Elsevier

The Lancet

Volume 343, Issue 8910, 4 June 1994, Pages 1383-1385
The Lancet

Articles
Antibodies to glutamic acid decarboxylase as predictors of insulin-dependent diabetes mellitus before clinical onset of disease

https://doi.org/10.1016/S0140-6736(94)92521-6Get rights and content

Abstract

We have done a study designed to ascertain the effectiveness of measuring antibodies to glutamic acid decarboxylase (anti-GAD) in predicting insulin-dependent diabetes mellitus (IDDM). Anti-GAD was measured in prediabetic sera from 151 women aged 20-39 years with newly diagnosed diabetes mellitus who had been identified through a nationwide diabetes register. Multiple serum samples had been collected from these women up to 10 years before the clinical onset of diabetes during their earlier pregnancies. Anti-GAD was measured with a radioimmunoprecipitation assay. Anti-GAD was detected in 82% of 28 women with IDDM, in 36% of 11 women with non-insulin-dependent diabetes mellitus, and in 5% of 112 women with gestational diabetes mellitus. In a random sample of 100 non-diabetic young Finnish women, none had anti-GAD. The sensitivity of the anti-GAD assay for predicting IDDM was 82 1% and the specificity was 100%. The longest time of anti-GAD positivity before clinical onset of IDDM was 10 years. Once positive, anti-GAD levels remained stable and no patients became negative after a positive test during the prediabetic period. Anti-GAD is a valuable early predictive marker and is associated with a very high risk for development of IDDM.

References (30)

  • A. Reetz et al.

    GABA and pancreatic beta-cells: co-localization of glutamic acid decarboxylase (GAD) and GABA with synaptic-like microvesicles suggests their role in GABA storage and secretion

    EMBO J

    (1991)
  • Dl Kaufman et al.

    Autoimmunity to two forms of glutamic decarboxylase in insulin-dependent diabetes mellitus

    J Clin Invest

    (1992)
  • Ch Thivolet et al.

    Glutamic acid decarboxylase (GAD) autoantibodies are additional predictive markers of type 1 (insulin-dependent) diabetes mellitus in high risk individuals

    Diabetologia

    (1992)
  • Mj Rowley et al.

    Antibodies to glutamic acid decarboxylase discriminate major type of diabetes mellitus

    Diabetes

    (1992)
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