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Acute Effects of Lixisenatide on Energy Intake in Healthy Subjects and Patients with Type 2 Diabetes: Relationship to Gastric Emptying and Intragastric Distribution.

ABSTRACT: Glucagon-like peptide-1 receptor agonists induce weight loss, which has been suggested to relate to the slowing of gastric emptying (GE). In health, energy intake (EI) is more strongly related to the content of the distal, than the total, stomach. We evaluated the effects of lixisenatide on GE, intragastric distribution, and subsequent EI in 15 healthy participants and 15 patients with type 2 diabetes (T2D). Participants ingested a 75-g glucose drink on two separate occasions, 30 min after lixisenatide (10 mcg) or placebo subcutaneously, in a randomised, double-blind, crossover design. GE and intragastric distribution were measured for 180 min followed by a buffet-style meal, where EI was quantified. Relationships of EI with total, proximal, and distal stomach content were assessed. In both groups, lixisenatide slowed GE markedly, with increased retention in both the proximal (p < 0.001) and distal (p < 0.001) stomach and decreased EI (p < 0.001). EI was not related to the content of the total or proximal stomach but inversely related to the distal stomach at 180 min in health on placebo (r = -0.58, p = 0.03) but not in T2D nor after lixisenatide in either group. In healthy and T2D participants, the reduction in EI by lixisenatide is unrelated to changes in GE/intragastric distribution, consistent with a centrally mediated effect.

SUBMITTER: Jalleh R

PROVIDER: S-EPMC7400134 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Acute Effects of Lixisenatide on Energy Intake in Healthy Subjects and Patients with Type 2 Diabetes: Relationship to Gastric Emptying and Intragastric Distribution.

Jalleh Ryan R Pham Hung H Marathe Chinmay S CS Wu Tongzhi T Buttfield Madeline D MD Hatzinikolas Seva S Malbert Charles H CH Rigda Rachael S RS Lange Kylie K Trahair Laurence G LG Feinle-Bisset Christine C Rayner Christopher K CK Horowitz Michael M Jones Karen L KL

Nutrients 20200701 7

Glucagon-like peptide-1 receptor agonists induce weight loss, which has been suggested to relate to the slowing of gastric emptying (GE). In health, energy intake (EI) is more strongly related to the content of the distal, than the total, stomach. We evaluated the effects of lixisenatide on GE, intragastric distribution, and subsequent EI in 15 healthy participants and 15 patients with type 2 diabetes (T2D). Participants ingested a 75-g glucose drink on two separate occasions, 30 min after lixis ...[more]

PMID: 32630191

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Project description:Impaired fundic accommodation (FA) limits fundic relaxation and the ability to act as a reservoir for food. Assessing intragastric meal distribution (IMD) during gastric emptying scintigraphy (GES) allows for a simple measure of FA. The 3 goals of this study were to evaluate trained readers' (nuclear medicine and radiology physicians) visual assessments of FA from solid-meal GES; develop software to quantify GES IMD; and correlate symptoms of gastroparesis with IMD and gastric emptying. Methods: After training to achieve a consensus interpretation of GES FA, 4 readers interpreted FA in 148 GES studies from normal volunteers and patients. Mixture distribution and κ-agreement analyses were used to assess reader consistency and agreement of scoring of FA. Semiautomated software was used to quantify IMD (ratio of gastric counts in the proximal stomach to those in the total stomach) at 0, 1, 2, 3, and 4 h after ingestion of a meal. Receiver-operating-characteristic analysis was performed to optimize the diagnosis of abnormal IMD at 0 min (IMD0) with impaired FA. IMD0, GES, water load testing, and symptoms were then compared in 177 patients with symptoms of gastroparesis. Results: Reader pairwise weighted κ-values for the visual assessment of FA averaged 0.43 (moderate agreement) for normal FA versus impaired FA. Readers achieved 84.0% consensus and 85.8% reproducibility in assessing impaired FA. IMD0 based on the division of the stomach into proximal and distal halves averaged 0.809 (SD, 0.083) for normal FA and 0.447 (SD, 0.132) (P < 0.01) for impaired FA. On the basis of receiver-operating-characteristic analysis, the optimal cutoff for IMD0 discrimination of normal FA from impaired FA was 0.568 (sensitivity, 86.7%; specificity, 91.7%). Of 177 patients with symptoms of gastroparesis, 129 (72.9%) had delayed gastric emptying; 25 (14.1%) had abnormal IMD0 Low IMD0 (impaired FA) was associated with increased early satiety (P = 0.02). Conclusion: FA can be assessed visually during routine GES with moderate agreement and high reader consistency. Visual and quantitative assessments of FA during GES can yield additional information on gastric motility to help explain patients' symptoms.

Project description:BackgroundThe digestion of food is known to alter the hemodynamics of the body significantly. The purpose of this study was to study the postprandial changes in stroke volume (SV), cardiac output (CO) and left ventricular (LV) longitudinal systolic and diastolic functions measured with tissue Doppler imaging, in relation to gastric emptying rate (GER), satiety, and glucose and insulin concentrations in healthy subjects.MethodsTwenty-three healthy subjects were included in this study. The fasting and postprandial changes at 30 min and 110 min in CO, heart rate (HR) and blood pressure were measured. Moreover, tissue Doppler imaging systolic (S'), early (E') and late (A') mitral annular diastolic velocities were measured in the septal (s) and lateral (l) walls. Glucose and insulin concentrations, and satiety were measured before and 15, 30, 45, 60, 90, and 120 min after the start of the meal. The GER was calculated as the percentage change in the antral cross-sectional area 15-90 min after ingestion of the meal.ResultsThis study show that both CO, systolic longitudinal ventricular velocity of the septum (S's) and lateral wall (S'l), the early diastolic longitudinal ventricular velocity of the lateral wall (E'l), the late diastolic longitudinal ventricular velocity of the septum (A's) and lateral wall (A'l) increase significantly, and were concomitant with increased satiety, antral area, glucose and insulin levels. The CO, HR and SV at 30 min were significantly higher, and the diastolic blood pressure was significantly lower, than the fasting. The satiety was correlated to HR and diastolic blood pressure. The insulin level was correlated to HR.ConclusionsThis study shows that postprandial CO, HR, SV and LV longitudinal systolic and diastolic functions increase concomitantly with increased satiety, antral area, and glucose and insulin levels. Therefore, patients should not eat prior to, or during, cardiac evaluation as the effects of a meal may affect the results and their interpretation.

Dataset Information

Acute Effects of Lixisenatide on Energy Intake in Healthy Subjects and Patients with Type 2 Diabetes: Relationship to Gastric Emptying and Intragastric Distribution.

Publications

Acute Effects of Lixisenatide on Energy Intake in Healthy Subjects and Patients with Type 2 Diabetes: Relationship to Gastric Emptying and Intragastric Distribution.

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