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  • 1
    Electronic Resource
    Electronic Resource
    Evidence of an accelerated B-cell destruction in HLA-Dw3/Dw4 heterozygous children with Type 1 (insulin-dependent) diabetes (1986)
    Springer
    Diabetologia 29 (1986), S. 347-351 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; C-peptide ; HLA ; clinical remission ; metabolic control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The possible association between residual B-cell function and specific HLA antigens in Type 1 (insulin-dependent) diabetes was studied in a cross-sectional series of 144 diabetic children and adolescents, as well as in a prospective series of 44 newly diagnosed diabetic subjects who were observed for the initial 2 years of their diabetes. In the cross-sectional study, the HLA-Dw3/Dw4 heterozygotes had a lower mean serum C-peptide concentration during 1980, 0.03 ±0.01 nmol/l (mean ± SEM) vs. 0.09 ± 0.01 nmol/1 (p 〈 0.02), as well as a lower 24-h urinary C-peptide excretion, 0.27 ±0.06 nmol/m2 vs. 1.34 ± 0.19 nmol/m2 (p 〈 0.05), than the other subjects. In addition, the Dw3/Dw4 heterozygotes had a clinical remission of shorter duration, 113 ± 47 days vs. 203 ± 22 days (p 〈 0.05), and a higher mean glycosylated haemoglobin level during 1980, 14.8 ± 0.05% vs. 13.7 ± 0.2% (p 〈 0.05), than those without the Dw3/Dw4 combination. In the prospective study the serum C-peptide concentrations were of the same magnitude in the Dw3/Dw4 heterozygotes and the other subjects during the first month. Subsequently the C-peptide concentrations in the subjects with the Dw3/Dw4 combination started to decrease 2 months earlier than in the other subjects. The Dw3/Dw4 children had a significantly lower serum C-peptide concentration at 21 months, 0.01 ± 0.01 nmol/1 vs. 0.13 ± 0.02 nmol/1 (p〈0.01), and at 24 months, 0.03 ±0.01 nmol/1 vs. 0.12 ± 0.02 nmol/l (p 〈 0.05). Our observations suggest that Dw3/Dw4 heterozygosity is, at least in children, associated with a distinct form of Type 1 diabetes characterized by a rapid B-cell destruction, a clinical remission of short duration and poor metabolic control. This expands the concept of genetic heterogeneity within Type 1 diabetes in childhood, and may have important implications for research on the aetiology, pathogenesis and natural history of the disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00903342
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Insulin autoantibodies at the clinical manifestation of Type 1 (insulin-dependent) diabetes — a poor predictor of clinical course and antibody response to exogenous insulin (1988)
    Springer
    Diabetologia 31 (1988), S. 129-133 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes ; insulin autoantibodies ; islet cell antibodies ; metabolic control ; C-peptide ; clinical remission
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To study the possible clinical significance of the appearance of insulin autoantibodies prior to the diagnosis of Type 1 (insulin-dependent) diabetes, and their value in predicting the antibody response to exogenous insulin, we observed 46 newly diagnosed diabetic children and adolescents over the year following diagnosis for the occurrence and duration of clinical remission, daily insulin dose, metabolic control, residual B-cell function, insulin-binding antibodies and conventional as well as complement-fixing islet cell antibodies. Insulin-binding antibodies were determined using both monoiodinated human and porcine insulin. Sixteen children (34.7%) were positive for insulin autoantibodies upon diagnosis of Type 1 diabetes. These subjects were significantly younger (6.2±1.0 versus 10.8±0.8 years; mean±SEM, p〈0.001), and their haemoglobin A1 levels were lower (14.1±0.6 versus 16.0±0.8%, p〈0.05) at diagnosis than in the insulin autoantibody negative group. There were no significant differences in the occurrence and duration of clinical remission between insulin autoantibody-positive and -negative test groups. Daily insulin dose, haemoglobin A1 and serum C-peptide concentrations were of the same magnitude in both groups after the diagnosis, and no association could be found between the presence of insulin autoantibodies at diagnosis and persistently positive islet cell antibodies. In tests conducted 3 months after diagnosis, the group of patients with insulin autoantibodies showed significantly higher levels (p〈0.05) of antibodies binding human insulin than the group negative for insulin autoantibodies, but no significant differences could be found between the insulin binding titres of the two groups in subsequent analyses. Those who were still positive for conventional islet cell antibodies one year after diagnosis had significantly higher levels of antibodies binding human insulin (34.6±6.1 versus 12.9±1.7%, p〈0.05) as well as antibodies binding porcine insulin (33.0±5.9 versus 12.7±2.9%, p〈0.05) than the other subjects. Our observations suggest that insulin autoantibodies developing before the diagnosis of Type 1 diabetes have no influence on the clinical course of the disease over the first year following diagnosis, and they appear to serve as a poor predictor of the antibody response to insulin treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00276844
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
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