| 1. |
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| 2. |
- Kim, Kwangwoo, et al.
(author)
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High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci
- 2015
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 74:3
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Journal article (peer-reviewed)abstract
- Objective A highly polygenic aetiology and high degree of allele-sharing between ancestries have been well elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. Methods We analysed Korean rheumatoid arthritis case-control samples using the Immunochip and genome-wide association studies (GWAS) array to search for new risk alleles of rheumatoid arthritis with anticitrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data for a total sample size of 9299 Korean and 45 790 European case-control samples. Results We identified eight new rheumatoid arthritis susceptibility loci (TNFSF4, LBH, EOMES, ETS1-FLI1, COG6, RAD51B, UBASH3A and SYNGR1) that passed a genome-wide significance threshold (p<5x10(-8)), with evidence for three independent risk alleles at 1q25/TNFSF4. The risk alleles from the seven new loci except for the TNFSF4 locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of single nucleotide polymorphisms (SNPs) that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs. Conclusions This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases.
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| 3. |
- Kim, Hye-Jin, et al.
(author)
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Diffusible hydrogen behavior and delayed fracture of cold rolled martensitic steel in consideration of automotive manufacturing process and vehicle service environment
- 2020
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In: Journal of Materials Research and Technology. - : Elsevier Editora Ltda. - 2238-7854. ; 9:6, s. 13483-13501
-
Journal article (peer-reviewed)abstract
- This study aims to elucidate the behavior of diffusible hydrogen and delayed fracture in martensitic steel with 1500 MPa strength during automotive painting process and under vehicle service conditions. A sequential process of automotive pretreatment line and vehicle service environment is simulated to evaluate the hydrogen pick up in each process. In case of the automotive painting line, the absorption of hydrogen is within the common range in the process of phosphating treatment and electrodeposition. The baking process plays an effective role for desorbing the diffusible hydrogen absorbed during the automotive pre-treatment such as zinc-phosphating, and electrodeposition process. In case of the corrosion environment under the automotive driving conditions, hydrogen induced delayed fracture is accelerated as the exposure time increases. Further, it is clarified that severe plastic deformation are the significant factors for hydrogen induced delayed fracture under with low pH value and present of chloride ion in a chemical solution parameter. In summary, hydrogen is transported constantly during electrodeposition sequential line process of automobile manufacturing below the hydrogen content of 0.5 ppm, which is not critical value for leading to hydrogen delayed fracture based on results of slow strain rate tensile tests. However, exposure to extreme conditions under service environment of vehicle, such as acidic solution and chloride chemistry solution that result in high level of hydrogen absorption, severe plastic deformation in the sheared edge, and constantly applied internal or external stresses, can cause the hydrogen induced delayed fracture in the fully martensitic steels. © 2020 The Authors
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| 4. |
- Agardh, Daniel, et al.
(author)
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Clinical Features of Celiac Disease: A Prospective Birth Cohort.
- 2015
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In: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 135:4, s. 627-634
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Journal article (peer-reviewed)abstract
- To investigate clinical features of celiac disease (CD) and their association with risk factors for CD in a genetic risk birth cohort.
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| 5. |
- Andrén Aronsson, Carin, et al.
(author)
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Age at Gluten Introduction and Risk of Celiac Disease.
- 2015
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In: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 135:2, s. 239-245
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Journal article (peer-reviewed)abstract
- The goal of this study was to determine whether age at introduction to gluten was associated with risk for celiac disease (CD) in genetically predisposed children.
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| 6. |
- Andrén Aronsson, Carin, et al.
(author)
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Association of gluten intake during the first 5 years of life with incidence of celiac disease autoimmunity and celiac disease among children at increased risk
- 2019
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In: JAMA - Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484. ; 322:6, s. 514-523
-
Journal article (peer-reviewed)abstract
- Importance: High gluten intake during childhood may confer risk of celiac disease. Objectives: To investigate if the amount of gluten intake is associated with celiac disease autoimmunity and celiac disease in genetically at-risk children. Design, Setting, and Participants: The participants in The Environmental Determinants of Diabetes in the Young (TEDDY), a prospective observational birth cohort study designed to identify environmental triggers of type 1 diabetes and celiac disease, were followed up at 6 clinical centers in Finland, Germany, Sweden, and the United States. Between 2004 and 2010, 8676 newborns carrying HLA antigen genotypes associated with type 1 diabetes and celiac disease were enrolled. Screening for celiac disease with tissue transglutaminase autoantibodies was performed annually in 6757 children from the age of 2 years. Data on gluten intake were available in 6605 children (98%) by September 30, 2017. Exposures: Gluten intake was estimated from 3-day food records collected at ages 6, 9, and 12 months and biannually thereafter until the age of 5 years. Main Outcomes and Measures: The primary outcome was celiac disease autoimmunity, defined as positive tissue transglutaminase autoantibodies found in 2 consecutive serum samples. The secondary outcome was celiac disease confirmed by intestinal biopsy or persistently high tissue transglutaminase autoantibody levels. Results: Of the 6605 children (49% females; median follow-up: 9.0 years [interquartile range, 8.0-10.0 years]), 1216 (18%) developed celiac disease autoimmunity and 447 (7%) developed celiac disease. The incidence for both outcomes peaked at the age of 2 to 3 years. Daily gluten intake was associated with higher risk of celiac disease autoimmunity for every 1-g/d increase in gluten consumption (hazard ratio [HR], 1.30 [95% CI, 1.22-1.38]; absolute risk by the age of 3 years if the reference amount of gluten was consumed, 28.1%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 34.2%; absolute risk difference, 6.1% [95% CI, 4.5%-7.7%]). Daily gluten intake was associated with higher risk of celiac disease for every 1-g/d increase in gluten consumption (HR, 1.50 [95% CI, 1.35-1.66]; absolute risk by age of 3 years if the reference amount of gluten was consumed, 20.7%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 27.9%; absolute risk difference, 7.2% [95% CI, 6.1%-8.3%]). Conclusions and Relevance: Higher gluten intake during the first 5 years of life was associated with increased risk of celiac disease autoimmunity and celiac disease among genetically predisposed children.
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| 7. |
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| 8. |
- Haghighi, Mona, et al.
(author)
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A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Journal article (peer-reviewed)abstract
- Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
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| 9. |
- Hagopian, William, et al.
(author)
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Co-occurrence of Type 1 Diabetes and Celiac Disease Autoimmunity
- 2017
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In: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 140:5
-
Journal article (peer-reviewed)abstract
- BACKGROUND AND OBJECTIVES: Few birth cohorts have prospectively followed development of type 1 diabetes (T1D) and celiac disease (CD) autoimmunities to determine timing, extent of co-occurrence, and associated genetic and demographic factors.METHODS: In this prospective birth cohort study, 8676 children at high genetic risk of both diseases were enrolled and 5891 analyzed in median follow-up of 66 months. Along with demographic factors and HLA-DR-DQ, genotypes for HLA-DPB1 and 5 non-HLA loci conferring risk of both T1D and CD were analyzed.RESULTS: Development of persistent islet autoantibodies (IAs) and tissue transglutaminase autoantibodies (tTGAs), as well as each clinical disease, was evaluated quarterly from 3 to 48 months of age and semiannually thereafter. IAs alone appeared in 367, tTGAs alone in 808, and both in 90 children. Co-occurrence significantly exceeded the expected rate. IAs usually, but not always, appeared earlier than tTGAs. IAs preceding tTGAs was associated with increasing risk of tTGAs (hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.15-1.91). After adjusting for country, sex, family history, and all other genetic loci, significantly greater co-occurrence was observed in children with a T1D family history (HR: 2.80), HLA-DR3/4 (HR: 1.94) and single-nucleotide polymorphism rs3184504 at SH2B3 (HR: 1.53). However, observed co-occurrence was not fully accounted for by all analyzed factors.CONCLUSIONS: In early childhood, T1D autoimmunity usually precedes CD autoimmunity. Preceding IAs significantly increases the risk of subsequent tTGAs. Co-occurrence is greater than explained by demographic factors and extensive genetic risk loci, indicating that shared environmental or pathophysiological mechanisms may contribute to the increased risk.
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| 10. |
- Hård af Segerstad, Elin M., et al.
(author)
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Daily intake of milk powder and risk of celiac disease in early childhood : A nested case-control study
- 2018
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In: Nutrients. - : MDPI AG. - 2072-6643. ; 10:5
-
Journal article (peer-reviewed)abstract
- Milk powder and gluten are common components in Swedish infants’ diets. Whereas large intakes of gluten early in life increases the risk of celiac disease in genetically at-risk Swedish children, no study has yet evaluated if intake of milk powder by 2 years of age is associated with celiac disease. A 1-to-3 nested case-control study, comprised of 207 celiac disease children and 621 controls matched for sex, birth year, and HLA genotype, was performed on a birth cohort of HLA-DR3-DQ2 and/or DR4-DQ8-positive children. Subjects were screened annually for celiac disease using tissue transglutaminase autoantibodies (tTGA). Three-day food records estimated the mean intake of milk powder at ages 6 months, 9 months, 12 months, 18 months, and 24 months. Conditional logistic regression calculated odds ratios (OR) at last intake prior to seroconversion of tTGA positivity, and for each time-point respectively and adjusted for having a first-degree relative with celiac disease and gluten intake. Intake of milk powder prior to seroconversion of tTGA positivity was not associated with celiac disease (OR = 1.00; 95% CI = 0.99, 1.03; p = 0.763). In conclusion, intake of milk powder in early childhood is not associated with celiac disease in genetically susceptible children.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Johnson, Suzanne Bennett, et al.
(author)
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The Environmental Determinants of Diabetes in the Young (TEDDY) Study: predictors of early study withdrawal among participants with no family history of type 1 diabetes.
- 2011
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In: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X. ; 12, s. 165-171
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Journal article (peer-reviewed)abstract
- Johnson SB, Lee H-S, Baxter J, Lernmark B, Roth R, Simell T for the TEDDY Study Group. The Environmental Determinants of Diabetes in the Young (TEDDY) Study: predictors of early study withdrawal among participants with no family history of type 1 diabetes. Objective: The Environmental Determinants of Diabetes in the Young (TEDDY) study seeks to identify environmental triggers of autoimmunity and type 1 diabetes mellitus (T1DM) in children at increased human-leukocyte-antigen conferred genetic risk for this disease. The objective of this study was to identify predictors of early withdrawal from TEDDY among families with no immediate family history of T1DM. Method: Logistic multiple regression was used to discriminate 2994 (83%) families currently active in the TEDDY study for ≥1 yr from 763 (17%) families who withdrew in the first year. Data collected on the screening form at the time of the child's birth and from interview and questionnaire data obtained at the baby's first study visit (at ≤4.5 months of age) were used. Results: Significant and independent predictors of early withdrawal included country of residence, young maternal age, no father participation, and female gender of the study participant. Mothers of children who withdrew were more likely to report smoking during pregnancy, abstaining from alcohol, and reducing their work hours or not working at all during pregnancy. Mothers who withdrew were also more likely to underestimate their child's risk for T1DM and fail to respond to multiple items on the enrollment questionnaires or interview. Among mothers with accurate risk perceptions, those experiencing high anxiety about their child's risk were more likely to be early withdrawals. Conclusions: Identifying families at high risk for study withdrawal at the time of enrollment allows for targeting these families with individually tailored plans to help maintain their participation in the study.
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| 15. |
- Koletzko, Sibylle, et al.
(author)
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Caesarean Section on The Risk of Celiac Disease in the Offspring : The Teddy Study
- 2018
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In: Journal of Pediatric Gastroenterology and Nutrition. - 0277-2116. ; 66:3, s. 417-424
-
Journal article (peer-reviewed)abstract
- OBJECTIVE:: Caesarean section (C-section) is associated with various immune-mediated diseases in the offspring. We investigated the relationship between mode of delivery and celiac disease (CD) and CD autoimmunity (CDA) in a multinational birth cohort. METHODS:: From 2004 to 2010 infants from the general population who tested positive for HLA DR3-DQ2 or DR4-DQ8 were enrolled in The Environmental Determinants for Diabetes in the Young (TEDDY) study. Children were annually screened for transglutaminase autoantibodies, if positive re-tested after 3–6 months and those persistently positive defined as CDA. Associations of C-section with maternal (age, education level, parity, pre-pregnancy weight, diabetes, smoking, weight gain during pregnancy) and child characteristics (gestational age, birth weight) were examined by Fisherʼs exact test or Wilcoxon rank-sum test. Hazard ratios (HRs) for CDA or CD were calculated by Cox proportional hazard regression models. RESULTS:: Of 6,087 analyzed singletons 1600 (26%) were born by C-section (Germany 38%, US 37%, Finland 18%, Sweden 16%), the remaining vaginally without instrumental support; 979 (16%) had developed CDA and 343 (6%) CD. C-section was associated with lower risk for CDA (HR?=?0.85, [95% CI 0.73, 0.99], p?=?0.032) and CD (HR?=?0.75, [95% CI 0.58, 0.98], p?=?0.034). After adjusting for country, sex, HLA-genotype, CD in family, maternal education and breastfeeding duration, significance was lost for CDA (HR?=?0.91, [95% CI 0.78, 1.06], p?=?0.20) and CD (HR?=?0.85, [95% CI 0.65, 1.11], p?=?0.24). Pre-surgical ruptured membranes had no influence on CDA or CD development. CONCLUSION:: C-section is not associated with increased risk for CDA or CD in the offspring.
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| 16. |
- Lee, Hye-Seung, et al.
(author)
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Biomarker discovery study design for type 1 diabetes in The Environmental Determinants of Diabetes in the Young (TEDDY) study
- 2014
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In: Diabetes/Metabolism Research & Reviews. - : Wiley. - 1520-7552. ; 30:5, s. 424-434
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Journal article (peer-reviewed)abstract
- Aims The Environmental Determinants of Diabetes in the Young planned biomarker discovery studies on longitudinal samples for persistent confirmed islet cell autoantibodies and type 1 diabetes using dietary biomarkers, metabolomics, microbiome/viral metagenomics and gene expression. Methods This article describes the details of planning The Environmental Determinants of Diabetes in the Young biomarker discovery studies using a nested case-control design that was chosen as an alternative to the full cohort analysis. In the frame of a nested case-control design, it guides the choice of matching factors, selection of controls, preparation of external quality control samples and reduction of batch effects along with proper sample allocation. Results and conclusion Our design is to reduce potential bias and retain study power while reducing the costs by limiting the numbers of samples requiring laboratory analyses. It also covers two primary end points (the occurrence of diabetes-related autoantibodies and the diagnosis of type 1 diabetes). The resulting list of case-control matched samples for each laboratory was augmented with external quality control samples. Copyright (C) 2013 John Wiley & Sons, Ltd.
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| 17. |
- Lindfors, Katri, et al.
(author)
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Metagenomics of the faecal virome indicate a cumulative effect of enterovirus and gluten amount on the risk of coeliac disease autoimmunity in genetically at risk children : The TEDDY study
- 2020
-
In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 69:8, s. 1416-1422
-
Journal article (peer-reviewed)abstract
- Objective: Higher gluten intake, frequent gastrointestinal infections and adenovirus, enterovirus, rotavirus and reovirus have been proposed as environmental triggers for coeliac disease. However, it is not known whether an interaction exists between the ingested gluten amount and viral exposures in the development of coeliac disease. This study investigated whether distinct viral exposures alone or together with gluten increase the risk of coeliac disease autoimmunity (CDA) in genetically predisposed children. Design: The Environmental Determinants of Diabetes in the Young study prospectively followed children carrying the HLA risk haplotypes DQ2 and/or DQ8 and constructed a nested case-control design. From this design, 83 CDA case-control pairs were identified. Median age of CDA was 31 months. Stool samples collected monthly up to the age of 2 years were analysed for virome composition by Illumina next-generation sequencing followed by comprehensive computational virus profiling. Results: The cumulative number of stool enteroviral exposures between 1 and 2 years of age was associated with an increased risk for CDA. In addition, there was a significant interaction between cumulative stool enteroviral exposures and gluten consumption. The risk conferred by stool enteroviruses was increased in cases reporting higher gluten intake. Conclusions: Frequent exposure to enterovirus between 1 and 2 years of age was associated with increased risk of CDA. The increased risk conferred by the interaction between enteroviruses and higher gluten intake indicate a cumulative effect of these factors in the development of CDA.
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| 18. |
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| 19. |
- Liu, Edwin, et al.
(author)
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Risk of pediatric celiac disease according to HLA haplotype and country.
- 2014
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In: New England Journal of Medicine. - 0028-4793. ; 371:1, s. 42-49
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Journal article (peer-reviewed)abstract
- The presence of HLA haplotype DR3-DQ2 or DR4-DQ8 is associated with an increased risk of celiac disease. In addition, nearly all children with celiac disease have serum antibodies against tissue transglutaminase (tTG).
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| 20. |
- Lundgren, Markus, et al.
(author)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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In: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
-
Journal article (peer-reviewed)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 21. |
- Lynch, Kristian F., et al.
(author)
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Gestational respiratory infections interacting with offspring HLA and CTLA-4 modifies incident β-cell autoantibodies
- 2018
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In: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411. ; 86, s. 93-103
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Journal article (peer-reviewed)abstract
- β-cell autoantibodies against insulin (IAA), GAD65 (GADA) and IA-2 (IA-2A) precede onset of childhood type 1 diabetes (T1D). Incidence of the first appearing β-cell autoantibodies peaks at a young age and is patterned by T1D-associated genes, suggesting an early environmental influence. Here, we tested if gestational infections and interactions with child's human leukocyte antigen (HLA) and non-HLA genes affected the appearance of the first β-cell autoantibody. Singletons of mothers without diabetes (n = 7472) with T1D-associated HLA-DR-DQ genotypes were prospectively followed quarterly through the first 4 years of life, then semiannually until age 6 years, using standardized autoantibody analyses. Maternal infections during pregnancy were assessed via questionnaire 3-4.5 months post-delivery. Polymorphisms in twelve non-HLA genes associated with the first appearing β-cell autoantibodies were included in a Cox regression analysis. IAA predominated as the first appearing β-cell autoantibody in younger children (n = 226, median age at seroconversion 1.8 years) and GADA (n = 212; 3.2 years) in children aged ≥2 years. Gestational infections were not associated with the first appearing β-cell autoantibodies overall. However, gestational respiratory infections (G-RI) showed a consistent protective influence on IAA (HR 0.64, 95% CI 0.45-0.91) among CTLA4-(AG, GG) children (G-RI*. CTLA4 interaction, p = 0.002). The predominant associations of HLA-DR-DQ 4-8/8-4 with IAA and HLA-DR-DQ 3-2/3-2 with GADA were not observed if a G-RI was reported (G-RI*HLA-DR-DQ interaction, p = 0.03). The role of G-RI may depend on offspring HLA and CTLA-4 alleles and supports a bidirectional trigger for IAA or GADA as a first appearing β-cell autoantibody in early life.
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| 22. |
- Mattila, Markus, et al.
(author)
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Plasma ascorbic acid and the risk of islet autoimmunity and type 1 diabetes : the TEDDY study
- 2020
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 63:2, s. 278-286
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Journal article (peer-reviewed)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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| 23. |
- Niinistö, Sari, et al.
(author)
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Children's erythrocyte fatty acids are associated with the risk of islet autoimmunity
- 2021
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Journal article (peer-reviewed)abstract
- Our aim was to investigate the associations between erythrocyte fatty acids and the risk of islet autoimmunity in children. The Environmental Determinants of Diabetes in the Young Study (TEDDY) is a longitudinal cohort study of children at high genetic risk for type 1 diabetes (n = 8676) born between 2004 and 2010 in the U.S., Finland, Sweden, and Germany. A nested case-control design comprised 398 cases with islet autoimmunity and 1178 sero-negative controls matched for clinical site, family history, and gender. Fatty acids composition was measured in erythrocytes collected at the age of 3, 6, and 12 months and then annually up to 6 years of age. Conditional logistic regression models were adjusted for HLA risk genotype, ancestry, and weight z-score. Higher eicosapentaenoic and docosapentaenoic acid (n - 3 polyunsaturated fatty acids) levels during infancy and conjugated linoleic acid after infancy were associated with a lower risk of islet autoimmunity. Furthermore, higher levels of some even-chain saturated (SFA) and monounsaturated fatty acids (MUFA) were associated with increased risk. Fatty acid status in early life may signal the risk for islet autoimmunity, especially n - 3 fatty acids may be protective, while increased levels of some SFAs and MUFAs may precede islet autoimmunity.
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| 24. |
- Norris, Jill M., et al.
(author)
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Plasma 25-Hydroxyvitamin D concentration and risk of islet autoimmunity
- 2018
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 67:1, s. 146-154
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Journal article (peer-reviewed)abstract
- We examined the association between plasma 25- hydroxyvitamin D [25(OH)D] concentration and islet autoimmunity (IA) and whether vitamin D gene polymorphisms modify the effect of 25(OH)D on IA risk. We followed 8,676 children at increased genetic risk of type 1 diabetes at six sites in the U.S. and Europe. We defined IA as positivity for at least one autoantibody (GADA, IAA, or IA-2A) on two or more visits. We conducted a risk set sampled nested casecontrol study of 376 IA case subjects and up to 3 control subjects per case subject. 25(OH)D concentrationwas measured on all samples prior to, and including, the first IA positive visit. Nine polymorphisms in VDR, CYP24A, CYP27B1, GC, and RXRA were analyzed as effect modifiers of 25(OH)D. Adjusting for HLA-DR-DQ and ancestry, higher childhood 25(OH)D was associated with lower IA risk (odds ratio = 0.93 for a 5 nmol/L difference; 95% CI 0.89, 0.97). Moreover, this association was modified by VDR rs7975232 (interaction P = 0.0072), where increased childhood 25(OH)D was associated with a decreasing IA risk based upon number of minor alleles: 0 (1.00; 0.93, 1.07), 1 (0.92; 0.89, 0.96), and 2 (0.86; 0.80, 0.92). Vitamin D and VDR may have a combined role in IA development in children at increased genetic risk for type 1 diabetes.
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| 25. |
- Salami, Falastin, et al.
(author)
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Reduction in White Blood Cell, Neutrophil, and Red Blood Cell Counts Related to Sex, HLA, and Islet Autoantibodies in Swedish TEDDY Children at Increased Risk for Type 1 Diabetes
- 2018
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In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 67:11, s. 2329-2336
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Journal article (peer-reviewed)abstract
- Islet autoantibodies (IAs) precede the clinical onset of type 1 diabetes (T1D); however, the knowledge is limited about whether the prodrome affects complete blood counts (CBCs) in 4- to 12-year-old children with increased genetic risk for T1D. This study tested whether CBCs were altered in 4- to 12-year-old children without (n = 376) or with one or several IAs against insulin, GAD65, or IA-2 (n = 72). CBC was analyzed during longitudinal follow-up in 448 Swedish children enrolled in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A linear mixed-effects model was used to assess potential association between IA and CBC measurements over time. The white blood cell and neutrophil counts were reduced in children with IAs, primarily in boys. In contrast, girls had lower levels of hemoglobin and hematocrit. Positivity for multiple IAs showed the lowest counts in white blood cells and neutrophils in boys and red blood cells, hemoglobin, and hematocrit in girls. These associations were primarily observed in children with the HLA-DR3-DQ2/DR4-DQ8 genotype. We conclude that the reduction in neutrophils and red blood cells in children with multiple IAs and HLA-DR3-DQ2/DR4-DQ8 genotype may signal a sex-dependent islet autoimmunity detected in longitudinal CBCs.
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