Diabetologia

, Volume 42, Issue 6, pp 671–677

Early expression and high prevalence of islet autoantibodies for DR3/4 heterozygous and DR4/4 homozygous offspring of parents with Type I diabetes: The German BABYDIAB study

  • M. Schenker
  • M. Hummel
  • K. Ferber
  • M. Walter
  • E. Keller
  • E. D. Albert
  • H.-U. Janka
  • C. Kastendiek
  • M. Sorger
  • F. Louwen
  • A.-G. Ziegler
Articles

Abstract

Aims/hypothesis. Islet autoantibodies precede the clinical onset of Type I (insulin-dependent) diabetes mellitus. The cumulative development of such autoantibodies in infants followed from birth and in particular infants with high-risk HLA genotypes is poorly defined, but such information is essential to design trials to prevent islet autoimmunity. Methods. HLA genotypes were determined in offspring of parents with Type I diabetes who were followed from birth for at least 2 years (median follow-up: 3.1 years) and who were characterised for the expression of insulin, GAD65, IA-2 and islet cell autoantibodies at birth, 9 months, 2 and 5 years of age. Results. The HLA genotypes DRB1*03/04(DQB1 *57non-Asp) and DRB1*04/04(DQB1*57non-Asp) were present in 7.1 % and 5.0 % of offspring of parents with Type I diabetes. The frequency of both genotypes was increased in offspring who developed islet autoantibodies within the first 2 years of life (27.3 % vs 5.5 %, odds ratio 6.3 [p = 0.002] and 22.7 % vs 4.2 %, odds ratio 6.6 [p = 0.003]) and half of all offspring who developed antibodies had these genotypes. Other genotypes were not associated with an increase in risk. By life-table analysis, the cumulative risk of developing islet autoantibodies by the age of 2 years was 20 % (95 % CI 9.4,30.6) for offspring carrying either the DRB1*03/04(DQB1 *57non-Asp) or the DRB1*04/04(DQB1*57non-Asp) genotype compared with 2.7 % (95 % CI 1.2,4.2) for offspring without these genotypes (p < 0.0001). Conclusion/interpretation. These data show that early appearance of islet autoantibodies is remarkably frequent for DR3/4 heterozygous and DR4/4 homozygous offspring and indicate that primary prevention could be considered once available in an offspring cohort selected for these genotypes. [Diabetologia (1999) 42: 671–677]

Keywords HLA genotype Type I diabetes islet autoimmunity autoantibody appearance. 

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • M. Schenker
    • 1
  • M. Hummel
    • 1
  • K. Ferber
    • 1
  • M. Walter
    • 1
  • E. Keller
    • 2
  • E. D. Albert
    • 2
  • H.-U. Janka
    • 3
  • C. Kastendiek
    • 3
  • M. Sorger
    • 4
  • F. Louwen
    • 5
  • A.-G. Ziegler
    • 1
  1. 1.Third Medical Department, Munich-Schwabing Hospital and Diabetes Research Institute, Munich, GermanyDE
  2. 2.Laboratory for Immunogenetics, Ludwig-Maximilians-University, Munich, GermanyDE
  3. 3.Central Hospital Bremen-North, Bremen, GermanyDE
  4. 4.Medical Polyclinic, Bonn, GermanyDE
  5. 5.Obstetric Department, University of Münster, GermanyDE

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