1,721,003 research outputs found
Quantitative estimation of disposition index from postprandial glucose data across the spectrum of glucose tolerance
Get PDFDisposition index (DI), defined as the product of insulin sensitivity and b-cell responsivity, is the best measure of b-cell function. This is usually assessed from plasma glucose and insulin, and sometimes C-peptide, data either from surrogate indices or model-based methods. However, the recent advent of continuous glucose monitoring (CGM) systems in non-insulin-treated individuals raises the possibility of its quantification in outpatients. As a first step, we propose a method to assess DI from glucose concentration data only and validated it against the oral minimal model (OMM). To do so, we used data from two clinical dataset with mixed meal tolerance test (MTT) studies in non-insulin-treated individuals: the first consisted of 14 individuals with type 2 diabetes studied twice, either after receiving a DPP-4 inhibitor or a placebo before the meal, whereas the second consisted of 62 individuals with and without pre- or type 2 diabetes. A third, simulated, dataset consisted of 100 virtual subjects from the Padova Type 2 Diabetes Simulator was used for additional tests. Plasma glucose, insulin, and C-peptide concentrations were used to estimate the reference DI from the OMM (DIMM), whereas glucose data only were used to calculate the proposed DI (DIG). DIG was well correlated with DIMM in both the clinical and simulated datasets (R between 0.88 and 0.79, P < 0.001), and exhibited the same between-visit or between-group pattern. DIG can be used to assess therapy effectiveness and degree of glucose tolerance using glucose data only, paving the way to potentially assess b-cell function in real-life conditions using CGM
A Model for the Estimation of Hepatic Insulin Extraction after a Meal
No full textModeling hepatic insulin sensitivity during a meal: validation against the euglycemic hyperinsulinemic clamp. Am J Physiol Endocrinol Metab 304: E819-E825, 2013. First published February 26, 2013; doi:10.1152/ajpendo.00482.2012.-Recently, we proposed a model describing the suppression of endogenous glucose production (EGP) during a meal. It assumes that EGP suppression depends on glucose concentration and its rate of change and on delayed insulin action. Hepatic insulin sensitivity (S-I(Lmeal)) can be derived from EGP model parameters. This model was shown to adequately describe EGP profiles measured with multiple tracer techniques; however, S-I(Lmeal) has never been compared directly with its euglycemic hyperinsulinemic clamp counterpart (S-I(Lclamp)). To do so, 62 subjects with different degrees of glucose tolerance underwent a triple-tracer mixed meal. Fifty-seven subjects also underwent a labeled ([3-H-3]glucose) euglycemic hyperinsulinemic clamp. From the triple-tracer meal data, virtually model-independent estimates of EGP were obtained using the tracer-to-tracee clamp technique, and the EGP model was identified in each subject. Model fit was satisfactory, and S-I(Lmeal) was estimated with good precision. Correlation between S-I(Lclamp) and S-I(Lmeal) was good (r = 0.72, P < 0.001); however, S-I(Lmeal) was lower than S-I(Lclamp) (4.60 +/- 0.64 vs. 8.73 +/- 1.07 10(-4) dl.kg(-1).min(-1) per mu U/ml, P < 0.01). This difference may be due to different ranges of insulin explored during the two tests (Delta I-clamp = 15.60 +/- 1.61 vs. Delta I-meal = 83.37 +/- 10.71 mu U/ml) as well as steady- vs. non-steady-state glucose and insulin profiles. In conclusion, the new EGP model provides an estimate of hepatic insulin sensitivity during a meal that is in good agreement with that derived in the same individuals with a hyperinsulinemic clamp. When used in conjunction with the minimal model, the approach potentially enables estimation of hepatic insulin sensitivity from a single-tracer labeled meal or oral glucose tolerance test
1551-P: Impaired β-Cell Responsiveness to Glucagon in Type 2 Diabetes Mellitus Assessed by a New C-Peptide Minimal Model
No full textNonlinear Mixed Effects Modeling of Glucagon Kinetics in Healthy Subjects
Get PDFObjective: To date, the lack of a model of glucagon kinetics precluded the possibility of estimating and studying glucagon secretion in vivo, e.g., using deconvolution, as done for other hormones like insulin and C-peptide. Here, we used a nonlinear mixed effects technique to develop a robust population model of glucagon kinetics, able to describe both the typical population kinetics (TPK) and the between-subject variability (BSV), and relate this last to easily measurable subject characteristics. Methods: Thirty-four models of increasing complexity (variably including covariates and correlations among random effects) were identified on glucagon profiles obtained from 53 healthy subjects, who received a constant infusion of somatostatin to suppress endogenous glucagon production, followed by a continuous infusion of glucagon (65 ng/kg/min). Model selection was performed based on its ability to fit the data, provide precise parameter estimates, and parsimony criteria. Results: A two-compartment model was the most parsimonious. The model was able to accurately describe both the TPK and the BSV of model parameters as function of body mass and body surface area. Parameters were precisely estimated, with central volume of distribution V1 = 5.46 L and peripheral volume of distribution V2 = 5.51 L. The introduction of covariates resulted in a significant shrinkage of the unexplained BSV and considerably improved the model fit. Conclusion: We developed a robust population model of glucagon kinetics. Significance: This model provides a deeper understanding of glucagon kinetics and is usable to estimate glucagon secretion in vivo by deconvolution of plasma glucagon concentration data
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Model-Based Quantification of Glucagon-Like Peptide-1-Induced Potentiation of Insulin Secretion in Response to a Mixed Meal Challenge
Get PDFBackground: Glucagon-like peptide-1 (GLP-1) is a powerful insulin secretagogue that is secreted in response to meal ingestion. The ability to quantify the effect of GLP-1 on insulin secretion could provide insights into the pathogenesis and treatment of diabetes. We used a modification of a model of GLP-1 action on insulin secretion using data from a hyperglycemic clamp with concomitant GLP-1 infusion. We tested this model using data from a mixed meal test (MMT), thereby measuring GLP-1-induced potentiation of insulin secretion in response to a meal. Materials and Methods: The GLP-1 model is based on the oral C-peptide minimal model and assumes that over-basal insulin secretion depends linearly on GLP-1 concentration through the parameter , representing the -cell sensitivity to GLP-1. The model was tested on 62 subjects across the spectrum of glucose tolerance (age, 531 years; body mass index, 29.70.6kg/m(2)) studied with an MMT and provided a precise estimate of both -cell responsivity and indices. By combining with a measure of L-cell responsivity to glucose, one obtains a potentiation index (PI) (i.e., a measure of the L-cell's function in relation to prevailing -cell sensitivity to GLP-1). Results: Model-based measurement of GLP-1-induced insulin secretion demonstrates that the PI is significantly reduced in people with impaired glucose tolerance, compared with those with normal glucose tolerance. Conclusions: We describe a model that can quantitate the GLP-1-based contribution to insulin secretion in response to meal ingestion. This methodology will allow a better understanding of -cell function at various stages of glucose tolerance
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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