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 immunosorbant 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 antiTopII, 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 b-cell function and higher frequencies of autoantibodies.

Prevalence of Glutamic Acid Decarboxylase Antibody Positivity and its Association with Insulin Secretion and Sensitivity in Autoimmune Thyroid Disease: A Pilot Study

“…Hashimoto's thyroiditis is the most common autoimmune thyroid disorder (Weetman and McGregor, 1994). Type 1 diabetes which results from the autoimmune destruction of pancreas b-cell destruction through T cell-mediated immunity is frequently associated with circulating antibodies to insulin (IAA), islet cell cytoplasmic antigens (ICA), GAD-Ab and protein thyrosine phosphatase like-protein (IA-2ab) (Bottazzo et al, 1974;Palmer et al, 1983;Baekkeskov et al, 1990;Lan et al, 1996;Jun et al, 2002b) These two diseases, both of which have an autoimmune nature, can be seen concomitantly (Kawasaki et al, 1995;McCanlies et al, 1998;Fernandez-Castaner et al, 1999;Hansen et al, 1999;Rattarasam et al, 2000;Franzese et al, 2000;Shiau et al, 2000;Jaeger et al, 2001; Barrova et al, 2004). GAD-Ab, which plays a role in type 1 diabetes mellitus is more commonly encountered in patients with Hashimoto's thyroiditis compared to the normal population, even without the presence of full blown diabetes (Kawasaki et al, 1995).…”

Distinct changes to pancreatic volume rather than pancreatic autoantibody positivity: Insights into immune checkpoint inhibitors induced diabetes mellitus

“…Furthermore, race may also contribute to the difference in autoantibody prevalence, with studies in Asia showing a lower prevalence of GAD-Ab in newly diagnosed patients with T1DM compared to people from European countries. [21,[28][29][30][31] Therefore, baseline pancreatic autoantibody testing may not be useful for predicting susceptibility to ICI-DM.…”

Influence of age at diagnosis and duration of diabetes on the positivity of glutamic acid decarboxylase antibody in South-Brazilian type 1 diabetes mellitus

“…Our data is in agreement with international studies that show that sensitivity of the GADA is greater in older individuals at diagnosis. 8,9,15,21–25 GADA is considered the most prevalent antibody in type 1 DM with age of onset above 20 years, 9 and its rate of positivity is constant with ages in the range of 10–40 years in some series. 9,26 GADA sensitivity is also greater than the anti-islet and the anti-insulin antibodies in adults, and it is, therefore, the most sensitive autoimmunity marker in this age range.…”

“…Racial and ethnical differences have also been shown to influence the prevalence of GADA. 16 Prevalence of GADA positivity in other countries is variable, reported to be around 45.8% in Chinese population, 25 23% in Mexicans 33 and, in European patients, it varies from 39% in longstanding patients with age at diabetes diagnosis below 15 years, to 97% in patients recently diagnosed and with age at diagnosis older than 15 years. 15 Therefore, the ethnic background should be taken into account to predict the performance of the test.…”