TEDDY - The Environmental Determinants of Diabetes in the Young

• ClinicalTrials.gov Identifier: NCT00279318
• Recruitment Status: Active, not recruiting
• First Posted: January 19, 2006
• Last Update Posted: June 21, 2022
• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Environmental Health Sciences (NIEHS); Juvenile Diabetes Research Foundation; Centers for Disease Control and Prevention
• Information provided by (Responsible Party): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Description

Brief Summary:

The long-term goal of the TEDDY study is the identification of infectious agents, dietary factors, or other environmental agents, including psychosocial factors which trigger T1DM in genetically susceptible individuals or which protect against the disease. Identification of such factors will lead to a better understanding of disease pathogenesis and result in new strategies to prevent, delay or reverse T1DM.

Condition or disease
Type 1 Diabetes Mellitus

Detailed Description:

Epidemiologic patterns suggest that viruses, nutrition, toxic agents or socioeconomic psychosocial factors may contribute to the etiology alone or in combination. Elucidation is confounded by the long interval between exposure and onset of clinical disease, as well as the interaction of multiple genes and/or insults, which appear to interact in a complex manner. Numerous studies have investigated environmental influences but have yielded conflicting results. This may be in part due to the failure to account for genetic susceptibility, begin observation at early ages or in utero, and/or monitor subjects long term and frequently.

Hypotheses:

1. Initiation of persistent beta-cell autoimmunity and progression from beta-cell autoimmunity to diabetes is increased with:

   1. Exposure to a trigger factor during pregnancy, such as infections, preeclampsia, blood incompatibility, or birth weight.
   2. Differences in the timing of the introduction and/or the type of dietary constituents that include exposure to cereals or gluten, exposure to cow's milk during infancy and/or childhood, and short duration of breast- feeding;
   3. Lower intake of serum 25 hydroxyvitamin D in early infancy, vitamin E, anti-oxidants (e.g., carotenoids, ascorbic acid, selenium, or omega-3 fatty acids);
   4. Higher frequency of specific (e.g., enterovirus, rotavirus, or bacterial) infections, or non-specific childhood infections including those that exhibit molecular mimicry;
   5. Increased exposure to routine childhood immunizations and their timing;
   6. Environmental factors that may be contained in drinking water (e.g., low concentrations of zinc or high concentrations of nitrates, or lower pH levels);
   7. Exposure to household pets, and various allergies;
   8. Excessive weight gain;
   9. Increased psychological stress.
2. The risk of persistent beta-cell autoimmunity is lower in children from the general population than in offspring or siblings of T1DM patients when stratifying for the HLA DR-DQ genotype and exposure to environmental triggers.
3. The interaction of HLA DR-DQ genotype with exposure to dietary or infectious factors leads to increased incidence of beta-cell autoimmunity and T1DM.
4. We expect that in some families study participation will be associated with affective (anxiety, depression) and behavioral responses (e.g. actions to prevent possible T1DM).

Study Design

• Study Type: Observational
• Actual Enrollment: 8667 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Consortium for Identification of Environmental Triggers of Type 1 Diabetes
• Study Start Date: September 2004
• Estimated Primary Completion Date: September 2025
• Estimated Study Completion Date: September 2025

Groups and Cohorts

Group/Cohort
General Population, First Degree Relative; Newborns with high risk HLA in the general population or having a first-degree relative affected with T1DM.

Outcome Measures

Primary Outcome Measures :

1. Appearance of one or more islet cell autoantibodies: GADA, IAA, or IA-2A confirmed at two consecutive visits. [ Time Frame: September 2025 ]

Secondary Outcome Measures :

1. Development of T1DM [ Time Frame: September 2025 ]

Biospecimen Retention:   Samples With DNA

Serum, plasma, PBMCs, stool, urine, saliva, nasal swabs, nail clippings, water, teeth

Eligibility Criteria

• Ages Eligible for Study: up to 4 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Childen up to 4 months of age with specified HLA are enrolled and followed longitudnally until 15 years of age

Criteria

Inclusion Criteria:

• Newborns with high risk HLA in the general population or having a first- degree relative affected with T1DM
• Newborns are less than 4 months of age

Exclusion Criteria:

• Have an illness or birth defect that precludes long-term follow-up or involves use of treatment that may alter the natural history of diabetes (e.g. steroids or insulin)
• Refuses to have blood and stool samples stored at the NIDDK Repository

Contacts and Locations

Locations

United States, Colorado

University of Colorado Health Sciences Center

Denver, Colorado, United States, 80262

United States, Florida

Augusta University

Gainesville, Florida, United States, 32608

United States, Georgia

Augusta University

Atlanta, Georgia, United States, 30342

Augusta University

Augusta, Georgia, United States, 30912

United States, Washington

Pacific Northwest Research Institute

Seattle, Washington, United States, 98122

Finland

Turku University Central Hospital

Turku, Finland, 20520

Germany

Diabetes Research Institute

Munich, Germany, 80804

Sweden

Lund University

Malmo, Sweden, 20502

Sponsors and Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

National Institute of Allergy and Infectious Diseases (NIAID)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute of Environmental Health Sciences (NIEHS)

Juvenile Diabetes Research Foundation

Centers for Disease Control and Prevention

Investigators

• Principal Investigator: Jeffrey P. Krischer, PhD; University of South Florida
• Principal Investigator: Marian J. Rewers, MD, PhD; University of Colorado Health Science Center
• Principal Investigator: William A. Hagopian, MD, PhD; Pacific Northwest Research Institute
• Principal Investigator: Ake Lernmark, MD, PhD; Lund University
• Principal Investigator: Jorma Toppari, MD, PhD; University of Turku
• Principal Investigator: Richard McIndoe, PhD; Augusta University Research Institute, Inc.
• Principal Investigator: Anette G. Ziegler, MD; Diabetes Research Institute
• Study Director: Beena Akolkar, PhD; National Institutes of Diabetes and Digestive Kidney Diseases

More Information

Additional Information:

TEDDY Study Public site 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Krischer JP, Liu X, Lernmark A, Hagopian WA, Rewers MJ, She JX, Toppari J, Ziegler AG, Akolkar B; TEDDY Study Group. Predictors of the Initiation of Islet Autoimmunity and Progression to Multiple Autoantibodies and Clinical Diabetes: The TEDDY Study. Diabetes Care. 2022 Oct 1;45(10):2271-2281. doi: 10.2337/dc21-2612.

Melin J, Lynch KF, Lundgren M, Aronsson CA, Larsson HE, Johnson SB; TEDDY Study Group. Is staff consistency important to parents' satisfaction in a longitudinal study of children at risk for type 1 diabetes: the TEDDY study. BMC Endocr Disord. 2022 Jan 10;22(1):19. doi: 10.1186/s12902-021-00929-w.

Krischer JP, Liu X, Lernmark A, Hagopian WA, Rewers MJ, She JX, Toppari J, Ziegler AG, Akolkar B; TEDDY Study Group. Characteristics of children diagnosed with type 1 diabetes before vs after 6 years of age in the TEDDY cohort study. Diabetologia. 2021 Oct;64(10):2247-2257. doi: 10.1007/s00125-021-05514-3. Epub 2021 Jul 22.

Johnson RK, Tamura R, Frank N, Uusitalo U, Yang J, Niinisto S, Andren Aronsson C, Ziegler AG, Hagopian W, Rewers M, Toppari J, Akolkar B, Krischer J, Virtanen SM, Norris JM; TEDDY Study Group. Maternal food consumption during late pregnancy and offspring risk of islet autoimmunity and type 1 diabetes. Diabetologia. 2021 Jul;64(7):1604-1612. doi: 10.1007/s00125-021-05446-y. Epub 2021 Mar 30.

Frank NM, Lynch KF, Uusitalo U, Yang J, Lonnrot M, Virtanen SM, Hyoty H, Norris JM; TEDDY Study Group. The relationship between breastfeeding and reported respiratory and gastrointestinal infection rates in young children. BMC Pediatr. 2019 Sep 18;19(1):339. doi: 10.1186/s12887-019-1693-2.

Hippich M, Beyerlein A, Hagopian WA, Krischer JP, Vehik K, Knoop J, Winker C, Toppari J, Lernmark A, Rewers MJ, Steck AK, She JX, Akolkar B, Robertson CC, Onengut-Gumuscu S, Rich SS, Bonifacio E, Ziegler AG; TEDDY Study Group; Teddy Study Group. Genetic Contribution to the Divergence in Type 1 Diabetes Risk Between Children From the General Population and Children From Affected Families. Diabetes. 2019 Apr;68(4):847-857. doi: 10.2337/db18-0882. Epub 2019 Jan 17.

Hagopian WA, Erlich H, Lernmark A, Rewers M, Ziegler AG, Simell O, Akolkar B, Vogt R Jr, Blair A, Ilonen J, Krischer J, She J; TEDDY Study Group. The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants. Pediatr Diabetes. 2011 Dec;12(8):733-43. doi: 10.1111/j.1399-5448.2011.00774.x. Epub 2011 May 12.

• Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• ClinicalTrials.gov Identifier: NCT00279318
• Other Study ID Numbers: DK095300; DK100238; DK106955; 1UC4DK095300-01 ( U.S. NIH Grant/Contract ); 1UC4DK100238-01 ( U.S. NIH Grant/Contract ); 1UC4DK106955-01 ( U.S. NIH Grant/Contract ); 1UC4DK112243-01 ( U.S. NIH Grant/Contract ); 1UC4DK117483-01 ( U.S. NIH Grant/Contract ); 1U01DK124166-01 ( U.S. NIH Grant/Contract ); 1U01DK128847-01 ( U.S. NIH Grant/Contract )
• First Posted: January 19, 2006
• Last Update Posted: June 21, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Data are available at the NIDDK Central Repository https://repository.niddk.nih.gov/studies/teddy/?query=teddy
• URL: https://repository.niddk.nih.gov/studies/teddy/?query=teddy

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Environment; Exposures; Diet; Toxins; Psychosocial; Infectious Agents; Bacterial; Viral; Immunizations; Autoantibody

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases