Abstract

Objective. The aim of the study was to compare the genetic risk defined by HLA-DQB1 alleles and the disease-associated autoantibodies in Estonian children and adult patients with new-onset type 1 diabetes (T1D).
Methods. The study involved 44 children and adolescents 2−18 years of age and 49 adults 20−62 years of age with new-onset T1D, seen in two main hospitals in 2001−2003 in Estonia, and 164 healthy controls. HLADQB1 genotyping included alleles *02, *0302, *0301, *0602 and *0603. The patients and the controls were classified into four risk groups (high, moderate, low and decreased risk) based on combinations of the alleles predisposing to T1D (*02, *0302) or protecting from the disease (*0301, *0602 and *0603). In all patients islet cell antibodies (ICA), autoantibodies to glutamic acid decarboxylase (GADA), tyrosine phosphatase (IA-2A), and insulin (IAA) were determined.
Results. The high risk genotype was present in 22.6% of the patients and 3.6% of the controls (p<0.0001). Of the patients 19.4% and of the controls 5.5% carried moderate risk genotypes (p = 0.0011). There was no significant difference in the prevalence of low risk genotypes between the patients and the controls. However, decreased risk (protective) genotypes were present in 61% of the control subjects vs. 20.4% of the patients (p<0.0001). Comparison of the prevalence of high, moderate and low risk and protective genotypes in the patients with disease onset in childhood or adulthood revealed no differences between the groups. In children with T1D the prevalence of IA-2A, GADA, ICA and IAA was 81.8, 79.5, 65.9 and 50%, respectively. Among the adults 51, 63.3, 46.9 and 22.9% of the patients had IA-2A, GADA, ICA and IAA, respectively. Diagnostic sensitivity for T1D, using the combined testing of IA-2A and GADA, was 95.5% in the children and 73.5% in the adults.
Conclusions. The manifestation of T1D is rather common also in adults in Estonia. The genetic risk for T1D defined by HLA-DQB1 alleles is similar in young- and adult-onset disease. Combined testing of GADA and IA- 2A may help to confirm the diagnosis of T1D in clinical practice, especially in adults.