delayed diagnosis of celiac disease

BUN	OR	95%CI	P value
BUN or less tendency for 4.3 mmol/L	0.67	0.23-1.93	0.44
BUN > tendency for 4.3 mmol/L	1.39	1.04-1.99	0.04

BUN: Blood urea nitrogen.

Table 6 Effect of each stratification factor on the relationship between blood urea nitrogen and delayed diagnosis

Variables	OR	95%CI	P value
Gender
Female	1.49	1.11-1.99	0.008
Male	1.26	0.88-1.8	0.206
Age (year)
< 45	1.26	0.89-1.69	0.197
45-65	1.67	0.91-3.06	0.099
> 65	1.24	0.88-1.75	0.215
Typing
Non-classical celiac disease	3.71	1.38-9.95	0.009
Classic celiac disease	1.26	1.01-1.57	0.042
Ethnic groups
Han nationality	1.45	0.8-2.65	0.224
Uygur	1.17	0.9-1.53	0.245
Kazak	1.64	1.02-2.64	0.040
Other ethnic	3.24	0.6-17.35	0.171
Combined vitamin D deficiency
No vitamin D deficiency	1.57	1.19-2.09	0.002
Have a vitamin D deficiency	0.86	0.53-1.38	0.528
Presence of anemia
No anemia	1.76	1.25-2.48	0.001
Having anemia	1.07	0.82-1.4	0.613
Number of hospitalizations
≤ 3	1.65	0.9-3.05	0.107
> 3	1.31	1.02-1.67	0.032
Level of education
Below junior high school	1.74	1.13-2.68	0.012
High school	1.2	0.83-1.75	0.339
Bachelor's degree or above	1.26	0.88-1.82	0.208
Job
Freelance	1.49	1.03-2.15	0.032
Contract	1.32	1-1.75	0.052
Pathology
Marsh II	1.29	0.98-1.7	0.073
Marsh III	1.5	1.05-2.16	0.027