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In insulin-autoantibody-positive children from the general population, antibody affinity identifies those at high and

M Schlosser1, K Koczwara, H Kenk

  • 1Institute of Pathophysiology, University of Greifswald, Karlsburg, Germany.

Diabetologia
|July 13, 2005
PubMed

Insights

Insulin autoantibody (IAA) affinity can predict type 1 diabetes risk in children. Higher IAA affinity indicates a greater likelihood of developing diabetes, aiding in early risk stratification.

Area of Science:

  • Immunology
  • Endocrinology
  • Pediatrics

Background:

  • Insulin autoantibodies (IAA) are key predictors of type 1 diabetes onset.
  • However, not all IAA-positive children progress to diabetes, necessitating better risk stratification methods.
  • IAA affinity has shown promise in identifying high-risk individuals within affected families.

Purpose of the Study:

  • To evaluate insulin autoantibody (IAA) affinity as a marker for stratifying type 1 diabetes risk in the general IAA-positive pediatric population.
  • To determine if IAA affinity can differentiate between children who will and will not develop type 1 diabetes or multiple islet autoantibodies.

Main Methods:

  • Assessed IAA affinity using competitive binding assays with labeled insulin and varying concentrations of cold insulin and proinsulin.
  • Sera were analyzed from 46 IAA-positive children in the Karlsburg Type 1 Diabetes Risk Study.
  • The study population comprised schoolchildren from north-eastern Germany.

Main Results:

  • IAA affinity varied significantly, ranging from 5 x 10(6) to 1.2 x 10(11) l/mol.
  • Children who developed multiple islet autoantibodies or diabetes exhibited higher IAA affinity (median 3.5 x 10(9) l/mol) compared to those who did not (median 1.3 x 10(8) l/mol; p<0.0001).
  • A threshold of >= 10(9) l/mol correctly identified 22/24 high-risk children and 18/22 low-risk children. Proinsulin-reactive IAA also showed significantly higher affinity (p<0.0001).

Conclusions:

  • Insulin autoantibody (IAA) affinity measurement is a robust method for identifying individuals at high risk for type 1 diabetes.
  • This assay can effectively stratify risk among IAA-positive children.
  • High-affinity IAA is strongly associated with progression to type 1 diabetes.
Abstract

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