Skip to main content

The Environmental Determinants of Diabetes in the Young (TEDDY) Study: 2018 Update

Abstract

Purpose of Review

The environmental triggers of islet autoimmunity leading to type 1 diabetes (T1D) need to be elucidated to inform primary prevention. The Environmental Determinants of Diabetes in the Young (TEDDY) Study follows from birth 8676 children with T1D risk HLA-DR-DQ genotypes in the USA, Finland, Germany, and Sweden. Most study participants (89%) have no first-degree relative with T1D. The primary outcomes include the appearance of one or more persistent islet autoantibodies (islet autoimmunity, IA) and clinical T1D.

Recent Findings

As of February 28, 2018, 769 children had developed IA and 310 have progressed to T1D. Secondary outcomes include celiac disease and autoimmune thyroid disease. While the follow-up continues, TEDDY has already evaluated a number of candidate environmental triggers, including infections, probiotics, micronutrient, and microbiome.

Summary

TEDDY results suggest that there are multiple pathways leading to the destruction of pancreatic beta-cells. Ongoing measurements of further specific exposures, gene variants, and gene-environment interactions and detailed “omics” studies will provide novel information on the pathogenesis of T1D.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Group DERI. Secular trends in incidence of childhood IDDM in 10 countries. Diabetes. 1990;39(7):858–64.

    Article  Google Scholar 

  2. Patterson CC, Dahlquist GG, Gyurus E, Green A, Soltesz G. Incidence trends for childhood type 1 diabetes in Europe during 1989-2003 and predicted new cases 2005–20: a multicentre prospective registration study. Lancet. 2009;373(9680):2027–33.

    PubMed  Article  Google Scholar 

  3. Mayer-Davis EJ, Lawrence JM, Dabelea D, Divers J, Isom S, Dolan L, et al. Incidence trends of type 1 and type 2 diabetes among youths, 2002–2012. N Engl J Med. 2017;376(15):1419–29.

    PubMed  PubMed Central  Article  Google Scholar 

  4. National Center for Chronic Disease Prevention and Health Promotion DoDT. National diabetes statistics report, 2017. Estimates of diabetes and its burden in the United States. 2017. http://www.diabetes.org/assets/pdfs/basics/cdc-statistics-report-2017.pdf.

  5. Rewers M, Ludvigsson J. Environmental risk factors for type 1 diabetes. Lancet. 2016;387(10035):2340–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  6. TEDDY Study Group. The Environmental Determinants of Diabetes in the Young (TEDDY) study: study design. Pediatr Diabetes. 2007;8(5):286–98.

    Article  Google Scholar 

  7. TEDDY Study Group. The Environmental Determinants of Diabetes in the Young (TEDDY) study. Ann N Y Acad Sci. 2008;1150:1–13.

    PubMed Central  Article  Google Scholar 

  8. Lonnrot M, Lynch KF, Elding Larsson H, et al. Respiratory infections are temporally associated with initiation of type 1 diabetes autoimmunity: the TEDDY study. Diabetologia. 2017;60(10):1931–40. TEDDY reports that respiratory infections increase the risk of islet autoimmunity in young children. Islet autoimmunity developed in 454 out of 7869 high-risk children followed from birth. Each infection in a 9-month period increased the subsequent risk of autoimmunity by 6%.

    PubMed  PubMed Central  Article  Google Scholar 

  9. Uusitalo U, Liu X, Yang J, Aronsson CA, Hummel S, Butterworth M, et al. Association of early exposure of probiotics and islet autoimmunity in the TEDDY study. JAMA Pediatr. 2016;170(1):20–8.

    PubMed  PubMed Central  Article  Google Scholar 

  10. Uusitalo U, Lee HS, Andren Aronsson C, et al. Early infant diet and islet autoimmunity in the TEDDY study. Diabetes Care. 2018;41(3):522–30.

    PubMed  Article  PubMed Central  Google Scholar 

  11. Lundgren M, Steed LJ, Tamura R, et al. Analgesic antipyretic use among young children in the TEDDY study: no association with islet autoimmunity. BMC Pediatr. 2017;17(1):127.

    PubMed  PubMed Central  Article  Google Scholar 

  12. Ziegler AG, Pflueger M, Winkler C, Achenbach P, Akolkar B, Krischer JP, et al. Accelerated progression from islet autoimmunity to diabetes is causing the escalating incidence of type 1 diabetes in young children. J Autoimmun. 2011;37(1):3–7.

    PubMed  PubMed Central  Article  Google Scholar 

  13. Hummel S, Beyerlein A, Tamura R, Uusitalo U, Andrén Aronsson C, Yang J, et al. First infant formula type and risk of islet autoimmunity in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Diabetes Care. 2017;40(3):398–404.

    PubMed  PubMed Central  Article  Google Scholar 

  14. Elding Larsson H, Vehik K, Haller MJ, Liu X, Akolkar B, Hagopian W, et al. Growth and risk for islet autoimmunity and progression to type 1 diabetes in early childhood: The Environmental Determinants of Diabetes in the Young study. Diabetes. 2016;65(7):1988–95.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  15. Elding Larsson H, Lynch KF, Lonnrot M, et al. Pandemrix(R) vaccination is not associated with increased risk of islet autoimmunity or type 1 diabetes in the TEDDY study children. Diabetologia. 2018;61(1):193–202.

    CAS  PubMed  Article  Google Scholar 

  16. Beyerlein A, Liu X, Uusitalo UM, Harsunen M, Norris JM, Foterek K, et al. Dietary intake of soluble fiber and risk of islet autoimmunity by 5 y of age: results from the TEDDY study. Am J Clin Nutr. 2015;102(2):345–52.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. Torn C, Hadley D, Lee HS, et al. Role of type 1 diabetes-associated SNPs on risk of autoantibody positivity in the TEDDY study. Diabetes. 2015;64(5):1818–29.

    PubMed  Article  CAS  Google Scholar 

  18. Torn C, Liu X, Hagopian W, et al. Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY study. Sci Rep. 2016;6:27887.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  19. Sharma A, Liu X, Hadley D, Hagopian W, Chen WM, Onengut-Gumuscu S, et al. Identification of non-HLA genes associated with development of islet autoimmunity and type 1 diabetes in the prospective TEDDY cohort. J Autoimmun. 2018;89:90–100.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  20. Krischer JP, Liu X, Lernmark A, Hagopian WA, Rewers MJ, She JX, et al. The influence of type 1 diabetes genetic susceptibility regions, age, sex, and family history on the progression from multiple autoantibodies to type 1 diabetes: a TEDDY study report. Diabetes. 2017;66(12):3122–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  21. Bonifacio E, Beyerlein A, Hippich M, Winkler C, Vehik K. Genetic scores to stratify risk of developing multiple islet autoantibodies and type 1 diabetes: a prospective study in children. PLoS Med. 2018;15(4):e1002548.

    PubMed  PubMed Central  Article  Google Scholar 

  22. Norris JM, Lee HS, Frederiksen B, Erlund I, Uusitalo U, Yang J, et al. Plasma 25-hydroxyvitamin D concentration and risk of islet autoimmunity. Diabetes. 2018;67(1):146–54. TEDDY provides evidence for a protective effect of higher plasma vitamin D levels for development of islet autoimmunity in high-risk children. However, this protective effect is limited to children who carry specific vitamin D receptor genotypes.

    CAS  PubMed  Article  Google Scholar 

  23. Lynch KF, Lee HS, Torn C, et al. Gestational respiratory infections interacting with offspring HLA and CTLA-4 modifies incident beta-cell autoantibodies. J Autoimmun. 2018;86:93–103.

    CAS  PubMed  Article  Google Scholar 

  24. Krischer JP, Lynch KF, Lernmark A, Hagopian WA, Rewers MJ, She JX, et al. Genetic and environmental interactions modify the risk of diabetes-related autoimmunity by 6 years of age: the TEDDY study. Diabetes Care. 2017;40(9):1194–202. TEDDY demonstrates an apparent heterogeneity of type 1 diabetes and the underlying genetic and environmental determinants.

    PubMed  PubMed Central  Article  Google Scholar 

  25. Russell CD, Baillie JK. Treatable traits and therapeutic targets: goals for systems biology in infectious disease. Curr Opin Syst Biol. 2017;2:140–6.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Hagopian WA, Erlich H, Lernmark A, Rewers M, Ziegler AG, Simell O, et al. The environmental determinants of diabetes in the young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants. Pediatr Diabetes. 2011;12(8):733–43.

    PubMed  PubMed Central  Article  Google Scholar 

  27. Cucca F, Lampis R, Frau F, Macis D, Angius E, Masile P, et al. The distribution of DR4 haplotypes in Sardinia suggests a primary association of type I diabetes with DRB1 and DQB1 loci. Hum Immunol. 1995;43(4):301–8.

    CAS  PubMed  Article  Google Scholar 

  28. Erlich HA, Valdes AM, Noble JA. Prediction of type 1 diabetes. Diabetes. 2013;62(4):1020–1.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  29. Insel RA, Dunne JL, Atkinson MA, Chiang JL, Dabelea D, Gottlieb PA, et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care. 2015;38(10):1964–74.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  30. Vehik K, Fiske SW, Logan CA, Agardh D, Cilio CM, Hagopian W, et al. Methods, quality control and specimen management in an international multicentre investigation of type 1 diabetes: TEDDY. Diabetes Metab Res Rev. 2013;29(7):557–67.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care. 2017;40(Suppl 1):S11–24.

    Article  Google Scholar 

  32. Elding Larsson H, Vehik K, Gesualdo P, Akolkar B, Hagopian W, Krischer J, et al. Children followed in the TEDDY study are diagnosed with type 1 diabetes at an early stage of disease. Pediatr Diabetes. 2014;15(2):118–26.

    PubMed  Article  Google Scholar 

  33. Elding Larsson H, Vehik K, Bell R, Dabelea D, Dolan L, Pihoker C, et al. Reduced prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes in young children participating in longitudinal follow-up. Diabetes Care. 2011;34(11):2347–52.

    PubMed  PubMed Central  Article  Google Scholar 

  34. Steck AK, Larsson HE, Liu X, Veijola R, Toppari J, Hagopian WA, et al. Residual beta-cell function in diabetes children followed and diagnosed in the TEDDY study compared to community controls. Pediatr Diabetes. 2017;18(8):794–802.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  35. Harjutsalo V, Sund R, Knip M, Groop PH. Incidence of type 1 diabetes in Finland. JAMA. 2013;310(4):427–8.

    CAS  PubMed  Article  Google Scholar 

  36. Bendas A, Rothe U, Kiess W, Kapellen TM, Stange T, Manuwald U, et al. Trends in incidence rates during 1999-2008 and prevalence in 2008 of childhood type 1 diabetes mellitus in Germany—model-based national estimates. PLoS One. 2015;10(7):e0132716.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  37. Hanberger L, Birkebaek N, Bjarnason R, Drivvoll AK, Johansen A, Skrivarhaug T, et al. Childhood diabetes in the Nordic countries: a comparison of quality registries. J Diabetes Sci Technol. 2014;8(4):738–44.

    PubMed  PubMed Central  Article  Google Scholar 

  38. Lee HS, Briese T, Winkler C, et al. Next-generation sequencing for viruses in children with rapid-onset type 1 diabetes. Diabetologia. 2013;56(8):1705–11.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  39. Vehik K, Lynch KF, Schatz DA, Akolkar B, Hagopian W, Rewers M, et al. Reversion of beta-cell autoimmunity changes risk of type 1 diabetes: TEDDY study. Diabetes Care. 2016;39(9):1535–42.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  40. Steck AK, Vehik K, Bonifacio E, Lernmark A, Ziegler AG, Hagopian WA, et al. Predictors of progression from the appearance of islet autoantibodies to early childhood diabetes: The Environmental Determinants of Diabetes in the Young (TEDDY). Diabetes Care. 2015;38(5):808–13.

    PubMed  PubMed Central  Article  Google Scholar 

  41. Yu L, Dong F, Miao D, Fouts AR, Wenzlau JM, Steck AK. Proinsulin/insulin autoantibodies measured with electrochemiluminescent assay are the earliest indicator of prediabetic islet autoimmunity. Diabetes Care. 2013;36(8):2266–70.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  42. Yu LZ, Miao D, Waugh K, Jiang L, Steck A, Liu L, et al. Electrochemiluminescence-based IAA and GADA assays detect the appearance of islet autoimmunity earlier than radioimmunoassay in a significant proportion of children. San Francisco: Immunology of Diabetes Society; 2017.

    Google Scholar 

  43. Kohler M, Beyerlein A, Vehik K, et al. Joint modeling of longitudinal autoantibody patterns and progression to type 1 diabetes: results from the TEDDY study. Acta Diabetol. 2017;54(11):1009–17.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  44. Ilonen J, Hammais A, Laine AP, Lempainen J, Vaarala O, Veijola R, et al. Patterns of beta-cell autoantibody appearance and genetic associations during the first years of life. Diabetes. 2013;62(10):3636–40.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  45. Ziegler AG, Bonifacio E. Age-related islet autoantibody incidence in offspring of patients with type 1 diabetes. Diabetologia. 2012;55(7):1937–43.

    CAS  PubMed  Article  Google Scholar 

  46. Ziegler AG, Hummel M, Schenker M, Bonifacio E. Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB study. Diabetes. 1999;48(3):460–8.

    CAS  PubMed  Article  Google Scholar 

  47. Hagopian WA, Sanjeevi CB, Kockum I, Landin-Olsson M, Karlsen AE, Sundkvist G, et al. Glutamate decarboxylase-, insulin-, and islet cell-antibodies and HLA typing to detect diabetes in a general population-based study of Swedish children. J Clin Invest. 1995;95(4):1505–11.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  48. Krischer JP, Lynch KF, Schatz DA, et al. The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study. Diabetologia. 2015;58(5):980–7.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. de Goffau MC, Luopajarvi K, Knip M, Ilonen J, Ruohtula T, Harkonen T, et al. Fecal microbiota composition differs between children with beta-cell autoimmunity and those without. Diabetes. 2013;62:1238–44.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  50. Parkes M, Cortes A, van Heel DA, Brown MA. Genetic insights into common pathways and complex relationships among immune-mediated diseases. Nat Rev Genet. 2013;14(9):661–73.

    CAS  PubMed  Article  Google Scholar 

  51. Cooper JD, Howson JM, Smyth D, et al. Confirmation of novel type 1 diabetes risk loci in families. Diabetologia. 2012;55(4):996–1000.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  52. Stanford SM, Bottini N. PTPN22: the archetypal non-HLA autoimmunity gene. Nat Rev Rheumatol. 2014;10(10):602–11.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  53. Roepstorff K, Grovdal L, Grandal M, Lerdrup M, van Deurs B. Endocytic downregulation of ErbB receptors: mechanisms and relevance in cancer. Histochem Cell Biol. 2008;129(5):563–78.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  54. Muller D, Telieps T, Eugster A, et al. Novel minor HLA DR associated antigens in type 1 diabetes. Clin Immunol. 2018;194:87–91.

    PubMed  Article  CAS  Google Scholar 

  55. Bian X, Wasserfall C, Wallstrom G, Wang J, Wang H, Barker K, et al. Tracking the antibody immunome in type 1 diabetes using protein arrays. J Proteome Res. 2017;16(1):195–203.

    CAS  PubMed  Article  Google Scholar 

  56. Ziegler AG, Danne T, Dunger DB, Berner R, Puff R, Kiess W, et al. Primary prevention of beta-cell autoimmunity and type 1 diabetes—the Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) perspectives. Mol Metab. 2016;5(4):255–62.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  57. Hommel A, Haupt F, Delivani P, Winkler C, Stopsack M, Wimberger P, et al. Screening for type 1 diabetes risk in newborns: the Freder1k pilot study in Saxony. Horm Metab Res. 2018;50(1):44–9.

    CAS  PubMed  Article  Google Scholar 

  58. Lonnrot M, Lynch K, Larsson HE, et al. A method for reporting and classifying acute infectious diseases in a prospective study of young children: TEDDY. BMC Pediatr. 2015;15:24.

    PubMed  PubMed Central  Article  Google Scholar 

  59. Kemppainen KM, Lynch KF, Liu E, Lönnrot M, Simell V, Briese T, et al. Factors that increase risk of celiac disease autoimmunity after a gastrointestinal infection in early life. Clin Gastroenterol Hepatol. 2017;15(5):694–702.e695.

    PubMed  Article  Google Scholar 

  60. Kemppainen KM, Vehik K, Lynch KF, Larsson HE, Canepa RJ, Simell V, et al. Association between early-life antibiotic use and the risk of islet or celiac disease autoimmunity. JAMA Pediatr. 2017;171(12):1217–25.

    PubMed  PubMed Central  Article  Google Scholar 

  61. Salami F, Abels M, Hyoty H, et al. Detection of Latobacilli in monthly mail-in stool samples from 3–18 months old infants at genetic risk for type 1 diabetes. Int Journal of Probiotics Prebiotics. 2012;7(3–4):135–44.

    CAS  Google Scholar 

  62. Stewart CJ, Ajami NJ, O’Brien JL, et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature. 2018;563.

  63. Vatanen T, Franzosa EA, Schwager R, et al. The human gut microbiome of early onset type 1 diabetes from the TEDDY study. Nature. 2018;563.

  64. Sioofy-Khojine A-B, Oikarinen S, Honkanen H, Huhtala H, Lehtonen JP, Briese T, et al. Molecular epidemiology of enteroviruses in young children at increased risk of type 1 diabetes. PLoS One. 2018;13:e0201959.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  65. Nurminen N, Oikarinen S, Hyoty H. Virus infections as potential targets of preventive treatments for type 1 diabetes. Rev Diabet Stud. 2012;9(4):260–71.

    PubMed  Article  Google Scholar 

  66. Uusitalo U, Kronberg-Kippila C, Aronsson CA, Schakel S, Schoen S, Mattisson I, et al. Food composition database harmonization for between-country comparisons of nutrient data in the TEDDY study. J Food Compost Anal. 2011;24(4–5):494–505.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  67. Joslowski G, Yang J, Aronsson CA, Ahonen S, Butterworth M, Rautanen J, et al. Development of a harmonized food grouping system for between-country comparisons in the TEDDY study. J Food Compost Anal. 2017;63:79–88.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  68. Aronsson CA, Vehik K, Yang J, Uusitalo U, Hay K, Joslowski G, et al. Use of dietary supplements in pregnant women in relation to sociodemographic factors—a report from The Environmental Determinants of Diabetes in the Young (TEDDY) study. Public Health Nutr. 2013;16(8):1390–402.

    PubMed  PubMed Central  Article  Google Scholar 

  69. Andren Aronsson C, Uusitalo U, Vehik K, et al. Age at first introduction to complementary foods is associated with sociodemographic factors in children with increased genetic risk of developing type 1 diabetes. Matern Child Nutr. 2015;11(4):803–14.

    PubMed  Article  Google Scholar 

  70. Hummel S, Vehik K, Uusitalo U, McLeod W, Aronsson CA, Frank N, et al. Infant feeding patterns in families with a diabetes history—observations from The Environmental Determinants of Diabetes in the Young (TEDDY) birth cohort study. Public Health Nutr. 2014;17(12):2853–62.

    PubMed  Article  Google Scholar 

  71. Yang J, Tamura RN, Uusitalo UM, Aronsson CA, Silvis K, Riikonen A, et al. Vitamin D and probiotics supplement use in young children with genetic risk for type 1 diabetes. Eur J Clin Nutr. 2017;71(12):1449–54.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  72. Niinistö SEI, Lee H-S, Uusitalo U, Salminen I, Aronsson CA, Hummel S, et al. Higher EPA and DPA status in erythrocyte during infancy is associated with reduced risk of islet autoimmunity. San Francisco: Immunologu of Diabetes Society; 2017.

    Google Scholar 

  73. Hyppönen E, Virtanen SM, Kenward MG, Knip M, Akerblom HK, Childhood Diabetes in Finland Study Group. Obesity, increased linear growth, and risk of type 1 diabetes in children. Diabetes Care. 2000;23(12):1755–60.

  74. Knip M, Reunanen A, Virtanen SM, Nuutinen M, Viikari J, Akerblom HK. Does the secular increase in body mass in children contribute to the increasing incidence of type 1 diabetes? Pediatr Diabetes. 2008;9(3 Pt 2):46–9.

    PubMed  Article  Google Scholar 

  75. Wilkin TJ. The accelerator hypothesis: weight gain as the missing link between type I and type II diabetes. Diabetologia. 2001;44(7):914–22.

    CAS  PubMed  Article  Google Scholar 

  76. Dahlquist G. Can we slow the rising incidence of childhood-onset autoimmune diabetes? The overload hypothesis. Diabetologia. 2006;49(1):20–4.

    CAS  PubMed  Article  Google Scholar 

  77. Hagopian W, Lee HS, Liu E, Rewers M, She JX, Ziegler AG, et al. Co-occurrence of type 1 diabetes and celiac disease autoimmunity. Pediatrics. 2017;140(5):e20171305.

    PubMed  Article  Google Scholar 

  78. Liu E, Lee HS, Aronsson CA, Hagopian WA, Koletzko S, Rewers MJ, et al. Risk of pediatric celiac disease according to HLA haplotype and country. N Engl J Med. 2014;371(1):42–9.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  79. Agardh D, Lee HS, Kurppa K, Simell V, Aronsson CA, Jorneus O, et al. Clinical features of celiac disease: a prospective birth cohort. Pediatrics. 2015;135(4):627–34.

    PubMed  PubMed Central  Article  Google Scholar 

  80. Sharma A, Liu X, Hadley D, Hagopian W, Liu E, Chen WM, et al. Identification of non-HLA genes associated with celiac disease and country-specific differences in a large, international pediatric cohort. PLoS One. 2016;11(3):e0152476.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  81. Hadley D, Hagopian W, Liu E, et al. HLA-DPB1*04:01 protects genetically susceptible children from celiac disease autoimmunity in the TEDDY study. Am J Gastroenterol. 2015;110(6):915–20.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  82. Andren Aronsson C, Lee HS, Koletzko S, et al. Effects of gluten intake on risk of celiac disease: a case-control study on a Swedish birth cohort. Clin Gastroenterol Hepatol. 2016;14(3):403–409.e403.

    CAS  PubMed  Article  Google Scholar 

  83. Aronsson CA, Lee HS, Liu E, Uusitalo U, Hummel S, Yang J, et al. Age at gluten introduction and risk of celiac disease. Pediatrics. 2015;135(2):239–45.

    PubMed  PubMed Central  Article  Google Scholar 

  84. Johnson SB, Lynch KF, Roth R, Schatz D. My child is islet autoantibody positive: impact on parental anxiety. Diabetes Care. 2017;40(9):1167–72.

    PubMed  PubMed Central  Article  Google Scholar 

  85. Swartling U, Lynch K, Smith L, Johnson SB. Parental estimation of their child’s increased type 1 diabetes risk during the first 2 years of participation in an international observational study: results from the TEDDY study. J Empir Res Hum Res Ethics. 2016;11(2):106–14.

    PubMed  PubMed Central  Article  Google Scholar 

  86. Roth R, Lynch K, Lernmark B, Baxter J, Simell T, Smith L, et al. Maternal anxiety about a child’s diabetes risk in the TEDDY study: the potential role of life stress, postpartum depression, and risk perception. Pediatr Diabetes. 2015;16(4):287–98.

    PubMed  Article  Google Scholar 

  87. Smith LB, Lynch KF, Baxter J, Lernmark B, Roth R, Simell T, et al. Factors associated with maternal-reported actions to prevent type 1 diabetes in the first year of the TEDDY study. Diabetes Care. 2014;37(2):325–31.

    PubMed  PubMed Central  Article  Google Scholar 

  88. Johnson SB, Lynch KF, Baxter J, Lernmark B, Roth R, Simell T, et al. Predicting later study withdrawal in participants active in a longitudinal birth cohort study for 1 year: the TEDDY study. J Pediatr Psychol. 2016;41(3):373–83.

    PubMed  Article  Google Scholar 

  89. Lernmark B, Lynch K, Baxter J, et al. Participant experiences in the environmental determinants of diabetes in the young study: common reasons for withdrawing. J Diabetes Res. 2016;2720650:2016.

    Google Scholar 

  90. Haghighi M, Johnson SB, Qian X, Lynch KF, Vehik K, Huang S. A comparison of rule-based analysis with regression methods in understanding the risk factors for study withdrawal in a pediatric study. Sci Rep. 2016;6:30828.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  91. Yang J, Lynch KF, Uusitalo UM, Foterek K, Hummel S, Silvis K, et al. Factors associated with longitudinal food record compliance in a paediatric cohort study. Public Health Nutr. 2016;19(5):804–13.

    PubMed  Article  Google Scholar 

  92. Johnson SB, Lynch KF, Lee HS, Smith L, Baxter J, Lernmark B, et al. At high risk for early withdrawal: using a cumulative risk model to increase retention in the first year of the TEDDY study. J Clin Epidemiol. 2014;67(6):609–11.

    PubMed  PubMed Central  Article  Google Scholar 

  93. Lernmark B, Lynch K, Ballard L, et al. Reasons for staying as a participant in the environmental determinants of diabetes in the young (TEDDY) longitudinal study. J Clin Trials. 2012;2(2).

  94. Baxter J, Vehik K, Johnson SB, Lernmark B, Roth R, Simell T. Differences in recruitment and early retention among ethnic minority participants in a large pediatric cohort: the TEDDY study. Contemp Clin Trials. 2012;33(4):633–40.

    PubMed  PubMed Central  Article  Google Scholar 

Download references

Acknowledgements

The TEDDY Study Group (see Appendix)

Funding

The TEDDY Study is funded by U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, UC4 DK117483, and Contract No. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Child Health and Human Development (NICHD), National Institute of Environmental Health Sciences (NIEHS), Centers for Disease Control and Prevention (CDC), and JDRF. This work supported in part by the NIH/NCATS Clinical and Translational Science Awards to the University of Florida (UL1 TR000064) and the University of Colorado (UL1 TR001082).

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to Marian Rewers.

Ethics declarations

Conflict of Interest

Marian Rewers, William Hagopian, Jin-Xiong She, Desmond Schatz, Anette-G Ziegler, Beena Akolkar, and Jeffrey Krischer declare that they have no conflict of interest.

Heikki Hyöty reports grants from National Institute of Health (NIH) to carry out the TEDDY study; and being a Shareholder and member of the board of Vactech Ltd., which develops vaccines against picornaviruses.

Ake Lernmark is a Member of the Scientific Advisory Board of Diamyd Medical AB, Stockholm, Sweden.

Jorma Toppari reports grants from NIH/NIDDK.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors. The TEDDY study was approved by local institutional review or ethics boards at each site (University of Washington, Seattle; University of Colorado; Medical College of Georgia, Augusta; University of South Florida, Tampa; University of Turku, Finland; Technische Universitat, Munich, Germany; Lund University, Malmo, Sweden) and is monitored by an External Evaluation Committee formed by the National Institutes of Health.

Additional information

This article is part of the Topical Collection on Pathogenesis of Type 1 Diabetes

Appendix: TEDDY Study Acknowledgments

Appendix: TEDDY Study Acknowledgments

The TEDDY Study Group

Colorado Clinical Center: Marian Rewers, M.D., Ph.D., PI1,4,5,6,10,11, Kimberly Bautista12, Judith Baxter9,10,12,15, Daniel Felipe-Morales, Kimberly Driscoll, Ph.D.9, Brigitte I. Frohnert, M.D.2,14, Marisa Gallant, M.D.13, Patricia Gesualdo2,6,12,14,15, Michelle Hoffman12,13,14, Rachel Karban12, Edwin Liu, M.D.13, Jill Norris, Ph.D.2,3,12, Adela Samper-Imaz, Andrea Steck, M.D.3,14, Kathleen Waugh6,7,12,15, Hali Wright12. University of Colorado, Anschutz Medical Campus, Barbara Davis Center for Childhood Diabetes.

Finland Clinical Center: Jorma Toppari, M.D., Ph.D., PI¥^1,4,11,14, Olli G. Simell, M.D., Ph.D., Annika Adamsson, Ph.D.^12, Suvi Ahonen*±§, Heikki Hyöty, M.D., Ph.D.*±6, Jorma Ilonen, M.D., Ph.D.¥¶3, Sanna Jokipuu^, Leena Karlsson^, Miia Kähönenμ¤, Mikael Knip, M.D., Ph.D.*±5, Mirva Koreasalo*±§2, Kalle Kurppa, M.D., Ph.D.*±13, Tiina Latva-ahoμ¤, Maria Lönnrot, M.D., Ph.D.*±6, Markus Mattila*, Elina Mäntymäki^, Katja Multasuoμ¤, Tiina Niininen±*12, Sari Niinistö±§2, Mia Nyblom*±, Sami Oikarinen, Ph.D.*±, Paula Ollikainenμ¤, Petra Rajala^, Jenna Rautanen±§, Anne Riikonen*±§, Minna Romo^, Suvi Ruohonen^, Juulia Rönkäμ¤, Satu Simell, M.D., Ph.D.¥13, Tuula Simell, Ph.D.¥12, Maija Sjöberg¥^12,14, Aino Steniusμ¤12, Sini Vainionpää^, Eeva Varjonen¥^12, Riitta Veijola, M.D., Ph.D.μ¤14, Suvi M. Virtanen, M.D., Ph.D.*±§2, Mari Vähä-Mäkilä^, Mari Åkerlund*±§, Katri Lindfors, Ph.D.*13 ¥University of Turku, *University of Tampere, μUniversity of Oulu, ^Turku University Hospital, Hospital District of Southwest Finland, ±Tampere University Hospital, ¤Oulu University Hospital, §National Institute for Health and Welfare, Finland, University of Kuopio.

Georgia/Florida Clinical Center: Jin-Xiong She, Ph.D., PI1,3,4,11, Desmond Schatz, M.D.*4,5,7,8, Diane Hopkins12, Leigh Steed12,13,14,15, Jennifer Bryant, Janey Adams*12, Katherine Silvis2, Michael Haller, M.D.*14, Melissa Gardiner, Richard McIndoe, Ph.D., Ashok Sharma, Stephen W. Anderson, M.D.^, Laura Jacobsen, M.D.*14, John Marks, DHSc.*14, P.D. Towe*. Center for Biotechnology and Genomic Medicine, Augusta University. *University of Florida, ^Pediatric Endocrine Associates, Atlanta.

Germany Clinical Center: Anette G. Ziegler, M.D., PI1,3,4,11, Andreas Beyerlein, Ph.D.2, Ezio Bonifacio Ph.D.*5, Anita Gavrisan, Cigdem Gezginci, Anja Heublein, Michael Hummel, M.D.13, Sandra Hummel, Ph.D.2, Andrea Keimer2, Annette Knopff7, Charlotte Koch, Sibylle Koletzko, M.D.¶13, Claudia Ramminger, Roswith Roth, Ph.D.9, Marlon Scholz, Joanna Stock9,12,14, Katharina Warncke, M.D.14, Lorena Wendel, Christiane Winkler, Ph.D.2,12,15. Forschergruppe Diabetes e.V. and Institute of Diabetes Research, Helmholtz Zentrum München, Forschergruppe Diabetes, and Klinikum rechts der Isar, Technische Universität München. *Center for Regenerative Therapies, TU Dresden, Dr. von Hauner Children’s Hospital, Department of Gastroenterology, Ludwig Maximillians University Munich.

Sweden Clinical Center: Åke Lernmark, Ph.D., PI1,3,4,5,6,8,10,11,15, Daniel Agardh, M.D., Ph.D.13, Carin Andrén Aronsson, Ph.D.2,12,13, Maria Ask, Jenny Bremer, Ulla-Marie Carlsson, Corrado Cilio, Ph.D., M.D.5, Emelie Ericson-Hallström, Annika Fors, Lina Fransson, Thomas Gard, Rasmus Bennet, Carina Hansson, Susanne Hyberg, Hanna Jisser, Fredrik Johansen, Berglind Jonsdottir, M.D., Ph.D., Silvija Jovic, Helena Elding Larsson, M.D., Ph.D. 6,14, Marielle Lindström, Markus Lundgren, M.D., Ph.D.14, Maria Månsson-Martinez, Maria Markan, Jessica Melin12, Zeliha Mestan, Caroline Nilsson, Karin Ottosson, Kobra Rahmati, Anita Ramelius, Falastin Salami, Sara Sibthorpe, Anette Sjöberg, Birgitta Sjöberg, Carina Törn, Ph.D. 3,15, Anne Wallin, Åsa Wimar14, Sofie Åberg. Lund University.

Washington Clinical Center: William A. Hagopian, M.D., Ph.D., PI1,3,4, 5, 6,7,11,13, 14, Michael Killian6,7,12,13, Claire Cowen Crouch12,14,15, Jennifer Skidmore2, Ashley Akramoff, Jana Banjanin, Masumeh Chavoshi, Kayleen Dunson, Rachel Hervey, Rachel Lyons, Arlene Meyer, Denise Mulenga, Jared Radtke, Davey Schmitt, Julie Schwabe, Sarah Zink. Pacific Northwest Research Institute.

Pennsylvania Satellite Center: Dorothy Becker, M.D., Margaret Franciscus, MaryEllen Dalmagro-Elias Smith2, Ashi Daftary, M.D., Mary Beth Klein, Chrystal Yates. Children’s Hospital of Pittsburgh of UPMC.

Data Coordinating Center: Jeffrey P. Krischer, Ph.D.,PI1,4,5,10,11, Sarah Austin-Gonzalez, Maryouri Avendano, Sandra Baethke, Rasheedah Brown12,15, Brant Burkhardt, Ph.D.5,6, Martha Butterworth2, Joanna Clasen, David Cuthbertson, Christopher Eberhard, Steven Fiske9, Dena Garcia, Jennifer Garmeson, Veena Gowda, Kathleen Heyman, Belinda Hsiao, Francisco Perez Laras, Hye-Seung Lee, Ph.D.1,2,13,15, Shu Liu, Xiang Liu, Ph.D.2,3,9,14, Kristian Lynch, Ph.D. 5,6,9,15, Colleen Maguire, Jamie Malloy, Cristina McCarthy12,15, Aubrie Merrell, Steven Meulemans, Hemang Parikh, Ph.D.3, Ryan Quigley, Cassandra Remedios, Chris Shaffer, Laura Smith, Ph.D.9,12, Susan Smith12,15, Noah Sulman, Ph.D., Roy Tamura, Ph.D.1,2,13, Ulla Uusitalo, Ph.D.2,15, Kendra Vehik, Ph.D.4,5,6,14,15, Ponni Vijayakandipan, Keith Wood, Jimin Yang, Ph.D., R.D.2,15. Past staff: Michael Abbondondolo, Lori Ballard, David Hadley, Ph.D., Wendy McLeod. University of South Florida.

Project scientist: Beena Akolkar, Ph.D.1,3,4,5,6,7,10,11. National Institutes of Diabetes and Digestive and Kidney Diseases.

Other contributors: Kasia Bourcier, Ph.D.5, National Institutes of Allergy and Infectious Diseases. Thomas Briese, Ph.D.6,15, Columbia University. Suzanne Bennett Johnson, Ph.D.9,12, Florida State University. Eric Triplett, Ph.D.6, University of Florida.

Committees:

1Ancillary Studies, 2Diet, 3Genetics, 4Human Subjects/Publicity/Publications, 5Immune Markers, 6Infectious Agents, 7Laboratory Implementation, 8Maternal Studies, 9Psychosocial, 10Quality Assurance, 11Steering, 12Study Coordinators, 13Celiac Disease, 14Clinical Implementation, 15Quality Assurance Subcommittee on Data Quality.

Teddy Study Group: Affiliated Laboratories

Laboratory personnel should be copied-and-pasted for inclusion in the TEDDY Study Group Appendix on relevant manuscripts. Please review the labs below to determine which locations should be included in your manuscript’s Acknowledgements. (The Repository should be included for any manuscript referring to lab data.)

Autoantibody Reference Laboratories: Liping Yu, M.D.^5, Dongmei Miao, M.D.^, Polly Bingley, M.D., FRCP*5, Alistair Williams*, Kyla Chandler*, Olivia Ball*, Ilana Kelland*, Sian Grace*, Ben Gillard*. ^Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, *Bristol Medical School, University of Bristol UK.

Cortisol Laboratory: Elisabeth Aardal Eriksson, M.D., Ph.D., Ing-Marie Lundgren, Ewa Lönn Karlsson, Dzeneta Nezirevic Dernroth, Ph.D. Department of Clinical Chemistry, Linköping University Hospital, Linköping, Sweden.

Dietary Biomarkers Laboratory: Iris Erlund, Ph.D.2, Irma Salminen, Jouko Sundvall, Nina Kangas, Petra Arohonka. National Institute for Health and Welfare, Helsinki, Finland.

HbA1c Laboratory: Randie R. Little, Ph.D., Curt Rohlfing. Diabetes Diagnostic Laboratory, Dept. of Pathology, University of Missouri School of Medicine.

HLA Reference Laboratory: William Hagopian3, MD, PhD, Masumeh Chavoshi, Jared Radtke, Julie Schwabe. Pacific Northwest Research Institute, Seattle WA. (Previously Henry Erlich, Ph.D.3, Steven J. Mack, Ph.D., Anna Lisa Fear. Center for Genetics, Children’s Hospital Oakland Research Institute.)

Metabolomics Laboratory: Oliver Fiehn, Ph.D., Bill Wikoff, Ph.D., Brian Defelice, Dmitry Grapov, Ph.D., Tobias Kind, Ph.D., Mine Palazoglu, Luis Valdiviez, Benjamin Wancewicz, Gert Wohlgemuth, Joyce Wong. UC Davis Metabolomics Center.

Metagenomics and Microbiome Laboratory: Joseph F. Petrosino, Ph.D.6*, Nadim J. Ajami, Ph.D.*, Richard E. Lloyd, Ph.D.6*, Matthew C. Ross, Ph.D.*, Jacqueline L. O’Brien, Ph.D.*, Diane S. Hutchinson, Ph.D.*, Daniel P. Smith, Ph.D.*, Matthew C. Wong*, Xianjun Tian, Ph.D.*, Tulin Ayvaz*, Auriole Tamegnon*, Nguyen Truong*, Hannah Moreno*, Lauren Riley*, Eduardo Moreno*, Tonya Bauch*, Lenka Kusic*, Ginger Metcalf^, Donna Muzny^, HarshaVArdhan Doddapaneni, Ph.D.^, Richard Gibbs, Ph.D.^. *Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, ^Human Genome Sequencing Center, Baylor College of Medicine.

OGTT Laboratory: Santica M. Marcovina, Ph.D., Sc.D., Vinod P. Gaur, Ph.D., Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington.

Proteomics Laboratory: Richard D. Smith, Ph.D., Thomas O. Metz, Ph.D., Charles Ansong, Ph.D., Bobbie-Jo Webb-Robertson, Ph.D., Hugh D. Mitchell, Ph.D., Ernesto S. Nakayasu, Ph.D., and Wei-Jun Qian, Ph.D. Pacific Northwest National Laboratory.

Repository: Sandra Ke, Niveen Mulholland, Ph.D. NIDDK Biosample Repository at Fisher BioServices.

RNA Laboratory and Gene Expression Laboratory: Jin-Xiong She, Ph.D., PI1,3,4,11, Richard McIndoe, Ph.D., Haitao Liu, M.D., John Nechtman, Yansheng Zhao, Na Jiang, M.D., Yanna Tian, M.S. Guangkuo Dong, M.S. Jinfiniti Biotech, LLC.

SNP Laboratory: Stephen S. Rich, Ph.D.3, Wei-Min Chen, Ph.D.3, Suna Onengut-Gumuscu, Ph.D.3, Emily Farber, Rebecca Roche Pickin, Ph.D., Jonathan Davis, Jordan Davis, Dan Gallo, Jessica Bonnie, Paul Campolieto. Center for Public Health Genomics, University of Virginia.

Thyroid Laboratory: William E. Winter, M.D., David L. Pittman. UF Health Pathology Laboratories’ Endocrinology Laboratory, University of Florida.

Committees:

1Ancillary Studies, 2Diet, 3Genetics, 4Human Subjects/Publicity/Publications, 5Immune Markers, 6Infectious Agents, 7Laboratory Implementation, 8Maternal Studies, 9Psychosocial, 10Quality Assurance, 11Steering, 12Study Coordinators, 13Celiac Disease, 14Clinical Implementation, 15Quality Assurance Subcommittee on Data Quality.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Rewers, M., Hyöty, H., Lernmark, Å. et al. The Environmental Determinants of Diabetes in the Young (TEDDY) Study: 2018 Update. Curr Diab Rep 18, 136 (2018). https://doi.org/10.1007/s11892-018-1113-2

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11892-018-1113-2

Keywords

  • Type 1 diabetes
  • Autoimmunity
  • Children