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Plasma ascorbic acid and the risk of islet autoimmunity and type 1 diabetes : the TEDDY study

Mattila, Markus ; Erlund, Iris ; Lee, Hye Seung ; Niinistö, Sari ; Uusitalo, Ulla ; Andrén Aronsson, Carin LU ; Hummel, Sandra ; Parikh, Hemang LU ; Rich, Stephen S. and Hagopian, William , et al. (2020) In Diabetologia 63(2). p.278-286
Abstract

Aims/hypothesis: 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. Methods: 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... (More)

Aims/hypothesis: 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. Methods: 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. Results: 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]). Conclusions/interpretation: 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. Data availability: 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.

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published
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keywords
Autoimmunity, Plasma ascorbic acid, Single nucleotide polymorphism, SNP, Transporter genes, Type 1 diabetes, Vitamin C
in
Diabetologia
volume
63
issue
2
pages
278 - 286
publisher
Springer
external identifiers
  • scopus:85075252645
  • pmid:31728565
ISSN
0012-186X
DOI
10.1007/s00125-019-05028-z
language
English
LU publication?
yes
id
6c5570c9-1815-4877-98c0-14bbee5df421
date added to LUP
2019-12-11 12:26:56
date last changed
2020-03-12 03:00:26
@article{6c5570c9-1815-4877-98c0-14bbee5df421,
  abstract     = {<p>Aims/hypothesis: 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. Methods: 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. Results: 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]). Conclusions/interpretation: 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. Data availability: 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.</p>},
  author       = {Mattila, Markus and Erlund, Iris and Lee, Hye Seung and Niinistö, Sari and Uusitalo, Ulla and Andrén Aronsson, Carin and Hummel, Sandra and Parikh, Hemang and Rich, Stephen S. and Hagopian, William and Toppari, Jorma and Lernmark, Åke and Ziegler, Anette G. and Rewers, Marian and Krischer, Jeffrey P. and Norris, Jill M. and Virtanen, Suvi M.},
  issn         = {0012-186X},
  language     = {eng},
  number       = {2},
  pages        = {278--286},
  publisher    = {Springer},
  series       = {Diabetologia},
  title        = {Plasma ascorbic acid and the risk of islet autoimmunity and type 1 diabetes : the TEDDY study},
  url          = {http://dx.doi.org/10.1007/s00125-019-05028-z},
  doi          = {10.1007/s00125-019-05028-z},
  volume       = {63},
  year         = {2020},
}