Genetic, autoimmune, and clinical characteristics of childhood- and adult-onset type 1 diabetes.
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.


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.
Sabbah
E
E
Department of Pediatrics, University of Oulu, Finland.
Savola
K
K
Ebeling
T
T
Kulmala
P
P
Vähäsalo
P
P
Ilonen
J
J
Salmela
P I
PI
Knip
M
M
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D001323:Autoantibodies / Q000097:blood*; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002096:C-Peptide / Q000097:blood; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D005387:Finland; D005968:Glutamate Decarboxylase / Q000276:immunology; D006442:Glycated Hemoglobin / Q000032:analysis; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006785:Hospitals, University; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male
D001323:Autoantibodies; D001786:Blood Glucose; D002096:C-Peptide; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; D000949:Histocompatibility Antigens Class II; C069051:HLA-DQB1 antigen; C024211:islet cell antibody