A1 Refereed original research article in a scientific journal
Extended Family History of Type 1 Diabetes and Phenotype and Genotype of Newly Diagnosed Children
Authors: Parkkola Anna, Härkönen Taina, Ryhänen Samppa J, Ilonen Jorma, Knip Mikael, the Finnish Pediatric Diabetes Register
Publisher: American Diabetes Association
Publication year: 2013
Journal: Diabetes Care
Number in series: 2
Volume: 36
Issue: 2
First page : 348
Last page: 354
Number of pages: 7
ISSN: 0149-5992
DOI: https://doi.org/10.2337/dc12-0445
Abstract
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 beta-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 beta-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 beta-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 beta-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 casesmay 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. Diabetes Care 36:348-354, 2013
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 beta-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 beta-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 beta-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 beta-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 casesmay 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. Diabetes Care 36:348-354, 2013
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