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Diabetologia. 2019 Nov 14. doi: 10.1007/s00125-019-05028-z. [Epub ahead of print]

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

Author information

1
Faculty of Social Sciences/Health Sciences, Tampere University, Tampere, Finland.
2
Department of Public Health Solutions, National Institute for Health and Welfare, PO Box 30, FI-00271, Helsinki, Finland.
3
Department of Government Services, National Institute for Health and Welfare, Helsinki, Finland.
4
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
5
Department of Clinical Sciences, Lund University, Malmö, Sweden.
6
Institute of Diabetes Research, Helmholtz Zentrum München, Munich, Germany.
7
Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
8
Forschergruppe Diabetes e.V., Helmhtoltz Zentrum München, Munich, Germany.
9
Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
10
Pacific Northwest Research Institute, Seattle, WA, USA.
11
Department of Pediatrics, Turku University Hospital, Turku, Finland.
12
Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland.
13
Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO, USA.
14
Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO, USA.
15
Faculty of Social Sciences/Health Sciences, Tampere University, Tampere, Finland. suvi.virtanen@thl.fi.
16
Department of Public Health Solutions, National Institute for Health and Welfare, PO Box 30, FI-00271, Helsinki, Finland. suvi.virtanen@thl.fi.
17
Center for Child Health Research, Tampere University and Tampere University Hospital, Tampere, Finland. suvi.virtanen@thl.fi.
18
Science Centre, Tampere University Hospital, Tampere, Finland. suvi.virtanen@thl.fi.

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 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.

KEYWORDS:

Autoimmunity; Plasma ascorbic acid; SNP; Single nucleotide polymorphism; Transporter genes; Type 1 diabetes; Vitamin C

PMID:
31728565
DOI:
10.1007/s00125-019-05028-z

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