Objective - To characterise the performance of β-cell during a standard oral glucose tolerance test (OGTT). Design - Fifty-six subjects were studied. A minimal analogic model of β-cell secretion during the OGTT was applied to all OGTTs (see below). The amount of insulin secreted over 120′ in response to oral glucose (OGTT-ISR; Insulin Units 120/-1 m-2 BSA) and an index of βcell secretory 'force' (β-Index; pmol·min-2·m-2 BSA) were computed with the aid of the model. In protocol A, 10 healthy subjects underwent two repeat 75 g OGTT with frequent (every l0′- 15′) blood sampling for glucose and C-peptide to test the reproducibility of OGTT-ISR and β-Index with a complete or a reduced data set. In protocol B, 7 healthy subjects underwent three OGTTs (50, 100 or 150 g), to test the stability of the β-Index under different glucose loads. In protocol C, 29 subjects (15 with normal glucose tolerance, 7 with impaired glucose tolerance and 7 with newly diagnosed type 2 diabetes) underwent two repeat 75 g OGTT with reduced (every 30′ for 120′) blood sampling to compare the reproducibility and the discriminant ratio (DR) of OGTT-ISR and β-index with the insulinogenic index (IG-Index: Δ Insulin 30′-Basal/Δ Glucose 30′-Basal). In protocol D, 20 subjects (14 with normal glucose tolerance, 5 with impaired glucose tolerance and 1 with newly-diagnosed type 2 diabetes) underwent a 75 g OGTT and an intravenous glucose tolerance test (IVGTT) on separate days to explore the relationships between acute (0′- 10′) insulin response (AIR) during the IVGTT and β-index and OGTT-ISR during the OGTT. Results - In all protocols, the minimal analogic model of C-peptide secretion achieved a reasonable fit of the experimental data. In protocol A, a good reproducibility of both β-index and OGTT-ISR was observed with both complete and reduced (every 30′) data sets. In protocol B, increasing the oral glucose load caused progressive increases in OGTT-ISR (from 2·63 ± 0·70 to 5·11 ± 0·91 Units·120/-1·m-2 BSA; P< 0·01), but the β-index stayed the same (4·14 ± 0·35 vs. 4·29 ± 0·30 vs. 4·30 ± 0·33 pmol·min-2·m-2 BSA). In protocol C, both OGTT-ISR and β-index had lower day-to-day CVs (17·6 ± 2·2 and 12·4 ± 2.4%, respectively) and higher DRs (2·57 and 1·74, respectively) than the IG-index (CV: 35·5 ± 6·3%; DR: 0·934). OGTT-ISR was positively correlated to BMI (P < 0·03), whereas β-index was inversely related to both fasting and 2 h plasma glucose (P < 0·01 for both). In protocol D, βindex, but not OGTT-ISR, was significantly correlated to AIR (r = 0·542, P < 0·02). Conclusions - Analogically modelling β-cell function during the OGTT provides a simple, useful tool for the physiological assessment of β-cell function.
Assessment of β-cell function during the oral glucose tolerance test by a minimal model of insulin secretion
Bonora, E.;CARUSO, BEATRICE;
2001-01-01
Abstract
Objective - To characterise the performance of β-cell during a standard oral glucose tolerance test (OGTT). Design - Fifty-six subjects were studied. A minimal analogic model of β-cell secretion during the OGTT was applied to all OGTTs (see below). The amount of insulin secreted over 120′ in response to oral glucose (OGTT-ISR; Insulin Units 120/-1 m-2 BSA) and an index of βcell secretory 'force' (β-Index; pmol·min-2·m-2 BSA) were computed with the aid of the model. In protocol A, 10 healthy subjects underwent two repeat 75 g OGTT with frequent (every l0′- 15′) blood sampling for glucose and C-peptide to test the reproducibility of OGTT-ISR and β-Index with a complete or a reduced data set. In protocol B, 7 healthy subjects underwent three OGTTs (50, 100 or 150 g), to test the stability of the β-Index under different glucose loads. In protocol C, 29 subjects (15 with normal glucose tolerance, 7 with impaired glucose tolerance and 7 with newly diagnosed type 2 diabetes) underwent two repeat 75 g OGTT with reduced (every 30′ for 120′) blood sampling to compare the reproducibility and the discriminant ratio (DR) of OGTT-ISR and β-index with the insulinogenic index (IG-Index: Δ Insulin 30′-Basal/Δ Glucose 30′-Basal). In protocol D, 20 subjects (14 with normal glucose tolerance, 5 with impaired glucose tolerance and 1 with newly-diagnosed type 2 diabetes) underwent a 75 g OGTT and an intravenous glucose tolerance test (IVGTT) on separate days to explore the relationships between acute (0′- 10′) insulin response (AIR) during the IVGTT and β-index and OGTT-ISR during the OGTT. Results - In all protocols, the minimal analogic model of C-peptide secretion achieved a reasonable fit of the experimental data. In protocol A, a good reproducibility of both β-index and OGTT-ISR was observed with both complete and reduced (every 30′) data sets. In protocol B, increasing the oral glucose load caused progressive increases in OGTT-ISR (from 2·63 ± 0·70 to 5·11 ± 0·91 Units·120/-1·m-2 BSA; P< 0·01), but the β-index stayed the same (4·14 ± 0·35 vs. 4·29 ± 0·30 vs. 4·30 ± 0·33 pmol·min-2·m-2 BSA). In protocol C, both OGTT-ISR and β-index had lower day-to-day CVs (17·6 ± 2·2 and 12·4 ± 2.4%, respectively) and higher DRs (2·57 and 1·74, respectively) than the IG-index (CV: 35·5 ± 6·3%; DR: 0·934). OGTT-ISR was positively correlated to BMI (P < 0·03), whereas β-index was inversely related to both fasting and 2 h plasma glucose (P < 0·01 for both). In protocol D, βindex, but not OGTT-ISR, was significantly correlated to AIR (r = 0·542, P < 0·02). Conclusions - Analogically modelling β-cell function during the OGTT provides a simple, useful tool for the physiological assessment of β-cell function.
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