Pandemrix® vaccination is not associated with increased risk of islet autoimmunity or type 1 diabetes in the TEDDY study children

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.

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Primary Dietary Intervention Study to Reduce the Risk of Islet Autoimmunity in Children at Increased Risk for Type 1 Diabetes: The BABYDIET study

Diabetes Care ◽

10.2337/dc10-2456 ◽

2011 ◽

Vol 34 (6) ◽

pp. 1301-1305 ◽

Cited By ~ 141

Author(s):

S. Hummel ◽

M. Pfluger ◽

M. Hummel ◽

E. Bonifacio ◽

A.-G. Ziegler

Keyword(s):

Type 1 Diabetes ◽

Intervention Study ◽

Dietary Intervention ◽

Islet Autoimmunity ◽

Dietary Intervention Study ◽

Increased Risk

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Evidence of Stage- and Age-Related Heterogeneity of Non-HLA SNPs and Risk of Islet Autoimmunity and Type 1 Diabetes: The Diabetes Autoimmunity Study in the Young

Clinical and Developmental Immunology ◽

10.1155/2013/417657 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 16

Author(s):

Brittni N. Frederiksen ◽

Andrea K. Steck ◽

Miranda Kroehl ◽

Molly M. Lamb ◽

Randall Wong ◽

...

Keyword(s):

Type 1 Diabetes ◽

Cox Regression ◽

Islet Autoimmunity ◽

Candidate Snps ◽

Age Related ◽

Increased Risk ◽

Restricted Cubic Splines ◽

Candidate Loci ◽

Hispanic White

Previously, we examined 20 non-HLA SNPs for association with islet autoimmunity (IA) and/or progression to type 1 diabetes (T1D). Our objective was to investigate fourteen additional non-HLA T1D candidate SNPs for stage- and age-related heterogeneity in the etiology of T1D. Of 1634 non-Hispanic white DAISY children genotyped, 132 developed IA (positive for GAD, insulin, or IA-2 autoantibodies at two or more consecutive visits); 50 IA positive children progressed to T1D. Cox regression was used to analyze risk of IA and progression to T1D in IA positive children. Restricted cubic splines were used to model SNPs when there was evidence that risk was not constant with age.C1QTNF6(rs229541) predicted increased IA risk (HR: 1.57, CI: 1.20–2.05) but not progression to T1D (HR: 1.13, CI: 0.75–1.71). SNP (rs10517086) appears to exhibit an age-related effect on risk of IA, with increased risk before age 2 years (age 2 HR: 1.67, CI: 1.08–2.56) but not older ages (age 4 HR: 0.84, CI: 0.43–1.62).C1QTNF6(rs229541), SNP (rs10517086), andUBASH3A(rs3788013) were associated with development of T1D. This prospective investigation of non-HLA T1D candidate loci shows that some SNPs may exhibit stage- and age-related heterogeneity in the etiology of T1D.

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Omega-3 Polyunsaturated Fatty Acid Intake and Islet Autoimmunity in Children at Increased Risk for Type 1 Diabetes

JAMA ◽

10.1001/jama.298.12.1420 ◽

2007 ◽

Vol 298 (12) ◽

pp. 1420 ◽

Cited By ~ 182

Author(s):

Jill M. Norris ◽

Xiang Yin ◽

Molly M. Lamb ◽

Katherine Barriga ◽

Jennifer Seifert ◽

...

Keyword(s):

Type 1 Diabetes ◽

Fatty Acid ◽

Polyunsaturated Fatty Acid ◽

Islet Autoimmunity ◽

Fatty Acid Intake ◽

Omega 3 ◽

Acid Intake ◽

Increased Risk

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Gluten Intake and Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in Children at Increased Risk of the Disease: The Diabetes Autoimmunity Study in the Young (DAISY)

Diabetes Care ◽

10.2337/dc18-2315 ◽

2019 ◽

Vol 42 (5) ◽

pp. 789-796 ◽

Cited By ~ 13

Author(s):

Nicolai A. Lund-Blix ◽

Fran Dong ◽

Karl Mårild ◽

Jennifer Seifert ◽

Anna E. Barón ◽

...

Keyword(s):

Type 1 Diabetes ◽

Islet Autoimmunity ◽

Increased Risk

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Consumption of differently processed milk products in infancy and early childhood and the risk of islet autoimmunity

British Journal Of Nutrition ◽

10.1017/s0007114520000744 ◽

2020 ◽

Vol 124 (2) ◽

pp. 173-180

Author(s):

Katariina Koivusaari ◽

Essi Syrjälä ◽

Sari Niinistö ◽

Hanna-Mari Takkinen ◽

Suvi Ahonen ◽

...

Keyword(s):

Type 1 Diabetes ◽

Fermented Milk ◽

Population Based ◽

Food Composition ◽

Islet Autoimmunity ◽

Milk Consumption ◽

Milk Products ◽

Increased Risk ◽

Fermented Milk Products

AbstractSeveral prospective studies have shown an association between cows’ milk consumption and the risk of islet autoimmunity and/or type 1 diabetes. We wanted to study whether processing of milk plays a role. A population-based birth cohort of 6081 children with HLA-DQB1-conferred risk to type 1 diabetes was followed until the age of 15 years. We included 5545 children in the analyses. Food records were completed at the ages of 3 and 6 months and 1, 2, 3, 4 and 6 years, and diabetes-associated autoantibodies were measured at 3–12-month intervals. For milk products in the food composition database, we used conventional and processing-based classifications. We analysed the data using a joint model for longitudinal and time-to-event data. By the age of 6 years, islet autoimmunity developed in 246 children. Consumption of all cows’ milk products together (energy-adjusted hazard ratio 1·06; 95 % CI 1·02, 1·11; P = 0·003), non-fermented milk products (1·06; 95 % CI 1·01, 1·10; P = 0·011) and fermented milk products (1·35; 95 % CI 1·10, 1·67; P = 0·005) was associated with an increased risk of islet autoimmunity. The early milk consumption was not associated with the risk beyond 6 years. We observed no clear differences based on milk homogenisation and heat treatment. Our results are consistent with the previous studies, which indicate that high milk consumption may cause islet autoimmunity in children at increased genetic risk. The study did not identify any specific type of milk processing that would clearly stand out as a sole risk factor apart from other milk products.

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