Abstract
Glucagon-like peptide-1 (GLP-1) receptor agonist treatment is beneficial for the human glucose metabolism, and GLP-1 secretion is greatly enhanced following Roux-en-Y gastric bypass (RYGB). To elucidate the relationship between GLP-1 concentrations and insulin sensitivity in subjects with class II/III obesity without diabetes and to assess the relation between GLP-1 and the improvements in glucose metabolism following RYGB. Clinical research facility in a university hospital. We recruited 35 patients scheduled for RYGB and assessed their plasma GLP-1, insulin, and glucose responses to a high-fat mixed meal. Basal and insulin-mediated glucose fluxes were determined during a 2-step hyperinsulinemic-euglycemic clamp with stable isotope-labeled tracers. Out of 35 subjects, 10 were studied both before surgery and at 1 year of follow-up. Plasma GLP-1 increased following the high-fat mixed meal. Postprandial GLP-1 excursions correlated positively with hepatic and peripheral insulin sensitivity, but not with body mass index. At 1 year after RYGB, participants had lost 24% ± 6% of their body weight. Plasma GLP-1, insulin, and glucose levels peaked earlier and higher after the mixed meal. The positive association between the postprandial GLP-1 response and peripheral insulin sensitivity persisted. Postprandial GLP-1 concentrations correlate with insulin sensitivity in subjects with class II/III obesity without diabetes before and 1 year after RYGB. Increased GLP-1 signaling in postbariatric patients may, directly or indirectly, contribute to the observed improvements in insulin sensitivity and metabolic health.
Highlights
Glucagon-like peptide-1 (GLP-1) plays a crucial role in the regulation of the glucose metabolism
A pancreatic clamp study with GLP-1 infusions revealed that GLP-1 has no independent effects on lipolysis when its effect on insulin secretion is blocked by somatostatin [16]; we do note that hormone levels in the portal circulation are below physiological levels during a pancreatic clamp, which complicates the interpretation of these studies
The Mixed Meal Test (MMT) GLP-1 response (GLP-1 AUC0–240) correlated negatively with glucose area under the curve (AUC) and insulin AUC (Fig. 2A,B), indicating that higher postprandial GLP-1 release is associated with better glucose tolerance during a MMT
Summary
Glucagon-like peptide-1 (GLP-1) plays a crucial role in the regulation of the glucose metabolism. In T2D, GLP-1 analogues stimulate insulin release and lower glycated hemoglobin (HbA1C) levels [3], and induce weight loss [4] by reducing food intake [5]. The latter effect has extended the potential use of GLP-1 receptor agonists to weight loss therapy in patients without diabetes but with obesity [6]. The objectives of the present study were to assess the relationship between postprandial GLP-1 and insulin sensitivity in subjects with class II/III obesity without diabetes and to explore the relationship between postprandial GLP1 levels and the improvements of glucose and lipid metabolism following RYGB
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