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 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 60-180min. 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)H2]-glucose and labeling of the 2 glucose loads with [1-(2)H]-glucose and U-(13)C-glucose). In both Study 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 (ie, higher secretion at the same glycemia) was stronger (1.08+/-0.02 fold 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 hours totalled 60+/-6 g for the first load and 52+/-5 g for the second load (p=ns). Fasting endogenous glucose production (13.3+/-0.6 micromol.min(-1).kgFFM(-1)) averaged 6.0+/-3.8 micromol.min(-1).kgFFM(-1) between 0-180min and 1.7+/-2.6 between 180-360min (p<0.03). Glucose potentiation and stronger suppression of endogenous glucose release are the main mechanisms underlying the Staub-Traugott effect. Key words: Staub-Traugott effect, glucose potentiation, glucose tolerance, ss-cell function.