Improved tolerance to sequential glucose loading (Staub-Traugott effect): size and mechanisms.
Improved glucose tolerance to sequential glucose loading (Staub-Traugott effect) is an important determinant of day-to-day glycemic exposure. Its mechanisms have not been clearly established. We recruited 17 healthy volunteers to receive two sequential oral glucose tolerance tests (OGTTs), at time 0 min and 180 min (Study I). The protocol was repeated on a separate day (Study II) except that plasma glucose was clamped at 8.3 mmol/l between 60 and 180 min. beta-Cell function was analyzed by mathematical modeling of C-peptide concentrations. In a subgroup, glucose kinetics were measured by a triple-tracer technique (infusion of [6,6-(2)H(2)]glucose and labeling of the 2 glucose loads with [1-(2)H]glucose and [U-(13)C]glucose). In both Studies I and II, the plasma glucose response to the second OGTT equaled 84 +/- 2% (P = 0.003) of the response to the first OGTT. Absolute insulin secretion was lower (37.8 +/- 4.3 vs. 42.8 +/- 5.1 nmol/m(2), P = 0.02), but glucose potentiation (i.e., higher secretion at the same glycemia) was stronger (1.08 +/- 0.02- vs. 0.92 +/- 0.02-fold, P = 0.006), the increment being higher in Study II (+36 +/- 5%) than Study I (+19 +/- 6%, P < 0.05). In pooled data, a higher glucose area during the first OGTT was associated with a higher potentiation during the second OGTT (rho=0.60, P = 0.002). Neither insulin clearance nor glucose clearance differed between loads, and appearance of glucose over 3 h totalled 60 +/- 6 g for the first load and 52 +/- 5 g for the second load (P = not significant). Fasting endogenous glucose production [13.3 +/- 0.6 micromol x min(-1) x kg fat-free mass (FFM)(-1)] averaged 6.0 +/- 3.8 micromol x min(-1) x kg FFM(-1) between 0 and 180 min and 1.7 +/- 2.6 between 180 and 360 min (P < 0.03). Glucose potentiation and stronger suppression of endogenous glucose release are the main mechanisms underlying the Staub-Traugott effect.
Bonuccelli
Sandra
S
Department of Internal Medicine, University of Pisa School of Medicine, Pisa, Italy.
Muscelli
Elza
E
Gastaldelli
Amalia
A
Barsotti
Elisabetta
E
Astiarraga
Brenno D
BD
Holst
Jens J
JJ
Mari
Andrea
A
Ferrannini
Ele
E
D000328:Adult; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D002096:C-Peptide; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D005947:Glucose / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018149:Glucose Intolerance / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D005951:Glucose Tolerance Test / Q000379:methods; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000187:drug effects
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005947:Glucose