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  • 1
    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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  • 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
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 1 (1986), S. 218-229 
    ISSN: 0887-3585
    Keywords: colicin E1 ; site-directed mutagenesis ; ion channel ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Cleavage of colicin E1 molecules with a variety of proteases or with cyanogen bromide (CNBr) generates COOH-terminal fragments which have channel-forming activity similar to that of intact colicin in planar lipid bilayer membranes. The smallest channel-forming fragment obtained by CNBr cleavage of the wild-type molecule consists of the C-terminal 152 amino acids. By the use of oligonucleotide-directed mutagenesis, we have made nine mutants along this 152 amino acid peptide, in which an amino acid was replaced by methionine in order to create a new CNBr cleavage site. The smallest of the CNBr-cleaved C-terminal fragments with channel-forming activity, in planar bilayer membranes, was generated by cleavage at new Met position 428 and has 94 amino acids, whereas a 75 amino acid peptide produced by cleavage of a new Met at position 447 did not have channel activity. The NH2-terminus of the channel-forming domain of colicin E1 appears therfore to lie between residues 428 and 447. Since, however, the last six C-terminal residues of the colicin can be removed without changing activity, the number of amino acids necessary to form the channel is 88 or less. In addition, the unique Cys residue in colicin E1 was replaced by Gly, and nine mutants were then made with Cys placed at sequential locations along the peptide for eventual use as sulfhydryl attachment sites to determine the local environment of the replaced amino acid. In the course of making 21 mutants, eight charged residues have been replaced by uncharged Met or Cys without changing the biological activity of the intact molecule.It has been proposed previously that the conformation of the colicin E1 channel is a barrel formed from five or six α-helices, each having 20 amino acids spanning the membrane and two to four residues making the turn at the boundary of the membrane. Our finding that 88 amino acids can make an active channel, combined with recently reported stoichiometric evidence that the channel is a monomer excludes this model and adds significant constraints which can be used in building a molecular model of the channel.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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