Higher prevalence of autoantibodies to insulin and GAD65 in Swedish compared to Lithuanian children with type 1 diabetes.
We compared the prevalence of beta-cell autoantibodies and genetic risk factors in Sweden and Lithuania. Ninety-six patients from Sweden and 96 from Lithuania matched for age and gender (1-15 years old, median age 9.0 years) were included. We analyzed autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and the protein tyrosine phosphatase like IA-2 (IA-2A) as well as risk-associated polymorphisms of HLA, insulin and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) genes. The frequency of patients positive for IAA and GADA was higher in Sweden than in Lithuania (p = 0.043 and 0.032). The differences remained even when the patients were matched for HLA, insulin and CTLA-4 risk genotypes. Patients with low levels of IAA had higher levels of HbA1c and ketones at diagnosis. The frequency of the risk haplotype DR4-DQ8 was higher in Swedish than in Lithuanian patients (p = 0.004), as well as the high-risk combination of DR4-DQ8 and DR3-DQ2 haplotypes (p = 0.009). Our results suggest that autoimmune process against insulin and GAD(65) is more common at diagnosis in children in areas with high incidence of type 1 diabetes (T1D), independent of genetic risk markers. Furthermore, the disease in patients with insulin autoantibodies seems to be clinically milder.
Holmberg
Hanna
H
Department of Molecular and Clinical Medicine, Clinical Research Center, Division of Pediatrics and Diabetes Research Centre, Faculty of Health Sciences, Linköpings Universitet, Sweden. hanho@imk.liu.se
Vaarala
Outi
O
Sadauskaite-Kuehne
Vaiva
V
Ilonen
Jorma
J
Padaiga
Zilvinas
Z
Ludvigsson
Johnny
J
D000293:Adolescent; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity / Q000235:genetics; D001786:Blood Glucose / Q000032:analysis; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000453:epidemiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005968:Glutamate Decarboxylase / Q000097:blood*; D006442:Glycated Hemoglobin / Q000032:analysis; D006683:HLA-DQ Antigens / Q000235:genetics; D015803:HLA-DR3 Antigen / Q000235:genetics; D015804:HLA-DR4 Antigen / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007328:Insulin / Q000097:blood; D007330:Insulin Antibodies / Q000097:blood*; D050417:Insulin-Secreting Cells / Q000276:immunology; D007527:Isoenzymes / Q000097:blood*; D008097:Lithuania / Q000453:epidemiology; D008297:Male; D011110:Polymorphism, Genetic; D013548:Sweden / Q000453:epidemiology
D001323:Autoantibodies; D001786:Blood Glucose; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D006683:HLA-DQ Antigens; D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen; D007328:Insulin; D007330:Insulin Antibodies; D007527:Isoenzymes; C401141:glutamate decarboxylase 2