Feasibility of genetic and immunological prediction of type I diabetes in a population-based birth cohort

Diabetologia. 2001 Mar;44(3):290-7. doi: 10.1007/s001250051616.

Abstract

Aims/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 at-risk 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 (x not equal to *02, *0301, *0602) were invited to autoantibody follow-up. The children who developed signs of beta-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 beta-cell autoimmunity in the children at-risk.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Autoantibodies / blood
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / epidemiology*
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology
  • Feasibility Studies
  • Female
  • Finland / epidemiology
  • Follow-Up Studies
  • Genetic Testing*
  • Genotype
  • HLA-DQ Antigens / genetics*
  • HLA-DQ beta-Chains
  • Humans
  • Incidence
  • Infant, Newborn
  • Islets of Langerhans / immunology
  • Longitudinal Studies
  • Male
  • Predictive Value of Tests
  • Risk Assessment
  • Risk Factors
  • Time Factors

Substances

  • Autoantibodies
  • HLA-DQ Antigens
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen