Journal Article10.2337/DIAB.35.5.620
Relation Between Insulin Antibody and Complement-Fixing Islet Cell Antibody at Clinical Diagnosis of IDDM
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TL;DR: The results suggest that IBAs developing before diagnosis serve as an indicator of clinical and genetic heterogeneity within IDDM rather than as a marker of autoimmune β-cell destruction.
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Abstract: To test the hypothesis that insulin-binding antibodies (IBAs) appearing in the circulation before insulin treatment are markers of β-cell damage, we studied the prevalence of IBAs and both conventional (IF-ICAs)- and complement (CF-ICAs)-fixing cytoplasmic islet cell antibodies in 60 newly diagnosed diabetic children with a mean age of 9.5 yr. Seventeen (28.3%) had an insulin binding exceeding the upper range (2.8%) of that observed in 68 age-matched controls. The IBA-positive subjects were characterized by a younger age of onset [6.2 ± 4.0 (SD) vs. 10.8 ± 3.2 yr; P < 0.001], lower glycosylated hemoglobin A, levels (14.1 ± 3.1 vs. 16.0 ± 3.0%; P < 0.05), lower serum C-peptide concentrations (0.12 ± 0.07 vs. 0.20 ± 0.17 nmol/L; P < 0.05), and an increased frequency of HLA-Dw4 (9/13 vs. 11/37; P < 0.05). There was no significant relation between IBAs and serum C-peptide concentrations after age adjustment by multiple regression analysis. Forty-three children (75%) were positive for IF-ICA and 38 (63.3%) for CF-ICA. Twelve IBA-positive diabetics (70.6%) had IFICA as well as CF-ICA in their serum. No association could be observed between IBA and either IF-ICA or CF-ICA, however. The results suggest that IBAs developing before diagnosis serve as an indicator of clinical and genetic heterogeneity within IDDM rather than as a marker of autoimmune β-cell destruction.
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Citations
A Comparison of Childhood and Adult Type I Diabetes Mellitus
TL;DR: It is concluded that Type I diabetes that begins in adulthood is characterized by a longer symptomatic period before diagnosis, better preservation of residual beta-cell function, and lower frequencies of insulin autoantibodies and HLA-D3/D4 heterozygosity than Type I Diabetes that starts in childhood or adolescence.
312
The First Signs of β-Cell Autoimmunity Appear in Infancy in Genetically Susceptible Children from the General Population: The Finnish Type 1 Diabetes Prediction and Prevention Study
T. Kimpimäki,A. Kupila,A M Hämäläinen,A M Hämäläinen,Marika Kukko,Marika Kukko,P. Kulmala,P. Kulmala,K. Savola,K. Savola,Tuula Simell,Päivi Keskinen,Jorma Ilonen,Jorma Ilonen,Olli Simell,Mikael Knip,Mikael Knip,Mikael Knip +17 more
TL;DR: It is suggested that young children in the general population with a strong human-leukocyte-antigen-DQ-defined genetic risk of type 1 diabetes show signs of beta-cell autoimmunity proportionally more often than those with a moderate genetic risk.
249
Competitive Insulin Autoantibody Assay: Prospective Evaluation of Subjects at High Risk for Development of Type I Diabetes Mellitus
P. Vardi,Sergio Atala Dib,M Tuttleman,J. Connelly,M Grinbergs,A Radizabeh,William J. Riley,Noel K. Maclaren,George S. Eisenbarth,J. S. Soeldner +9 more
TL;DR: This simple radioimmunoassay appears to have requisite specificity and sensitivity to allow screening populations at risk to develop type I diabetes.
207
Multiple immunological abnormalities in patients with type 1 (insulin-dependent) diabetes mellitus.
D. W. Drell,A. L. Notkins +1 more
TL;DR: Revue sur les nombreuses anomalies immunologiques rencontrees dans la diabete de type I: certaines sont transitoires, la plupart pourraient etre liees a l'insuffisance en insuline ou a sa regulation defectueuse.
IA-2 antibodies - a sensitive marker of IDDM with clinical onset in childhood and adolescence
K. Savola,Ezio Bonifacio,E Sabbah,Petri Kulmala,Paula Vähäsalo,J Karjalainen,Eva Tuomilehto-Wolf,J Meriläinen,Hans K. Åkerblom,Mikael Knip +9 more
TL;DR: Almost all patients with newly diagnosed childhood IDDM can be identified by screening with these four autoantibodies, suggesting that IA-2A may be a more specific marker of beta-cell destruction than GADA, which have been shown to associate with the DR3 allele and thyroid autoimmunity.
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Insulin antibodies in insulin-dependent diabetics before insulin treatment
Jerry P. Palmer,Christopher M. Asplin,Peter Clemons,Kenneth R. Lyen,Olga Tatpati,Prima Raghu,Thomas L. Paquette +6 more
TL;DR: These insulin antibodies are present in a large percentage of newly diagnosed, untreated diabetics and may be an immune marker of B-cell damage.
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Complement-fixing islet-cell antibodies in type-i diabetes: possible monitors of active beta-cell damage
TL;DR: Investigations in type I diabetics, non-diabetic polyendocrine patients, and unaffected first-degree relatives of type I diabetic probands show that the complement-fixing islet-cell antibodies are more closely related to the onset of clinical disease than the conventional is let-cell antibody, and they tend to disappear more rapidly.
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Value of insulin autoantibodies as serum markers for insulin-dependent diabetes mellitus.
Terence J. Wilkin,Mary Armitage,Cecily Casey,David Pyke,Hoskins Pj,Michel Rodier,Jose-Luis Diaz,Richard David Leslie +7 more
TL;DR: Observations suggest that IAA do not always presage diabetes and are probably not a consequence of the disease; they may reflect an inherited autoimmune tendency to diabetes.
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Can Future Type I Diabetes Be Predicted? A Study in Families of Affected Children
TL;DR: In Northern European populations, some 30% of HLA-identical siblings are expected to be diabetic by the age of 30 yr, and this risk is significantly higher than that in haplo-identICAL siblings (one haplotype in common) P = 0.008).
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An association between complement-fixing cytoplasmic islet cell antibodies and endogenous insulin secretion in children with insulin-dependent diabetes mellitus.
TL;DR: The result contradicts the hypothesis, based on studies in vitro, that CF-ICA should be involved in the selective beta- cell damage in IDDM and suggests that complement-fixing antibodies are seen only if the beta-cell mass is sufficiently preserved.
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