Mechanisms Regulating Insulin Response to Intragastric Glucose in Lean and Non-Diabetic Obese Subjects: A Randomized, Double-Blind, Parallel-Group Trial

• Published in: PloS one Vol. 11; no. 3; p. e0150803
• Main Authors: Meyer-Gerspach, Anne Christin, Cajacob, Lucian, Riva, Daniele, Herzog, Raphael, Drewe, Juergen, Beglinger, Christoph, Wölnerhanssen, Bettina K.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04.03.2016; Public Library of Science (PLoS)
• Subjects: Adult; Biology and Life Sciences; Blood glucose; Blood Glucose - analysis; Body mass; Body Mass Index; Body Weight; C-Peptide - blood; Case-Control Studies; Complications and side effects; Diabetes; Diabetes Mellitus; Double-Blind Method; Double-blind studies; Drinking water; Emptying; Fasting; Female; Gastric Emptying; Gastric Inhibitory Polypeptide - blood; Gastroenterology; Gastrointestinal surgery; Genetic aspects; Glucagon; Glucagon - blood; Glucagon-like peptide 1; Glucagon-Like Peptide 1 - blood; Glucose; Glucose - administration & dosage; Glucose - metabolism; Hormones; Humans; Hyperglycemia; Hyperinsulinemia; Incretins - metabolism; Insulin; Insulin - blood; Insulin - metabolism; Insulin Resistance; Male; Medicine and Health Sciences; Metabolism; Middle Aged; Obesity; Obesity - blood; Obesity - metabolism; Peptides; Physical Sciences; Physiological aspects; Randomization; Secretion; Secretions; Small intestine; Young Adult; Switzerland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0150803

The changes in blood glucose concentrations that result from an oral glucose challenge are dependent on the rate of gastric emptying, the rate of glucose absorption and the rate of insulin-driven metabolism that include the incretins, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). The rate of insulin-driven metabolism is clearly altered in obese subjects, but it is controversial which of these factors is predominant. We aimed to quantify gastric emptying, plasma insulin, C-peptide, glucagon and glucose responses, as well as incretin hormone secretions in obese subjects and healthy controls during increasing glucose loads. The study was conducted as a randomized, double-blind, parallel-group trial in a hospital research unit. A total of 12 normal weight (6 men and 6 women) and 12 non-diabetic obese (BMI > 30, 6 men and 6 women) participants took part in the study. Subjects received intragastric loads of 10 g, 25 g and 75 g glucose dissolved in 300 ml tap water. Main outcome measures were plasma GLP-1 and GIP, plasma glucagon, glucose, insulin, C-peptide and gastric emptying. The primary findings are: i) insulin resistance (P < 0.001) and hyperinsulinemia (P < 0.001); ii) decreased insulin disposal (P < 0.001); iii) trend for reduced GLP-1 responses at 75 g glucose; and iv) increased fasting glucagon levels (P < 0.001) in obese subjects. It seems that, rather than changes in incretin secretion, fasting hyperglucagonemia and consequent hyperglycemia play a role in reduced disposal of insulin, contributing to hyperinsulinemia and insulin resistance. ClinicalTrials.gov NCT01875575.