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Routine OGTT: a robust model including incretin effect for precise identification of insulin sensitivity and secretion in a single individual.

De Gaetano A, Panunzi S, Matone A, Samson A, Vrbikova J, Bendlova B, Pacini G - PLoS ONE (2013)

Bottom Line: ANOVA on kxgi values across groups resulted significant overall (P<0.001), and post-hoc comparisons highlighted the presence of three different groups: NGT (8.62×10(-5)±9.36×10(-5) min(-1)pM(-1)), IFG (5.30×10(-5)±5.18×10(-5)) and combined IGT, IFG+IGT and T2DM (2.09×10(-5)±1.95×10(-5), 2.38×10(-5)±2.28×10(-5) and 2.38×10(-5)±2.09×10(-5) respectively).No significance was obtained when comparing ISCOMO or ISDMMO across groups.The kxgi index, reflecting insulin secretion dependency on glycemia, also significantly differentiates clinically diverse subject groups.

View Article: PubMed Central - PubMed

Affiliation: Institute of System Analysis and Informatics (IASI) A. Ruberti, National Research Council (CNR), Rome, Italy.

ABSTRACT
In order to provide a method for precise identification of insulin sensitivity from clinical Oral Glucose Tolerance Test (OGTT) observations, a relatively simple mathematical model (Simple Interdependent glucose/insulin MOdel SIMO) for the OGTT, which coherently incorporates commonly accepted physiological assumptions (incretin effect and saturating glucose-driven insulin secretion) has been developed. OGTT data from 78 patients in five different glucose tolerance groups were analyzed: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), impaired fasting glucose (IFG), IFG+IGT, and Type 2 Diabetes Mellitus (T2DM). A comparison with the 2011 Salinari (COntinuos GI tract MOdel, COMO) and the 2002 Dalla Man (Dalla Man MOdel, DMMO) models was made with particular attention to insulin sensitivity indices ISCOMO, ISDMMO and kxgi (the insulin sensitivity index for SIMO). ANOVA on kxgi values across groups resulted significant overall (P<0.001), and post-hoc comparisons highlighted the presence of three different groups: NGT (8.62×10(-5)±9.36×10(-5) min(-1)pM(-1)), IFG (5.30×10(-5)±5.18×10(-5)) and combined IGT, IFG+IGT and T2DM (2.09×10(-5)±1.95×10(-5), 2.38×10(-5)±2.28×10(-5) and 2.38×10(-5)±2.09×10(-5) respectively). No significance was obtained when comparing ISCOMO or ISDMMO across groups. Moreover, kxgi presented the lowest sample average coefficient of variation over the five groups (25.43%), with average CVs for ISCOMO and ISDMMO of 70.32% and 57.75% respectively; kxgi also presented the strongest correlations with all considered empirical measures of insulin sensitivity. While COMO and DMMO appear over-parameterized for fitting single-subject clinical OGTT data, SIMO provides a robust, precise, physiologically plausible estimate of insulin sensitivity, with which habitual empirical insulin sensitivity indices correlate well. The kxgi index, reflecting insulin secretion dependency on glycemia, also significantly differentiates clinically diverse subject groups. The SIMO model may therefore be of value for the quantification of glucose homeostasis from clinical OGTT data.

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Comparison between fitting with predicted and interpolated insulin concentrations.Observed glucose and insulin data (circles) for one NGT patient. The COMO fitted model (dotted line) is shown together with the SIMO model either when insulin is fitted (solid black line) or when insulin is interpolated (dashed line).
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pone-0070875-g006: Comparison between fitting with predicted and interpolated insulin concentrations.Observed glucose and insulin data (circles) for one NGT patient. The COMO fitted model (dotted line) is shown together with the SIMO model either when insulin is fitted (solid black line) or when insulin is interpolated (dashed line).

Mentions: The problem introduced by incorrectly using interpolated noisy observations as forcing function for model fit was explored, for the newly proposed model, by using interpolated insulin instead of predicted insulin. Figure 6 compares, for one NGT patient, the fitting performance of the COMO model (dotted line) with the SIMO model either when insulin is fitted (solid black line) or when insulin is interpolated (dashed line).


Routine OGTT: a robust model including incretin effect for precise identification of insulin sensitivity and secretion in a single individual.

De Gaetano A, Panunzi S, Matone A, Samson A, Vrbikova J, Bendlova B, Pacini G - PLoS ONE (2013)

Comparison between fitting with predicted and interpolated insulin concentrations.Observed glucose and insulin data (circles) for one NGT patient. The COMO fitted model (dotted line) is shown together with the SIMO model either when insulin is fitted (solid black line) or when insulin is interpolated (dashed line).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3756988&req=5

pone-0070875-g006: Comparison between fitting with predicted and interpolated insulin concentrations.Observed glucose and insulin data (circles) for one NGT patient. The COMO fitted model (dotted line) is shown together with the SIMO model either when insulin is fitted (solid black line) or when insulin is interpolated (dashed line).
Mentions: The problem introduced by incorrectly using interpolated noisy observations as forcing function for model fit was explored, for the newly proposed model, by using interpolated insulin instead of predicted insulin. Figure 6 compares, for one NGT patient, the fitting performance of the COMO model (dotted line) with the SIMO model either when insulin is fitted (solid black line) or when insulin is interpolated (dashed line).

Bottom Line: ANOVA on kxgi values across groups resulted significant overall (P<0.001), and post-hoc comparisons highlighted the presence of three different groups: NGT (8.62×10(-5)±9.36×10(-5) min(-1)pM(-1)), IFG (5.30×10(-5)±5.18×10(-5)) and combined IGT, IFG+IGT and T2DM (2.09×10(-5)±1.95×10(-5), 2.38×10(-5)±2.28×10(-5) and 2.38×10(-5)±2.09×10(-5) respectively).No significance was obtained when comparing ISCOMO or ISDMMO across groups.The kxgi index, reflecting insulin secretion dependency on glycemia, also significantly differentiates clinically diverse subject groups.

View Article: PubMed Central - PubMed

Affiliation: Institute of System Analysis and Informatics (IASI) A. Ruberti, National Research Council (CNR), Rome, Italy.

ABSTRACT
In order to provide a method for precise identification of insulin sensitivity from clinical Oral Glucose Tolerance Test (OGTT) observations, a relatively simple mathematical model (Simple Interdependent glucose/insulin MOdel SIMO) for the OGTT, which coherently incorporates commonly accepted physiological assumptions (incretin effect and saturating glucose-driven insulin secretion) has been developed. OGTT data from 78 patients in five different glucose tolerance groups were analyzed: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), impaired fasting glucose (IFG), IFG+IGT, and Type 2 Diabetes Mellitus (T2DM). A comparison with the 2011 Salinari (COntinuos GI tract MOdel, COMO) and the 2002 Dalla Man (Dalla Man MOdel, DMMO) models was made with particular attention to insulin sensitivity indices ISCOMO, ISDMMO and kxgi (the insulin sensitivity index for SIMO). ANOVA on kxgi values across groups resulted significant overall (P<0.001), and post-hoc comparisons highlighted the presence of three different groups: NGT (8.62×10(-5)±9.36×10(-5) min(-1)pM(-1)), IFG (5.30×10(-5)±5.18×10(-5)) and combined IGT, IFG+IGT and T2DM (2.09×10(-5)±1.95×10(-5), 2.38×10(-5)±2.28×10(-5) and 2.38×10(-5)±2.09×10(-5) respectively). No significance was obtained when comparing ISCOMO or ISDMMO across groups. Moreover, kxgi presented the lowest sample average coefficient of variation over the five groups (25.43%), with average CVs for ISCOMO and ISDMMO of 70.32% and 57.75% respectively; kxgi also presented the strongest correlations with all considered empirical measures of insulin sensitivity. While COMO and DMMO appear over-parameterized for fitting single-subject clinical OGTT data, SIMO provides a robust, precise, physiologically plausible estimate of insulin sensitivity, with which habitual empirical insulin sensitivity indices correlate well. The kxgi index, reflecting insulin secretion dependency on glycemia, also significantly differentiates clinically diverse subject groups. The SIMO model may therefore be of value for the quantification of glucose homeostasis from clinical OGTT data.

Show MeSH
Related in: MedlinePlus