Genetic, autoimmune, and clinical characteristics of childhood- and adult-onset type 1 diabetes
Genetic, autoimmune, and clinical characteristics of childhood- and adult-onset type 1 diabetes. E Sabbah , K Savola , T Ebeling , P Kulmala , P Vähäsalo , J Ilonen , P I Salmela and M Knip Department of Pediatrics, University of Oulu, Finland. Abstract OBJECTIVE: To assess whether there are any dif...
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Published in | Diabetes care Vol. 23; no. 9; pp. 1326 - 1332 |
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Main Authors | , , , , , , , |
Format | Journal Article Conference Proceeding |
Language | English |
Published |
Alexandria, VA
American Diabetes Association
01.09.2000
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Subjects | |
Online Access | Get full text |
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Summary: | Genetic, autoimmune, and clinical characteristics of childhood- and adult-onset type 1 diabetes.
E Sabbah ,
K Savola ,
T Ebeling ,
P Kulmala ,
P Vähäsalo ,
J Ilonen ,
P I Salmela and
M Knip
Department of Pediatrics, University of Oulu, Finland.
Abstract
OBJECTIVE: To assess whether there are any differences in genetic, autoimmune, or clinical features between type 1 diabetes
presenting in childhood and that diagnosed later. RESEARCH DESIGN AND METHODS: We studied 352 individuals (252 children and
adolescents <20 years of age and 100 adults > or =20 years of age) manifesting clinical signs of type 1 diabetes over a period
of 7.5 years at a university hospital in northern Finland with a primary catchment area population of approximately 300,000.
The patients were analyzed for susceptible and protective HLA-DQB1 alleles (*02, *0302, *0301, *0602, *0603, and *0604), islet
cell antibodies (ICA), insulin autoantibodies, and antibodies to GAD and IA-2 (IA-2A). Their clinical symptoms and signs were
recorded at diagnosis. RESULTS: The adult patients carried the high-risk DQB1*02/0302 genotype less frequently than the children
and more often had protective genotypes. They also had a decreased frequency of all 4 single autoantibody specificities and
of multiple (> or =3) autoantibodies. The proportion of patients testing negative for all autoantibodies was lower among the
children than among the adults. IA-2A were associated with the DQB1*0302/x genotype in both the children and adults, and the
same held true for ICA among the adults. The adults were characterized by a higher proportion of males, a longer duration
of symptoms, and a lower frequency of infections during the preceding 3 months. In addition, they had a higher relative body
weight on admission and milder signs of metabolic decompensation (higher pH, base excess, and bicarbonate concentrations)
and a lower glycated hemoglobin level at diagnosis than the children. CONCLUSIONS: Clinical manifestation of type 1 diabetes
before the age of 20 years is associated with a strong HLA-defined genetic disease susceptibility, an intensive humoral immune
response to various beta-cell antigens, a higher frequency of preceding infections, and a shorter duration of symptoms and
more severe metabolic decompensation at diagnosis. Taken together, these observations suggest that the age at clinical onset
of type 1 diabetes is determined by the intensity of the beta-cell-destructive process, which is modulated by both genetic
and environmental factors. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0149-5992 1935-5548 |
DOI: | 10.2337/diacare.23.9.1326 |