Prevalence of islet cell antibodies, insulin antibodies and hyperglycaemia in 2291 schoolchildren

Bergua, M; Solé, Judith; Marion, G. B.; Perez, M. C.; Recasens, A; Fernández, Javier Rodríguez; Casamitjana, Roser; Gomis, Ramón

doi:10.1007/bf00296996

Cited by 38 publications

(24 citation statements)

References 10 publications

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“…The determination of antibodies to the 64K protein, radiobinding competitive insulin autoantibodies (CIAA) and immunogenetic markers have not been included in published population studies so far [19][20][21]. Based on the study of a random population aged 7-21 years we show that in ICA positive non-diabetic individuals antibodies to the 64K antigen, CF-ICA and CIAA are closely correlated with impaired Beta-cell function, the HLA DR4 phenotype and the absence of Asp at position 57 of the HLA DQ ~ chain.…”

Section: Discussionmentioning

confidence: 99%

Antibodies to the Mr 64,000 (64K) protein in islet cell antibody positive non-diabetic individuals indicate high risk for impaired Beta-cell function

et al. 1992

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Summary.A prospective study of a normal childhood population identified 44 islet cell antibody positive individuals. These subjects were typed for HLA DR and DQ alleles and investigated for the presence of antibodies to the Mr 64,000 (64K) islet cell antigen, complement-fixing islet cell antibodies and radiobinding insulin autoantibodies to determine their potency in detecting subjects with impaired Beta-cell function. At initial testing 64K antibodies were found in six of 44 islet cell antibody positive subjects (13.6 %). The same sera were also positive for complement-fixing islet cell antibodies and five of them had insulin autoantibodies. During the follow-up at 18 months, islet cell antibodies remained detectable in 50 % of the subjects studied. In all six cases who were originally positive, 64K antibodies were persistently detectable, whereas complement-fixing islet cell antibodies became negative in two of six and insulin autoantibodies in one of five individuals. HLA DR4 (p < 0.005) and absence of asparic acid (Asp) at position 57 of the HLA DQ 13 chain (p < 0.05) were significantly increased in subjects with 64K antibodies compared with control subjects. Of 40 individuals tested in the intravenous glucose tolerance test, three had a first phase insulin response below the first percentile of normal control subjects. Two children developed Type i (insulin-dependent) diabetes mellitus after 18 and 26 months, respectively. Each of these subjects was non-Asp homozygous and had persistent islet cell and 64K antibodies. We conclude that 64K antibodies, complement-fixing islet cell antibodies and insulin autoantibodies represent sensitive serological markers in assessing high risk for a progression to Type 1 diabetes in islet cell antibody positive non-diabetic individuals.

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Section: Discussionmentioning

confidence: 99%

Antibodies to the Mr 64,000 (64K) protein in islet cell antibody positive non-diabetic individuals indicate high risk for impaired Beta-cell function

et al. 1992

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“…[27,29,42,89,[92][93][94][95][96][97]102,104,105,107,[112][113][114] children [89,146]. The broadening of the autoimmune response to epitopes of different islet-cell antigens, commonly referred to as intermolecular epitope spreading, is associated with an increased probability of developing diabetes, which is also reflected by an enhanced T-cell reactivity to different islet-cell antigens [40,41,[146][147][148][149].…”

Section: Insulinmentioning

confidence: 99%

Developments in the prediction of type 1 diabetes mellitus, with special reference to insulin autoantibodies

Franke

Galloway

Wilkin

2005

Diabetes Metab. Res. Rev.

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The prodromal phase of type 1 diabetes is characterised by the appearance of multiple islet-cell related autoantibodies (Aab). The major target antigens are islet-cell antigen, glutamic acid decarboxylase (GAD), protein-tyrosine phosphatase-2 (IA-2) and insulin. Insulin autoantibodies (IAA), in contrast to the other autoimmune markers, are the only beta-cell specific antibodies. There is general consensus that the presence of multiple Aab (> or = 3) is associated with a high risk of developing diabetes, where the presence of a single islet-cell-related Aab has usually a low predictive value. The most commonly used assay format for the detection of Aab to GAD, IA-2 and insulin is the fluid-phase radiobinding assay. The RBA does not identify or measure Aab, but merely detects its presence. However, on the basis of molecular studies, disease-specific constructs of GAD and IA-2 have been employed leading to somewhat improved sensitivity and specificity of the RBA. Serological studies have shown epitope restriction of IAA that can differentiate diabetes-related from unrelated IAA, but current assays do not distinguish between disease-predictive and non-predictive IAA or between IAA and insulin antibodies (IA). More recently, phage display technology has been successful in identifying disease-specific anti-idiotopes of insulin. In addition, phage display has facilitated the in vitro production of antibodies with high affinity. Identification of disease-specific anti-idiotopes of insulin should enable the production of a high affinity reagent against the same anti-idiotope. Such a development would form the basis of a disease-specific radioimmunoassay able to identify and measure particular idiotypes, rather than merely detect and titrate IAA.

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“…So far, two European populationbased studies have been published. In the Spanish study an ELISA test was used for IAA determination [3], while in the Finnish study IAA were not determined at all [10].…”

Section: Discussionmentioning

confidence: 99%

Insulin autoantibodies as determined by competitive radiobinding assay are positively correlated with impaired beta-cell function — The Ulm-Frankfurt population study

et al. 1991

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Summary. Out of a random population of 4208non-diabetic pupils without a family history of Type I diabetes 44 (1.05%) individuals had islet cell antibody (ICA) levels greater or equal to 5 Juvenile Diabetes Foundation (JDF) units. 39 of these ICA-positives could be repeatedly tested for circulating insulin autoantibodies (CIAA) using a competitive radiobinding assay. The results were compared with the insulin responses in the intravenous glucose tolerance tests (IVGTT) and with HLA types. Six pupils were positive for CIAA. All of them had complement-fixing ICA, and 5 of them were HLA-DR4 positive. Three of the 6 showed a first-phase insulin response below the first percentile of normal controls. Our data indicate that in population-based studies CIAA can be considered as a high risk marker for impaired beta-cell function in non-diabetic ICA-positive individuals.

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Prevalence of islet cell antibodies, insulin antibodies and hyperglycaemia in 2291 schoolchildren

Cited by 38 publications

References 10 publications

Antibodies to the Mr 64,000 (64K) protein in islet cell antibody positive non-diabetic individuals indicate high risk for impaired Beta-cell function

Antibodies to the Mr 64,000 (64K) protein in islet cell antibody positive non-diabetic individuals indicate high risk for impaired Beta-cell function

Developments in the prediction of type 1 diabetes mellitus, with special reference to insulin autoantibodies

Insulin autoantibodies as determined by competitive radiobinding assay are positively correlated with impaired beta-cell function — The Ulm-Frankfurt population study

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