Effect of Glycemia on Plasma Incretins and the Incretin Effect During Oral Glucose Tolerance Test

The incretin effect, reflecting the enhancement of postpran-dial insulin secretion by factors including the intestinal hor-mones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), increases in proportion to meal size. However, it is unknown whether the incretin effect is dependent on ambient glucose. The goal of this study was to determine the effect of plasma glycemia on the incretin effect. Thirteen healthy subjects consumed 50 g oral glucose solution mixed with D-xylose during fixed hyperglycemia at 8 and 10.5 mmol/L, on 3 separate days, twice at lower glycemia (LOW) and once at higher values (HIGH). The relative increase in insulin release after glucose ingestion at fixed hyperglycemia, a surrogate for the incretin effect, was similar among all three studies. The GLP-1 response to oral glucose was significantly lower at higher plasma glycemia, as was the appearance of D-xylose after th