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Oral Glucose Tolerance Test Minimal Model Indexes of ß-Cell Function and Insulin Sensitivity

From the Department of Electronics and Informatics (E.B., G.T., C.C.), University of Padova, Padova, Italy; the Department of Medicine (M.K.C.), The University of Chicago, Chicago, Illinois; and the Department of Medicine (K.S.P.), Washington University School of Medicine, St. Louis, Missouri.

Address correspondence and reprint requests to Claudio Cobelli, Dipartimento di Elettronica e Informatica, Via Gradenigo 6a, 35131 Padova, Italy. E-mail: cobelli{at}dei.unipd.it .

The simultaneous assessment of quantitative indexes of insulin secretion and action in a single individual is important when quantifying their relative role in the evolution of glucose tolerance in different physiopathological states. Available methods quantify these indexes in relatively nonphysiological conditions, e.g., during glucose clamps or intravenous glucose tolerance tests. Here, we present a method based on a physiological test applicable to large-scale genetic and epidemiologic studies—the oral glucose tolerance test (OGTT). Plasma C-peptide, insulin, and glucose data from a frequently sampled OGTT with 22 samples throughout 300 min (FSOGTT_300-22) were analyzed in 11 subjects with various degrees of glucose tolerance. In each individual, two indexes of pancreatic sensitivity to glucose (_s [10⁹ min^-1] and _d [10⁹]) and the insulin sensitivity index (S_I) (10⁵ dl/kg per min per pmol/l) were estimated by using the minimal model of C-peptide secretion and kinetics originally proposed for intravenous graded glucose infusion and the minimal model approach recently proposed for meal/OGTTs. The indexes obtained from FSOGTT_300-22 were used as a reference for internal validation of OGTT protocols with reduced sampling schedules. Our results show that 11 samples in a 300-min period (OGTT_300-11) is the test of choice because the indexes it provides (_s = 36 ± 3 [means ± SE]; _d = 710 ± 111; S_I = 10.2 ± 2.4) show excellent correlation and are not statistically different from those of FSOGTT_300-22 (_s = 33 ± 3; _d = 715 ± 120; S_I = 10.1 ± 2.3). In conclusion, OGTT_300-11, interpreted with C-peptide and glucose minimal models, provides a quantitative description of ß-cell function and insulin sensitivity in a single individual while preserving the important clinical classification of glucose tolerance provided by the standard 120-min OGTT.

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