Refereed journal article or data article (A1)

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




List of AuthorsKrischer Jeffrey P., Liu Xiang, Lernmark Åke, Hagopian William A., Rewers Marian J., She Jin-Xiong, Toppari Jorma, Ziegler Anette-G., Akolkar Beena; on behalf of the TEDDY Study Group

PublisherSPRINGER

Publication year2021

JournalDiabetologia

Journal name in sourceDIABETOLOGIA

Journal acronymDIABETOLOGIA

Volume number64

Start page2247

End page2257

Number of pages11

ISSN0012-186X

eISSN1432-0428

DOIhttp://dx.doi.org/10.1007/s00125-021-05514-3


Abstract

Aims/hypothesis Prognostic 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.

Methods Genetically 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.

Results Children 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.


Last updated on 2022-10-02 at 08:50