Progression to multifactorial diseases is determined jointly by genes and environment. A valid approach for the prediction and prevention of such diseases might be to define at birth, or at an early age, the population at increased genetic risk by analysing the risk genes or risk alleles, the subsequent follow-up of those at risk, and the appropriate implementation of preventive measures at optimum time, if available. The feasibility and acceptance of population-wide genetic tests aimed at an early recognition of the risk of common multifactorial diseases with clinical presentation later in life is not known.The Type I Diabetes Prediction and Prevention project (DIPP) is an effort to predict and search for means to delay or prevent the disease in a large population-based cohort of children in Finland. The case of Type I diabetes is probably a useful model for the prediction and prevention of chronic, multifactorial Diabetologia (2001) AbstractAims/hypothesis. Population-wide genetic screening of susceptibility to multifactorial diseases will become relevant as knowledge of the pathogenesis of these diseases increases and preventive interventions are identified. Methods. Feasibility and acceptance of neonatal genetic screening for Type I (insulin-dependent) diabetes mellitus susceptibility and adherence of the atrisk children to frequent autoantibody follow-up were studied. Screening was offered to all families. The infants with HLA-DQB1 genotypes *02/*0302 and *0302/x (x¹*02, *0301, *0602) were invited to autoantibody follow-up. The children who developed signs of b-cell autoimmunity were invited to a separate prevention trial. Results. The parents of 31 526 babies born between November 1994 and April 1999 (94.4 % of those eligible) agreed to genetic screening. We found that 4651 infants (14.8 %) had increased genetic risk (2.5 to 15 times that of the general population) for Type I (insulin-dependent) diabetes mellitus, and 80 % of them joined the autoantibody surveillance. At the age of 1, 2, 3 and 4 years, 74, 69, 68 and 76 % of the at-risk children, respectively, attended the follow-up. A total of 17 of the 22 children (77 %) who were born during the study period and have developed diabetes carry the risk genotypes we currently use for screening. Conclusions/interpretation. Population-based screening of genetic susceptibility for Type I diabetes, linked with a possibility to participate later in a prevention trial, is highly accepted in Finland and identifies about 75 % of those developing diabetes at an early age. Families adhere well to the frequent measurement of signs of b-cell autoimmunity in the children at-risk. [Diabetologia (2001) 44: 290±297]

The described strategy for genetic prediction of Type 1 diabetes mellitus relies on the convenient genotyping procedure and could be applied in large scale screening projects such as DIPP.

The near-automatic typing procedure developed is attractive for large-scale screening projects, such as diabetes prevention and intervention trials.

No abstract

Timing of onset of autoimmunity is a prerequisite for unmasking triggers and pathogenesis of type 1 diabetes. We followed 4,590 consecutive newborns with 8 or 3% HLA-DQB1 conferred risk for type 1 diabetes at 3-, 6-, or 12-month intervals up to 5.5 years of age. Islet cell autoantibodies (ICAs) and, in the 137 children with ICAs, insulin autoantibodies (IAAs), GAD65 autoantibodies (GADAs), and IA-2 protein autoantibodies (IA2As) were measured. Children with high genetic risk developed ICAs more often than those with moderate risk (log-rank P ‫؍‬ 0.0015); 85 and 91% remained ICA negative by 5 years of age, respectively. The time of appearance of biochemical autoantibodies was then compared with the appearance of ICAs. IAAs and GADAs emerged usually before ICAs (means ؊1.8 and ؊1.5 months, respectively) and IA-2As after ICAs (mean 2.0 months). Ninety-five percent of all IAAs, GADAs, and IA-2As seroconversions occurred in a cluster (؊12 to 8 months) around the ICA seroconversion. We conclude that diabetes-associated autoantibodies emerged in children with predisposing HLA-DQB1 alleles after 3 months of age at a constant tempo, determined by the genetic risk level, usually in the order of IAA, GADA, ICA, and IA-2A. Seroconversion to multiple autoantibody positivity usually occurred tightly clustered in time. Diabetes 51:646 -651, 2002