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  • 1
    ISSN: 1432-0428
    Keywords: 32–33 splet-proinsulin ; Total cholesterol ; high density lipoprotein cholisterol ; plasminogen activator inhibitor ; Blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Standard radioimmunoassay for insulin may substantially overestimate levels of insulin because of cross-reaction with other insulin-like molecules. We have measured concentrations of insulin, intact proinsulin and 32–33 split proinsulin using two-site monoclonal antibody based immunoradiometric assays, and of insulin by a standard radioimmunoassay (“immunoreactive insulin”) in 51 Type 2 (noninsulin-dependent) diabetic subjects in the fasting state. The relationships of these concentrations were sought with those of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride, plasminogen activator inhibitor, blood pressure, and indices of body fat distribution. Significant relationships were apparent between concentrations of “immunoreactive insulin” as measured by standard radioimmunoassay and triglyceride (r s=0.42, p〈0.001), total cholesterol (r s=0.25, p=0.038), high density lipoprotein cholesterol (r s=−0.30, p=0.018) and body mass index (r s=0.30, p=0.017), but only the relationships with triglyceride (r s=0.36, p=0.006) and body mass index (r s=0.26, p=0.034) remained significant when concentrations of immunoradiometrically measured insulin were employed. Concentrations of 32—33 split proinsulin, which comprises the major insulin-like molecule in these subjects, correlated positively with triglyceride (r s=0.33, p=0.009), total cholesterol (r s=0.23, p=0.050), and plasminogen activator inhibitor (r s=0.26, p=0.049), and negatively with high density lipoprotein cholesterol (r s=−0.29, p=0.021). Concentrations of “immunoreactive insulin” and immunoradiometric assay insulin showed significant positive correlaion with both systolic (r s=0.24, p=0.044 and r s=0.29, p=0.020 respectively), and diastolic blood pressure (r s=0.48, p〈0.001 and n=0.42, p=0.001 respectively), while those of intact proinsulin and 32–33 split proinsulin correlated only with diastolic blood pressure (r s=0.33, p=0.009 and r s=0.31, p=0.014 respectively). Using multiple regression analysis, and including age, sex, race and body mass index in the analyses, concentrations of intact proinsulin and 32–33 split proinsulin, but not immunoradiometric assay insulin, were significantly related to diastolic blood pressure. When all three molecules were incorporated into a single model, only 32–33 split proinsulin was related to diastolic blood pressure (F-change=6.91, [5,43 degrees of freedom]; p=0.012). Thus, high concentrations of insulin-like molecules are associated with changes in recognised cardiovascular risk factor in patients with Type 2 (non-insulin-dependent) diabetes mellitus.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 35 (1992), S. 1170-1172 
    ISSN: 1432-0428
    Keywords: Myotonic dystrophy ; proinsulin ; insulin resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hyperinsulinaemia is a reported feature of the inherited multisystem disorder myotonic dystrophy. This phenomenon has been attributed to a compensatory beta cell response to tissue insulin resistance. In this study, circulating concentrations of insulin, proinsulin, and split proinsulin molecules were determined after an overnight fast in ten patients with myotonic dystrophy using two-site monoclonal antibody-based immunoradiometric assays. Results were compared with ten healthy control subjects matched for age, gender, and body mass index. Oral glucose tolerance (75 g), as defined by World Health Organization criteria, was normal in all subjects. Fasting plasma immunoreactive insulin concentration, as determined using a conventional radioimmunoassay, was almost three times higher (p〈0.005) in the myotonic dystrophy patients than the healthy control subjects. By contrast, fasting concentrations (mean±SEM) of C-peptide (0.75±0.09 vs 0.52±0.03 nmol/l, p=0.07) and immunoradiometrically-determined insulin (60±12 vs 38±4 pmol/l, p=0.09) were not significantly different between the groups. Fasting concentrations of proinsulin (10.3±2.9 vs 1.6±0.3 pmol/l, p〈0.01), and 32–33 split proinsulin (7.8±2.5 vs 2.9±0.4 pmol/l, p〈0.05) were significantly elevated in the patients with myotonic dystrophy. Accordingly, the mean fasting proinsulin∶insulin ratio, expressed as a percentage, was significantly increased in the myotonic patients (20±5 vs 4±1%, p〈0.01). The overall C-peptide response to the oral glucose challenge was significantly greater in the myotonic patients compared with the healthy control subjects (p〈0.001). These results provide corroborative evidence of increased beta-cell secretion in myotonic dystrophy. In addition, myotonic dystrophy is characterised by elevated plasma concentrations of proinsulin-like molecules which may cross-react in insulin radioimmunoassays.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Impaired glucose tolerance ; non-insulin-dependent diabetes mellitus ; fetal growth ; ponderal index at birth ; placental weight to birthweight ratio
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A follow-up study was carried out to determine whether reduced fetal growth is associated with the development of impaired glucose tolerance in men and women aged 50 years. Standard oral glucose tolerance tests were carried out on 140 men and 126 women born in Preston (Lancashire, UK) between 1935 and 1943, whose size at birth had been measured in detail. Those subjects found to have impaired glucose tolerance or non-insulin-dependent diabetes mellitus had lower birthweight, a smaller head circumference and were thinner at birth. They also had a higher ratio of placental weight to birthweight. The prevalence of impaired glucose tolerance or diabetes fell from 27% in subjects who weighed 2.50 kg (5.5 pounds) or less at birth to 6% in those who weighed more than 3.41 kg (7.5 pounds) (p 〈 0.002 after adjusting for body mass index). Plasma glucose concentrations taken at 2-h in the glucose tolerance test fell progressively as birthweight increased (p 〈 0.004), as did 2-h plasma insulin concentrations (p 〈 0.001). The trends with birthweight were independent of duration of gestation and must therefore be related to reduced rates of fetal growth. These findings confirm the association between impaired glucose tolerance in adult life and low birthweight previously reported in Hertfordshire (UK), and demonstrate it in women as well as men. It is suggested that the association reflects the long-term effects of reduced growth of the endocrine pancreas and other tissues in utero. This may be a consequence of maternal undernutrition.
    Type of Medium: Electronic Resource
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