Routine OGTT: A Robust Model Including Incretin Effect for Precise Identification of Insulin Sensitivity and Secretion in a Single IndividualReport as inadecuate

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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−1pM−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.

Author: Andrea De Gaetano, Simona Panunzi , Alice Matone, Adeline Samson, Jana Vrbikova, Bela Bendlova, Giovanni Pacini



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