Diabetologia

, Volume 45, Issue 12, pp 1658–1666 | Cite as

IA-2 autoantibodies predict impending Type I diabetes in siblings of patients

  •  K. Decochez
  •  I. De Leeuw
  •  B. Keymeulen
  •  C. Mathieu
  •  R. Rottiers
  •  I. Weets
  •  E. Vandemeulebroucke
  •  I. Truyen
  •  L. Kaufman
  •  F. Schuit
  •  D. Pipeleers
  •  F. Gorus
Rapid Communication

Abstract

Aims/hypothesis. Multiple islet autoantibody positivity is currently believed to best predict progression to Type I (insulin-dependent) diabetes mellitus. We compared its predictive value with that of positivity for a particular type of islet autoantibody, directed against the IA-2 antigen.

Methods. Autoantibodies against islet cell cytoplasm (ICA), insulin (IAA), GAD (GADA) and IA-2 (IA-2A) were measured at initial sampling in 1724 non-diabetic siblings (median age [range]:16 [0–39] years) of Type I diabetic patients with a median follow-up of 50 months.

Results. On initial sampling 11% of siblings were positive for one antibody type or more and 2.1% for three of more types. During follow-up, 27 antibody-positive siblings developed diabetes. Using survival analysis, the risk for clinical onset within 5 years was 34% in subjects positive for three or more types compared with 13% in those with one type or more. Progression to diabetes amounted to 12% within 5 years among siblings positive for IAA, 20% for ICA, 19% for GADA but 59% for IA-2A (p<0.001 vs absence of the respective antibody). IA-2A were detected in 1.7% of all siblings and in 56% of the prediabetic subjects on first sampling. Initial positivity for two or three antibody markers was associated with a higher progression rate in IA-2A positive as compared to IA-2A negative siblings (p=0.001). In absence of IA-2A initial positivity for another antibody (IAA, ICA or GADA) conferred a low (<10% within 5 years) risk of diabetes compared to subjects lacking this antibody.

Conclusions/interpretation. In siblings of Type I diabetic patients, IA-2A positivity is a more direct predictor of impending clinical onset than multiple antibody positivity per se. Assessment of IA-2A status allows us to select subjects with homogeneously high risk of diabetes for participation in prevention trials.

Type I diabetes siblings prediction prevention IA-2 autoantibodies GAD autoantibodies insulin autoantibodies islet cell antibodies HLA-DQ 

Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  •  K. Decochez
    • 2
  •  I. De Leeuw
    • 3
  •  B. Keymeulen
    • 2
  •  C. Mathieu
    • 4
  •  R. Rottiers
    • 5
  •  I. Weets
    • 2
  •  E. Vandemeulebroucke
    • 2
  •  I. Truyen
    • 2
  •  L. Kaufman
    • 6
  •  F. Schuit
    • 2
  •  D. Pipeleers
    • 2
  •  F. Gorus
    • 2
  1. 1.Diabetes Research Centre, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
  2. 2.Diabetes Research Centre, Free University of Brussels, Brussels, Belgium
  3. 3.Department of Endocrinology, University of Antwerp, Antwerp, Belgium
  4. 4.Department of Endocrinology, University of Leuven, Leuven, Belgium
  5. 5.Department of Endocrinology, University of Ghent, Ghent, Belgium
  6. 6.Department of Biostatistics, Free University of Brussels, Brussels, Belgium

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