The Environmental Determinants of Diabetes in the Young (TEDDY) study: study design

Lernmark, Åke; Almgren, Peter; Aronsson, Carin Andrén; Andersson, Ellen; Svensson, Sylvia Bianconi; Carlsson, Ulla-Marie; Cilio, Corrado; Gerardsson, Joanna; Gustavsson, B.; Hansson, Anna; Hansson, Gertie; Jönsson, Ida; Ivarsson, Sten; Larsson, Helena; Karlsson, Elli; Παπαδοπούλου, Αναστασία; Lernmark, Barbro; Massadakis, Theodosia; Ramelius, Anita; Sedig-Järvirova, Monica; Sjöberg, Birgitta Janerot; Wallin, Anne; Wimar, Åsa

doi:10.1111/j.1399-5448.2007.00269.x

Cited by 279 publications

(185 citation statements)

References 64 publications

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“…The primary objective of TEDDY is to identify genetic, gestational, and environmental risk factors for islet autoantibodies, type 1 diabetes, or both in children at increased risk for type 1 diabetes on the basis of their two HLA haplotypes (HLA genotype). 3 Because the major HLA genotypes that confer a risk of type 1 diabetes also confer a risk of celiac disease, we explored the genetic and environmental contributions to the development of celiac disease autoimmunity and celiac disease in this cohort.…”

Section: Methodsmentioning

confidence: 99%

Risk of Pediatric Celiac Disease According to HLA Haplotype and Country

et al. 2014

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BACKGROUND 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). METHODS We studied 6403 children with HLA haplotype DR3–DQ2 or DR4–DQ8 prospectively from birth in the United States, Finland, Germany, and Sweden. The primary end point was the development of celiac disease autoimmunity, which was defined as the presence of tTG antibodies on two consecutive tests at least 3 months apart. The secondary end point was the development of celiac disease, which was defined for the purpose of this study as either a diagnosis on biopsy or persistently high levels of tTG antibodies. RESULTS The median follow-up was 60 months (interquartile range, 46 to 77). Celiac disease autoimmunity developed in 786 children (12%). Of the 350 children who underwent biopsy, 291 had confirmed celiac disease; an additional 21 children who did not undergo biopsy had persistently high levels of tTG antibodies. The risks of celiac disease autoimmunity and celiac disease by the age of 5 years were 11% and 3%, respectively, among children with a single DR3–DQ2 haplotype, and 26% and 11%, respectively, among those with two copies (DR3–DQ2 homozygosity). In the adjusted model, the hazard ratios for celiac disease autoimmunity were 2.09 (95% confidence interval [CI], 1.70 to 2.56) among heterozygotes and 5.70 (95% CI, 4.66 to 6.97) among homozygotes, as compared with children who had the lowest-risk genotypes (DR4–DQ8 heterozygotes or homozygotes). Residence in Sweden was also independently associated with an increased risk of celiac disease autoimmunity (hazard ratio, 1.90; 95% CI, 1.61 to 2.25). CONCLUSIONS Children with the HLA haplotype DR3–DQ2, especially homozygotes, were found to be at high risk for celiac disease autoimmunity and celiac disease early in childhood. The higher risk in Sweden than in other countries highlights the importance of studying environmental factors associated with celiac disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.)

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Section: Methodsmentioning

confidence: 99%

Risk of Pediatric Celiac Disease According to HLA Haplotype and Country

et al. 2014

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“…Written informed consent was obtained from the parents. The study was approved by the ethical committees of the participating sites [13]. …”

Section: Methodsmentioning

confidence: 99%

“…Exposure in children with a rapid progression to clinical diabetes may possibly take place at a higher dose or in a shorter time window before the appearance of islet autoimmunity. We therefore examined the history of infections and fever and analysed plasma samples by unbiased deep sequencing for the presence of viruses in the period around the initiation of islet autoimmunity in children who transitioned within 6 months from autoimmunity to disease in The Environmental Determinants of Diabetes in the Young (TEDDY) study [13]. …”

Section: Introductionmentioning

confidence: 99%

Next-generation sequencing for viruses in children with rapid-onset type 1 diabetes

Briese

Winkler

et al. 2013

Diabetologia

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Aims/hypothesis Viruses are candidate causative agents in the pathogenesis of autoimmune (type 1) diabetes. We hypothesised that children with a rapid onset of type 1 diabetes may have been exposed to such agents shortly before the initiation of islet autoimmunity, possibly at high dose, and thus study of these children could help identify viruses involved in the development of autoimmune diabetes. Methods We used next-generation sequencing to search for viruses in plasma samples and examined the history of infection and fever in children enrolled in The Environmental Determinants of Diabetes in the Young (TEDDY) study who progressed to type 1 diabetes within 6 months from the appearance of islet autoimmunity, and in matched islet-autoantibody-negative controls. Results Viruses were not detected more frequently in plasma from rapid-onset patients than in controls during the period surrounding seroconversion. In addition, infection histories were found to be similar between children with rapid-onset diabetes and control children, although episodes of fever were reported less frequently in children with rapid-onset diabetes. Conclusions/interpretation These findings do not support the presence of viraemia around the time of seroconversion in young children with rapid-onset type 1 diabetes.

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“…A multimember multinational epidemiological study, TEDDY 'The Environmental Determinants of Diabetes in the Young', is in progress to identify the infectious agents, dietary factors and other environmental factors associated with an increased risk of autoimmunity and T1D [45]. TEDDY is an observational cohort study in which newborns younger than 4 months and with the high-risk HLA alleles in the general population, or with firstdegree relatives who have T1D, are enrolled.…”

Section: Prospective Studiesmentioning

confidence: 99%

Enteroviruses and type 1 diabetes: towards a better understanding of the relationship

Jaïdane

Sauter

Sané

et al. 2010

Reviews in Medical Virology

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Environmental factors, especially viruses, are involved in the initiation or the acceleration of type 1 diabetes (T1D) pathogenesis. Epidemiological data strongly suggest that enteroviruses, such as coxsackievirus B4 (CV-B4), can be associated with T1D. It has been demonstrated that enterovirus infections were significantly more prevalent in at risk individuals, such as siblings of diabetic patients, when they developed anti-beta-cell autoantibodies or T1D, and in recently diagnosed diabetic patients, compared with control subjects. The isolation of CV-B4 from the pancreas of diabetic patients strengthened the hypothesis of a relationship between the virus and the disease. Studies performed in vitro and in vivo in animal models helped to discover mechanisms of the infection of pancreas and other tissues, potentially able to play a role in the pathogenesis of T1D. Interestingly, it cannot be excluded that enteroviruses behave as half-devil half-angel since experimental studies suggest that, in certain conditions, these agents would be able to protect individuals against the disease. All of the plausible mechanisms by which enterovirus may be related to T1D will be reviewed here.

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The Environmental Determinants of Diabetes in the Young (TEDDY) study: study design

Cited by 279 publications

References 64 publications

Risk of Pediatric Celiac Disease According to HLA Haplotype and Country

Risk of Pediatric Celiac Disease According to HLA Haplotype and Country

Next-generation sequencing for viruses in children with rapid-onset type 1 diabetes

Enteroviruses and type 1 diabetes: towards a better understanding of the relationship

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