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Characteristics of Slow Progression to Type 1 Diabetes in Children With Increased HLA-Conferred Disease Risk.
J Clin Endocrinol Metab. 2019 11 01; 104(11):5585-5594.JC

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 β-cell destruction and mediate preservation of β-cell function.

OBJECTIVE

To identify demographic, genetic, and immunological characteristics of slow progression from seroconversion to clinical T1D.

DESIGN

HLA-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.

Authors+Show Affiliations

Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.Immunogenetics Laboratory, Institute of Biomedicine, University of Turku and Clinical Microbiology, Turku University Hospital, Turku, Finland. Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland.Immunogenetics Laboratory, Institute of Biomedicine, University of Turku and Clinical Microbiology, Turku University Hospital, Turku, Finland.Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland. Institute of Biomedicine and Centre for Population Health Research, University of Turku, Turku, Finland.Department of Pediatrics, PEDEGO Research Group, Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland.Immunogenetics Laboratory, Institute of Biomedicine, University of Turku and Clinical Microbiology, Turku University Hospital, Turku, Finland.Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland. Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland. Folkhälsan Research Center, Helsinki, Finland.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31314077

Citation

Pöllänen, Petra M., et al. "Characteristics of Slow Progression to Type 1 Diabetes in Children With Increased HLA-Conferred Disease Risk." The Journal of Clinical Endocrinology and Metabolism, vol. 104, no. 11, 2019, pp. 5585-5594.
Pöllänen PM, Lempainen J, Laine AP, et al. Characteristics of Slow Progression to Type 1 Diabetes in Children With Increased HLA-Conferred Disease Risk. J Clin Endocrinol Metab. 2019;104(11):5585-5594.
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. The Journal of Clinical Endocrinology and Metabolism, 104(11), 5585-5594. https://doi.org/10.1210/jc.2019-01069
Pöllänen PM, et al. Characteristics of Slow Progression to Type 1 Diabetes in Children With Increased HLA-Conferred Disease Risk. J Clin Endocrinol Metab. 2019 11 1;104(11):5585-5594. PubMed PMID: 31314077.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characteristics of Slow Progression to Type 1 Diabetes in Children With Increased HLA-Conferred Disease Risk. AU - Pöllänen,Petra M, AU - Lempainen,Johanna, AU - Laine,Antti-Pekka, AU - Toppari,Jorma, AU - Veijola,Riitta, AU - Ilonen,Jorma, AU - Siljander,Heli, AU - Knip,Mikael, PY - 2019/05/07/received PY - 2019/07/11/accepted PY - 2019/7/18/pubmed PY - 2020/6/4/medline PY - 2019/7/18/entrez SP - 5585 EP - 5594 JF - The Journal of clinical endocrinology and metabolism JO - J. Clin. Endocrinol. Metab. VL - 104 IS - 11 N2 - 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 β-cell destruction and mediate preservation of β-cell function. OBJECTIVE: To identify demographic, genetic, and immunological characteristics of slow progression from seroconversion to clinical T1D. DESIGN: HLA-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. SN - 1945-7197 UR - https://www.unboundmedicine.com/medline/citation/31314077/Characteristics_of_Slow_Progression_to_Type_1_Diabetes_in_Children_With_Increased_HLA_Conferred_Disease_Risk_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2019-01069 DB - PRIME DP - Unbound Medicine ER -