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Extended Family History of Type 1 Diabetes and Phenotype and Genotype of Newly Diagnosed Children
OBJECTIVE: To determine the frequency of newly diagnosed diabetic children with first- and second-degree relatives affected by type 1 diabetes and to characterize the effects of this positive family history on clinical markers, signs of β-cell autoimmunity, and HLA genotype in the index case. RESEAR...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554291/ https://www.ncbi.nlm.nih.gov/pubmed/23033245 http://dx.doi.org/10.2337/dc12-0445 |
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author | Parkkola, Anna Härkönen, Taina Ryhänen, Samppa J. Ilonen, Jorma Knip, Mikael |
author_facet | Parkkola, Anna Härkönen, Taina Ryhänen, Samppa J. Ilonen, Jorma Knip, Mikael |
author_sort | Parkkola, Anna |
collection | PubMed |
description | OBJECTIVE: To determine the frequency of newly diagnosed diabetic children with first- and second-degree relatives affected by type 1 diabetes and to characterize the effects of this positive family history on clinical markers, signs of β-cell autoimmunity, and HLA genotype in the index case. RESEARCH DESIGN AND METHODS: Children (n = 1,488) with type 1 diabetes diagnosed under 15 years of age were included in a cross-sectional study from the Finnish Pediatric Diabetes Register. Data on family history of diabetes and metabolic decompensation at diagnosis were collected using a questionnaire. Antibodies to β-cell autoantigens (islet cell antibodies, insulin autoantibodies, GAD antibodies, and antibodies to the islet antigen 2 molecule) and HLA genotypes were analyzed. RESULTS: A total of 12.2% of the subjects had a first-degree relative with type 1 diabetes (father 6.2%, mother 3.2%, and sibling 4.8%) and 11.9% had an affected second-degree relative. Children without affected relatives had lower pH (P < 0.001), higher plasma glucose (P < 0.001) and β-hydroxybutyrate concentrations (P < 0.001), a higher rate of impaired consciousness (P = 0.02), and greater weight loss (P < 0.001). There were no differences in signs of β-cell autoimmunity. The familial cases carried the HLA DR4-DQ8 haplotype more frequently than sporadic cases (74.0 vs. 67.0%, P = 0.02). CONCLUSIONS: When the extended family history of type 1 diabetes is considered, the proportion of sporadic diabetes cases may be reduced to <80%. A positive family history for type 1 diabetes associates with a less severe metabolic decompensation at diagnosis, even when only second-degree relatives are affected. Autoantibody profiles are similar in familial and sporadic type 1 diabetes, suggesting similar pathogenetic mechanisms. |
format | Online Article Text |
id | pubmed-3554291 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-35542912014-02-01 Extended Family History of Type 1 Diabetes and Phenotype and Genotype of Newly Diagnosed Children Parkkola, Anna Härkönen, Taina Ryhänen, Samppa J. Ilonen, Jorma Knip, Mikael Diabetes Care Original Research OBJECTIVE: To determine the frequency of newly diagnosed diabetic children with first- and second-degree relatives affected by type 1 diabetes and to characterize the effects of this positive family history on clinical markers, signs of β-cell autoimmunity, and HLA genotype in the index case. RESEARCH DESIGN AND METHODS: Children (n = 1,488) with type 1 diabetes diagnosed under 15 years of age were included in a cross-sectional study from the Finnish Pediatric Diabetes Register. Data on family history of diabetes and metabolic decompensation at diagnosis were collected using a questionnaire. Antibodies to β-cell autoantigens (islet cell antibodies, insulin autoantibodies, GAD antibodies, and antibodies to the islet antigen 2 molecule) and HLA genotypes were analyzed. RESULTS: A total of 12.2% of the subjects had a first-degree relative with type 1 diabetes (father 6.2%, mother 3.2%, and sibling 4.8%) and 11.9% had an affected second-degree relative. Children without affected relatives had lower pH (P < 0.001), higher plasma glucose (P < 0.001) and β-hydroxybutyrate concentrations (P < 0.001), a higher rate of impaired consciousness (P = 0.02), and greater weight loss (P < 0.001). There were no differences in signs of β-cell autoimmunity. The familial cases carried the HLA DR4-DQ8 haplotype more frequently than sporadic cases (74.0 vs. 67.0%, P = 0.02). CONCLUSIONS: When the extended family history of type 1 diabetes is considered, the proportion of sporadic diabetes cases may be reduced to <80%. A positive family history for type 1 diabetes associates with a less severe metabolic decompensation at diagnosis, even when only second-degree relatives are affected. Autoantibody profiles are similar in familial and sporadic type 1 diabetes, suggesting similar pathogenetic mechanisms. American Diabetes Association 2013-02 2013-01-17 /pmc/articles/PMC3554291/ /pubmed/23033245 http://dx.doi.org/10.2337/dc12-0445 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Original Research Parkkola, Anna Härkönen, Taina Ryhänen, Samppa J. Ilonen, Jorma Knip, Mikael Extended Family History of Type 1 Diabetes and Phenotype and Genotype of Newly Diagnosed Children |
title | Extended Family History of Type 1 Diabetes and Phenotype and Genotype of Newly Diagnosed Children |
title_full | Extended Family History of Type 1 Diabetes and Phenotype and Genotype of Newly Diagnosed Children |
title_fullStr | Extended Family History of Type 1 Diabetes and Phenotype and Genotype of Newly Diagnosed Children |
title_full_unstemmed | Extended Family History of Type 1 Diabetes and Phenotype and Genotype of Newly Diagnosed Children |
title_short | Extended Family History of Type 1 Diabetes and Phenotype and Genotype of Newly Diagnosed Children |
title_sort | extended family history of type 1 diabetes and phenotype and genotype of newly diagnosed children |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554291/ https://www.ncbi.nlm.nih.gov/pubmed/23033245 http://dx.doi.org/10.2337/dc12-0445 |
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