Clinical and genetic characteristics of diabetic patients with high-titer (>10,000 U/ml) of antibodies to glutamic acid decarboxylase
Introduction
Type 1 diabetes mellitus is considered to be an organ-specific autoimmune disease, with both genetic and environmental factors contributing to the development of the disease. Although different gene alleles and haplotypes are linked with type 1 diabetes in different ethnic groups, specific HLA class II-DR and −DQ haplotypes are associated with the susceptibility to type 1 diabetes. However, the age of onset of type 1 diabetes is variable and it has been reported that the frequencies of some type 1 diabetes susceptibility HLA class II alleles and/or haplotypes may vary depending on the age of disease onset [1], [2]. It has also been reported that several polymorphisms of MHC classes I and III genes and interleukin genes are associated with the age at onset of type 1 diabetes [3], [4], [5], [6], [7], [8], [9].
Autoantibodies to glutamic acid decarboxylase (anti-GADab) [10] have both diagnostic and predictive value as immunological markers of type 1 diabetes, not only in juvenile-onset type 1 diabetes but also in patients with adult-onset diabetes diagnosed initially with type 2 diabetes either as slowly progressive type 1 (insulin-dependent) diabetes mellitus (SPIDDM) or latent autoimmune diabetes in adults (LADA) [11], [12], [13], [14], [15], [16]. However, it is well known that anti-GADabs also occur in typical type 2 diabetes patients and that not all patients with anti-GADab develop insulin dependency. Harrison et al. have reported that high concentrations of anti-GADab are associated with slower progression to clinical disease [17]. Although anti-GADab are also found in stiff-man-syndrome (SMS) [1], [18], [19], [20] and autoimmune polyendocrine syndrome (APES) [20], [21], [22], the anti-GADab profiles in these two diseases differ from those in patient with type 1 diabetes.
In the present study, we investigated the clinical characteristics and genetic background of patients with diabetes with high-titers of anti-GADab (>10,000 U/ml).
Section snippets
Patients
A total of 13 diabetic patients (6 males, 7 females) with a high-titer of anti-GADab (>10,000 U/ml) were identified from previously reported studies of anti-GADab screening in approximately 4500 patients with adult-onset diabetes and 228 patients with juvenile-onset diabetes [7], [8], [9], [23]. Twenty-eight middle-aged (14 males, 14 females; age 35–51 years; mean age at onset 39.1 ± 2.8 years) and 13 elderly (5 males, 8 females; age 66–79 years; mean age at onset 52.6 ± 7.8 years) patients with an
Results
A titer of anti-GADab >10,000 U/ml was found in 13 of the approximately 4500 patients with adult-onset diabetes, whereas it was not found in 228 patients with juvenile-onset diabetes. Table 1 shows the clinical profile and genetic background of these 13 patients with an anti-GADab titer >10,000 U/ml. The mean (±S.D.) age was 70.8 ± 3.9 years (range, 64–78), while the age at onset of diabetes was 50.4 ± 5.4 years (range, 43–61). One patient had Graves’ disease (Pt. no. 3) and one patient received
Discussion
The aim of this study was to investigate the clinical aspects and genetic background of patients with diabetes with a high-titer of anti-GAD antibodies. While we found a high-titer of anti-GADabs of >10,000 U/ml in elderly diabetic patients, we did not find similarly high titers of antibodies in patients with either juvenile-onset type 1 diabetes or LADA. Several studies have demonstrated that a high-titer of anti-GADab is a good predictor for the development of insulin-requiring diabetes in
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