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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
    European journal of pediatrics 157 (1997), S. S7 
    ISSN: 1432-1076
    Keywords: Key words Fetal growth ; Blood pressure ; Glucose tolerance ; Programming ; HPA axis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is now a large body of evidence to support the hypothesis that events in fetal life permanently alter the structure or function of an individual, programming later adult disease. Reduced birth weight is associated with higher blood pressure in childhood and adult life, and thinness at birth with glucose intolerance and non-insulin dependent diabetes mellitus. Programming of the hypothalamo-pituitary-adrenal (HPA) axis is an attractive hypothesis linking fetal experience and later disease, as an excess of glucocorticoids may be associated with hypertension and glucose intolerance. Moreover, animal data support this hypothesis. Exposing fetal rats to glucocorticoid reduces birth weight and leads to raised blood pressure, as well as to alterations in the HPA axis. Data on the long-term effects of exposure to glucocorticoids in human subjects are limited. Recently, however, reduced size at birth was found to be associated with higher fasting 9 a.m. plasma cortisol concentrations in adults. Raised plasma cortisol concentrations were, in turn, associated with higher blood pressure, and inversely related to measures of glucose tolerance. Conclusion Programming of the HPA axis by events in fetal life may be one of the mechanisms linking reduced size at birth with raised blood pressure and glucose intolerance in later life. Studies of the effects of antenatal and neonatal dexamethasone administration on later blood pressure and glucose tolerance may be warranted.
    Type of Medium: Electronic Resource
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