Relationship between autoantibodies against glutamic acid decarboxylase, thyroglobulin/thyroid microsome and DNA topoisomerase II in the clinical manifestation of patients with type 1 diabetes mellitus in Taiwan

Abstract

Objective: In a preliminary cross-sectional study, we discovered that DNA topoisomerase II autoantibodies (anti-TopII) were detected in 49.2% of 195 Chinese type 1 diabetes mellitus (type 1 DM) patients with a mean age of 14.5 years and a mean duration of disease of 4.6 years. In order to demonstrate the relationship between anti-TopII and other immunological characteristics in Chinese type 1 DM patients, and to evaluate its putative prediction efficacy in Chinese patients, we simultaneously examined the frequency of anti-glutamic acid decarboxylase autoantibodies (anti-GAD), anti-TopII, antithyroglobulin/antimicrosomal autoantibodies (ATA/AMiA) and C- peptide concentrations in our patients in the present study. Design and Methods: The frequency of anti-GAD and C-peptide levels, anti-TopII, and ATA/AMiA were examined in our patients by radioimmunoassay, enzyme-linked immunosorbent assay and hemagglutination respectively. Univariate comparisons were performed using Student's t-test for normal distributed data and Chi- square test for diclomatous data. Multivariate analysis was used for interpreting the independent risk factors which increased the incidence of anti-TopII. Results and Conclusions: The positivities for anti-GAD, anti- TopII, ATA/AMiA and C-peptide were 45.8%, 50.2%, 13.4% and 11.4% respectively. Anti-GAD and anti-TopII frequencies in our patients were similar when we stratified the patients by age, age at onset and duration. These observations imply that anti-GAD and anti-TopII remain persistent in Chinese patients with long-term type 1 DM duration. The most interesting finding is that anti-TopII frequency is more persistent than anti-GAD in our patients, especially when the diabetic duration is longer than 11 years. This indicates that anti-TopII, rather than anti-GAD, might act as a better indicator for monitoring the pathogenesis of Chinese type 1 DM patients especially in patients with a long-standing duration of disease. The late age of onset (>18 years) is a risk factor which increased the incidence of anti- TopII according to multivariate analysis. We further analyzed different manifestations between the youth- and adult-onset type 1 DM and found that adult-onset type 1 DM is characterized by better preservation of residual β- cell function and higher frequencies of autoantibodies.