Assessment of β‐cell function during the oral glucose tolerance test by a minimal model of insulin secretion

A Cretti, M Lehtovirta, E Bonora… - European journal of …, 2001 - Wiley Online Library
A Cretti, M Lehtovirta, E Bonora, B Brunato, MG Zenti, F Tosi, M Caputo, B Caruso, LC Groop
European journal of clinical investigation, 2001Wiley Online Library
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 β‐cell 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 …
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 β‐cell 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 10′−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·min2·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, β‐index, 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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