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

Abstract

Background/ObjectivesThe 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.Subjects/MethodsThe 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.ResultsMain 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.ConclusionsIt 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.Trial RegistrationClinicalTrials.gov NCT01875575

Effect of L-Tryptophan and L-Leucine on Gut Hormone Secretion, Appetite Feelings and Gastric Emptying Rates in Lean and Non-Diabetic Obese Participants: A Randomized, Double-Blind, Parallel-Group Trial

“…Test solutions were labeled with 50 mg of 13 C-sodium acetate [15]. As described in detail previously [10], at fixed time intervals after administration of the test solution (15, 30, 45, 60, 75, 90, 105, 180, 210 and 240 min), end-expiratory breath samples were taken into a 100 mL foil bag. The 13 C-exhalation was determined by non-dispersive infrared spectroscopy using an isotope ratio mass spectrophotometer (IRIS ® ; Wagner Analysen Technik, Bremen, Germany), and expressed as the relative difference (δ ‰) from the universal reference standard (carbon from Pee Dee Belemnite limestone).…”

“…The 13 C-exhalation was determined by non-dispersive infrared spectroscopy using an isotope ratio mass spectrophotometer (IRIS ® ; Wagner Analysen Technik, Bremen, Germany), and expressed as the relative difference (δ ‰) from the universal reference standard (carbon from Pee Dee Belemnite limestone). The calculation of percent of administered dose of 13 C excreted per hour (%dose/h) has previously been described in detail [10]. …”

“…A secondary outcome was to investigate gastric emptying rates of L-trp and L-leu. As the obese have a disturbed glycemic control with increased glucose and insulin concentrations [10], we were also interested in comparing the effects between lean and non-diabetic obese participants. The selection of the L-trp doses was based close to the daily intake recommended by the World Health Organization, WHO [11, 12].…”

Ketogenic diets: Opportunities and limitations in practical application (LITERATURE REVIEW)

“…Insulin in overweight patients does not only suppress lipolysis but also slows down fat absorbtion. Unfortunately, insulin makes it more effectively when the body weight is higher, which was reported by a research team from Basel University Clinic (156,159). It was shown that glucose load in patients with body mass index ≥ 30 kg/m 2 increases the level of insulin more than when BMI ≤ 25 kg/m 2 .…”

Characterizing the dynamic interaction among gastric emptying, glucose absorption, and glycemic control in nondiabetic obese adults

“…Horowitz et al (17) showed that gastric emptying accounts for one-third of the variance in the postprandial glucose kinetics of healthy individuals. Further studies suggest that the dynamics of gastric emptying is altered in obese patients (18,24,28) affecting glucose absorption and postprandial glycemia (16,27,32,40).…”