Combined Analysis of GAD65 and ICA512(IA-2) Autoantibodies in Organ and Non-organ-specific Autoimmune Diseases Confers High Specificity for Insulin-dependent Diabetes Mellitus

Pietropaolo, Massimo; Peakman, Mark; Pietropaolo, Susan L.; Zanone, Maria M.; Foley, Thomas P.; Becker, Dorothy J.; Trucco, Massimo

doi:10.1006/jaut.1997.0170

Cited by 65 publications

(43 citation statements)

References 51 publications

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“…We measured one of the most widely used markers for the diagnosis and prediction of type 1 diabetes, GAD65 AA (7,32,33), in a well-characterized diabetic and nondiabetic population aged Ն40 years from the NHANES III. We observed that the prevalence of GAD65 AAs was higher in diabetic participants compared with nondiabetic participants in non-Hispanic whites and non-Hispanic blacks but not in Mexican Americans.…”

Section: Discussionmentioning

confidence: 99%

Islet Cell Autoimmunity in a Triethnic Adult Population of the Third National Health and Nutrition Examination Survey

et al. 2004

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Markers of humoral islet cell autoimmunity, such as autoantibodies (AAs) against the 65-kDa isoform of GAD (GAD65), serve as determinants of risk for autoimmune diabetes. Despite the high prevalence of diabetes in U.S. racial and ethnic minority adult populations, little is known concerning the prevalence of GAD65 AA in these groups. We estimated the prevalence of GAD65 AA in 1,064 diabetic and 1,036 nondiabetic participants who were 40 -90 years of age from the Third National Health and Nutrition Examination Survey (NHANES III), which provides a representative ethnic sample of the U.S. diabetic population. The prevalence of GAD65 AA was higher in diabetic participants compared with nondiabetic participants in non-Hispanic whites (n ‫؍‬ 920; 6.3% vs. 2.0%; P ‫؍‬ 0.001) and non-Hispanic blacks (n ‫؍‬ 534; 3.7% vs. 1.3%; P ‫؍‬ 0.08) but not in Mexican Americans (n ‫؍‬ 646; 1.2% vs. 2.6%; P ‫؍‬ 0.18). Among diabetic non-Hispanic whites and non-Hispanic blacks, being GAD65 AA positive was associated with lower BMI and C-peptide (P < 0.05). These results may reflect the outcome of an autoimmune process leading to ␤-cell destruction/dysfunction in non-Hispanic white and nonHispanic black adult diabetic patients as it occurs in a similar manner in type 1 diabetes. Among diabetic Mexican Americans, the lower prevalence of GAD65 AA suggests a lower frequency of autoimmune-related diabetes.

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Section: Discussionmentioning

confidence: 99%

Islet Cell Autoimmunity in a Triethnic Adult Population of the Third National Health and Nutrition Examination Survey

et al. 2004

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“…Data are %, means ± SD, or medians (interquartile range) for non-normal variables. The cutoff points for both GAD65 and IA-2 autoantibodies were established as the 99th percentile of autoantibody levels calculated using 280 control subjects for both radioimmunoassays (40). Values shown in bold type are statistically significant.…”

Section: R E S U Lt Smentioning

confidence: 99%

Evidence of islet cell autoimmunity in elderly patients with type 2 diabetes.

et al. 2000

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In light of an occurring growth of elderly people a ffected by type 2 diabetes and recent observations indicating that type 2 diabetes may be a disease of the innate immune system, we evaluated whether signs of islet cell autoimmunity are associated with an abnormal glucose control, the presence of insulin requirement, or an activation of the acute-phase response in older individuals with type 2 diabetes. GAD65 and IA-2 autoantibodies along with the acute-phase response markers fibrinogen and C-reactive protein were tested in 196 serum samples from patients with type 2 diabetes and in 94 nondiabetic control subjects over the age of 6 5 years from the Pittsburgh cohort of the Cardiovascular Health Study. Of the diabetic patients, 12% (24 of 196) had autoantibodies against GAD65 and/or IA-2, a prevalence significantly higher than that found in nondiabetic individuals (1 of 94, 1.1%; P = 0.001). Type 2 diabetic patients who were positive for GAD65 and/or IA-2 autoantibodies (Ab + ), as compared with those negative for these autoantibodies (Ab -), had an abnormal oral glucose tolerance test (OGTT) (P = 0.03) before and a higher frequency of oral hypoglycemic treatment (P = 0.003) at the time of autoantibody testing. No differences were seen in the percentage of insulin requirement in the two groups. Moreover, a statistically significant increase in fibrinogen (P = 0.005) and C-reactive protein levels (P = 0.025) was found in t y p e 2 diabetic patients with high levels of GAD65 and/or IA-2 autoantibodies as compared with Ab -patients and control subjects. In conclusion, in type 2 diabetic subjects ≥65 years old, the presence of islet cell autoimmunity is associated with an impairment of the acute-phase insulin secretion, as revealed by an OGTT. A pronounced activation of the acute-phase response, found to be associated with islet cell autoimmunity, may in part explain this defect in insulin secretion. These findings not only have direct implications for adequate classification and treatment of diabetes in the elderly, but also for understanding the autoimmune/inflammatory mechanisms involved in the pathogenesis of hyperglycemia. D i a b e t e s 4 9 :3 2-38, 2000

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“…About 5-9% of type 2 DM patients are LADA subjects with anti-GAD (8,9). On the other hand, combined screening for IA-2A and anti-GAD has proved to be a powerful approach with which to identify subjects at risk for type 1 DM in large-scale population studies according to several recent reports (18,19). Since the percentage and prediction of LADA in the Chinese population is still an enigma, our finding that anti-TopII positivity is associated with older age of onset is tempting us to investigate whether anti-TopII can differentiate LADA in Chinese type 2 DM.…”

Section: Discussionmentioning

confidence: 99%

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

Shiau¹,

Tsai²,

Hwang

et al. 2000

European Journal of Endocrinology

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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.

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Combined Analysis of GAD65 and ICA512(IA-2) Autoantibodies in Organ and Non-organ-specific Autoimmune Diseases Confers High Specificity for Insulin-dependent Diabetes Mellitus

Cited by 65 publications

References 51 publications

Islet Cell Autoimmunity in a Triethnic Adult Population of the Third National Health and Nutrition Examination Survey

Islet Cell Autoimmunity in a Triethnic Adult Population of the Third National Health and Nutrition Examination Survey

Evidence of islet cell autoimmunity in elderly patients with type 2 diabetes.

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

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