[ Diabetes Solutions ]

Glutamic acid decarboxylase autoantibodies in preclinical insulin-dependent diabetes.


To study the persistence of Type I (insulin-dependent) diabetes mellitus associated autoantibodies and their relation to genetic risk markers and clinical characteristics of the disease after clinical manifestation, serum samples were obtained from 90 children and adolescents at diagnosis and 2, 5 and 10 years later. 8, 98122 Messina, Italy; tel 39 090 293 6528; fax 39 090 292 1554; email domenico.cucinotta{at}unime.it. ICA were present in 45.4 per cent of patients with juvenile insulin-dependent diabetes (IDD) during the first six months of disease and in 29.1 per cent of patients between 6 and 12 months of disease onset; ICA presence decreased to 19.2 per cent and 20.6 per cent after one and five years of duration of diabetes. Of the relatives who progressed to diabetes, 94% had at least one of these autoantibodies on the first screening, while ICA proved to be the most sensitive single marker (sensitivity 74%). Although used in fewer laboratories, the ELISA for IA-2A also improved and achieved AUC equivalent to those of in-house RIA, although results of the two assay formats correlated less well than for GADA. Autoimmune liver disease, particularly AIH type 2, has been reported to develop in patients with T1D, and vice versa [3–7]. Larger therapeutic doses may be required because of antibody-induced insulin resistance.

Islet cell antibodies have been largely abandoned because the indirect immunofluorescence assays are complex, labor-intensive, and hard to standardize. Our laboratory participated in the latest 2010 Diabetes Antibody Standardization Program. We conclude that (i) GAD is an (auto)antigen in a majority of subjects operationally defined as having preclinical IDDM, (ii) pancreatic islet and brain GAD are likely to be cross-reactive, and (iii) the majority of GAD antibodies are directed away from the catalytic site of the brain enzyme. These findings demonstrated that CPH-Abs may allow discrimination of a more latent subset of adult-onset autoimmune diabetes (LADA) whose features are intermediate between those with classic GAD-Ab+ LADA and patients with Ab− T2D. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. The IAA, GAD, and IA-2 levels were log-transformed for analyses.

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