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.

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.

scholarly journals Minimal model SGoverestimation and SIunderestimation: improved accuracy by a Bayesian two-compartment model

1999 ◽  
Vol 277 (3) ◽  
pp. E481-E488 ◽  
Author(s):  
Claudio Cobelli ◽  
Andrea Caumo ◽  
Matteo Omenetto
Keyword(s):  
Insulin Sensitivity ◽  
Minimal Model ◽  
Compartment Model ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Glucose Kinetics ◽  
Intravenous Glucose ◽  
Glucose Effectiveness ◽  
Normal Humans ◽  
Improved Accuracy

The intravenous glucose tolerance test (IVGTT) single-compartment minimal model (1CMM) method has recently been shown to overestimate glucose effectiveness and underestimate insulin sensitivity. Undermodeling, i.e., use of single- instead of two-compartment description of glucose kinetics, has been advocated to explain these limitations. We describe a new two-compartment minimal model (2CMM) into which we incorporate certain available knowledge on glucose kinetics. 2CMM is numerically identified using a Bayesian approach. Twenty-two standard IVGTT (0.30 g/kg) in normal humans were analyzed. In six subjects, the clamp-based index of insulin sensitivity ([Formula: see text]) was also measured. 2CMM glucose effectiveness ([Formula: see text]) and insulin sensitivity ([Formula: see text]) were, respectively, 60% lower ( P < 0.0001) and 35% higher ( P < 0.0001) than the corresponding 1CMM [Formula: see text] and[Formula: see text] indexes: 2.81 ± 0.29 (SE) vs.[Formula: see text] = 4.27 ± 0.33 ml ⋅ min−1 ⋅ kg−1and [Formula: see text] = 11.67 ± 1.71 vs.[Formula: see text] = 8.68 ± 1.62 102ml ⋅ min−1 ⋅ kg−1per μU/ml. [Formula: see text] was not different from[Formula: see text] = 12.61 ± 2.13 102ml ⋅ min−1 ⋅ kg−1per μU/ml (nonsignificant), whereas [Formula: see text]was 60% lower ( P < 0.02). In conclusion, a new 2CMM has been presented that improves the accuracy of glucose effectiveness and insulin sensitivity estimates of the classic 1CMM from a standard IVGTT in normal humans.

scholarly journals When MINMOD Artifactually Interprets Strong Insulin Secretion as Weak Insulin Action

2021 ◽  
Vol 12 ◽  
Author(s):  
Joon Ha ◽  
Ranganath Muniyappa ◽  
Arthur S. Sherman ◽  
Michael J. Quon
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Minimal Model ◽  
Insulin Response ◽  
Reference Method ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Intravenous Glucose ◽  
Model Studies ◽  
Increased Risk

We address a problem with the Bergman-Cobelli Minimal Model, which has been used for 40 years to estimate SI during an intravenous glucose tolerance test (IVGTT). During the IVGTT blood glucose and insulin concentrations are measured in response to an acute intravenous glucose load. Insulin secretion is often assessed by the area under the insulin curve during the first few minutes (Acute Insulin Response, AIR). The issue addressed here is that we have found in simulated IVGTTs, representing certain contexts, Minimal Model estimates of SI are inversely related to AIR, resulting in artifactually lower SI. This may apply to Minimal Model studies reporting lower SI in Blacks than in Whites, a putative explanation for increased risk of T2D in Blacks. The hyperinsulinemic euglycemic clamp (HIEC), the reference method for assessing insulin sensitivity, by contrast generally does not show differences in insulin sensitivity between these groups. The reason for this difficulty is that glucose rises rapidly at the start of the IVGTT and reaches levels independent of SI, whereas insulin during this time is determined by AIR. The minimal model in effect interprets this combination as low insulin sensitivity even when actual insulin sensitivity is unchanged. This happens in particular when high AIR results from increased number of readily releasable insulin granules, which may occur in Blacks. We conclude that caution should be taken when comparing estimates of SI between Blacks and Whites.

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.

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.

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