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  • 1
    Electronic Resource
    Electronic Resource
    C-Peptide in children with juvenile diabetes (1976)
    Springer
    Diabetologia 12 (1976), S. 627-630 
    Details
    ISSN: 1432-0428
    Keywords: Juvenile diabetes ; C-peptide ; remission ; ketonuria ; insulin antibodies ; total IRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Serum C-peptide, insulin-binding IgG and total insulin (IRI) were determined in 96 juvenile diabetics aged 4–21 years, with onset of diabetes at the age of 1–16 years and with 2–17 years' duration of diabetes. Thirty-four patients (35.4%) had detectable levels of C-peptide (≥ 0.04 pmol/ml). Compared to non-diabetic adults, 19 had values below the normal range, 12 showed values within the normal range (0.18–0.63 pmol/ml) and 3 rated above normal. There was a negative correlation between the fasting C-peptide concentration and the degree of ketonuria at the onset of diabetes and a positive correlation between C-peptide levels and the incidence of postinitial remission periods. Patients without detectable C-peptide had significantly higher levels of insulin antibodies than those who had detectable levels of C-peptide. The possibility of a relationship between the intensity of the initial treatment of diabetes and the preservation of the B-cell function is discussed, as well as the possibility of insulin antibodies being a cause of B-cell exhaustion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01220642
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  • 2
    Electronic Resource
    Electronic Resource
    A prospective analysis of antibodies reacting with pancreatic islet cells in insulin-dependent diabetic children (1981)
    Springer
    Diabetologia 20 (1981), S. 471-474 
    Details
    ISSN: 1432-0428
    Keywords: Insulin-dependent diabetes ; islet cell antibodies ; islet cell surface antobodies ; autoimmunity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Islet cell cytoplasmic and cell surface antibodies along with other autogenic tissue antibodies were determined prospectively from the day of diagnosis of insulin-dependent diabetes in a group of children and adolescents. Prior to the initiation of insulin therapy 30 out of 33 were antibody-positive, 67% having islet cytoplasmic antibodies and 67% islet cell surface antibodies. Among 74 age- and sex-matched non-diabetic individuals 1% had islet cell cytoplasmic antibodies and 3% had islet cell surface antibodies. A prospective analysis in 17 patients showed a diminishing prevalence of islet cell antibodies with increasing duration of diabetes. Islet cell cytoplasmic or cell surface antibodies were found independently of each other or in combination and with various patterns of persistence. The results indicate a strong association of islet cell antibodies with the onset of insulin-dependent diabetes in childhood and adolescence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00253410
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  • 3
    Electronic Resource
    Electronic Resource
    The immunogenicity of insulin preparation. Antibody levels before and after transfer to highly purified porcine insulin (1980)
    Springer
    Diabetologia 19 (1980), S. 511-515 
    Details
    ISSN: 1432-0428
    Keywords: Insulin antibodies ; proinsulin antibodies ; pancreatic polypeptide antibodies ; a-component antibodies ; total serum immunoreactive insulin ; insulin immunogenicity ; insulin-dependent diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ninety-two insulin-dependent diabetics (aged 4–20 years, mean±SD: 13±4) with a duration of diabetes from 2 to 17 years (7±3) were transferred from Lente or NPH (5 × crystallised insulin) to Monotard insulin (highly purified insulin). Total serum immunoreactive insulin levels and concentrations of antibodies against insulin, porcine proinsulin, a-component and pancreatic polypeptide were determined prior to [I] and at a mean of 220 [II], 460 [III], 830 [IV], and 1170 [V] days after the change. All but two subjects had insulin antibodies (IgG) at the start, with a mean value of 2864 μU/ml. There was a significant fall in the mean insulin antibody level between [I] and [II] to 2165 μU/ml (p〈10-7), followed by an increase between [II] and [III] whereafter a slight decrease was observed being significant between [III] and [IV], as well as between [IV] and [V] (p〈0.05); some patients showed a constant fall over the entire period, while others showed fluctuations. Total serum insulin showed a similar pattern, with a mean value of 1141 μU/ml at [I] declining to 522 μU/ml at [V]. The percentage fall between [I] and [V] was greater (54%) than that in the insulin antibodies (30%). Antibodies against acomponent, proinsulin and pancreatic polypeptide were present in 96%, 72% and 41% of the patients respectively before the change in therapy. There was a decline in these antibodies between each sampling (p values between 〈10-3 and 10-8) and, at the end of the investigation antibodies against a-component were above the detection limit in only 4 patients, and none of the patients showed antibodies against proinsulin or pancreatic polypeptide. Thus, removal of the impurities, including the hormonal contaminants of insulin, leads to a slow fall in antibodies to insulin and a much faster disappearance of antibodies against acomponent, proinsulin and pancreatic polypeptide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00253177
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  • 4
    Electronic Resource
    Electronic Resource
    Insulin autoantibodies are associated with islet cell antibodies; their relation to insulin antibodies and B-cell function in diabetic children (1988)
    Springer
    Diabetologia 31 (1988), S. 647-651 
    Details
    ISSN: 1432-0428
    Keywords: Insulin autoantibodies ; islet cell antibodies ; insulin antibodies ; C-peptide ; children ; Type 1 (insulin-dependent) diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Blood was drawn from 74 children, 3–16 years old, at diagnosis of Type 1 (insulin-dependent) diabetes and before the first insulin injection. Insulin autoantibodies were detected with a polyethylen-glycol-method in 27/74 (36.4%) and with an immuno-electrophoretic method in 6/74 (8.1%). Islet cell cytoplasmic antibodies detected by indirect immuno-fluorescence were found in 49/74 patients (66.2%), who included as many as 23 of the 27 patients with insulin autoantibodies determined with the polyethylen-glycol-method (p〈0.01). The proportion of insulin autoantibody-positive patients who developed insulin antibodies during the first 9 months of insulin treatment was not significantly greater (51.8%) than that of insulin autoantibody-negative patients (44.6%), but patients with both islet cell antibodies and insulin autoantibodies at diagnosis produced more insulin antibodies during the first 9 months (p〈0.05). There was no difference in fasting or meal stimulated serum C-peptide after 3, 9 or 18 months as related to occurrence of insulin autoantibodies and/or islet cell antibodies. The correlation between insulin autoantibodies and islet cell antibodies indicates that both types of autoantibodies reflect the same immunological process, although the lack of correlation to C-peptide may indicate that they play a minor causal role. In addition, the results show that patients with an active autoimmune process evidently tend to produce more insulin antibodies during the first months of insulin treatment, but the islet cell antibodies and insulin autoantibodies-positive patients had at least as good residual B-cell function as patients without autoantibodies at diagnosis. If insulin antibodies produced as a response to exogenous insulin do have a negative effect on B-cell function our present results suggest that such mechanisms are of minor importance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278746
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  • 5
    Electronic Resource
    Electronic Resource
    Insulin antibodies in diabetic children treated with monocomponent porcine insulin from the onset: relationship to B-cell function and partial remission (1984)
    Springer
    Diabetologia 26 (1984), S. 138-141 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; children ; insulin antibodies ; C-peptide ; partial remission ; insulin requirement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin antibodies expressed as insulin binding capacity of IgG were determined in 50 Type 1 (insulin-dependent) diabetic children who have been treated with monocomponent porcine insulin from the onset of the disease. During the follow-up period of 0.5–5.5 years (mean±SD: 3.2±1.6 years), 26 out of 50 patients (52%) developed detectable insulin antibodies. These patients had significantly lower maximal C-peptide responses to a standardized breakfast 9 months after onset of diabetes (mean 0.24pmol/m1, p〈0.001) than those without insulin antibodies (mean 0.47 pmol/ml). In addition, patients with antibodies showed both significantly higher insulin requirements at 9 months (p〈0.05), and shorter remissions (p〈0.01) than those without. It is concluded that even ‘small’ amounts of insulin antibodies may be biologically significant and have negative effects on B-cell function and metabolic balance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00281121
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  • 6
    Electronic Resource
    Electronic Resource
    Low dose linomide in Type I juvenile diabetes of recent onset: a randomised placebo-controlled double blind trial (1998)
    Springer
    Diabetologia 41 (1998), S. 1040-1046 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Linomide ; Type I diabetes.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The quinoline-3-carboxamide, linomide, protects non-obese diabetic mice from diabetes. The effects of linomide on insulin needs and beta cell function were studied in recent juvenile Type I diabetes in a double-blind trial. Patients with recent onset diabetes were randomly assigned to treatment with a fixed dose of 2.5 mg linomide (42 patients) or placebo (21 patients) for 1 year, in addition to insulin and diet. Glycated haemoglobin was 10–15 % lower at 9 months (p = 0.003) and 12 months (p 〈 0.05) in the linomide group. The insulin dose was 32–40 % smaller in the linomide group at 3 (p 〈 0.03), 6 (p 〈 0.02), 9 (p 〈 0.001) and 12 months (p = 0.01). Insulin doses correlated negatively with C peptide values (p = 0.001–0.002). The trend for higher C peptide values in the linomide group did not reach significance. In a post hoc subgroup analysis performed in 40 patients (25 from the linomide group and 15 from the placebo group) who still had detectable residual beta cell function at entry, linomide was associated with 45–59 % higher C peptide value at 6 months (p 〈 0.05), 9 months (p 〈 0.05) and 12 months (p 〈 0.05). The main adverse effects of linomide were mild transitory anaemia (45 vs 10 % in the linomide and placebo groups), thrombocytopenia (24 vs 10 %), and mild joint discomfort (45 vs 5 %) with no clinical signs. In conclusion, low-dose linomide reduced the insulin needs in patients with juvenile Type I diabetes of recent onset and improved beta cell function in patients who still had detectable beta cell function at entry. These results support further clinical and experimental studies to define the effects of linomide in Type I diabetes provided the safety of linomide is reliably established. [Diabetologia (1998) 41: 1040–1046]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051028
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  • 7
    Electronic Resource
    Electronic Resource
    Relating homology between the Epstein-Barr virus BOLF1 molecule and HLA-DQw8 β chain to recent onset Type 1 (insulin-dependent) diabetes mellitus (1991)
    Springer
    Diabetologia 34 (1991), S. 33-39 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; molecular mimicry ; Epstein-Barr virus ; class II MHC molecules ; EBV BOLF1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A role for the Epstein-Barr virus in initiating Type 1 (insulin-dependent) diabetes mellitus has been proposed since Epstein-Barr virus BOLF1(497–513) AVTPL RIFIVPPAAEY has an 11 amino acid identity with HLA-DQw8β (49–60) AVTPL GPPAAEY. Rabbit antisera to the BOLF1 (496–515) peptide crossreacted with the homologous DQw8β (44–63) peptide but not with the related DQw7β(44–63) peptide, which differed from the DQw8 peptide only in an ALA to ASP substitution in position 57. Antisera to DQw8β(49–60) reacted with the DQw8β(44–63) peptide and BOLF1 (496–515), but not with DQw7β (44–63). The antiserum to the BOLF1 peptide bound to denatured class II major histocompatibility complex β chains from Epstein-Barr virus-transformed DQw8-positive lymphocytes in an immunoblotting analysis. Epstein-Barr virus antibodies were detected at equal frequencies and similar titres in sera of 30 patients with Type 1 diabetes (16 of 30;63%) and in sera of 20 non-diabetic control subjects (13 of 20;65%). Sera from diabetic patients did not bind to DQw8β (44–63) or BOLF1(496–515) peptides. From these data we conclude that there is no simple relationship between serological evidence of Epstein-Barr virus infection and crossreactions between homologous Epstein-Barr virus and class II major histocompatibility complex peptides.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00404022
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  • 8
    Electronic Resource
    Electronic Resource
    Seasonality of Type 1 (insulin-dependent) diabetes mellitus: values of C-peptide, insulin antibodies and haemoglobin A1c show evidence of a more rapid loss of insulin secretion in epidemic patients (1989)
    Springer
    Diabetologia 32 (1989), S. 84-91 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; seasonal variation ; epidemic ; non-epidemic ; C-peptide ; insulin antibodies ; haemoglobin A1c ; HLA-DR types
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary According to month of diagnosis, 165 children who developed Type 1 (insulin-dependent) diabetes mellitus at the age of 0–16.2 years (mean±SD, 7.6±4.1 years) could be divided into 69 patients diagnosed during peak seasons (epidemic cases) and 96 patients diagnosed during months of low incidence (non-epidemic cases). Seasonality of onset of symptoms and of diagnosis was observed in both sexes in all age groups. The patients diagnosed during peak seasons had shorter duration of symptoms (13.2±8.1 days) as compared to 22.9±10.3 days; p〈0.001 in the patients diagnosed during months of low incidence. At diagnosis, 88.4% (61/69) of the epidemic group had ketonuria as compared to 71.9% (69/96); p〈0.06 in the non-epidemic patients. The values of C-peptide, insulin antibodies, haemoglobin A1c and HLA-DR phenotype frequencies in the 69 epidemic patients were compared with those of the 96 non-epidemic patients. In the epidemic patients, the C-peptide values of 0.11±0.05 mmol/l at diagnosis had increased to 0.12±0.05 mmol/l at one month and 0.13±0.06 mmol/l at 3 months. These values were significantly lower (p〈0.001) than in the non-epidemic patients at the same time points: 0.17±0.08 nmol/l; p〈0.001, 0.23±0.11 nmol/l; p〈0.001, and 0.22±0.10 nmol/l. Values of insulin antibodies (U/l) of 0.06±0.03, 0.05±0.05 and 0.17±0.10 in the epidemic group compared to 0.014±0.015, 0.02±0.01, and 0.04±0.04 in the non-epidemic group at the same aforementioned time points also showed significant differences (p〈0.001). Differences in these variables between the two groups continued until four years after diagnosis. Significant differences were also observed in the values of haemoglobin A1c and HLA-DR phenotype frequencies in the two groups. The results suggest that children with Type 1 diabetes can be divided into two sub-groups with different early clinical course which might depend on a different aetiology, related both to seasonal variation at diagnosis and to a genetic heterogeneity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00505179
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  • 9
    Electronic Resource
    Electronic Resource
    A high weight gain early in life is associated with an increased risk of Type 1 (insulin-dependent) diabetes mellitus (1994)
    Springer
    Diabetologia 37 (1994), S. 91-94 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; aetiology ; early growth ; breast feeding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Growth during the first years of life in relation to type of feeding in infancy was retrospectively studied in an unselected population-based group of 297 children who had been diagnosed with Type 1 (insulin-dependent) diabetes mellitus before the age of 15 years (probands) and 792 individually-matched referent subjects. Reliable data were collected from child welfare clinics. Probands weighed slightly less at birth but their weight gain at 6, 9, 18 and 30 months of age was significantly greater (p〈0.02) than that of referent children. The weight gain of children who had never been breast-fed was more marked than that of breast-fed children; this was found for both probands and referent children. But also among exclusively breast-fed children (〉 2 months), probands gained significantly more in weight from birth up to 18 and 30 months of age than exclusively breast-fed referent children. Early weight gain appears to be a risk factor for development of Type 1 diabetes. The lower weight gain in breast-fed compared to non-breast-fed children may explain the protective effect of breast feeding against Type 1 diabetes observed in several studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428783
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  • 10
    Electronic Resource
    Electronic Resource
    Subclinical nerve dysfunction in children and adolescents with IDDM (1995)
    Springer
    Diabetologia 38 (1995), S. 685-692 
    Details
    ISSN: 1432-0428
    Keywords: Insulin-dependent diabetes mellitus ; children ; neuropathy ; nerve conduction velocity ; glycaemic control ; height
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The purpose of this study was to investigate whether young insulin-dependent diabetic patients still develop peripheral nerve dysfunction when using modern multiple insulin injection therapy and to elucidate if this correlated with various disease parameters. Seventy-five patients, 7 to 20 years old with a duration of diabetes of more than 3 years, and 128 age-matched healthy control subjects underwent bilateral studies of median, peroneal, and sural nerves. Presence of diabetes lowered motor conduction velocity (p〈0.0001), sensory conduction velocity (p〈0.0001) and sensory nerve action potential (p〈0.05) in all examined nerves. The mean change in conduction velocity induced by diabetes was −4.8 m/s in the peroneal nerve, −3.3 m/s in the median motor nerve, −2.6 m/s in the sural nerve and −2.4 m/s in the median sensory nerve. Fifty-seven percent of the patients had abnormal conduction (values outside 95% predictive interval) which was seen most often in the motor nerves, especially in the peroneal nerve (41%) followed by the median nerve (24%). In multiple regression analysis, long-term poor metabolic control and increased body length correlated with nerve dysfunction identified in most examined parameters. Three patients had signs or symptoms suggestive of neuropathy. It is concluded that despite modern multiple insulin injection therapy, with reasonably good metabolic control, nerve dysfunction is still common in children and adolescents with insulin-dependent diabetes mellitus. Risk factors are increased height and long-term poor metabolic control.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401840
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