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Claudio Cobelli - One of the best experts on this subject based on the ideXlab platform.
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the oral Minimal Model method
Diabetes, 2014Co-Authors: Claudio Cobelli, Rita Basu, Gianna Toffolo, Chiara Dalla Man, Adrian Vella, Robert A RizzaAbstract:The simultaneous assessment of insulin action, secretion, and hepatic extraction is key to understanding postprandial glucose metabolism in nondiabetic and diabetic humans. We review the oral Minimal method (i.e., Models that allow the estimation of insulin sensitivity, β-cell responsivity, and hepatic insulin extraction from a mixed-meal or an oral glucose tolerance test). Both of these oral tests are more physiologic and simpler to administer than those based on an intravenous test (e.g., a glucose clamp or an intravenous glucose tolerance test). The focus of this review is on indices provided by physiological-based Models and their validation against the glucose clamp technique. We discuss first the oral Minimal Model method rationale, data, and protocols. Then we present the three Minimal Models and the indices they provide. The disposition index paradigm, a widely used β-cell function metric, is revisited in the context of individual versus population Modeling. Adding a glucose tracer to the oral dose significantly enhances the assessment of insulin action by segregating insulin sensitivity into its glucose disposal and hepatic components. The oral Minimal Model method, by quantitatively portraying the complex relationships between the major players of glucose metabolism, is able to provide novel insights regarding the regulation of postprandial metabolism.
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nonlinear mixed effects to improve glucose Minimal Model parameter estimation a simulation study in intensive and sparse sampling
IEEE Transactions on Biomedical Engineering, 2009Co-Authors: Paolo Denti, Paolo Vicini, Alessandra Bertoldo, Claudio CobelliAbstract:Intravenous glucose tolerance test (IVGTT) Minimal Model parameters are commonly estimated by weighted least squares (WLSs) on each subject data. Sometimes, with sparse data, individual parameters cannot be satisfactorily obtained. In such cases, a population approach could be preferable. These methods allow borrowing information across all subjects simultaneously, quantifying population features directly, and subsequently, deriving individual parameter estimates. In this paper, we assessed different estimation methods on simulated datasets. Besides the standard WLS approach, we applied iterative procedures (iterative two-stage (ITS) and global two-stage (GTS) methods) as well as nonlinear mixed-effects Models (NLMEMs), where the likelihood is based on Model linearization: first-order (FO), FO conditional estimation (FOCE), and Laplace (LAP) approximations. The synthetic dataset, initially very rich, was progressively reduced (by 50% and 75%) in order to assess the robustness of the results in sparsely sampled situations. Our results show that, even with intensive sampling, population approaches provide more reliable parameter estimates. Moreover, these estimates are remarkably more robust when the data become scarce. ITS and GTS encounter critical problems when single subjects have very poor sampling schedules, whereas the NLMEM (excluding FO) methods are more versatile and able to cope with such situations. FOCE appears as the most satisfactory approach.
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the glucose Minimal Model population vs individual parameter estimation
IFAC Proceedings Volumes, 2006Co-Authors: Claudio Cobelli, Alessandra Bertoldo, Paolo ViciniAbstract:Abstract Glucose Minimal Model parameters are commonly estimated by applying weighted nonlinear least squares separately to each subject's data. Because of the Model's nonlinearity the parameter precision of the single-compartment Minimal Model is not always satisfactory, especially in presence of a reduced sampling schedule. In the current work, the use of population analysis through nonlinear mixed effects Models is evaluated and its performance tested against the parameter estimates obtained by the standard individual approach through weighted nonlinear least squares.
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two hour seven sample oral glucose tolerance test and meal protocol Minimal Model assessment of β cell responsivity and insulin sensitivity in nondiabetic individuals
Diabetes, 2005Co-Authors: Chiara Dalla Man, Rita Basu, Robert A Rizza, Gianna Toffolo, Kenneth S Polonsky, Marco Campioni, Claudio CobelliAbstract:Highly informative yet simple protocols to assess insulin secretion and action would considerably enhance the quality of epidemiological and large-scale clinical trials. In an effort to develop such protocols, a 5-h, 11-sample oral glucose tolerance test (OGTT) was performed in 100 individuals and a 7-h, 21-sample meal in another 100. Plasma glucose, insulin, and C-peptide concentrations were measured. We show that virtually the same Minimal Model assessment of β-cell responsivity (dynamic [Φd] and static [Φs]), insulin sensitivity ( S i), and disposition index (DI) can be obtained with a reduced seven-sample 2-h protocol: Φd, reduced versus full: 871.50 vs. 873.32, r = 0.98 in OGTT and 494.88 vs. 477.99 10−9, r = 0.91 in meal; Φs: 42.36 vs. 44.35, r = 0.88 in OGTT and 35.31 vs. 35.37 10−9 min−1, r = 0.90 in meal; S i: 24.33 vs. 22.77 10−5 dl · kg−1 · min−1 per pmol/l, r = 0.89 in OGTT and 19.03 vs. 19.77 10−5 dl · kg−1 · min−1 per pmol/l, r = 0.85 in meal; and DI: 1,282.26 vs. 1,273.23, r = 0.84 in OGTT and 726.92 vs. 776.97 10−14 dl · kg−1 · min−2 per pmol/l, r = 0.84 in meal. This reduced protocol will facilitate the study of insulin secretion and action under physiological conditions in nondiabetic humans.
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two hour seven sample oral glucose tolerance test and meal protocol Minimal Model assessment of β cell responsivity and insulin sensitivity in nondiabetic individuals
Diabetes, 2005Co-Authors: Chiara Dalla Man, Rita Basu, Robert A Rizza, Gianna Toffolo, Kenneth S Polonsky, Marco Campioni, Claudio CobelliAbstract:Highly informative yet simple protocols to assess insulin secretion and action would considerably enhance the quality of epidemiological and large-scale clinical trials. In an effort to develop such protocols, a 5-h, 11-sample oral glucose tolerance test (OGTT) was performed in 100 individuals and a 7-h, 21-sample meal in another 100. Plasma glucose, insulin, and C-peptide concentrations were measured. We show that virtually the same Minimal Model assessment of beta-cell responsivity (dynamic [Phi(d)] and static [Phi(s)]), insulin sensitivity (Si), and disposition index (DI) can be obtained with a reduced seven-sample 2-h protocol: Phi(d), reduced versus full: 871.50 vs. 873.32, r = 0.98 in OGTT and 494.88 vs. 477.99 10(-9), r = 0.91 in meal; Phi(s): 42.36 vs. 44.35, r = 0.88 in OGTT and 35.31 vs. 35.37 10(-9) min(-1), r = 0.90 in meal; Si: 24.33 vs. 22.77 10(-5) dl x kg(-1) x min(-1) per pmol/l, r = 0.89 in OGTT and 19.03 vs. 19.77 10(-5) dl x kg(-1) x min(-1) per pmol/l, r = 0.85 in meal; and DI: 1,282.26 vs. 1,273.23, r = 0.84 in OGTT and 726.92 vs. 776.97 10(-14) dl . kg(-1) x min(-2) per pmol/l, r = 0.84 in meal. This reduced protocol will facilitate the study of insulin secretion and action under physiological conditions in nondiabetic humans.
R N Bergman - One of the best experts on this subject based on the ideXlab platform.
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Minimal Model perspective from 2005
Hormone Research in Paediatrics, 2005Co-Authors: R N BergmanAbstract:The Minimal Model was proposed over 25 years ago. Despite (or because of) its simplicity it continues to be used today – both as a clinical tool and an approach to understanding the composite effects
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Minimal Model based insulin sensitivity has greater heritability and a different genetic basis than homeostasis Model assessment or fasting insulin
Diabetes, 2003Co-Authors: R N Bergman, Mohammed F Saad, Daniel J. Zaccaro, Richard M. Watanabe, Steven M. Haffner, Jill M. Norris, Lynne E. Wagenknecht, James E. Hokanson, Jerome I. Rotter, Steven S. RichAbstract:Insulin resistance is an important risk factor for development of type 2 diabetes as well as other chronic conditions, including hypertension, cardiovascular disease, and colon cancer. To find genes for insulin resistance it is necessary to assess insulin action in large populations. We have previously measured insulin action in a large cohort of subjects (Insulin Resistance and Atherosclerosis Study [IRAS] Family Study) using the Minimal Model approach. In this study, we compare sensitivity from the Minimal Model (insulin sensitivity index [S(I)]) with the measure of insulin resistance emanating from the homeostasis Model assessment (HOMA) approach. The former measure emerges from the glycemic response to endogenous and exogenous insulin; the latter is based solely on fasting measures of glucose and insulin. A total of 112 pedigrees were represented, including 1,362 individuals with full phenotypic assessment. Heritability of S(I) was significantly greater than that for HOMA (0.310 vs. 0.163) and for fasting insulin (0.171), adjusted for age, sex, ethnicity, and BMI. In addition, correlation between S(I) and either HOMA or fasting insulin was only approximately 50% accounted for by genetic factors, with the remainder accounted for by environment. Thus S(I), a direct measure of insulin sensitivity, is determined more by genetic factors rather than measures such as HOMA, which reflect fasting insulin.
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insulin sensitivity from meal tolerance tests in normal subjects a Minimal Model index
The Journal of Clinical Endocrinology and Metabolism, 2000Co-Authors: Andrea Caumo, R N Bergman, Claudio CobelliAbstract:In this report a new approach is introduced that allows estimation of insulin sensitivity (SI) from orally ingested glucose during an oral glucose tolerance test (OGTT) or a meal glucose tolerance test (MGTT) in normal subjects. The method hinges on the classic Minimal Model of glucose kinetics that is coupled with an equation describing the rate of appearance of glucose into the circulation after oral glucose ingestion. The Model provides an estimate of SI in a given individual based on simple area under the curve type of calculations. To prove the reliability of the new approach, MGTT studies performed in 10 normal subjects were analyzed and the SI index from the MGTT was compared with the SI index obtained in the same subjects from an insulin-modified, frequently sampled iv glucose test (FSIGT). SI from the MGTT was 13.6 ± 3.9 × 10−4 dL/kg·min/μU·mL and was strongly correlated to the SI from the FSIGT (rs = 0.89; P < 0.01). In conclusion, this study shows that in normal subjects the Minimal Model can b...
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differences between the tolbutamide boosted and the insulin modified Minimal Model protocols
Diabetes, 1997Co-Authors: Mohammed F Saad, Garry M Steil, Wagdy W Kades, Maged F Ayad, Wagih A Elsewafy, Rima Boyadjian, Sujata Jinagouda, R N BergmanAbstract:The insulin-modified frequently sampled Intravenous glucose tolerance test (FSIGTT) with Minimal Model analysis (MINMOD) was compared with the tolbutamide protocol and the glucose clamp in 35 nondiabetic subjects (age 38 ± 2 years [mean ± SE], BMI 27.2 ± 0.9 kg/m 2 ). Each subject underwent two FSIGTTs, one with tolbutamide (300 mg) and the other with insulin (0.03 U/kg) and a euglycemic hyperinsulinemic clamp (40 mU · m −2 · min −1 ). Insulin sensitivity was determined from each FSIGTT with MINMOD and from the clamp. Insulin sensitivity indexes ( S I ) from the two FSIGTTs were significantly correlated ( r = 0.77, P S I(insuiin) was 29 ± 4% lower than S I(toibutamide) . Both S I(insuiin) and Sictoibutamide) correlated significantly with S I(ciamp) ( r = 0.70 and 0.71, P S I(toibutamide) was on average 13 ± 6% lower than S I(ciamp) (4.51 ± 0.40 vs. 5.36 ± 0.36 × 10 −2 , P = 0.009), whereas S I(insulin) Was 44 ± 4% lower. S G(tolbutamide) and S G(insulin) were not different (1.88 ± 0.10 vs. 2.01 ± 0.09 × 10 −2 min −1 , P = 0.167) and were significantly correlated ( r = 0.50, P = 0.002). Thus, insulin sensitivity estimates from both protocols correlate significantly with each other and with the clamp. They are quantitatively discrepant, however, possibly due to differences in the route of insulin delivery, saturation of insulin action, and/or tolbutamide-induced proinsulin release. Data obtained from these two MINMOD protocols are not directly comparable, and the same protocol must be used in any single cross-sectional or longitudinal study.
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a comparison between the Minimal Model and the glucose clamp in the assessment of insulin sensitivity across the spectrum of glucose tolerance insulin resistance atherosclerosis study
Diabetes, 1994Co-Authors: Mohammed F Saad, Wagdy W Kades, Richard M. Watanabe, Randy L Anderson, Ami Laws, Yiider I Chen, R E Sands, Dee Pei, Peter J Savage, R N BergmanAbstract:An insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT) with Minimal Model analysis was compared with the glucose clamp in 11 subjects with normal glucose tolerance (NGT), 20 with impaired glucose tolerance (IGT), and 24 with non-insulin-dependent diabetes mellitus (NIDDM). The insulin sensitivity index (SI) was calculated from FSIGTT using 22- and 12-sample protocols (SI(22) and SI(12), respectively). Insulin sensitivity from the clamp was expressed as SI(clamp) and SIP(clamp). Minimal Model parameters were similar when calculated with SI(22) and SI(12). SI could not be distinguished from 0 in approximately 50% of diabetic patients with either protocol. SI(22) correlated significantly with SI(clamp) in the whole group (r = 0.62), and in the NGT (r = 0.53), IGT (r = 0.48), and NIDDM (r = 0.41) groups (P < 0.05 for each). SI(12) correlated significantly with SI(clamp) in the whole group (r = 0.55, P < 0.001) and in the NGT (r = 0.53, P = 0.046) and IGT (r = 0.58, P = 0.008) but not NIDDM (r = 0.30, P = 0.085) groups. When SI(22), SI(clamp), and SIP(clamp) were expressed in the same units, SI(22) was 66 +/- 5% (mean +/- SE) and 50 +/- 8% lower than SI(clamp) and SIP(clamp), respectively. Thus, Minimal Model analysis of the insulin-modified FSIGTT provides estimates of insulin sensitivity that correlate significantly with those from the glucose clamp. The correlation was weaker, however, in NIDDM. The insulin-modified FSIGTT can be used as a simple test for assessment of insulin sensitivity in population studies involving nondiabetic subjects. Additional studies are needed before using this test routinely in patients with NIDDM.
Gianna Toffolo - One of the best experts on this subject based on the ideXlab platform.
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the oral Minimal Model method
Diabetes, 2014Co-Authors: Claudio Cobelli, Rita Basu, Gianna Toffolo, Chiara Dalla Man, Adrian Vella, Robert A RizzaAbstract:The simultaneous assessment of insulin action, secretion, and hepatic extraction is key to understanding postprandial glucose metabolism in nondiabetic and diabetic humans. We review the oral Minimal method (i.e., Models that allow the estimation of insulin sensitivity, β-cell responsivity, and hepatic insulin extraction from a mixed-meal or an oral glucose tolerance test). Both of these oral tests are more physiologic and simpler to administer than those based on an intravenous test (e.g., a glucose clamp or an intravenous glucose tolerance test). The focus of this review is on indices provided by physiological-based Models and their validation against the glucose clamp technique. We discuss first the oral Minimal Model method rationale, data, and protocols. Then we present the three Minimal Models and the indices they provide. The disposition index paradigm, a widely used β-cell function metric, is revisited in the context of individual versus population Modeling. Adding a glucose tracer to the oral dose significantly enhances the assessment of insulin action by segregating insulin sensitivity into its glucose disposal and hepatic components. The oral Minimal Model method, by quantitatively portraying the complex relationships between the major players of glucose metabolism, is able to provide novel insights regarding the regulation of postprandial metabolism.
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two hour seven sample oral glucose tolerance test and meal protocol Minimal Model assessment of β cell responsivity and insulin sensitivity in nondiabetic individuals
Diabetes, 2005Co-Authors: Chiara Dalla Man, Rita Basu, Robert A Rizza, Gianna Toffolo, Kenneth S Polonsky, Marco Campioni, Claudio CobelliAbstract:Highly informative yet simple protocols to assess insulin secretion and action would considerably enhance the quality of epidemiological and large-scale clinical trials. In an effort to develop such protocols, a 5-h, 11-sample oral glucose tolerance test (OGTT) was performed in 100 individuals and a 7-h, 21-sample meal in another 100. Plasma glucose, insulin, and C-peptide concentrations were measured. We show that virtually the same Minimal Model assessment of β-cell responsivity (dynamic [Φd] and static [Φs]), insulin sensitivity ( S i), and disposition index (DI) can be obtained with a reduced seven-sample 2-h protocol: Φd, reduced versus full: 871.50 vs. 873.32, r = 0.98 in OGTT and 494.88 vs. 477.99 10−9, r = 0.91 in meal; Φs: 42.36 vs. 44.35, r = 0.88 in OGTT and 35.31 vs. 35.37 10−9 min−1, r = 0.90 in meal; S i: 24.33 vs. 22.77 10−5 dl · kg−1 · min−1 per pmol/l, r = 0.89 in OGTT and 19.03 vs. 19.77 10−5 dl · kg−1 · min−1 per pmol/l, r = 0.85 in meal; and DI: 1,282.26 vs. 1,273.23, r = 0.84 in OGTT and 726.92 vs. 776.97 10−14 dl · kg−1 · min−2 per pmol/l, r = 0.84 in meal. This reduced protocol will facilitate the study of insulin secretion and action under physiological conditions in nondiabetic humans.
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two hour seven sample oral glucose tolerance test and meal protocol Minimal Model assessment of β cell responsivity and insulin sensitivity in nondiabetic individuals
Diabetes, 2005Co-Authors: Chiara Dalla Man, Rita Basu, Robert A Rizza, Gianna Toffolo, Kenneth S Polonsky, Marco Campioni, Claudio CobelliAbstract:Highly informative yet simple protocols to assess insulin secretion and action would considerably enhance the quality of epidemiological and large-scale clinical trials. In an effort to develop such protocols, a 5-h, 11-sample oral glucose tolerance test (OGTT) was performed in 100 individuals and a 7-h, 21-sample meal in another 100. Plasma glucose, insulin, and C-peptide concentrations were measured. We show that virtually the same Minimal Model assessment of beta-cell responsivity (dynamic [Phi(d)] and static [Phi(s)]), insulin sensitivity (Si), and disposition index (DI) can be obtained with a reduced seven-sample 2-h protocol: Phi(d), reduced versus full: 871.50 vs. 873.32, r = 0.98 in OGTT and 494.88 vs. 477.99 10(-9), r = 0.91 in meal; Phi(s): 42.36 vs. 44.35, r = 0.88 in OGTT and 35.31 vs. 35.37 10(-9) min(-1), r = 0.90 in meal; Si: 24.33 vs. 22.77 10(-5) dl x kg(-1) x min(-1) per pmol/l, r = 0.89 in OGTT and 19.03 vs. 19.77 10(-5) dl x kg(-1) x min(-1) per pmol/l, r = 0.85 in meal; and DI: 1,282.26 vs. 1,273.23, r = 0.84 in OGTT and 726.92 vs. 776.97 10(-14) dl . kg(-1) x min(-2) per pmol/l, r = 0.84 in meal. This reduced protocol will facilitate the study of insulin secretion and action under physiological conditions in nondiabetic humans.
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Minimal Model estimation of glucose absorption and insulin sensitivity from oral test validation with a tracer method
American Journal of Physiology-endocrinology and Metabolism, 2004Co-Authors: Andrea Caumo, Rita Basu, Robert A Rizza, Gianna ToffoloAbstract:Measuring insulin sensitivity during the physiological milieu of oral glucose perturbation, e.g., a meal or an oral glucose tolerance test, would be extremely valuable but difficult since the rate of appearance of absorbed glucose is unknown. The reference method is a tracer two-step one: first, the rate of appearance of glucose (Ra mealref) is reconstructed by employing the tracer-to-tracee ratio clamp technique with two tracers and a Model of non-steady-state glucose kinetics; next, this Ra mealref is used as the known input of a Model describing insulin action on glucose kinetics to estimate insulin sensitivity (SIref). Recently, a nontracer method based on the oral Minimal Model (OMM) has been proposed to estimate simultaneously the above quantities, denoted Ra meal and SI, respectively, from plasma glucose and insulin concentrations measured after an oral glucose perturbation. This last method has obvious advantages over the tracer method, but its domain of validity has never been assessed against a ...
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oral glucose tolerance test Minimal Model indexes of β cell function and insulin sensitivity
Diabetes, 2001Co-Authors: Elena Breda, Gianna Toffolo, Melissa K Cavaghan, Kenneth S Polonsky, Claudio CobelliAbstract:The simultaneous assessment of quantitative indexes of insulin secretion and action in a single individual is important when quantifying their relative role in the evolution of glucose tolerance in different physiopathological states. Available methods quantify these indexes in relatively nonphysiological conditions, e.g., during glucose clamps or intravenous glucose tolerance tests. Here, we present a method based on a physiological test applicable to large-scale genetic and epidemiologic studies—the oral glucose tolerance test (OGTT). Plasma C-peptide, insulin, and glucose data from a frequently sampled OGTT with 22 samples throughout 300 min (FSOGTT 300-22 ) were analyzed in 11 subjects with various degrees of glucose tolerance. In each individual, two indexes of pancreatic sensitivity to glucose (Φ s [10 9 min -1 ] and Φ d [10 9 ]) and the insulin sensitivity index ( S I ) (10 5 dl/kg per min per pmol/l) were estimated by using the Minimal Model of C-peptide secretion and kinetics originally proposed for intravenous graded glucose infusion and the Minimal Model approach recently proposed for meal/OGTTs. The indexes obtained from FSOGTT 300-22 were used as a reference for internal validation of OGTT protocols with reduced sampling schedules. Our results show that 11 samples in a 300-min period (OGTT 300-11 ) is the test of choice because the indexes it provides (Φ s = 36 ± 3 [means ± SE]; Φ d = 710 ± 111; S I = 10.2 ± 2.4) show excellent correlation and are not statistically different from those of FSOGTT 300-22 (Φ s = 33 ± 3; Φ d = 715 ± 120; S I = 10.1 ± 2.3). In conclusion, OGTT 300-11 , interpreted with C-peptide and glucose Minimal Models, provides a quantitative description of β-cell function and insulin sensitivity in a single individual while preserving the important clinical classification of glucose tolerance provided by the standard 120-min OGTT.
Robert A Rizza - One of the best experts on this subject based on the ideXlab platform.
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the oral Minimal Model method
Diabetes, 2014Co-Authors: Claudio Cobelli, Rita Basu, Gianna Toffolo, Chiara Dalla Man, Adrian Vella, Robert A RizzaAbstract:The simultaneous assessment of insulin action, secretion, and hepatic extraction is key to understanding postprandial glucose metabolism in nondiabetic and diabetic humans. We review the oral Minimal method (i.e., Models that allow the estimation of insulin sensitivity, β-cell responsivity, and hepatic insulin extraction from a mixed-meal or an oral glucose tolerance test). Both of these oral tests are more physiologic and simpler to administer than those based on an intravenous test (e.g., a glucose clamp or an intravenous glucose tolerance test). The focus of this review is on indices provided by physiological-based Models and their validation against the glucose clamp technique. We discuss first the oral Minimal Model method rationale, data, and protocols. Then we present the three Minimal Models and the indices they provide. The disposition index paradigm, a widely used β-cell function metric, is revisited in the context of individual versus population Modeling. Adding a glucose tracer to the oral dose significantly enhances the assessment of insulin action by segregating insulin sensitivity into its glucose disposal and hepatic components. The oral Minimal Model method, by quantitatively portraying the complex relationships between the major players of glucose metabolism, is able to provide novel insights regarding the regulation of postprandial metabolism.
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two hour seven sample oral glucose tolerance test and meal protocol Minimal Model assessment of β cell responsivity and insulin sensitivity in nondiabetic individuals
Diabetes, 2005Co-Authors: Chiara Dalla Man, Rita Basu, Robert A Rizza, Gianna Toffolo, Kenneth S Polonsky, Marco Campioni, Claudio CobelliAbstract:Highly informative yet simple protocols to assess insulin secretion and action would considerably enhance the quality of epidemiological and large-scale clinical trials. In an effort to develop such protocols, a 5-h, 11-sample oral glucose tolerance test (OGTT) was performed in 100 individuals and a 7-h, 21-sample meal in another 100. Plasma glucose, insulin, and C-peptide concentrations were measured. We show that virtually the same Minimal Model assessment of β-cell responsivity (dynamic [Φd] and static [Φs]), insulin sensitivity ( S i), and disposition index (DI) can be obtained with a reduced seven-sample 2-h protocol: Φd, reduced versus full: 871.50 vs. 873.32, r = 0.98 in OGTT and 494.88 vs. 477.99 10−9, r = 0.91 in meal; Φs: 42.36 vs. 44.35, r = 0.88 in OGTT and 35.31 vs. 35.37 10−9 min−1, r = 0.90 in meal; S i: 24.33 vs. 22.77 10−5 dl · kg−1 · min−1 per pmol/l, r = 0.89 in OGTT and 19.03 vs. 19.77 10−5 dl · kg−1 · min−1 per pmol/l, r = 0.85 in meal; and DI: 1,282.26 vs. 1,273.23, r = 0.84 in OGTT and 726.92 vs. 776.97 10−14 dl · kg−1 · min−2 per pmol/l, r = 0.84 in meal. This reduced protocol will facilitate the study of insulin secretion and action under physiological conditions in nondiabetic humans.
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two hour seven sample oral glucose tolerance test and meal protocol Minimal Model assessment of β cell responsivity and insulin sensitivity in nondiabetic individuals
Diabetes, 2005Co-Authors: Chiara Dalla Man, Rita Basu, Robert A Rizza, Gianna Toffolo, Kenneth S Polonsky, Marco Campioni, Claudio CobelliAbstract:Highly informative yet simple protocols to assess insulin secretion and action would considerably enhance the quality of epidemiological and large-scale clinical trials. In an effort to develop such protocols, a 5-h, 11-sample oral glucose tolerance test (OGTT) was performed in 100 individuals and a 7-h, 21-sample meal in another 100. Plasma glucose, insulin, and C-peptide concentrations were measured. We show that virtually the same Minimal Model assessment of beta-cell responsivity (dynamic [Phi(d)] and static [Phi(s)]), insulin sensitivity (Si), and disposition index (DI) can be obtained with a reduced seven-sample 2-h protocol: Phi(d), reduced versus full: 871.50 vs. 873.32, r = 0.98 in OGTT and 494.88 vs. 477.99 10(-9), r = 0.91 in meal; Phi(s): 42.36 vs. 44.35, r = 0.88 in OGTT and 35.31 vs. 35.37 10(-9) min(-1), r = 0.90 in meal; Si: 24.33 vs. 22.77 10(-5) dl x kg(-1) x min(-1) per pmol/l, r = 0.89 in OGTT and 19.03 vs. 19.77 10(-5) dl x kg(-1) x min(-1) per pmol/l, r = 0.85 in meal; and DI: 1,282.26 vs. 1,273.23, r = 0.84 in OGTT and 726.92 vs. 776.97 10(-14) dl . kg(-1) x min(-2) per pmol/l, r = 0.84 in meal. This reduced protocol will facilitate the study of insulin secretion and action under physiological conditions in nondiabetic humans.
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Minimal Model estimation of glucose absorption and insulin sensitivity from oral test validation with a tracer method
American Journal of Physiology-endocrinology and Metabolism, 2004Co-Authors: Andrea Caumo, Rita Basu, Robert A Rizza, Gianna ToffoloAbstract:Measuring insulin sensitivity during the physiological milieu of oral glucose perturbation, e.g., a meal or an oral glucose tolerance test, would be extremely valuable but difficult since the rate of appearance of absorbed glucose is unknown. The reference method is a tracer two-step one: first, the rate of appearance of glucose (Ra mealref) is reconstructed by employing the tracer-to-tracee ratio clamp technique with two tracers and a Model of non-steady-state glucose kinetics; next, this Ra mealref is used as the known input of a Model describing insulin action on glucose kinetics to estimate insulin sensitivity (SIref). Recently, a nontracer method based on the oral Minimal Model (OMM) has been proposed to estimate simultaneously the above quantities, denoted Ra meal and SI, respectively, from plasma glucose and insulin concentrations measured after an oral glucose perturbation. This last method has obvious advantages over the tracer method, but its domain of validity has never been assessed against a ...
Rita Basu - One of the best experts on this subject based on the ideXlab platform.
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the oral Minimal Model method
Diabetes, 2014Co-Authors: Claudio Cobelli, Rita Basu, Gianna Toffolo, Chiara Dalla Man, Adrian Vella, Robert A RizzaAbstract:The simultaneous assessment of insulin action, secretion, and hepatic extraction is key to understanding postprandial glucose metabolism in nondiabetic and diabetic humans. We review the oral Minimal method (i.e., Models that allow the estimation of insulin sensitivity, β-cell responsivity, and hepatic insulin extraction from a mixed-meal or an oral glucose tolerance test). Both of these oral tests are more physiologic and simpler to administer than those based on an intravenous test (e.g., a glucose clamp or an intravenous glucose tolerance test). The focus of this review is on indices provided by physiological-based Models and their validation against the glucose clamp technique. We discuss first the oral Minimal Model method rationale, data, and protocols. Then we present the three Minimal Models and the indices they provide. The disposition index paradigm, a widely used β-cell function metric, is revisited in the context of individual versus population Modeling. Adding a glucose tracer to the oral dose significantly enhances the assessment of insulin action by segregating insulin sensitivity into its glucose disposal and hepatic components. The oral Minimal Model method, by quantitatively portraying the complex relationships between the major players of glucose metabolism, is able to provide novel insights regarding the regulation of postprandial metabolism.
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two hour seven sample oral glucose tolerance test and meal protocol Minimal Model assessment of β cell responsivity and insulin sensitivity in nondiabetic individuals
Diabetes, 2005Co-Authors: Chiara Dalla Man, Rita Basu, Robert A Rizza, Gianna Toffolo, Kenneth S Polonsky, Marco Campioni, Claudio CobelliAbstract:Highly informative yet simple protocols to assess insulin secretion and action would considerably enhance the quality of epidemiological and large-scale clinical trials. In an effort to develop such protocols, a 5-h, 11-sample oral glucose tolerance test (OGTT) was performed in 100 individuals and a 7-h, 21-sample meal in another 100. Plasma glucose, insulin, and C-peptide concentrations were measured. We show that virtually the same Minimal Model assessment of β-cell responsivity (dynamic [Φd] and static [Φs]), insulin sensitivity ( S i), and disposition index (DI) can be obtained with a reduced seven-sample 2-h protocol: Φd, reduced versus full: 871.50 vs. 873.32, r = 0.98 in OGTT and 494.88 vs. 477.99 10−9, r = 0.91 in meal; Φs: 42.36 vs. 44.35, r = 0.88 in OGTT and 35.31 vs. 35.37 10−9 min−1, r = 0.90 in meal; S i: 24.33 vs. 22.77 10−5 dl · kg−1 · min−1 per pmol/l, r = 0.89 in OGTT and 19.03 vs. 19.77 10−5 dl · kg−1 · min−1 per pmol/l, r = 0.85 in meal; and DI: 1,282.26 vs. 1,273.23, r = 0.84 in OGTT and 726.92 vs. 776.97 10−14 dl · kg−1 · min−2 per pmol/l, r = 0.84 in meal. This reduced protocol will facilitate the study of insulin secretion and action under physiological conditions in nondiabetic humans.
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two hour seven sample oral glucose tolerance test and meal protocol Minimal Model assessment of β cell responsivity and insulin sensitivity in nondiabetic individuals
Diabetes, 2005Co-Authors: Chiara Dalla Man, Rita Basu, Robert A Rizza, Gianna Toffolo, Kenneth S Polonsky, Marco Campioni, Claudio CobelliAbstract:Highly informative yet simple protocols to assess insulin secretion and action would considerably enhance the quality of epidemiological and large-scale clinical trials. In an effort to develop such protocols, a 5-h, 11-sample oral glucose tolerance test (OGTT) was performed in 100 individuals and a 7-h, 21-sample meal in another 100. Plasma glucose, insulin, and C-peptide concentrations were measured. We show that virtually the same Minimal Model assessment of beta-cell responsivity (dynamic [Phi(d)] and static [Phi(s)]), insulin sensitivity (Si), and disposition index (DI) can be obtained with a reduced seven-sample 2-h protocol: Phi(d), reduced versus full: 871.50 vs. 873.32, r = 0.98 in OGTT and 494.88 vs. 477.99 10(-9), r = 0.91 in meal; Phi(s): 42.36 vs. 44.35, r = 0.88 in OGTT and 35.31 vs. 35.37 10(-9) min(-1), r = 0.90 in meal; Si: 24.33 vs. 22.77 10(-5) dl x kg(-1) x min(-1) per pmol/l, r = 0.89 in OGTT and 19.03 vs. 19.77 10(-5) dl x kg(-1) x min(-1) per pmol/l, r = 0.85 in meal; and DI: 1,282.26 vs. 1,273.23, r = 0.84 in OGTT and 726.92 vs. 776.97 10(-14) dl . kg(-1) x min(-2) per pmol/l, r = 0.84 in meal. This reduced protocol will facilitate the study of insulin secretion and action under physiological conditions in nondiabetic humans.
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Minimal Model estimation of glucose absorption and insulin sensitivity from oral test validation with a tracer method
American Journal of Physiology-endocrinology and Metabolism, 2004Co-Authors: Andrea Caumo, Rita Basu, Robert A Rizza, Gianna ToffoloAbstract:Measuring insulin sensitivity during the physiological milieu of oral glucose perturbation, e.g., a meal or an oral glucose tolerance test, would be extremely valuable but difficult since the rate of appearance of absorbed glucose is unknown. The reference method is a tracer two-step one: first, the rate of appearance of glucose (Ra mealref) is reconstructed by employing the tracer-to-tracee ratio clamp technique with two tracers and a Model of non-steady-state glucose kinetics; next, this Ra mealref is used as the known input of a Model describing insulin action on glucose kinetics to estimate insulin sensitivity (SIref). Recently, a nontracer method based on the oral Minimal Model (OMM) has been proposed to estimate simultaneously the above quantities, denoted Ra meal and SI, respectively, from plasma glucose and insulin concentrations measured after an oral glucose perturbation. This last method has obvious advantages over the tracer method, but its domain of validity has never been assessed against a ...
