Objectives: The aim of the study was to explore the role of GLP-1 receptor activation on the counter-regulation and symptoms of hypoglycemia in subjects who have undergone gastric bypass surgery (GBP).
Design: Experimental hyperinsulinemic hypoglycemic clamp study.
Methods: 12 post-GBP subjects participated in a randomized cross-over study with two hyperinsulinemic, hypoglycemic clamps (glucose nadir 2.7 mmol/l) performed on separate days with concomitant infusions of the GLP-1 analogue exenatide or with saline, respectively. Continuous measurements of metabolites and counter-regulatory hormones as well as assessments of heart rate variability and symptoms of hypoglycemia were performed throughout the clamps.
Results: No effect of GLP-1 receptor activation on counter-regulatory hormones (glucagon, catecholamines cortisol, GH) or glucose infusion rate was seen, but we found indications of a downregulation of the sympathetic relative to the parasympathetic nerve activity, as reflected in heart rate variability. No significant differences in symptom of hypoglycemia were observed.
Conclusions/interpretation: Short term exposure to a GLP-1 receptor agonist does not seem to impact the counter-regulatory hormonal and metabolic responses in post-GBP subjects during hypoglycemic conditions, suggesting that the reduction of postprandial symptoms post-GBP seen with exogenous GLP-1 may be mediated by mechanism not directly involved in counter-regulation.