The Effect of Standard Versus Longer Intestinal Bypass on GLP-1 Regulation and Glucose Metabolism in Patients With Type 2 Diabetes Undergoing Roux-en-Y Gastric Bypass: The Long-Limb Study

• Published in: Diabetes care Vol. 44; no. 5; pp. 1082 - 1090
• Main Authors: Miras, Alexander Dimitri, Kamocka, Anna, Pérez-Pevida, Belén, Purkayastha, Sanjay, Moorthy, Krishna, Patel, Ameet, Chahal, Harvinder, Frost, Gary, Bassett, Paul, Castagnetto-Gissey, Lidia, Coppin, Lucy, Jackson, Nicola, Umpleby, Anne Margot, Bloom, Stephen Robert, Tan, Tricia, Ahmed, Ahmed Rashid, Rubino, Francesco
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.05.2021
• Subjects: Blood glucose; Body weight loss; Clamps; Clinical Care/Education/Nutrition/Psychosocial Research; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Gastric bypass; Gastrointestinal surgery; Glucagon; Glucagon-like peptide 1; Glucose; Glucose metabolism; Glucose tolerance; Insulin; Insulin secretion; Intestinal bypass; Intestine; Nutrients; Research design; Secretion; Sensitivity; Small intestine; Surgery; Weight loss
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc20-0762

Roux-en-Y gastric bypass (RYGB) characteristically enhances postprandial levels of glucagon-like peptide 1 (GLP-1), a mechanism that contributes to its profound glucose-lowering effects. This enhancement is thought to be triggered by bypass of food to the distal small intestine with higher densities of neuroendocrine L-cells. We hypothesized that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the postprandial peak in GLP-1, translating into higher insulin secretion and, thus, additional improvements in glucose tolerance. To investigate this, we conducted a mechanistic study comparing two variants of RYGB that differ in the length of intestinal bypass. A total of 53 patients with type 2 diabetes (T2D) and obesity were randomized to either standard limb RYGB (50-cm biliopancreatic limb) or long limb RYGB (150-cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycemic hyperinsulinemic clamps at baseline and 2 weeks and at 20% weight loss after surgery. Both groups exhibited enhancement in postprandial GLP-1 secretion and improvements in glycemia compared with baseline. There were no significant differences in postprandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity. The findings of this study demonstrate that lengthening of the intestinal bypass in RYGB does not affect GLP-1 secretion. Thus, the characteristic enhancement of GLP-1 response after RYGB might not depend on delivery of nutrients to more distal intestinal segments.