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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: 1432-5233
    Keywords: Key words Th-lymphocytes ; IFN-γ ; mRNA ; GAD65 ; coxsackie B virus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract At the clinical onset of insulin-dependent diabetes mellitus (type 1 diabetes), inflammation within the pancreatic islets of Langerhans causes insulitis. CD4+ or Th-lymphocytes will be activated after stimulation resulting in interferon-gamma (IFN-γ) production by Th1-like lymphocytes and/or interleukin-4 (IL-4) secretion from Th2-like lymphocytes. The antigens responsible for this activation are unknown, but studies have suggested glutamic acid decarboxylase (GAD) to be a possible candidate. One peptide from this enzyme (amino acid 247–279) with a similar amino acid sequence to coxsackie B virus may cause lymphocyte proliferation in diabetic patients. In this study we have shown that this peptide activates Th1-like lymphocytes which produce increased amounts of IFN-γ mRNA, but seldom mRNA for IL-4. Lymphocytes from healthy HLA-matched controls (DR3/4) did not respond with an upregulated mRNA expression for these cytokines when stimulated by the GAD-peptide (P〈0.05). A low or absent expression of IFN-γ mRNA was significantly correlated to a high fasting C-peptide at 3 months' duration (P〈0.05). In conclusion, we suggest that GAD65 is involved in the development of type 1 diabetes and that the Th1-response may play a role in the destruction of β cells.
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  • 3
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    Springer
    Diabetologia 12 (1976), S. 627-630 
    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.
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  • 4
    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.
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  • 5
    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.
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  • 6
    ISSN: 1432-0428
    Keywords: Type 1 diabetes in children ; immunogenicity ; monocomponent human insulin ; monocomponent porcine insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of the present study was to compare the immunogenicity of monocomponent human insulin with that of monocomponent porcine insulin in newly diagnosed Type 1 (insulin-dependent) diabetic children. One hundred and thirty-five patients at diagnosis of diabetes (age 1–18 years, mean age 9.3 years) were randomly allocated to treatment with either Monotard MC + Actrapid MC or Monotard HM + Actrapid HM in a double-blind trial conducted in Sweden, Finland, Norway and Denmark. The human and porcine insulin groups were identical at diagnosis with respect to age, sex and measures of metabolic control. At all times the mean insulin antibody levels and the percentage of antibody-positive patients were lower in the human group compared with the porcine group. At 3 and 12 months, the insulin antibody values were significantly lower in the human group than in the porcine group (p 〈 0.05, Wilcoxon's rank sum test). At 12 months, antibody values in the human group ranged from 0 to 1.2 U/l (mean 0.14 U/l) and in the porcine insulin group from 0–5.2 U/l (mean 0.63 U/l). It is therefore concluded that human monocomponent insulin has a lower immunogenicity than porcine insulin of the same purity in newly diagnosed diabetic children during the first year of insulin treatment.
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  • 7
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; children ; HLA-types ; heterogeneity symptoms at onset ; partial remission ; genetic susceptibility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The presence of HLA-DR 3 was analysed in 745 patients with Type 1 (insulin-dependent) diabetes with age at diagnosis between 1–19 years. HLA-DR 3 and/or 4 was found in 678/745 (91%) of the patients. Presence of DR 2 with neither DR 3 nor 4 was demonstrated in 15 patients. Patients with HLA-DR 3 without DR 4 presented with Type 1 diabetes more evenly over the year; they also presented without incidence peaks at 7 years or 10–11 years, as seen especially in DR 3/4 patients. The DR 3 patients more often had mild disease with less ketonuria at diagnosis, less often ketoacidotic symptoms and more often a subsequent partial remission. The apparently more severe disease among diabetic girls may, at least to some extent, be explained by their higher prevalence of HLA-DR4. The differences found were similar in North America and Europe. The results suggest that Type 1 diabetes is a genetically heterogenous disease and that HLA-typing may be a useful marker of this heterogeneity.
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  • 8
    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.
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  • 9
    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.
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  • 10
    ISSN: 1432-0428
    Keywords: 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. [Diabetologia (1995) 38: 685–692]
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