Assessment of beta-cell function during the oral glucose tolerance test by a minimal model of insulin secretion.
OBJECTIVE
To characterise the performance of beta-cell during a standard oral glucose tolerance test (OGTT).


METHODS
Fifty-six subjects were studied. A minimal analogic model of beta-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 beta-cell secretory 'force' (beta-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 beta-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 beta-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 beta-index with the insulinogenic index (IG-Index: Delta Insulin 30' - Basal/Delta 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 beta-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 beta-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 beta-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 beta-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 beta-index was inversely related to both fasting and 2 h plasma glucose (P < 0.01 for both). In protocol D, beta-index, but not OGTT-ISR, was significantly correlated to AIR (r = 0.542, P < 0.02).


CONCLUSIONS
Analogically modelling beta-cell function during the OGTT provides a simple, useful tool for the physiological assessment of beta-cell function.
Cretti
A
A
University of Verona School of Medicine, Verona, Italy.
Lehtovirta
M
M
Bonora
E
E
Brunato
B
B
Zenti
M G
MG
Tosi
F
F
Caputo
M
M
Caruso
B
B
Groop
L C
LC
Muggeo
M
M
Bonadonna
R C
RC
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism; D016002:Discriminant Analysis; D005240:Feasibility Studies; D005260:Female; D005951:Glucose Tolerance Test / Q000379:methods*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010455:Peptides / Q000097:blood; D011897:Random Allocation; D015203:Reproducibility of Results
D001786:Blood Glucose; D007328:Insulin; D010455:Peptides; C050632:polypeptide C