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Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children.
JAMA 2013; 309(23):2473-9JAMA

Abstract

IMPORTANCE

Type 1 diabetes usually has a preclinical phase identified by circulating islet autoantibodies, but the rate of progression to diabetes after seroconversion to islet autoantibodies is uncertain.

OBJECTIVE

To determine the rate of progression to diabetes after islet autoantibody seroconversion.

DESIGN, SETTING, AND PARTICIPANTS

Data were pooled from prospective cohort studies performed in Colorado (recruitment, 1993-2006), Finland (recruitment, 1994-2009), and Germany (recruitment, 1989-2006) examining children genetically at risk for type 1 diabetes for the development of insulin autoantibodies, glutamic acid decarboxylase 65 (GAD65) autoantibodies, insulinoma antigen 2 (IA2) autoantibodies, and diabetes. Participants were all children recruited and followed up in the 3 studies (Colorado, 1962; Finland, 8597; Germany, 2818). Follow-up assessment in each study was concluded by July 2012.

MAIN OUTCOMES AND MEASURES

The primary analysis was the diagnosis of type 1 diabetes in children with 2 or more autoantibodies. The secondary analysis was the diagnosis of type 1 diabetes in children with 1 autoantibody or no autoantibodies.

RESULTS

Progression to type 1 diabetes at 10-year follow-up after islet autoantibody seroconversion in 585 children with multiple islet autoantibodies was 69.7% (95% CI, 65.1%-74.3%), and in 474 children with a single islet autoantibody was 14.5% (95% CI, 10.3%-18.7%). Risk of diabetes in children who had no islet autoantibodies was 0.4% (95% CI, 0.2%-0.6%) by the age of 15 years. Progression to type 1 diabetes in the children with multiple islet autoantibodies was faster for children who had islet autoantibody seroconversion younger than age 3 years (hazard ratio [HR], 1.65 [95% CI, 1.30-2.09; P < .001]; 10-year risk, 74.9% [95% CI, 69.7%-80.1%]) vs children 3 years or older (60.9% [95% CI, 51.5%-70.3%]); for children with the human leukocyte antigen (HLA) genotype DR3/DR4-DQ8 (HR, 1.35 [95% CI, 1.09-1.68; P = .007]; 10-year risk, 76.6% [95% CI, 69.2%-84%]) vs other HLA genotypes (66.2% [95% CI, 60.2%-72.2%]); and for girls (HR, 1.28 [95% CI, 1.04-1.58; P = .02];10-year risk, 74.8% [95% CI, 68.0%-81.6%]) vs boys (65.7% [95% CI, 59.3%-72.1%]).

CONCLUSIONS AND RELEVANCE

The majority of children at risk of type 1 diabetes who had multiple islet autoantibody seroconversion progressed to diabetes over the next 15 years. Future prevention studies should focus on this high-risk population.

Authors+Show Affiliations

Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Ingolstaedter Landstrase 1, Neuherberg, Germany 85764. anette-g.ziegler@helmholtz-muenchen.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23780460

Citation

Ziegler, Anette G., et al. "Seroconversion to Multiple Islet Autoantibodies and Risk of Progression to Diabetes in Children." JAMA, vol. 309, no. 23, 2013, pp. 2473-9.
Ziegler AG, Rewers M, Simell O, et al. Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA. 2013;309(23):2473-9.
Ziegler, A. G., Rewers, M., Simell, O., Simell, T., Lempainen, J., Steck, A., ... Eisenbarth, G. S. (2013). Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA, 309(23), pp. 2473-9. doi:10.1001/jama.2013.6285.
Ziegler AG, et al. Seroconversion to Multiple Islet Autoantibodies and Risk of Progression to Diabetes in Children. JAMA. 2013 Jun 19;309(23):2473-9. PubMed PMID: 23780460.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. AU - Ziegler,Anette G, AU - Rewers,Marian, AU - Simell,Olli, AU - Simell,Tuula, AU - Lempainen,Johanna, AU - Steck,Andrea, AU - Winkler,Christiane, AU - Ilonen,Jorma, AU - Veijola,Riitta, AU - Knip,Mikael, AU - Bonifacio,Ezio, AU - Eisenbarth,George S, PY - 2013/6/20/entrez PY - 2013/6/20/pubmed PY - 2013/6/21/medline SP - 2473 EP - 9 JF - JAMA JO - JAMA VL - 309 IS - 23 N2 - IMPORTANCE: Type 1 diabetes usually has a preclinical phase identified by circulating islet autoantibodies, but the rate of progression to diabetes after seroconversion to islet autoantibodies is uncertain. OBJECTIVE: To determine the rate of progression to diabetes after islet autoantibody seroconversion. DESIGN, SETTING, AND PARTICIPANTS: Data were pooled from prospective cohort studies performed in Colorado (recruitment, 1993-2006), Finland (recruitment, 1994-2009), and Germany (recruitment, 1989-2006) examining children genetically at risk for type 1 diabetes for the development of insulin autoantibodies, glutamic acid decarboxylase 65 (GAD65) autoantibodies, insulinoma antigen 2 (IA2) autoantibodies, and diabetes. Participants were all children recruited and followed up in the 3 studies (Colorado, 1962; Finland, 8597; Germany, 2818). Follow-up assessment in each study was concluded by July 2012. MAIN OUTCOMES AND MEASURES: The primary analysis was the diagnosis of type 1 diabetes in children with 2 or more autoantibodies. The secondary analysis was the diagnosis of type 1 diabetes in children with 1 autoantibody or no autoantibodies. RESULTS: Progression to type 1 diabetes at 10-year follow-up after islet autoantibody seroconversion in 585 children with multiple islet autoantibodies was 69.7% (95% CI, 65.1%-74.3%), and in 474 children with a single islet autoantibody was 14.5% (95% CI, 10.3%-18.7%). Risk of diabetes in children who had no islet autoantibodies was 0.4% (95% CI, 0.2%-0.6%) by the age of 15 years. Progression to type 1 diabetes in the children with multiple islet autoantibodies was faster for children who had islet autoantibody seroconversion younger than age 3 years (hazard ratio [HR], 1.65 [95% CI, 1.30-2.09; P < .001]; 10-year risk, 74.9% [95% CI, 69.7%-80.1%]) vs children 3 years or older (60.9% [95% CI, 51.5%-70.3%]); for children with the human leukocyte antigen (HLA) genotype DR3/DR4-DQ8 (HR, 1.35 [95% CI, 1.09-1.68; P = .007]; 10-year risk, 76.6% [95% CI, 69.2%-84%]) vs other HLA genotypes (66.2% [95% CI, 60.2%-72.2%]); and for girls (HR, 1.28 [95% CI, 1.04-1.58; P = .02];10-year risk, 74.8% [95% CI, 68.0%-81.6%]) vs boys (65.7% [95% CI, 59.3%-72.1%]). CONCLUSIONS AND RELEVANCE: The majority of children at risk of type 1 diabetes who had multiple islet autoantibody seroconversion progressed to diabetes over the next 15 years. Future prevention studies should focus on this high-risk population. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/23780460/Seroconversion_to_multiple_islet_autoantibodies_and_risk_of_progression_to_diabetes_in_children_ L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2013.6285 DB - PRIME DP - Unbound Medicine ER -