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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
    ISSN: 1432-0428
    Keywords: Key words Impaired glucose tolerance ; insulin response ; cholesterol.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Risk factors predicting deterioration to diabetes mellitus were examined in 181 subjects with impaired glucose tolerance. Fifty-seven subjects had impaired glucose tolerance on one occasion followed by normal glucose tolerance at a repeat oral glucose tolerance test, and 124 subjects had impaired glucose tolerance on two successive oral glucose tolerance tests. Subjects were followed for a median period of 5.0 years (range 1.0–17.2). The age- and sex-adjusted cumulative incidence of diabetes at 10 years of follow-up was higher in subjects who had impaired glucose tolerance on both tests (70 %) than in those whose glucose tolerance was normal at the repeat test (53 %), [rate ratio (RR) = 1.6, 95 % confidence intervals (CI) = 1.0–2.5]. Proportional hazards analyses were used to identify baseline risk factors (measured at the repeat oral glucose tolerance test) for subsequent diabetes, and incidence rate ratios were calculated for the 90th percentile compared with the 10th percentile of each continuous variable for the whole group. In all subjects, in separate models, higher body mass index [RR = 2.0, 95 % CI = 2.2–9.9], high fasting serum insulin concentrations [RR = 2.4, 95 % CI = 1.4–4.2], and low early insulin response [RR = 0.5, 95 % CI = 0.3–0.8] 30 min after a glucose load were significant predictors for deterioration to diabetes. In a multivariate analysis which controlled for age and sex, 120-min post-load glucose, fasting insulin and late insulin response predicted diabetes. In subgroup analyses the predictors of diabetes were generally similar in subjects who had impaired glucose tolerance at only one test and those who had impaired glucose tolerance on both tests. These findings suggest that in those subjects with impaired glucose tolerance whose glucose tolerance has returned to normal, the risk of subsequent diabetes is high. Insulin resistance, impaired early insulin response, or both, are predictive of subsequent development of diabetes in Pima Indians with impaired glucose tolerance. [Diabetologia (1995) 38: 187–192]
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Impaired glucose tolerance ; insulin response ; cholesterol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Risk factors predicting deterioration to diabetes mellitus were examined in 181 subjects with impaired glucose tolerance. Fifty-seven subjects had impaired glucose tolerance on one occasion followed by normal glucose tolerance at a repeat oral glucose tolerance test, and 124 subjects had impaired glucose tolerance on two successive oral glucose tolerance tests. Subjects were followed for a median period of 5.0 years (range 1.0–17.2). The age- and sex-adjusted cumulative incidence of diabetes at 10 years of follow-up was higher in subjects who had impaired glucose tolerance on both tests (70%) than in those whose glucose tolerance was normal at the repeat test (53%), [rate ratio (RR)=1.6, 95% confidence intervals (CI)=1.0–2.5]. Proportional hazards analyses were used to identify baseline risk factors (measured at the repeat oral glucose tolerance test) for subsequent diabetes, and incidence rate ratios were calculated for the 90th percentile compared with the 10th percentile of each continuous variable for the whole group. In all subjects, in separate models, higher body mass index [RR=2.0, 95% CI=2.2–9.9], high fasting serum insulin concentrations [RR=2.4, 95% CI=1.4–4.2], and low early insulin response [RR=0.5, 95% CI=0.3–0.8] 30 min after a glucose load were significant predictors for deterioration to diabetes. In a multivariate analysis which controlled for age and sex, 120-min post-load glucose, fasting insulin and late insulin response predicted diabetes. In subgroup analyses the predictors of diabetes were generally similar in subjects who had impaired glucose tolerance at only one test and those who had impaired glucose tolerance on both tests. These findings suggest that in those subjects with impaired glucose tolerance whose glucose tolerance has returned to normal, the risk of subsequent diabetes is high. Insulin resistance, impaired early insulin response, or both, are predictive of subsequent development of diabetes in Pima Indians with impaired glucose tolerance.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Keywords Plasminogen activator inhibitor-1 ; fibrinolysis ; Pima Indians ; polymorphism ; genetic ; diabetes mellitus ; non-insulin-dependent.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Elevated plasminogen activator inhibitor-1 may contribute to vascular disease in diabetes mellitus. Pima Indians have a low incidence of cardiovascular disease despite having a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM) which in this population is not associated with elevated plasminogen activator inhibitor-1 activity. In Caucasians an insertion/deletion (4G/5G) polymorphism in the promoter region of the plasminogen activator inhibitor-1 gene that has been related to activity levels of its protein in plasma differentially binds repressor and enhancer elements. In 265 Pima Indians (133 diabetic, 132 non-diabetic, 129 male, 136 female, mean age 46.6, range 34–68 years) the promoter genotype frequencies were 23.0 % for 4G/4G, 49.8 % for 4G/5G and 27.2 % for 5G/5G compared to 35.4 %, 50.8 % and 13.8 % respectively (χ2 = 15.3, 2 df, p 〈 0.0005) previously reported in Caucasians with NIDDM. The mean plasma activity levels in the three genotypes in the Pima Indians were 18.2, 19.1 and 18.1 U/ml, respectively. Plasminogen activator inhibitor-1 activities correlated with plasma insulin (r = 0.38, p 〈 0.0001), body mass index (r = 0.24, p 〈 0.0001), and with triglyceride level (r = 0.12, p = 0.054) but there was no relationship between promoter genotype and activity. A steeper regression slope between plasminogen activator inhibitor-1 activity and triglycerides has been observed in Caucasians with the 4G/4G genotype as compared to Caucasians with the other genotypes. This was not found in the Pima population which may indicate a functional difference in this gene associated with reduced cardiovascular risk and may be involved in the lack of association of plasminogen activator inhibitor-1 levels with NIDDM in Pima Indians. [Diabetologia (1996) 39: 1512–1518]
    Type of Medium: Electronic Resource
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