Effects of acute GLP-1 analogue infusion on the glycemic and neurohormonal responses to meal test in non- hypoglycemic subjects after gastric bypass

The aim of this study was to assess the effects of acute Glucagon-like peptide-1 (GLP-1) receptor agonist administration on metabolic and endocrine responses to a standardized meal test in individuals who have undergone Roux-en-Y gastric bypass surgery (RYGB), and thus to uncover mechanisms that might be important in post-bariatric hypoglycemia. In a single-center, randomized crossover study, 10 patients without diabetes underwent two standardized high-carbohydrate meal tests with either saline (SAL) or exenatide (EXE) infusion, one year after RYGB. We assessed glucose, insulin, c-peptide, ACTH, cortisol, GH, adrenalin, noradrenalin, dopamine, glucagon, active GLP-1 and GIP. Gastric emptying rate was estimated with repeated paracetamol measurements. Heart rate variability was recorded as a marker of sympathetic nervous system activity. Postprandial glucose levels dropped below baseline levels in all subjects. Cortisol levels were higher during EXE infusion. As expected, insulin and c-peptide levels were higher with EXE. No other significant differences were observed in the measured hormones. EXE did not affect gastric emptying rate. HRV showed a decreased RR-interval during EXE infusion. During a meal test, acute exenatide infusion led to elevated cortisol levels but did not protect against post-prandial drops in glucose levels. Taken together with previous research, this implicates that alleviation of post-prandial hypoglycemia after RYGB via GLP-1 receptor agonist treatment likely involves other mechanisms than acute effects on conventional counter-regulatory hormones.