Estimation of insulin sensitivity and glucose clearance from minimal model: new insights from labeled IVGTT

1986 ◽  
Vol 250 (5) ◽  
pp. E591-E598 ◽  
Author(s):  
C. Cobelli ◽  
G. Pacini ◽  
G. Toffolo ◽  
L. Sacca
Keyword(s):  
Insulin Sensitivity ◽  
Minimal Model ◽  
Glucose Production ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Glucose Disposal ◽  
Model Estimate ◽  
Intravenous Glucose ◽  
Glucose Inhibition ◽  
Glucose Clearance

The "minimal model" of glucose disappearance provides noninvasive estimates of insulin sensitivity and glucose effectiveness from an intravenous glucose tolerance test (IVGTT). However, this model does not allow the separation of glucose production from utilization. To overcome this limitation, labeled glucose was injected along with cold glucose in six normal dogs, and both cold and labeled glucose time courses were monitored along with insulin concentration. A revised minimal model was fitted to tracer data to obtain new measures of insulin sensitivity (SI* = 6.41 +/- 0.91 10(-4) min-1 X microU-1 X ml-1) and fractional glucose clearance (SG* = 0.0092 +/- 0.0009 min-1). SG* was compared with a direct measure obtained by a hepatic arterial-venous difference technique, which yielded a value of 0.0097 +/- 0.0002, virtually identical to SG*, thereby validating the model estimate. When the original minimal model was identified from cold data, we obtained S1 = 4.52 +/- 1.39 and SG = 0.042 +/- 0.009. SI* and SG* were different from SI and SG, respectively. In particular SG overestimates fractional glucose clearance by approximately five times. The revised minimal model yields glucose disposal parameters SI* and SG* that are not affected by the confounding effect of insulin and glucose inhibition of glucose production. Limitations inherent in cold IVGTT and original minimal model are overcome by labeled IVGTT and the revised minimal model, while test simplicity remains.

scholarly journals Measurement of selective effect of insulin on glucose disposal from labeled glucose oral test minimal model

2005 ◽  
Vol 289 (5) ◽  
pp. E909-E914 ◽  
Author(s):  
Chiara Dalla Man ◽  
Andrea Caumo ◽  
Rita Basu ◽  
Robert Rizza ◽  
Gianna Toffolo ◽  
...  
Keyword(s):  
Minimal Model ◽  
Glucose Production ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Glucose Disposal ◽  
Oral Glucose ◽  
Intravenous Glucose ◽  
Selective Effect ◽  
Clamp Technique ◽  
Model Independent

The oral glucose minimal model (OMM) measures insulin sensitivity (SI) and the glucose rate of appearance (Ra) of ingested glucose in the presence of physiological changes of insulin and glucose concentrations. However, SI of OMM measures the overall effect of insulin on glucose utilization and glucose production. In this study we show that, by adding a tracer to the oral dose, e.g., of a meal, and by using the labeled version of OMM, OMM* to interpret the data, one can measure the selective effect of insulin on glucose disposal, [Formula: see text]. Eighty-eight individuals underwent both a triple-tracer meal with the tracer-to-tracee clamp technique, providing a model-independent reference of the Ra of ingested glucose ([Formula: see text]) and an insulin-modified labeled intravenous glucose tolerance test (IVGTT*). We show that OMM* provides not only a reliable means of tracing the Ra of ingested glucose (Ra meal) but also accurately measures [Formula: see text]. We do so by comparing OMM* Ra meal with the model-independent [Formula: see text] provided by the tracer-to-tracee clamp technique, while OMM* [Formula: see text] is compared with both [Formula: see text], obtained by using as known input [Formula: see text], and with [Formula: see text] measured during IVGTT*.

scholarly journals The hot IVGTT two-compartment minimal model: indexes  of glucose effectiveness and insulin sensitivity

1997 ◽  
Vol 273 (5) ◽  
pp. E1024-E1032 ◽  
Author(s):  
Paolo Vicini ◽  
Andrea Caumo ◽  
Claudio Cobelli
Keyword(s):  
Insulin Sensitivity ◽  
Minimal Model ◽  
Glucose Production ◽  
Normal Subjects ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Distribution Volume ◽  
Intravenous Glucose ◽  
Glucose Effectiveness

A two-compartment minimal model (2CMM) has been proposed [A. Caumo and C. Cobelli. Am. J. Physiol. 264 ( Endocrinol. Metab. 27): E829–E841, 1993] to describe intravenous glucose tolerance test (IVGTT) labeled (hereafter hot) glucose kinetics. This model, at variance with the one-compartment minimal model (1CMM), allows the estimation of a plausible profile of glucose production. The aim of this study is to show that the 2CMM also allows the assessment of insulin sensitivity ([Formula: see text]), glucose effectiveness ([Formula: see text]), and plasma clearance rate (PCR). The 2CMM was identified on stable-isotope IVGTTs performed in normal subjects ( n = 14). Results were (means ± SE) [Formula: see text] = 0.85 ± 0.14 ml ⋅ kg−1 ⋅ min−1, PCR = 2.02 ± 0.14 ml ⋅ kg−1 ⋅ min−1, and [Formula: see text] = 13.83 ± 2.54 × 10−2ml ⋅ kg−1 ⋅ min−1 ⋅ μU−1 ⋅ ml. The 1CMM was also identified; glucose effectiveness and insulin sensitivity indexes were [Formula: see text]V = 1.36 ± 0.08 ml ⋅ kg−1 ⋅ min−1and [Formula: see text] V = 12.98 ± 2.21 × 10−2ml ⋅ kg−1 ⋅ min−1 ⋅ μU−1 ⋅ ml, respectively, where V is the 1CMM glucose distribution volume.[Formula: see text]V was lower than PCR and higher than [Formula: see text] and did not correlate with either [ r = 0.45 (NS) and r = 0.50 (NS), respectively], whereas [Formula: see text]V was not different from and was correlated with[Formula: see text]( r = 0.95; P < 0.001).[Formula: see text] compares well ( r = 0.78; P < 0.001) with PCR normalized by the 2CMM total glucose distribution volume. In conclusion, the 2CMM is a powerful tool to assess glucose metabolism in vivo.

Assessment of insulin sensitivity with minimal model: role of model assumptions

1997 ◽  
Vol 272 (5) ◽  
pp. E925-E934 ◽  
Author(s):  
A. Mari
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Minimal Model ◽  
Glucose Production ◽  
Insulin Level ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Published Data ◽  
Intravenous Glucose

Insulin sensitivity is frequently assessed with the minimal model (MM) and the insulin-modified intravenous glucose tolerance test (MIVGTT). To ascertain the validity of this approach, the mechanisms by which the MM estimates glucose effectiveness and insulin sensitivity (SG and SI, respectively) from the data are analyzed theoretically. Published data and new labeled MIVGTTs in normal and non-insulin-dependent diabetic (NIDDM) subjects are used as reference data. One reason for the reported difficulty in estimating SI in NIDDM is the inadequacy of the MM to describe the data. SG is a biased estimate of the fractional glucose clearance (FGC) at basal insulin, and SI is a biased estimate of the average slope of the insulin concentration-FGC curve. The monocompartmental assumption and the role of glucose production in the MM are causes of bias. The bias is fairly constant across the spectrum of glucose tolerance (SG: approximately 150% overestimate; SI: approximately 30% underestimate). Also, SI is not expected to account satisfactorily for hepatic insulin sensitivity. Finally, by the use of SG and SI, FGC at a target insulin level (FGCMM) can be estimated. FGCMM agrees well with the analogous clamp index (difference 10%; correlation: r = 0.88, P < 0.002) and, in NIDDM, has a lower coefficient of variation than SI (57 vs. 82%). In conclusion, this analysis indicates that the MM is a sufficiently reliable method for the assessment of insulin sensitivity if it is used cautiously.

Modified protocols improve insulin sensitivity estimation using the minimal model

1987 ◽  
Vol 253 (6) ◽  
pp. E595-E602 ◽  
Author(s):  
Y. J. Yang ◽  
J. H. Youn ◽  
R. N. Bergman
Keyword(s):  
Standard Deviation ◽  
Insulin Sensitivity ◽  
Minimal Model ◽  
Insulin Response ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Improve Insulin Sensitivity ◽  
Intravenous Glucose ◽  
Sensitivity Estimation ◽  
Model Technique

We attempted to improve the precision of the estimation of insulin sensitivity (S1) from the minimal model technique by modifying insulin dynamics during a frequently sampled intravenous glucose tolerance test (FSIGT). Tolbutamide and somatostatin (SRIF) were used to change the insulin dynamics without directly affecting insulin sensitivity. Injection of tolbutamide (100 mg) at t = 20 min provoked an immediate secondary peak in insulin response, resulting in a greater integrated incremental insulin than the standard FSIGT. SRIF, injected at t = -1 min, delayed insulin secretion in proportion to the dose without any change in magnitude. Computer simulation was used to assess the precision of S1 estimation. Insulin dynamics from both standard and modified protocols were adjusted in magnitude, with the shape unchanged and analyzed to determine the effect of the magnitude of insulin response. Fractional standard deviation was reduced from 73% with the standard insulin profile to 23% with tolbutamide and 18% with the highest dose of SRIF. In addition, the fractional standard deviation of S1 estimates decreased exponentially with increasing magnitude of insulin response. Modified FSIGTs require a smaller insulin response than the standard protocol to achieve the same precision.

Assessment of Insulin Sensitivity in Man: A Comparison of Minimal Model- and Euglycaemic Clamp-Derived Measures in Health and Heart Failure

1994 ◽  
Vol 86 (3) ◽  
pp. 317-322 ◽  
Author(s):  
Jonathan W. Swan ◽  
Christopher Walton ◽  
Ian F. Godsland
Keyword(s):  
Heart Failure ◽  
Insulin Sensitivity ◽  
Minimal Model ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
High Dose ◽  
Sensitivity Index ◽  
Intravenous Glucose ◽  
Intravenous Glucose Tolerance

1. Simplified protocols for the measurement of insulin resistance will facilitate studies of this potentially important variable. 2. Using the euglycaemic clamp as the reference technique, we have assessed the validity of the insulin sensitivity index (inversely related to insulin resistance) obtained using a high-dose (500 mg/kg), unmodified intravenous glucose tolerance test with a 16 point sampling schedule and analysis using the minimal model of glucose disappearance. The two methods were compared in 10 clinically normal subjects and five patients with severe heart failure secondary to coronary heart disease. 3. The insulin sensitivity index of the minimal model was compared with four clamp-derived measures. Correlation coefficients of 0.72–0.92 (P < 0.01−P < 0.001) were obtained between the two methods over a wide range of insulin sensitivity [model values 1.03–14.63 min−1/(pmol/l) × 10−5]. Patients with heart failure had the lowest measures of insulin sensitivity. 4. The high-dose, unmodified intravenous glucose tolerance test with minimal model analysis is a straightforward and economical clinical procedure and provides a valid measure of insulin sensitivity, in health and disease.

The minimal model: an evolving methodology

2003 ◽  
Vol 105 (5) ◽  
pp. 531-532 ◽  
Author(s):  
Ian F. GODSLAND
Keyword(s):  
Insulin Sensitivity ◽  
Minimal Model ◽  
Model Identification ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Success Rates ◽  
Intravenous Glucose ◽  
Bayesian Techniques ◽  
Model Equations ◽  
New Phase

After more than 20 years, minimal model analysis of intravenous glucose tolerance test glucose and insulin concentrations continues to be widely employed in studies of insulin sensitivity and insulin resistance. Moreover, problems encountered in solving the minimal model equations continue to find new solutions. Bayesian techniques enable prior knowledge to be incorporated into parameter estimation routines. They offer particular advantages in the measurement of insulin sensitivity with the minimal model, and provide an elegant means of improving model identification success rates and parameter precision. This comment describes the study by Agbaje and colleagues in this issue of Clinical Science that exemplifies a new phase in the evolution of minimal model practice.

The hot IVGTT two-compartment minimal model: an improved version

2003 ◽  
Vol 284 (2) ◽  
pp. E317-E321 ◽  
Author(s):  
Gianna Toffolo ◽  
Claudio Cobelli
Keyword(s):  
Minimal Model ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Glucose Disposal ◽  
Parameter Estimates ◽  
Model Parameters ◽  
Single Individual ◽  
Intravenous Glucose ◽  
Proportional Effect ◽  
Effect Of Glucose

The two-compartment minimal model (2CMM) interpretation of a labeled intravenous glucose tolerance test (IVGTT) is a powerful tool to assess glucose metabolism in a single individual. It has been reported that a derived 2CMM parameter describing the proportional effect of glucose on insulin-independent glucose disposal can take physiologically unplausible negative values. In addition, precision of 2CMM parameter estimates is sometimes not satisfactory. Here we resolve the above issues by presenting an improved version of 2CMM that relies on a new assumption on the constant component Rd0 of insulin-independent glucose disposal. Here Rd0 is not fixed to 1 mg · kg−1 · min−1but instead is expressed as a fraction of steady-state glucose disposal. The new 2CMM is identified on the same stable labeled IVGTT data base on which the original 2CMM was formulated. A more reliable insulin-independent glucose disposal portrait is obtained while that of insulin action remains unchanged. The new 2CMM also improves the precision with which model parameters and metabolic indexes are estimated.

Relationship of insulin sensitivity to aerobic capacity in Standardbred mares and geldings

2005 ◽  
Vol 2 (3) ◽  
pp. 185-193 ◽  
Author(s):  
SE Pratt ◽  
RJ Geor ◽  
LJ McCutcheon
Keyword(s):  
Insulin Sensitivity ◽  
Aerobic Capacity ◽  
Serum Insulin ◽  
Insulin Response ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Glucose Disposal ◽  
Intravenous Glucose ◽  
Condition Score ◽  
Relationship Of

AbstractThe objective of this study was to determine the relationship between insulin sensitivity and aerobic capacity and serum adipocytokine (leptin, adiponectin) concentrations in 14 mature, unconditioned Standardbred horses (eight mares, six geldings). Each horse underwent a euglycaemic–hyperinsulinaemic clamp (EHC) and a frequently sampled intravenous glucose tolerance test (FSIGT) for assessment of insulin sensitivity. Aerobic capacity was determined by measurement of the peak rate of oxygen uptake (V˙O2peak) during an incremental exercise test (IET). Serum leptin and adiponectin concentrations were measured in baseline samples obtained before tests of insulin sensitivity. Mean body weight, condition score, V˙O2peak and run time during the IET did not differ between the sex groups. However, minimal model analysis of the FSIGT showed that insulin sensitivity (SI, ×10−4 l mU−1 min−1) was higher (P = 0.002) in geldings (4.21±0.78) than in mares (2.43±0.95), while the acute insulin response to glucose (AIRg) and glucose utilization independent of insulin (SG) were significantly higher in mares. Similarly, glucose uptake (M) per unit of serum insulin (I) during the EHC (M/I ratio) tended (P = 0.08) to be higher in geldings than in mares (×10−2 mg kg−1 min−1 per μU ml−1: 2.41±0.64 vs. 1.80±0.51). There was no significant relationship between V˙O2peak and measures of insulin sensitivity. Stepwise multiple linear regression modelling determined that sex (65%) and leptin concentrations (13.7%) accounted for 78.7% of the variance in SI, while 46% of the variance in M/I could be attributed to sex. It was concluded that aerobic capacity is not an important determinant of insulin-mediated glucose disposal in mature, untrained Standardbred horses. Further studies are needed to examine the influence of gender on insulin sensitivity in horses.

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