Effects of Physiological Hyperglycemia on Duodenal Motility and Flow Events, Glucose Absorption, and Incretin Secretion in Healthy Humans

Context: Acute hyperglycemia slows gastric emptying, but its effects on small intestinal motor activity and glucose absorption are unknown. In type 2 diabetes, the postprandial secretion of glucose-dependent insulinotropic polypeptide (GIP) is preserved, but that of glucagon-like peptide-1 (GLP-1) is possibly reduced; whether the latter is secondary to hyperglycemia or diabetes per se is unknown. Aim: The aim was to investigate the effects of acute hyperglycemia on duodenal motility and flow events, glucose absorption, and incretin hormone secretion. Methods: Nine healthy volunteers were studied on two occasions. A combined manometry/impedance catheter was positioned in the duodenum. Blood glucose was clamped at either 9 mmol/liter (hyperglycemia) or 5 mmol/liter (euglycemia) throughout the study. Manometry and impedance recordings continued between T = -10 min and T = 180 min. Between T = 0 and 60 min, an intraduodenal glucose infusion was given (similar to 3 kcal/min), together with (14)C-labeled 3-O-methylglucose (3-OMG) to evaluate glucose absorption. Results: Hyperglycemia had no effect on duodenal pressure waves or flow events during the 60 min of intraduodenal glucose infusion, when compared to euglycemia. During hyperglycemia, there was an increase in plasma GIP (P < 0.05) and (14)C-3-OMG (P < 0.05) but no effect on GLP-1 concentrations in response to the intraduodenal infusion, compared to euglycemia. Conclusion: Acute hyperglycemia in the physiological range has no effect on duodenal pressure waves and flow events but is associated with increased GIP secretion and rate of glucose absorption in response to intraduodenal glucose. (J Clin Endocrinol Metab 95: 3893-3900, 2010)