Antibodies to Pancreatic Islet Cells in Insulin-Dependent Diabetics With Coexistent Autoimmune Disease

MacCuish, A C; Irvine, W. J.; Barnes, Erin; Duncan, L. J. P.

doi:10.1016/s0140-6736(74)90281-5

Cited by 284 publications

(107 citation statements)

References 19 publications

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“…An immunological pathogenesis for Type 1 (insulin-dependent) diabetes mellitus is supported by the presence of inflammatory cells in the islets of Langerhans at onset [1][2][3] and of autoantibodies, reacting with pancreatic islet cells [4][5][6], insulin [7], or a Beta-cell Mr 64,000 (64K) protein [8], as early as several years prior to clinical onset [9][10][11][12].…”

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confidence: 99%

Risk for developing Type 1 (insulin-dependent) diabetes mellitus and the presence of islet 64K antibodies

et al. 1991

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Summary. First-degree relatives of Type i (insulin-dependent) diabetic patients are at increased risk for developing clinical diabetes. The presence of islet cell or insulin autoantibodies further identifies relatives at greater risk, but not all immunologic-marker-positive relatives progress to disease. Beta-cell dysfunction, however, seems to be more prevalent than clinical Type 1 diabetes, since stable subclinical pancreatic Beta-cell dysfunction may occur. Antibodies against a Mr 64,000 (64K) islet Beta-cell protein, identified as glutamic acid decarboxylase, have been reported both at and several years prior to the clinical onset of Type i diabetes. We measured 64K antibodies in first-degree relatives with varying degrees of Beta-cell dysfunction and risk for subsequent Type i diabetes to determine whether 64K antibodies improve the predictive power of islet cell antibodies and/or insulin autoantibodies. In the Seattle Family Study first-degree relatives of Type 1 diabetic patients are followed prospectively using detailed Beta-cell function tests, insulin sensitivity, quantitative evaluation of islet cell antibodies and fluid phase assay insulin autoantibodies. 64K antibodies were measured using dog islets. Relatives were selected, based on Beta-cell function to represent individuals at high (n = 6) and low (n = 30) risk for subsequent Type 1 diabetes. The 30 low-risk individuals followed-up for 78 months, had stable Beta-cell function, and six (20%) were negative for all autoantibodies, ten (33%) were positive for insulin autoantibodies, 16 (53%) were islet cell antibody positive While six (20%) were positive for 64K antibodies. In contrast, of the six subjects with progressively declining Beta-cell function who are therefore at high risk, two of whom have already developed Type i diabetes, two (33%) were positive for insulin autoantibodies, four (67%) were islet cell antibody positive, while all six (100%) were positive for 64K antibodies. We conclude that antibodies to the Mr 64,000 islet protein correlate with progressive Beta-cell dysfunction more closely than either islet cell antibodies or insulin autoantibodies, but can sometimes be present in individuals whose Beta-cell function remains stable over several years.

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confidence: 99%

Risk for developing Type 1 (insulin-dependent) diabetes mellitus and the presence of islet 64K antibodies

et al. 1991

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“…It has been suggested that the presence of anti-GAD may identify this subgroup. 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).…”

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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“…The introduction of new microscopes with epi-illumination made ICAs much easier to see. Islet immunofluorescence also escaped observation because it is weak relative to the bright staining seen with thyroid, gastric, and adrenal antibodies (85). Serendipity played a further role, since ICAs are found in 70-85% of recently diagnosed patients but disappear from the circulation over the course of time.…”

Section: Genetic Heterogeneitymentioning

confidence: 99%

The Discovery of Type 1 Diabetes

Gale

2001

Diabetes

124

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The etiological heterogeneity of idiopathic diabetes has been recognized for 25 years, and subdivision into type 1 and type 2 diabetes is fundamental to the way we think about the disease. Review of the literature suggests that the concept of type 1 diabetes as an immunemediated disease emerged rapidly over the period from 1974 to 1976 and showed many of the features of a classic paradigm shift. A few key observations triggered recognition and acceptance of the new paradigm, but the necessary context was provided by scientific developments in areas mainly unrelated to diabetes. The disease paradigm established by 1976 is still widely accepted, and its essential features have been modified only in detail by the revolution in molecular biology that has occurred over the intervening period. Notwithstanding, some of the underlying assumptions remain imprecise, unchallenged, or unconfirmed. Appreciation of the historical origin and subsequent evolution of these fundamental concepts could stimulate critical analysis and help prepare the way for a new paradigm. Diabetes 217-226, 2001

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Antibodies to Pancreatic Islet Cells in Insulin-Dependent Diabetics With Coexistent Autoimmune Disease

Cited by 284 publications

References 19 publications

Risk for developing Type 1 (insulin-dependent) diabetes mellitus and the presence of islet 64K antibodies

Risk for developing Type 1 (insulin-dependent) diabetes mellitus and the presence of islet 64K antibodies

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

The Discovery of Type 1 Diabetes

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