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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 62 (1984), S. 328-330 
    ISSN: 1432-1440
    Keywords: Continuous subcutaneous insulin infusion ; Free insulin concentration ; Fasting blood glucose ; Target values
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 17 type-I diabetic patients on continuous s.c. insulin infusion (CSII) therapy, potential interrelationships between fasting levels of blood glucose (BG), serum free insulin (free IRI), total (free and bound) insulin (total IRI) and insulinbinding immunglobulin G (IgGI) were evaluated. There was no consistent relationship between the basal s.c. infused insulin dosages and the associated insulinaemia or glycaemia. A significant inverse correlation was found between the fasting levels of serum free IRI and BG (P〈0.005). On the basis of this interrelationship, a target range of 90–110 mg/dl for fasting BG during CSII treatment is proposed.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 13 (1977), S. 571-577 
    ISSN: 1432-0428
    Keywords: Insulinoma ; malignant insulinoma ; proinsulin ; C-peptide ; insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The value of plasma insulin, human C-peptide and proinsulin estimation in the diagnosis of 15 insulinomas has been investigated. Measurement of plasma proinsulin in an overnight fasting sample diagnosed all the insulinomas studied, irrespective of the plasma glucose. Patients with insulinomas had plasma proinsulin in the range 0.04–4.2 pmol/l and normal values were less than 0.01 pmol/ml. If hypoglycaemia was present, an inappropriately raised plasma immunoreactive insulin (including proinsulin) was diagnostic, but this assay was of little assistance if the plasma glucose was normal. Hypoglycaemia was induced with fish insulin in twelve patients with insulinomas and eight normal subjects. Using an antiserum which did not detect fish insulin, but cross-reacted with human proinsulin, the endogenous immunoreactive insulin was suppressed in the normal subjects, but all insulinoma patients had impaired suppression. Assay of plasma human C-peptide, or of the combined immunoreactive C-peptide and proinsulin, discriminated less well and did not clearly diagnose three insulinomas which secreted proinsulin rather than insulin and C-peptide. Plasma human proinsulin values during induced hypoglycaemia gave excellent discrimination and should detect insulinomas irrespective of their degree of histological differentiation. The assay of plasma human proinsulin allows a suppression test to be performed with hypoglycaemia induced by any type of insulin. A raised plasma proinsulin in proportion to C-peptide suggests an undifferentiated insulinoma, which may be more likely to be malignant.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Human proinsulin ; radioimmunoassay ; standards
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two new batches of pancreatic human proinsulin have been compared with biosynthetic human proinsulin. Standards of these three proinsulin preparations were made on the basis of quantitative amino-acid analyses and compared in two proinsulin radioimmunoassays with a proinsulin standard prepared 14 years ago. The curves of the new standards were superimposable. However, they differed considerably from the curve of the old standard which proved to be only one-third of the strength of the new standards, thereby leading to a threefold over-estimation of proinsulin concentrations when the old standard is used. We conclude that the new standards should replace previously used standards.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 13 (1977), S. 13-17 
    ISSN: 1432-0428
    Keywords: Juvenile diabetes ; HLA ; C-peptide ; insulin antibodies ; total IRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary HLA-types were determined in 102 juvenile diabetics. HLA-B8 was found in 39 patients (RR 2.64; p 〈 0.01) and HLA-BW15 in 32 patients (RR 1.33; n.s.). HLA-B7 was found in 14 patients (RR 0.40; p 〈 0.05). There were no correlations between HLA-B8 or BW15 and family history of diabetes, occurrence of infection before onset of diabetes, ketonuria at onset or the age at onset of diabetes. Serum C-peptide, insulin binding capacity of IgG and total serum insulin, IRI, were determined in 94 patients who had had diabetes for more than two years and who were beyond the remission period. Measurable amounts of C-peptide were found in 33 patients (34.7%). There was no evidence of a relationship between any particular HLA-antigen and the B-cell function except for an increased incidence of detectable C-peptide in patients with HLA-B18 and a tendency to a decreased incidence of detectable C-peptide in patients with the combination HLA-B8, W15. Only four patients (4.3%) were lacking insulin antibodies. HLA-BW15 positive patients had higher levels of insulin antibodies than other groups, while HLA-B7 positive patients had lower levels. The results suggest that HLA-B7 and HLA-B 18 might be associated with a different and perhaps milder form of juvenile diabetes.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 13 (1977), S. 467-474 
    ISSN: 1432-0428
    Keywords: Radioimmunoassay ; human proinsulin ; insulin ; C-peptide ; oral glucose ; diabetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A routine radioimmunoassay for human proinsulin in serum has been developed. The reagents used were: antibodies against the C-peptide part of the proinsulin molecule, human proinsulin as the standard and125I-labelled synthetic human Tyr-C-peptide as the tracer. The first step in this assay comprises the binding of proinsulin to insulin antibodies covalently coupled to Sepharose (S-AIS). Although bound to the solid-phase S-AIS, the proinsulin retains its second immunogenic site, viz., the C-peptide part of the molecule, accessible. Hence a surplus of C-peptide antibodies is added to the S-AIS-bound proinsulin, and the residual amount of C-peptide antibody is determined by addition of125I-Tyr-C-peptide. The detection limit is approximately 0.01 pmol/ml. The advantages of this method are: (1) its high specificity (proinsulin is determined as a molecule having both an insulin and a C-peptide moiety), (2) its simplicity and rapid performance, and (3) the low detection limit of the assay. Fasting sera from 24 nondiabetics, 9 maturityonset diabetics and 10 newly diagnosed insulin requiring diabetics showed the following concentrations of proinsulin: 0.009±0.005, 0.022±0.23 and 0.010±0.009 pmol/ml (mean±SD). One hour after 1.75 g/kg oral glucose, the values increased to 0.052±0.023, 0.046±0.022 and 0.032±0.022 pmol/ml. The fasting proinsulin constituted 19, 23 and 17% of the IRI, respectively, whereas 1 h post glucose these values changed to 8, 9 and 31% of IRI. Serum from 10 insulin-treated diabetics containing insulin antibodies contained from 0–1.80 pmol/ml, whereas the C-peptide levels in the same patients were 0–0.35 pmol/ml. It is suggested that insulin requiring diabetics hypersecrete proinsulin due to the inability of their B-cell to arrange proinsulin in secretory granules for adequate proinsulin/insulin conversion.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Insulin ; cirrhosis ; C-peptide ; proinsulin ; oral glucose tolerance test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The levels of proinsulin, immunoreactive insulin, true insulin (calculated from the difference, namely immunoreactive insulin-proinsulin) and C-peptide were determined in the fasting state and during a 3-h oral glucose tolerance test after administration of 100 g of glucose in 12 patients with cirrhosis with normal oral glucose tolerance test (50 g) and in 12 healthy subjects serving as controls. In the patients with cirrhosis the serum levels of proinsulin and immunoreactive insulin were significantly higher in the fasting state and after glucose loading than in the healthy subjects. The serum level of true insulin was also higher in the patients with cirrhosis, but the difference was less pronounced and only significant at a few of the time points. The serum level of C-peptide was very similar in both groups. These results emphasize that cirrhosis is a condition in which the serum proinsulin level is raised and that this hyperproinsulinaemia contributes greatly to the increased immunoreactive insulin levels observed in patients with this disease.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Porcine NPH insulin ; semi-synthetic and biosynthetic human NPH insulin ; pharmacokinetics ; pharmacodynamics ; normal subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The plasma glucose, C-peptide and insulin responses to subcutaneously administered highly purified porcine, ‘semi-synthetic’ and ‘biosynthetic’ human isophane (NPH) insulin and diluting medium as control in normal male subjects were evaluated. Porcine and semi-synthetic human NPH insulins were administered at two dose levels of 0.15 and 0.30 U/kg body weight and biosynthetic human NPH at 0.15 U/kg body weight only. At the low dose level the three insulin preparations resulted in a similar maximal hypoglycaemic effect within 3–5 h after administration. However, over the remainder of the 11 h post-injection period, the plasma glucose level was lower after semi-synthetic human insulin. In contrast, at the 0.30 U/kg dose level, there was no difference in the early or late hypoglycaemic response between porcine and semi-synthetic human NPH insulins of equivalent pharmaceutical formulation. The clinical relevance of these findings needs further evaluation. The data suggest that for the ‘intermediate-acting’ NPH insulin preparations, both the species of insulin, nature and quantity of the retarding protein and their subsequent interaction may determine their time-action characteristics.
    Type of Medium: Electronic Resource
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  • 8
    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.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 21 (1981), S. 103-107 
    ISSN: 1432-0428
    Keywords: Thyrotoxicosis ; insulin secretion ; proinsulin ; C-peptide ; insulin immunoreactivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The plasma insulin, C-peptide and proinsulin concentrations were investigated in thyrotoxic patients and in normal controls after an overnight fast, during a 36 h fasting period, an intravenous glucose tolerance test and an oral glucose tolerance test. The main finding was a significantly raised concentration of proinsulin in plasma of patients with thyrotoxicosis. After an overnight fast the plasma proinsulin was 0.048±0.005 pmol/ml in 15 thyrotoxic patients compared with 0.023±0.012 pmol/ml in 15 euthyroid controls. A twofold rise of plasma proinsulin concentration was also found in thyrotoxic patients during a prolonged fast, and during intravenous and oral glucose tolerance tests. The immunoreactivity of proinsulin in the insulin radioimmunoassay gave rise to slightly elevated concentrations of immunoreactive insulin in thyrotoxic patients in all the conditions investigated. When insulin values were corrected for proinsulin crossreactivity, they were similar in euthyroid controls and thyrotoxic patients. The concentration of plasma C-peptide was not significantly altered in thyrotoxic patients during intravenous and oral glucose tolerance tests.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: C-peptide ; Type 1 diabetes ; B cell reserve ; children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary C-peptide was determined in 24-h urine collections and in fasting plasma of 27 Type 1 (insulin-dependent) diabetic children (duration of disease 0–6 years) and in 11 matched normal children. Grouping the patients according to duration of disease from onset to 6 years, it was found that in the first year of disease the B cell reserve was a mean of 4.89±1.95 pmol · mg creatinine-1. 24 h-1 compared with a mean of 24.51±2.91 pmol · mg-1 · 24 h-1 in the control group. A further diminution was seen with increase in the duration of disease, until after 6 years when only traces of C-peptide could be detected. There was a good correlation between the levels of plasma C-peptide and urinary C-peptide values as related to creatinine (r = 0.89; p = 〈 0.001). In view of this, and since it is simpler and less traumatic to obtain frequent urine samples from children than it is to obtain blood samples, it was felt that the determination of urinary C-peptide constitutes a valuable tool in the evaluation of the diabetic child.
    Type of Medium: Electronic Resource
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