Journal
DIABETES CARE
Volume 36, Issue 2, Pages 348-354Publisher
AMER DIABETES ASSOC
DOI: 10.2337/dc12-0445
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Funding
- Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research) [250114]
- Sigrid Juselius Foundation
- Novo Nordisk Foundation
- Liv and Halsa Fund
- Finnish Medical Foundation
- National Graduate School of Clinical Investigation
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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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