Effects of GLP-1 on counter-regulatory responses during hypoglycemia after GBP surgery

Abstract

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 Twelve 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 analog 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 improvement in symptomatic hypoglycemia post-GBP seen following treatment with GLP-1 receptor agonists may be mediated by mechanism not directly involved in counter-regulation.

Time Course of Metabolic, Neuroendocrine, and Adipose Effects During 2 Years of Follow-up After Gastric Bypass in Patients With Type 2 Diabetes

“…Total spectral power, the power of the low-frequency (P LF ; 0.04-0.15 Hz), and high-frequency (P HF ; 0.15-0.50 Hz) domains, all log-transformed, were analyzed, using MATLAB (MathWorks, Natick, MA, USA). The method of data extraction from the recorded electrocardiograms has been previously specified ( 24 ).…”

Postprandial Hypoglycemia in Patients after Gastric Bypass Surgery Is Mediated by Glucose-Induced IL-1β

“…These effects were independent of changes in either glucagon or GLP-1. However, this does not rule out additional mechanisms involving incretin hormones (Almby et al, 2019;Salehi et al, 2018;Smith et al, 2018) and meal composition. We can also not exclude that empagliflozin acted by reducing intestinal glucose absorption via SGLT1 inhibition, although this was unlikely due to its high selectivity for SGLT2 (Grempler et al, 2012).…”

Brunner’s Gland Hyperplasia in a Patient after Roux-Y Gastric Bypass: An Important Pitfall in GLP-1 Receptor Imaging

“…Antagonizing its effect by using exendin 9-39 lowers the rate of PBH [15]. However, there are also reports of successful treatment with GLP-1 agonists [16], but data on its mechanisms still need to be unravelled [17].…”