Introduction: Celiac disease (CD)-related antibody positivity in children with type 1 diabetes (T1D) may fluctuate and become negative spontaneously. There are uncertainties about the optimal tissue transglutaminase IgA (tTG-IgA) titre and timing of endoscopy in the diagnosis of CD, and this study aimed to contribute to the debate on the tTG-IgA threshold titre for endoscopy decisions in children with T1D. Methods: The data of 991 children with T1D who had undergone serologic evaluation for CD were analysed retrospectively. The tTG-IgA positivity rate and the upper limit of normal (ULN) tTG-IgA positivity were assessed. Participants were grouped according to the frequency, course, and test results of tTG-IgA tests. Those with and without histopathologic diagnosis of CD by endoscopic biopsy were compared in terms of tTG-IgA screening time and tTG-IgA predictive values. Results: In 10.2% (n:101) of all cases, tTG-IgA antibody was positive and endoscopic biopsy was performed in 68.3% (n:69) of these cases. Of all cases, 4.3% (n:43) were diagnosed with CD by endoscopic biopsy. A tTG-IgA titre of 7×ULN and above was found to be the best predictive value for the diagnosis of CD with 79.1% sensitivity, 80.8% specificity 87.2% positive predictive value, and 70% negative predictive value. Conclusions: Approximately 10% of antibody positive cases showed fluctuating and low-titre positivity, and no CD was detected by endoscopic biopsy in the group with fluctuating antibody course. The results of our study suggest that endoscopy in children with tTG-IgA levels 7×ULN or above may prevent both false-positive results and missed cases.

1.
Knip
M
.
Similarities and dissimilarities between type 1 diabetes and coeliac disease
.
Acta Paediatr
.
2023
;
112
(
10
):
2030
1
.
2.
Craig
ME
,
Prinz
N
,
Boyle
CT
,
Campbell
FM
,
Jones
TW
,
Hofer
SE
, et al
.
Prevalence of celiac disease in 52,721 youth with type 1 diabetes: international comparison across three continents
.
Diabetes Care
.
2017
;
40
(
8
):
1034
40
.
3.
Pham-Short
ADK
,
Donaghue
KC
,
Ambler
G
,
Chan
AK
,
Craig
ME
.
Coeliac disease in type 1 diabetes from 1990 to 2009: higher incidence in young children after longer diabetes duration
.
Diabet Med
.
2012
;
29
(
9
):
e286
9
.
4.
Pham-Short
A
,
Donaghue
KC
,
Ambler
G
,
Phelan
H
,
Twigg
S
,
Craig
ME
.
Screening for celiac disease in type 1 diabetes: a systematic review
.
Pediatrics
.
2015
;
136
(
1
):
e170
6
.
5.
Taczanowska
A
,
Schwandt
A
,
Amed
S
,
Tóth-Heyn
P
,
Kanaka-Gantenbein
C
,
Volsky
SK
, et al
.
Celiac disease in children with type 1 diabetes varies around the world: an international, cross-sectional study of 57 375 patients from the SWEET registry
.
J Diabetes
.
2021
;
13
(
6
):
448
57
.
6.
Fröhlich-Reiterer
E
,
Elbarbary
NS
,
Simmons
K
,
Buckingham
B
,
Humayun
KN
,
Johannsen
J
, et al
.
ISPAD Clinical Practice Consensus Guidelines 2022: other complications and associated conditions in children and adolescents with type 1 diabetes
.
Pediatr Diabetes
.
2022
;
23
(
8
):
1451
67
.
7.
Gülcü Taşkın
D
,
Ata
A
.
The screening of celiac serology in pediatric patients diagnosed with type 1 diabetes mellitus
.
Turk J Gastroenterol
.
2023
;
34
(
3
):
293
7
.
8.
Unal
E
,
Demiral
M
,
Baysal
B
,
Ağın
M
,
Devecioğlu
EG
,
Demirbilek
H
, et al
.
Frequency of celiac disease and spontaneous normalization rate of celiac serology in children and adolescent patients with type 1 diabetes
.
J Clin Res Pediatr Endocrinol
.
2021
;
13
(
1
):
72
9
.
9.
Sari
S
,
Yeşilkaya
E
,
Eğritaş
O
,
Bideci
A
,
Cinaz
P
,
Dalgiç
B
.
Prevalence of Celiac disease in Turkish children with type 1 diabetes mellitus and their non-diabetic first-degree relatives
.
Turk J Gastroenterol
.
2010
;
21
(
1
):
34
8
.
10.
Simsek
DG
,
Aycan
Z
,
Özen
S
,
Cetinkaya
S
,
Kara
C
,
Abalı
S
, et al
.
Diabetes care, glycemic control, complications, and concomitant autoimmune diseases in children with type 1 diabetes in Turkey: a multicenter study
.
J Clin Res Pediatr Endocrinol
.
2013
;
5
(
1
):
20
6
.
11.
Husby
S
,
Koletzko
S
,
Korponay-Szabó
I
,
Kurppa
K
,
Mearin
ML
,
Ribes-Koninckx
C
, et al
.
European society paediatric Gastroenterology, Hepatology and nutrition guidelines for diagnosing coeliac disease 2020
.
J Pediatr Gastroenterol Nutr
.
2020
;
70
(
1
):
141
56
.
12.
Castellaneta
S
,
Piccinno
E
,
Oliva
M
,
Cristofori
F
,
Vendemiale
M
,
Ortolani
F
, et al
.
High rate of spontaneous normalization of celiac serology in a cohort of 446 children with type 1 diabetes: a prospective study
.
Diabetes Care
.
2015
;
38
(
5
):
760
6
.
13.
Hatun
Ş
,
Dalgıç
B
,
Gökşen
D
,
Aydoğdu
S
,
Savaş Erdeve
Ş
,
Kuloğu
Z
, et al
.
Recommendations for clinical decision-making in children with type 1 diabetes and celiac disease: type 1 diabetes and celiac disease joint working group report
.
J Clin Res Pediatr Endocrinol
.
2022
;
14
(
1
):
1
9
.
14.
Wessels
M
,
Velthuis
A
,
van Lochem
E
,
Duijndam
E
,
Hoorweg-Nijman
G
,
de Kruijff
I
, et al
.
Raising the cut-off level of anti-tissue transglutaminase antibodies to detect celiac disease reduces the number of small bowel biopsies in children with type 1 diabetes: a retrospective study
.
J Pediatr
.
2020
;
223
:
87
92.e1
.
15.
Kamrath
C
,
Tittel
SR
,
Dunstheimer
D
,
Fröhlich-Reiterer
E
,
Freff
M
,
Böttcher
C
, et al
.
Early vs late histological confirmation of coeliac disease in children with new-onset type 1 diabetes
.
Diabetologia
.
2022
;
65
(
7
):
1108
18
.
16.
Marsh
MN
.
Mucosal pathology in gluten sensitivity
. In:
Marsh
MN
, editor.
Coeliac disease
.
Oxford
:
Blackwell Scientific Publications
;
1992
. p.
136
.
17.
Stahl
M
,
Koletzko
S
,
Andrén Aronsson
C
,
Lindfors
K
;
TEDDY Study Group
,
Liu
E
,
Agardh
D
, et al
.
Coeliac disease: what can we learn from prospective studies about disease risk
.
Lancet Child Adolesc Health
.
2024
;
8
(
1
):
63
74
.
18.
Guandalini
S
.
The when, why and whom to biopsy of type 1 diabetes mellitus children with positive anti-tissue transglutaminase serology
.
Saudi J Gastroenterol
.
2023
;
29
(
5
):
257
8
.
19.
O’Donnell
HK
,
Rasmussen
CG
,
Dong
F
,
Simmons
KM
;
ASK Study Group
;
Steck
AK
,
Frohnert
BI
, et al
.
Anxiety and risk perception in parents of children identified by population screening as high risk for type 1 diabetes
.
Diabetes Care
.
2023
;
46
(
12
):
2155
61
.
20.
Slae
M
,
Romem
A
,
Edri
S
,
Toker
O
,
Wilschanski
M
,
Strich
D
.
Celiac disease and celiac antibodies in DM1 patients: when are screening and biopsy recommended
.
Dig Dis Sci
.
2019
;
64
(
2
):
487
92
.
21.
Hagopian
W
,
Lee
HS
,
Liu
E
,
Rewers
M
;
TEDDY Study Group
;
She
JX
,
Ziegler
AG
, et al
.
Co-Occurrence of type 1 diabetes and celiac disease autoimmunity
.
Pediatrics
.
2017
;
140
(
5
):
e20171305
.
22.
Goodwin
G
.
Type 1 diabetes mellitus and celiac disease: distinct autoimmune disorders that share common pathogenic mechanisms
.
Horm Res Paediatr
.
2019
;
92
(
5
):
285
92
.
23.
Li Voon Chong
JS
,
Leong
KS
,
Wallymahmed
M
,
Sturgess
R
,
MacFarlane
IA
.
Is coeliac disease more prevalent in young adults with coexisting Type 1 diabetes mellitus and autoimmune thyroid disease compared with those with Type 1 diabetes mellitus alone
.
Diabet Med
.
2002
;
19
(
4
):
334
7
.
24.
Waisbourd-Zinman
O
,
Hojsak
I
,
Rosenbach
Y
,
Mozer-Glassberg
Y
,
Shalitin
S
,
Phillip
M
, et al
.
Spontaneous normalization of anti-tissue transglutaminase antibody levels is common in children with type 1 diabetes mellitus
.
Dig Dis Sci
.
2012
;
57
(
5
):
1314
20
.
25.
Krauthammer
A
,
Guz-Mark
A
,
Zevit
N
,
Marderfeld
L
,
Waisbourd-Zinman
O
,
Silbermintz
A
, et al
.
Age-dependent trends in the celiac disease: a tertiary center experience
.
J Pediatr Gastroenterol Nutr
.
2021
;
72
(
6
):
894
9
.
26.
Kurppa
K
,
Laitinen
A
,
Agardh
D
.
Coeliac disease in children with type 1 diabetes
.
Lancet Child Adolesc Health
.
2018
;
2
(
2
):
133
43
.
27.
Agardh
D
,
Lee
HS
,
Kurppa
K
,
Simell
V
;
TEDDY Study Group
,
Aronsson
CA
,
Jörneus
O
, et al
.
Clinical features of celiac disease: a prospective birth cohort
.
Pediatrics
.
2015
;
135
(
4
):
627
34
.
28.
Cerutti
F
,
Bruno
G
,
Chiarelli
F
,
Lorini
R
,
Meschi
F
,
Sacchetti
C
.
Younger age at onset and sex predict celiac disease in children and adolescents with type 1 diabetes
.
Diabetes Care
.
2004
;
27
(
6
):
1294
8
.
29.
Fröhlich-Reiterer
EE
,
Kaspers
S
,
Hofer
S
,
Schober
E
,
Kordonouri
O
,
Pozza
SBD
, et al
.
Anthropometry, metabolic control, and follow-up in children and adolescents with type1 diabetes mellitus and biopsy-proven celiac disease
.
J Pediatr
.
2011
;
158
(
4
):
589
93.e2
.
30.
Wilkes
M
,
Graber
E
,
Rapaport
R
.
Screening for celiac disease in youth with type 1 diabetes: are current recommendations adequate
.
J Diabetes
.
2021
;
13
(
6
):
525
6
.
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