scholarly journals Overestimation of minimal model glucose effectiveness in presence of insulin response is due to undermodeling

1998 ◽  
Vol 275 (6) ◽  
pp. E1031-E1036 ◽  
Author(s):  
Claudio Cobelli ◽  
Francesca Bettini ◽  
Andrea Caumo ◽  
Michael J. Quon
Keyword(s):  
Glucose Tolerance ◽  
Minimal Model ◽  
Insulin Response ◽  
Model Analysis ◽  
Published Data ◽  
Glucose Kinetics ◽  
Model Estimate ◽  
Intravenous Glucose ◽  
Glucose Effectiveness ◽  
Model Independent

Glucose effectiveness is an important determinant of glucose tolerance that can be derived from minimal model analysis of an intravenous glucose tolerance test (IVGTT). However, recent evidence suggests that glucose effectiveness is overestimated by minimal model analysis. Here we compare a new model-independent estimate of glucose effectiveness with the minimal model estimate by reanalyzing published data in which insulin-dependent diabetic subjects were each given IVGTTs under two conditions (Quon, M. J., C. Cochran, S. I. Taylor, and R. C. Eastman. Diabetes 43: 890–896, 1994). In one case, a basal insulin level was maintained (BI-IVGTT). In the second case, a dynamic insulin response was recreated (DI-IVGTT). Our results show that minimal model glucose effectiveness is very similar to the model-independent measurement during a BI-IVGTT but is three times higher during a DI-IVGTT. To investigate the causes of minimal model overestimation in the presence of a dynamic insulin response, Monte Carlo simulation studies on a two-compartment model of glucose kinetics with various insulin response patterns were performed. Results suggest that minimal model overestimation is due to single-compartment representation of glucose kinetics that results in a critical oversimplification in the presence of increasingly dynamic insulin secretion patterns.

scholarly journals Comparison of insulin sensitivity between healthy neonatal foals and horses using minimal model analysis

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262584
Author(s):  
Hannah M. Kinsella ◽  
Laura D. Hostnik ◽  
Hailey A. Snyder ◽  
Sarah E. Mazur ◽  
Ahmed M. Kamr ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Minimal Model ◽  
Cell Function ◽  
Insulin Response ◽  
Model Analysis ◽  
Intravenous Glucose Tolerance Test ◽  
Model Assessment ◽  
Intravenous Glucose ◽  
Glucose Ratio

The equine neonate is considered to have impaired glucose tolerance due to delayed maturation of the pancreatic endocrine system. Few studies have investigated insulin sensitivity in newborn foals using dynamic testing methods. The objective of this study was to assess insulin sensitivity by comparing the insulin-modified frequently sampled intravenous glucose tolerance test (I-FSIGTT) between neonatal foals and adult horses. This study was performed on healthy neonatal foals (n = 12), 24 to 60 hours of age, and horses (n = 8), 3 to 14 years of age using dextrose (300 mg/kg IV) and insulin (0.02 IU/kg IV). Insulin sensitivity (SI), acute insulin response to glucose (AIRg), glucose effectiveness (Sg), and disposition index (DI) were calculated using minimal model analysis. Proxy measurements were calculated using fasting insulin and glucose concentrations. Nonparametric statistical methods were used for analysis and reported as median and interquartile range (IQR). SI was significantly higher in foals (18.3 L·min-1· μIU-1 [13.4–28.4]) compared to horses (0.9 L·min-1· μIU-1 [0.5–1.1]); (p < 0.0001). DI was higher in foals (12 × 103 [8 × 103−14 × 103]) compared to horses (4 × 102 [2 × 102−7 × 102]); (p < 0.0001). AIRg and Sg were not different between foals and horses. The modified insulin to glucose ratio (MIRG) was lower in foals (1.72 μIUinsulin2/10·L·mgglucose [1.43–2.68]) compared to horses (3.91 μIU insulin2/10·L·mgglucose [2.57–7.89]); (p = 0.009). The homeostasis model assessment of beta cell function (HOMA-BC%) was higher in horses (78.4% [43–116]) compared to foals (23.2% [17.8–42.2]); (p = 0.0096). Our results suggest that healthy neonatal foals are insulin sensitive in the first days of life, which contradicts current literature regarding the equine neonate. Newborn foals may be more insulin sensitive immediately after birth as an evolutionary adaptation to conserve energy during the transition to extrauterine life.

Reduced glucose effectiveness associated with reduced insulin release: an artifact of the minimal-model method

1996 ◽  
Vol 271 (3) ◽  
pp. E485-E495 ◽  
Author(s):  
D. T. Finegood ◽  
D. Tzur
Keyword(s):  
Glucose Tolerance ◽  
Insulin Release ◽  
Minimal Model ◽  
Glucose Tolerance Test ◽  
Hormone Replacement ◽  
Tolerance Test ◽  
Secretory Function ◽  
Intravenous Glucose ◽  
Glucose Effectiveness ◽  
Model Method

We previously demonstrated that minimal model-derived estimates of glucose effectiveness (SG), based on the frequently sampled intravenous glucose tolerance test (SGFSIGT), were reduced in islet-transplanted or streptozotocin-treated dogs and in patients with insulin-dependent diabetes mellitus. To ascertain the validity of our observations, we compared SGFSIGT with estimates based on a basal hormone replacement glucose clamp (SGBRCLAMP) and a basal hormone replacement glucose tolerance test (SGBRGTT) in normal control (CNTL, n = 12) and streptozotocin-treated dogs with normal fasting plasma glucose (STZ-Rx, n = 9). SGFSIGT was reduced in STZ-Rx compared with CNTL (P < 0.05). However, neither SGBRCLAMP nor SGBRGTT was reduced in the STZ-Rx group (P > 0.05). Comparison of protocols for each subject indicated that SGFSIGT was greater than either SGBRCLAMP or SGBRGTT in control (P < 0.002) but not in STZ-Rx dogs (P > 0.1). The relationship of SGFSIGT to insulin secretory function suggests that our previous conclusion that SGFSIGT was reduced in subjects with limited insulin release may be an artifact of the minimal-model method. Our results suggest that caution must be exercised in the interpretation of differences in minimal-model estimates of SG between subject groups with significantly different levels of insulin secretory function.

Letters to the Editor

1998 ◽  
Vol 274 (3) ◽  
pp. E573-E576 ◽  
Author(s):  
Andrea Caumo ◽  
Claudio Cobelli
Keyword(s):  
Glucose Tolerance ◽  
Insulin Release ◽  
Minimal Model ◽  
Glucose Tolerance Test ◽  
Hormone Replacement ◽  
Tolerance Test ◽  
Secretory Function ◽  
Intravenous Glucose ◽  
Glucose Effectiveness ◽  
Model Method

The following is an abstract of the article discussed in the subsequent letter: Finegood, Diane T., and Dan Tzur. Reduced glucose effectiveness associated with reduced insulin release: an artifact of the minimal-model method. Am. J. Physiol. 271 ( Endocrinol. Metab. 34): E485–E495, 1996.—We previously demonstrated that minimal model-derived estimates of glucose effectiveness (SG), based on the frequently sampled intravenous glucose tolerance test (SG FSIGT), were reduced in islet-transplanted or streptozotocin-treated dogs and in patients with insulin-dependent diabetes mellitus. To ascertain the validity of our observations, we compared SG FSIGT with estimates based on a basal hormone replacement glucose clamp (SG BRCLAMP) and a basal hormone replacement glucose tolerance test (SG BRGTT) in normal control (CNTL, n = 12) and streptozotocin-treated dogs with normal fasting plasma glucose (STZ-Rx, n = 9). SG FSIGT was reduced in STZ-Rx compared with CNTL ( P < 0.05). However, neither SG BRCLAMP nor SG BRGTT was reduced in the STZ-Rx group ( P > 0.05). Comparison of protocols for each subject indicated that SG FSIGT was greater than either SG BRCLAMP or SG BRGTT in control ( P < 0.002) but not in STZ-Rx dogs ( P > 0.1). The relationship of SG FSIGT to insulin secretory function suggests that our previous conclusion that SG FSIGT was reduced in subjects with limited insulin release may be an artifact of the minimal-model method. Our results suggest that caution must be exercised in the interpretation of differences in minimal-model estimates of SG between subject groups with significantly different levels of insulin secretory function.

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.

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