Evidence map›Paper›PMID 34291312›Full record

ArticleDiabetologia2021

Characteristics of children diagnosed with type 1 diabetes before vs after 6 years of age in the TEDDY cohort study.

Jeffrey P Krischer, Xiang Liu, Åke Lernmark, William A Hagopian, Marian J Rewers, Jin-Xiong She, Jorma Toppari, Anette-G Ziegler, Beena Akolkar, TEDDY Study Group

Registry-linked trialOpen access · bronzeAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetologia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00279318 (Consortium for Identification of Environmental Triggers of Type 1 Diabetes), which is not on this map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00279318 completednot on this map

Consortium for Identification of Environmental Triggers of Type 1 Diabetes

TypeobservationalSponsorNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Ran2004 to 2025Enrolled8,667ConditionsType 1 Diabetes Mellitus
3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

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  12. Time to reframe the disease staging system for type 1 diabetes.The lancet. Diabetes & endocrinology · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 8 institutions in 4 countries.

Jeffrey P KrischerHealth Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA. jeffrey.krischer@epi.usf.edu.ORCID 0000-0003-4526-888X
Xiang LiuHealth Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.ORCID 0000-0002-8451-3465
Åke LernmarkDepartment of Clinical Sciences, Lund University/CRC, Skåne University Hospital SUS, Malmo, Sweden.ORCID 0000-0003-1735-0499
William A HagopianPacific Northwest Diabetes Research Institute, Seattle, WA, USA.ORCID 0000-0003-2979-0475
Marian J RewersBarbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, USA.ORCID 0000-0003-3829-9207
Jin-Xiong SheCenter for Biotechnology and Genomic Medicine, Augusta University, Augusta, GA, USA.ORCID 0000-0002-0966-6381
Jorma ToppariDepartment of Pediatrics, Turku University Hospital, Turku, Finland.ORCID 0000-0003-2228-334X
Anette-G ZieglerInstitute of Diabetes Research, Helmholtz Zentrum München, and Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e.V, Neuherberg, Germany.ORCID 0000-0002-6290-5548
Beena AkolkarNational Institute of Diabetes & Digestive & Kidney Diseases, Bethesda, MD, USA.ORCID 0000-0002-2351-5942
TEDDY Study Group
University of South Florida · USAugusta University · USLund University · SENational Institute of Diabetes and Digestive and Kidney Diseases · USPacific Northwest Diabetes Research Institute · USTUM Klinikum · DEUniversity of Colorado Anschutz Medical Campus · USUniversity of Turku · FI

Funding

Data Coordinating Center (DCC)for the Consortium for Identification of EnvironmenUC4DK095300 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2011 to 2011
$56.0M
NIH Prior Approval Process ProfessionalUL1TR002535 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2018 to 2022
$51.1M
Data Coordinating CenterU01DK063790 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2002 to 2006
$50.1M
Follow-up on Subjects, Integrative Data Analysis and Measurement of Viral Antibodies in The Environmental Determinants of Diabetes in The Young Study (TEDDY)U01DK124166 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2020 to 2022
$31.1M
NIDDK Follow-up on Subjects and Immunological Assessments in The Environmental Determinants of Diabetes In The Young Study (TEDDY) (UC4)UC4DK117483 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2017 to 2020
$30.4M
Establish a Data Coordinating Center (DCC) for the Consortium for Identification UC4DK100238 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2014 to 2014
$28.9M
The Study of Epigenetics and Infections in The Environmental Determinants of Diabetes in the Young (TEDDY)UC4DK112243 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2016 to 2016
$27.0M
Data Coordinating Center (DCC) for the Consortium for Identification of Environmental Determinants of Diabetes in the Young (TEDDY) StudyUC4DK106955 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2015 to 2015
$20.0M
The Environmental Determinants of Diabetes in Young (TEDDY0U01DK063863 · NIDDK · HOSPITAL DISTRICT OF SOUTHWEST FINLAND · PI TOPPARI, JORMA · 2003 to 2022
$13.5M
The Environmental Triggers of Diabetes (TEDDY) in SwedenU01DK063861 · NIDDK · UNIVERSITY OF WASHINGTON · PI LERNMARK, AKE · 2003 to 2022
$13.4M
THE TEDDY STUDY - COLORADO CLINICAL CENTERU01DK063821 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI REWERS, MARIAN J · 2003 to 2022
$12.3M
The TEDDY Study: Georgia/Florida Clinical CenterU01DK063865 · NIDDK · MEDICAL COLLEGE OF GEORGIA (MCG) · PI MCINDOE, RICHARD A. · 2003 to 2022
$12.3M
NCATS NIH HHS UL1 TR000064NCATS NIH HHS UL1 TR002535NIDDK NIH HHS HHSN267200700014CNIDDK NIH HHS U01 DK063790NIDDK NIH HHS U01 DK063821NIDDK NIH HHS U01 DK063829NIDDK NIH HHS U01 DK063836NIDDK NIH HHS U01 DK063861NIDDK NIH HHS U01 DK063863NIDDK NIH HHS U01 DK063865NIDDK NIH HHS U01 DK124166NIDDK NIH HHS UC4 DK063821NIDDK NIH HHS UC4 DK063829NIDDK NIH HHS UC4 DK063836NIDDK NIH HHS UC4 DK063861NIDDK NIH HHS UC4 DK063863NIDDK NIH HHS UC4 DK063865NIDDK NIH HHS UC4 DK095300NIDDK NIH HHS UC4 DK100238NIDDK NIH HHS UC4 DK106955NIDDK NIH HHS UC4 DK112243NIDDK NIH HHS UC4 DK117483
6 · The paper itself

Abstract

aims/hypothesisPrognostic factors and characteristics of children diagnosed with type 1 diabetes before 6 years of age were compared with those diagnosed at 6-13 years of age in the TEDDY study.

methodsGenetically high-risk children (n = 8502) were followed from birth for a median of 9.9 years; 328 (3.9%) were diagnosed with type 1 diabetes. Cox proportional hazard model was used to assess the association of prognostic factors with the risk of type 1 diabetes in the two age groups.

resultsChildren in the younger group tended to develop autoantibodies earlier than those in the older group did (mean age 1.5 vs 3.5 years), especially insulin autoantibodies (IAA), which developed earlier than GAD autoantibodies (GADA). Children in the younger group also progressed to diabetes more rapidly than the children in the older group did (mean duration 1.9 vs 5.4 years). Children with autoantibodies first appearing against insulinoma antigen-2 (IA-2A) were found only in the older group. The significant diabetes risk associated with the country of origin in the younger group was no longer significant in the older group. Conversely, the diabetes risk associated with HLA genotypes was statistically significant also in the older group. Initial seroconversion after and before 2 years of age was associated with decreased risk for diabetes diagnosis in children positive for multiple autoantibodies, but the diabetes risk did not decrease further with increasing age if initial seroconversion occurred after age 2. Diabetes risk associated with the minor alleles of rs1004446 (INS) was decreased in both the younger and older groups compared with other genotypes (HR 0.67). Diabetes risk was significantly increased with the minor alleles of rs2476601 (PTPN22) (HR 2.04 and 1.72), rs428595 (PPIL2) (HR 2.13 and 2.10), rs113306148 (PLEKHA1) (HR 2.34 and 2.21) and rs73043122 (RNASET2) (HR 2.31 and 2.54) (HR values represent the younger and older groups, respectively). CONCLUSIONS/INTERPRETATIONS: Diabetes at an early age is likely to be preceded by IAA autoantibodies and is a more aggressive form of the disease. Among older children, once multiple autoantibodies have been observed there does not seem to be any association between progression to diabetes and the age of the child or family history.

trial registrationClinicalTrials.gov identifier: NCT00279318.

Indexed as

AdolescentAutoantibodiesChildChild, PreschoolDiabetes Mellitus, Type 1FemaleFollow-Up StudiesHLA AntigensHumansInsulin AntibodiesIslets of LangerhansMalePrognosisProportional Hazards ModelsProspective StudiesReceptor-Like Protein Tyrosine Phosphatases, Class 8AutoantibodiesHLA AntigensInsulin AntibodiesPTPRN protein, humanReceptor-Like Protein Tyrosine Phosphatases, Class 8AutoimmunityType 1 diabetes

Identifiers

PMID34291312
PMCPMC8429233
OpenAlexW3185611804

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.