Charakterisierung der Glutamat Decarboxylase-Antikörper beim Prädiabetes und manifesten Typ I Diabetes

Abstract

Introduction:
The major goal of research in insulin dependent diabetes mellitus (IDDM) is the prevention of the progressive cell-destructive autoimmune disease. Therefore, prediction is necessary as early as possible. The detection of specific antibodies in serum samples is particularly helpful. The present work investigated the significance of glutamate decarboxylase antibodies (GAD ab) in comparison to the established markers namely: islet cell antibodies (ICA) and insulin autoantibodies (IAA). GAD ab are directed against an islet cell protein with the molecular weight of approx. 64 KD which has been identified as glutamate decarboxylase.

Aims of the study:
1.) Comparison of two different methods for the measurement of GAD ab (immunoprecipitation essay and radioimmunoassay (RIA)). 2.) Correlation of GAD ab to the known markers ICA and IAA. 3.) Influence of age, sex and time course on the markers. 4.) Evaluation of the markers for the prediction of IDDM in prediabetic subjects.

Study group:
75 individuals the majority of whom were part of the Giessen - Bad Oeynhausen prospective family study and whose sera were taken every 6 months. Eight of the 75 study subjects developed an IDDM during the observation period.

Results:
1.) The correlation between the GAD ab measurements with the immunoprecipitation assay and the RIA was highly significant. In contrast to the immunoprecipitation assay, the RIA is applicable for screening investigations. The advantages of the RIA are: ease of use, the use of recombinant GAD, lower amounts of radioactivity and the quantification of the results. 2.) The correlation of GAD ab to ICA and IAA was highly significant and significant, respectively. 3.) There was no correlation between the prevalence rates of antibodies with age or sex. GAD ab were detected in 7,7 % (3/39) of individuals before ICA and in 23,5 % (4/17) before IAA. 4.) Within the eight prediabetic subjects, the prevalence of GAD ab, ICA and IAA was 75 % (6/8), respectively. Using clinical criteria and the ICA status as a marker for increased risk of developing the disease, a highly significant correlation to risk was found for GAD ab- and IAA-positivity, respectively.

Summary:
The results show, that GAD ab are useful serological markers for the identification of the prediabetic stage in IDDM. They could be detected partly as unique markers in prediabetes or several years before ICA and IAA. They could therefore serve as useful tools in the diagnosis of early stages of the disease. This would allow early therapeutic interventions which could result in the prevention of the disease.

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