Diagnosis of autoimmune beta cell destruction by genetic risk analysis, autoantibody evaluation and the test of stimulated insulin secretion performance in first-degree relatives of diabetic patients. 208 Czech children and adults (101 boys and 107 girls, 186 siblings, 22 offspring of diabetic parents, aged 1 - 22 years, mean age 11.5 ± 5.4 years) were enrolled in the study. Complete DQB1, DQA1 typing and DRB1*04 subtyping were performed by the PCR in 202 subjects. Sera of all children were investigated for anti-GAD65, anti-IA2 and insulin antibodies using RIA methods. he cut-off normal levels were determined as the 99th percentile of 105 non-diabetic children. IVGTT was performed in children with significant titre of one or more autoantibodies. Total level of stimulated insulin secretion < 48 mU/l was assessed as defect of FPIR. Risk genotype DQA1*05-DQB1*0201/DQA1*03-DQB1*0302 (OR = 100, CI 95 % 13 - 730) was found in 24 of 202 first-degree relatives (12 %). 22 children (11 %) carried strong protective allele DQB1*0602 (OR = 0.03, CI 95 % 0.01 - 0.12). Autoantibody positivity was recognised in 9 of 208 children (2.9 %) and IVGTT was performed. Positivity of anti-GAD65, anti-IA2 or IAA was identifi-ed in 5 of 24 children with the highest risk genotype (21 %) and in 4 children of 113 with lower risk or neutral genotypes (3.5 %). Borderline positivity of one autoantibody was found in 1 boy with the highest risk genotype and in 2 children with lower risk genotypes. Only temporary antiGAD65 positivity was found in girl with protective genotype. ype 1 diabetes mellitus was diagno-sed in boy during IVGTT and disease manifested 6 months after IVGTT in girl with defect of FPIR. Standardised methods for prediction of ype 1 diabetes were introduced in first-degree relatives of diabetic patients. hese methods are used for Czech registry of diabetic children.

        Key words: Words: Autoimmune insulitis - Genetic risk - Autoantibody - Stimulated insulin secretion