Plasma ascorbic acid and the risk of islet autoimmunity and type 1 diabetes: the TEDDY study.
Autoimmunity
Plasma ascorbic acid
SNP
Single nucleotide polymorphism
Transporter genes
Type 1 diabetes
Vitamin C
Journal
Diabetologia
ISSN: 1432-0428
Titre abrégé: Diabetologia
Pays: Germany
ID NLM: 0006777
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
09
05
2019
accepted:
03
09
2019
pubmed:
16
11
2019
medline:
2
2
2021
entrez:
16
11
2019
Statut:
ppublish
Résumé
We studied the association of plasma ascorbic acid with the risk of developing islet autoimmunity and type 1 diabetes and examined whether SNPs in vitamin C transport genes modify these associations. Furthermore, we aimed to determine whether the SNPs themselves are associated with the risk of islet autoimmunity or type 1 diabetes. We used a risk set sampled nested case-control design within an ongoing international multicentre observational study: The Environmental Determinants of Diabetes in the Young (TEDDY). The TEDDY study followed children with increased genetic risk from birth to endpoints of islet autoantibodies (350 cases, 974 controls) and type 1 diabetes (102 cases, 282 controls) in six clinical centres. Control participants were matched for family history of type 1 diabetes, clinical centre and sex. Plasma ascorbic acid concentration was measured at ages 6 and 12 months and then annually up to age 6 years. SNPs in vitamin C transport genes were genotyped using the ImmunoChip custom microarray. Comparisons were adjusted for HLA genotypes and for background population stratification. Childhood plasma ascorbic acid (mean ± SD 10.76 ± 3.54 mg/l in controls) was inversely associated with islet autoimmunity risk (adjusted OR 0.96 [95% CI 0.92, 0.99] per +1 mg/l), particularly islet autoimmunity, starting with insulin autoantibodies (OR 0.94 [95% CI 0.88, 0.99]), but not with type 1 diabetes risk (OR 0.93 [95% Cl 0.86, 1.02]). The SLC2A2 rs5400 SNP was associated with increased risk of type 1 diabetes (OR 1.77 [95% CI 1.12, 2.80]), independent of plasma ascorbic acid (OR 0.92 [95% CI 0.84, 1.00]). Higher plasma ascorbic acid levels may protect against islet autoimmunity in children genetically at risk for type 1 diabetes. Further studies are warranted to confirm these findings. The datasets generated and analysed during the current study will be made available in the NIDDK Central Repository at https://www.niddkrepository.org/studies/teddy.
Identifiants
pubmed: 31728565
doi: 10.1007/s00125-019-05028-z
pii: 10.1007/s00125-019-05028-z
pmc: PMC6946743
doi:
Substances chimiques
Glucose Transporter Type 2
0
SLC2A2 protein, human
0
Ascorbic Acid
PQ6CK8PD0R
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
278-286Subventions
Organisme : NIDDK NIH HHS
ID : U01 DK063821
Pays : United States
Organisme : NIDDK NIH HHS
ID : UC4 DK063863
Pays : United States
Organisme : NIDDK NIH HHS
ID : UC4 DK117483
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK063863
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000064
Pays : United States
Organisme : NIDDK NIH HHS
ID : UC4 DK106955
Pays : United States
Organisme : NIDDK NIH HHS
ID : UC4 DK100238
Pays : United States
Organisme : NLM NIH HHS
ID : HHSN267200700014C
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001082
Pays : United States
Organisme : NIDDK NIH HHS
ID : UC4 DK112243
Pays : United States
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