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  • 1
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; insulin secretion ; Beta-cell function ; glucose tolerance test ; insulin resistance ; obesity ; hyperglycaemic clamp ; euglycaemic clamp ; plasma insulin ; plasma C-peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The plasma insulin or C-peptide response to a 90-min constant glucose infusion 5 mg · kg ideal body weight−1·min−1 provides Beta-cell assessment comparable to more intensive methods. In 14 diet-treated Type 2 (non-insulin-dependent) diabetic subjects and 12 non-diabetic subjects, plasma insulin and C-peptide concentrations gave near linear plots against simultaneous glucose values. The ‘glucose-insulin and glucose-C-peptide vectors’ (G-I and G-C vectors), could be extrapolated to predict insulin and C-peptide levels during a 12 mmol/l hyperglycaemic clamp. Predicted concentrations correlated with clamp concentrations, r = 0.94 and r = 0.98 respectively, p〈0.001, validating the vectors as empirical glucose dose-response curves. The vector slopes correlated highly with % Beta, a mathematical model-derived measure of Beta-cell function using constant infusion of glucose model assessment, Spearman r = 0.95 and 0.93 for insulin and C-peptide, respectively. G-I vector slopes in 21 diet-treated Type 2 diabetic subjects with fasting glucose (mean +1 SD) 7.5±2,3 mmol/1, were lower than in 28 non-diabetic subjects, (geometric mean, 1 SD range, 8.4 pmol/mmol (3.3–21.0) and 25.1 pmol/mmol (14.3–44.1), p〈0.001, respectively), indicating an impaired Beta-cell response. The G-I vector slopes correlated with obesity in both groups (r = 0.54 p〈0.02 and 0.72, p〈0.001 respectively), and, in 15 non-diabetic subjects, correlated inversely with insulin sensitivity as measured by a euglycaemic clamp (r = −0.66, p〈0.01).Thus,Beta-cell function needs to be interpreted in relation to obesity/insulin resistance and, taking obesity into account, only 4 of 21 diabetic patients had Betacell function (G-I vector slope) in the non-diabetic range. The fasting plasma glucose in the diabetic subjects correlated inversely with the obesity-corrected G-I and G-C vector slopes (partial r = −0.57, p 〈0.01 and −0.86, p〈0.001, respectively). The insulin or C-peptide response to the glucose infusion provides a direct empirical measure of the Beta-cell function, which can be interpreted in relation to obesity or to insulin resistance to assess underlying pancreatic responsiveness.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Insulin resistance ; β-cell function ; mathematical model ; glucose infusion ; Type 2 diabetes ; plasma insulin ; plasma glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Continuous infusion of glucose with model assessment (CIGMA) is a new method of assessing glucose tolerance, insulin resistance and β-cell function. It consists of a continuous glucose infusion 5 mg glucose/kg ideal body weight per min for 60 min, with measurement of plasma glucose and insulin concentrations. These are similar to postprandial levels, change slowly, and depend on the dynamic interaction between the insulin produced and its effect on glucose turnover. The concentrations can be interpreted using a mathematical model of glucose and insulin homeostasis to assess insulin resistance and β-cell function. In 23 subjects (12 normal and 11 with Type 2 (non-insulin-dependent diabetes) the insulin resistance measured by CIGMA correlated with that measured independently by euglycaemic clamp (Rs = 0.87, p 〈 0.0001). With normal insulin resistance defined as 1, the median resistance in normal subjects was 1.35 by CIGMA and 1.39 by clamp, and in diabetic patients 4.0 by CIGMA and 3.96 by clamp. In 21 subjects (10 normal and 11 Type 2 diabetic) the β-cell function measured by CIGMA correlated with steady-state plasma insulin levels during hyperglycaemic clamp at 10 mmol/l (Rs=0.64, p 〈 0.002). The CIGMA coefficient of variability was 21% for resistance and 19% for β-cell function. CIGMA is a simple, non-labour-intensive method for assessing insulin resistance and β-cell function in normal and Type 2 diabetic subjects who do not have glycosuria during the test.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: β-cell function ; insulin resistance ; mathematical model ; intravenous glucose tolerance test ; glucose clamp ; insulin receptors ; Type 2 diabetes ; insulin ; glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The steady-state basal plasma glucose and insulin concentrations are determined by their interaction in a feedback loop. A computer-solved model has been used to predict the homeostatic concentrations which arise from varying degrees of β-cell deficiency and insulin resistance. Comparison of a patient's fasting values with the model's predictions allows a quantitative assessment of the contributions of insulin resistance and deficient β-cell function to the fasting hyperglycaemia (homeostasis model assessment, HOMA). The accuracy and precision of the estimate have been determined by comparison with independent measures of insulin resistance and β-cell function using hyperglycaemic and euglycaemic clamps and an intravenous glucose tolerance test. The estimate of insulin resistance obtained by homeostasis model assessment correlated with estimates obtained by use of the euglycaemic clamp (Rs = 0.88, p 〈 0.0001), the fasting insulin concentration (Rs = 0.81, p 〈 0.0001), and the hyperglycaemic clamp, (Rs = 0.69, p 〈 0.01). There was no correlation with any aspect of insulin-receptor binding. The estimate of deficient β-cell function obtained by homeostasis model assessment correlated with that derived using the hyperglycaemic clamp (Rs = 0.61, p 〈 0.01) and with the estimate from the intravenous glucose tolerance test (Rs = 0.64, p 〈 0.05). The low precision of the estimates from the model (coefficients of variation: 31% for insulin resistance and 32% for β-cell deficit) limits its use, but the correlation of the model's estimates with patient data accords with the hypothesis that basal glucose and insulin interactions are largely determined by a simple feed back loop.
    Type of Medium: Electronic Resource
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