Characteristics of Slow Progression to Type 1 Diabetes in Children With Increased HLA-Conferred Disease Risk

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Pöllänen , P M , Lempainen , J , Laine , A-P , Toppari , J , Veijola , R , Ilonen , J , Siljander , H & Knip , M 2019 , ' Characteristics of Slow Progression to Type 1 Diabetes in Children With Increased HLA-Conferred Disease Risk ' , Journal of Clinical Endocrinology and Metabolism , vol. 104 , no. 11 , pp. 5585-5594 . https://doi.org/10.1210/jc.2019-01069

Title: Characteristics of Slow Progression to Type 1 Diabetes in Children With Increased HLA-Conferred Disease Risk
Author: Pöllänen, Petra M.; Lempainen, Johanna; Laine, Antti-Pekka; Toppari, Jorma; Veijola, Riitta; Ilonen, Jorma; Siljander, Heli; Knip, Mikael
Other contributor: University of Helsinki, HUS Children and Adolescents
University of Helsinki, Clinicum
University of Helsinki, HUS Children and Adolescents







Date: 2019-11
Language: eng
Number of pages: 10
Belongs to series: Journal of Clinical Endocrinology and Metabolism
ISSN: 0021-972X
DOI: https://doi.org/10.1210/jc.2019-01069
URI: http://hdl.handle.net/10138/312994
Abstract: Context: Characterization of slow progression to type 1 diabetes (T1D) may reveal novel means for prevention of T1D. Slow progressors might carry natural immunomodulators that delay beta-cell destruction and mediate preservation of beta-cell function. Objective: To identify demographic, genetic, and immunological characteristics of slow progression from seroconversion to clinical T1D. Design: H LA-susceptible children (n = 7410) were observed from birth for islet cell antibody (ICA), insulin autoantibody (IAA), glutamic acid decarboxylase (GADA), and islet antigen-2 autoantibodies (IA-2A), and for clinical T1D. Disease progression that lasted >= 7.26 years (slowest) quartile from initial seroconversion to diagnosis was considered slow. Autoantibody and genetic characteristics including 45 non-HLA single nucleotide polymorphisms (SNPs) predisposing to T1D were analyzed. Results: By the end of 2015, 1528 children (21 %) had tested autoantibody positive and 247 (16%) had progressed to T1D. The median delay from seroconversion to diagnosis was 8.7 years in slow (n = 62, 25%) and 3.0 years in other progressors. Compared with other progressors, slow progressors were less often multipositive, had lower ICA and IAA titers, and lower frequency of IA-2A at seroconversion. Slow progressors were born more frequently in the fall, whereas other progressors were born more often in the spring. Compared with multipositive nonprogressors, slow progressors were younger, had higher ICA titers, and higher frequency of IAA and multiple autoantibodies at seroconversion. We found no differences in the distributions of non-HLA SNPs between progressors. Conclusions: We observed differences in autoantibody characteristics and the season of birth among progressors, but no characteristics present at seroconversion that were specifically predictive for slow progression.
Subject: 3123 Gynaecology and paediatrics
GENOME-WIDE ASSOCIATION
BETA-CELL AUTOIMMUNITY
ISLET AUTOANTIBODY
YOUNG-CHILDREN
MELLITUS
CHILDHOOD
SUSCEPTIBILITY
POPULATION
SEROCONVERSION
METAANALYSIS
3121 General medicine, internal medicine and other clinical medicine
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