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  • 1
    ISSN: 1432-5233
    Keywords: Insulin-dependent diabetes ; Islet cell antibodies ; Complement-fixing ICA ; C-peptide ; Geographical variation ; Seasonal variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Finland and Sweden have the highest incidence of insulin-dependent diabetes in children in the world, about 3–4 times that of countries in the Mediterranean area, with the exception of Sardinia. We have collected information from several European clinics and from Pittsburgh, USA, in order to find out whether this difference in incidence is associated with corresponding differences of the disease pattern. Patients in Finland or Sweden (‘North’) and Pittsburgh were younger (〈10 years old) at diagnosis compared with those in the other clinics in Europe (P〈0.05 versusP〈0.02). In the North, boys were in excess (58%) in contrast to France (40%) and Pittsburgh (46%). Patients in the North had a shorter duration of symptoms (〈8 days;P〈0.001) and higher blood glucose (〉20 mmol/l;P〈0.05) than those attending the other European clinics. Irrespective of age, there were more ICA-positive patients in the North (94%) than in Berlin-Vienna (67%;P〈0.01) or in France (70%;P〈0.01). There was a tendency for non-diabetic parents and siblings in the North to have lower C-peptide values (〈0.26 pmol/ml) at the time of diagnosis of the proband and to be ICA-positive more often than relatives in the other European clinics. The seasonal variation of diagnosis, showed no obvious geographical differences, with recorded diagnosis always lowest during the summer. We conclude that certain factors seem to cause not only a high incidence of diabetes in children in Finland and Sweden but perhaps also a more aggressive early disease process.
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  • 2
    ISSN: 1432-0428
    Keywords: Islet cell antibody ; Type 1 (insulin-dependent) diabetes ; standards ; quality control ; Juvenile Diabetes Foundation units
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Forty-one assays were analysed at the 3rd International Workshop on the standardisation of islet cell antibodies. Analysis of precision demonstrated assays consistently detecting blind duplicates within one doubling dilution and capable of discriminating one doubling dilution differences in islet cell antibody concentration. Some assays, however, reported duplicates discrepantly by more than seven doubling dilutions, and consequently could not distinguish even large quantities of islet cell antibodies. Precision was best in assays from laboratories which had participated in all three Standardisation Workshops and was not dependent upon methodology. The use of the Juvenile, Diabetes Foundation reference islet cell antibody standard and standard curves reduced the scatter of results, and was best amongst assays with better precision. Twenty-seven assays reported all ten blood donor sera as negative. However, 14 assays did not, and specificity (negativity in health) was 〈50% in three assays. Low specificity was strongly associated with poor precision. The detection limit of assays ranged from 〈5 to 50 JDF units and was partially dependent upon methodology. Assays incorporating extended incubation had the lowest detection limits without a decrease in the specificity of the ten blood donor sera. Precise quantification is fundamental for the standardisation and comparability of islet cell antibodies. Precise quantitative assays have been identified and reference standards and common units established.
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  • 3
    ISSN: 1432-0428
    Keywords: Keywords Type I diabetes ; Type II diabetes ; HLA genotypes ; DQB1 genotype ; DRB1 genotype.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Juvenile-onset, insulin-dependent diabetes is associated with islet cell antibodies and with specific “high-risk” HLA-DRB1 and HLA-DQB1 genotypes. Patients with Type II (non-insulin-dependent) diabetes mellitus can have islet-related antibodies, but the genotypic associations at different ages of onset have not been evaluated. Our aim was to determine (i) the prevalence of DRB1 and DQB1 genotypes in patients at diagnosis of Type II diabetes at different ages from 25 to 65 years compared with the general population, and (ii) whether the presence of islet cell antibodies (ICA) or glutamic acid decarboxylase antibodies (GADA) or both by age is associated with different DRB1 and DQB1 genotypes. Methods. The antibodies to islet cells and those to glutamic acid decarboxylase were measured in 1712 white Caucasian diabetic subjects at diagnosis of diabetes and they were genotyped for HLA DRB1 * 03 and DRB1 * 04 and the high-risk DRB1 * 04-DQB1 * 0302 haplotype. To assess over-representation of high-risk alleles for Type I (insulin-dependent) diabetes mellitus, the prevalence of high-risk alleles in diabetic patients was expressed relative to the prevalence of low-risk alleles, non-DR3/non-DR4, that provided a reference denominator in both the diabetic patients and in 200 non-diabetic control subjects. The prevalence of ICA or GADA or both in patients with different HLA genotypes was assessed in those diagnosed in four age groups, 25–34 years, 35–44 years, 45–54 years and 55–65 years. Results. In Type II diabetic patients presenting at ages 25–34, 35–44 and 45–54 years, there was an increased prevalence of DR3/DR4 compared with the general population with approximately 6.5-fold, 2.9-fold, 2.1-fold over-representation, respectively (p 〈 0.0001, 〈 0.01, 〈 0.05) but this was not found in those aged 55–65 years old. In the group aged 25–34 years, 32 % of patients with ICA or GADA or both had DRB1 * 03/DRB1 * 04-DQB1 * 0302 compared with 10 % in those aged 55–65 years and expected 3 % prevalence. Conversely, only 14 % of those aged 25–34 years with antibodies had non-DR3/non-DR4, compared with 35 % in those aged 55–65 years. There was thus pronounced age heterogeneity in DRB1 and DQB1 predisposition to Type II diabetes. The antibodies displaced DRB1 or DQB1 genotypes in the multivariate model for requiring insulin therapy by 6 years of follow-up. Conclusion/hypothesis. The age of presentation of Type I diabetes in adulthood was in part dependent on the DRB1/DQB1 genotype. Islet cell antibodies and glutamic acid decarboxylase antibodies were strongly associated with DRB1 * 03/DRB1 * 04-DQB1 * 0302 in early adulthood but showed little relation with specific HLA genotypes after the age of 55 years. [Diabetologia (1999) 42: 608–616]
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Basic research in cardiology 92 (1997), S. 18-22 
    ISSN: 1435-1803
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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