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

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... cose was clamped at 8.3 mmol/l between 60 and 180 min. ␤-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 H2]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 Ϯ 2% (P ϭ 0.003) of the response to the first OGTT. Absolute insulin secretion was lower (37.8 Ϯ 4.3 vs. 42.8 Ϯ 5.1 nmol/m 2 , P ϭ 0.02), but glucose potentiation (i.e., higher secretion at the same glycemia) was stronger (1.08 Ϯ 0.02-vs. 0.92 Ϯ 0.02-fold, P ϭ 0.006), the increment being higher in Study II (ϩ36 Ϯ 5%) than Study I (ϩ19 Ϯ 6%, P Ͻ 0.05). In pooled data, a higher glucose area during the first OGTT was associated with a higher potentiation during the second OGTT (rhoϭ0.60, P ϭ 0.002). Neither insulin clearance nor glucose clearance differed between loads, and appearance of glucose over 3 h totalled 60 Ϯ 6 g for the first load and 52 Ϯ 5 g for the second load (P ϭ not significant). Fasting endogenous glucose production [13.3 Ϯ 0.6 mol ⅐ min Ϫ1 ⅐ kg fat-free mass (FFM) Ϫ1 ] averaged 6.0 Ϯ 3.8 mol ⅐ min Ϫ1 ⅐ kg FFM Ϫ1 between 0 and 180 min and 1.7 Ϯ 2.6 between 180 and 360 min (P Ͻ 0.03). Glucose potentiation and stronger suppression of endogenous glucose release are the main mechanisms underlying the Staub-Traugott effect.