The Prediction of Type 1 Diabetes in discordant and concordant families: 16 years of follow-up. Focus on the future

Abstract

For 40 years, research continues to improve the forecasting methods and the development of effective and safe methods of preventing type 1 diabetes mellitus (T1DM). Аim. Prediction of the early preclinical stage of T1DM. Materials and methods. We studied the predisposing and protective haplotypes (HLA-DRB1, gene DQ) together with immunological markers (ICA, GADA, IAA) in 224 discordant/concordant families. Results. At the Endocrinology Research Centre, population and family risks of the development of T1DM in Russia were calculated on the basis of population genetic approaches. The analysis of the prevalence of HLA genotypes among T1DM patients revealed that the high-risk haplotypes in the structure of genotype(s) DQ2 and/or DQ8 in combination with the others were 78%: of these genotypes DQ2/DQ8, DQ2/DQ2, and DQ8/DQ8 accounted for 35%; DQ2/X* and DQ8/X* accounted for 43%; and the low-risk genotype Х*/Х* accounted for 22%. The genotype Х/Х consisted of weaker predisposing haplotypes that were specific to the Russian population in combination with neutral haplotypes or those consisting of neutral haplotypes only. The analysis of patients with T1DM genotypes revealed that high-risk genotypes (DQ2/DQ8) were more common in ill children up to the age of 5 (33% of cases) than in T1DM children over 10 years (23%) (p=0.05). Conversely, the low-risk genotypes were significantly less likely to be found in children with manifestations of diabetes up to 5 years than in sick people over 10 years [5% and 13%, respectively (p

Keywords

• type 1 diabetes
• genetic susceptibility
• hla-haplotypes
• genotypes
• phenotypes
• autoantibodies to betbeta-cells