Stratification of type 1 diabetes risk on the basis of islet autoantibody characteristics

Diabetes. 2004 Feb;53(2):384-92. doi: 10.2337/diabetes.53.2.384.

Abstract

Family history of type 1 diabetes and autoantibodies to the islet antigens insulin (IAA), glutamate decarboxylase (GADA), and the protein tyrosine phosphatase-like protein IA-2 (IA-2A) are strong predictors of type 1 diabetes, but the rate of progression to diabetes in multiple islet autoantibody-positive relatives varies widely. We asked whether detailed characterization of islet autoantibodies that included determination of titer, epitope specificity, and IgG subclass would improve diabetes prediction in a large cohort of autoantibody-positive relatives. The study shows a strong association between risk and high titer, broad antibody responses to IA-2 and insulin. The highest risks were associated with high-titer IA-2A and IAA, IgG2, IgG3, and/or IgG4 subclass of IA-2A and IAA, and antibodies to the IA-2-related molecule IA-2beta. Using models based on these antibody characteristics, autoantibody-positive relatives can be classified into groups with risks of diabetes ranging from 7 to 89% within 5 years.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Autoantibodies / blood*
  • Diabetes Mellitus, Type 1 / classification
  • Diabetes Mellitus, Type 1 / epidemiology*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Family
  • Female
  • Glutamate Decarboxylase / immunology
  • Humans
  • Immunoglobulin G / blood
  • Insulin Antibodies / blood*
  • Male
  • Multivariate Analysis
  • Risk Assessment
  • Risk Factors

Substances

  • Autoantibodies
  • ICA512 autoantibody
  • Immunoglobulin G
  • Insulin Antibodies
  • islet cell antibody
  • Glutamate Decarboxylase