Meal and oral glucose tests for assessment of beta -cell function: modeling analysis in normal subjects.
We investigated beta-cell function and its relationship to insulin sensitivity in 17 normal volunteers. For insulin secretion (derived by C-peptide deconvolution), a mathematical model was applied to 24-h triple-meal tests (MT) as well as oral glucose tolerance tests (OGTT); insulin sensitivity was assessed by the euglycemic insulin clamp technique. The beta-cell model featured a glucose concentration-insulin secretion dose response (characterized by secretion at 5 mM glucose and slope), a secretion component proportional to the glucose concentration derivative, and a time-dependent potentiation factor (modulating the dose response and accounting for effects of sustained hyperglycemia and incretins). The beta-cell dose-response functions estimated from the whole 24-h MT, the first 2 h of the MT, and the OGTT differed systematically, because a different potentiation factor was involved. In fact, potentiation was higher than average during meals (1.6 +/- 0.1-fold during the first meal) and had a different time course in the MT and OGTT. However, if potentiation was accounted for, the 24- and 2-h MT and the OGTT yielded similar dose responses, and most beta-cell function parameters were intercorrelated (r = 0.50-0.86, P < or = 0.05). The potentiation factor was found to be related to plasma glucose-dependent insulin-releasing polypeptide concentrations (r = 0.49, P < 0.0001). Among beta-cell function parameters, only insulin secretion at 5 mM glucose from MT correlated inversely with insulin sensitivity (24-h MT: r = -0.74, P < 0.001; 2-h MT: r = -0.52, P < 0.05), whereas the dose-response slope and the OGTT parameters did not. In nine other subjects, reproducibility of model parameters was evaluated from repeated MTs. Coefficients of variation were generally approximately 20%, but the derivative component was less reproducible. We conclude that our model for the multiple MT yields useful information on beta-cell function, particularly with regard to the role of potentiation. With cautious interpretation, a 2-h MT or a standard OGTT can be used as surrogates of 24-h tests in assessing spontaneous beta-cell function.
Mari
Andrea
A
Consiglio Nazionale delle Ricerche Institute of Systems Science and Biomedical Engineering, 35127 Padua, Italy. mari@ladseb.pd.cnr.it
Schmitz
Ole
O
Gastaldelli
Amalia
A
Oestergaard
Torben
T
Nyholm
Birgit
B
Ferrannini
Ele
E
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005526:Food, Formulated; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005947:Glucose / Q000493:pharmacokinetics / Q000494:pharmacology; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D012016:Reference Values; D015203:Reproducibility of Results
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D005947:Glucose