ISSN:
1432-0428
Keywords:
Keywords HLA genotype
;
Type I diabetes
;
islet autoimmunity
;
autoantibody appearance.
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
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]
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s001250051214
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