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). A{cyrillic}im. 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 Kh{cyrillic}*/Kh{cyrillic}* accounted for 22%. The genotype Kh{cyrillic}/Kh{cyrillic} 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 <0.05)]. This is consistent with hereditary load of diabetes manifestations in young children and with the earlier data. The 16-year prospective surveillance showed that the manifestation of the disease occurred in 8.4% of siblings. The analysis of the frequency of autoantibodies revealed that autoantibodies were identified the most reliably prior to the manifestation of the disease compared with T1DM patients in the initial period and healthy siblings (eldest siblings without the disease during the whole monitoring period): 90%, 48.6% and 31%, respectively, p <0.05. Conclusion. The 16-year prospective surveillance in families with T1DM showed that the frequency of recurring diabetes cases was 8.4%, which exceeds the siblings' rate of risk of 6.4% that had been empirically calculated 20 years ago. This may be due to an increase in the incidence of T1D in the population and different methodological approaches (one-time screening versus long-term monitoring).