GI Dysfunctions in Diabetic Gastroenteropathy, Their Relationships With Symptoms, and Effects of a GLP-1 Antagonist

Abstract

Context: Delayed gastric emptying (GE) is common but often asymptomatic in diabetes. The relationship between symptoms, glycemia, and neurohormonal functions, including glucagonlike peptide 1 (GLP-1), are unclear.

Objectives: To assess whether GE disturbances, symptoms during a GE study, and symptoms during enteral lipid infusion explain daily symptoms and whether GLP-1 mediates symptoms during enteral lipid infusion.

Design: In this randomized controlled trial, GE, enteral lipid infusion, gastrointestinal (GI) symptoms during these assessments, autonomic functions, glycosylated hemoglobin (HbA1c), and daily GI symptoms (2-week Gastroparesis Cardinal Symptom Index diary) were evaluated. During enteral lipid infusion, participants received the GLP-1 antagonist exendin 9-39 or placebo.

Setting: Single tertiary referral center.

Participants: 24 healthy controls and 40 patients with diabetic gastroenteropathy.

Main outcome measures: GE, symptoms during enteral lipid infusion, and the effect of exendin 9-39 on the latter.

Results: In patients, GE was normal (55%), delayed (33%), or rapid (12%). During lipid infusion, GI symptoms tended to be greater (P = 0.06) in patients with diabetes mellitus (DM) than controls; exendin 9-39 did not affect symptoms. The HbA1c was inversely correlated with the mean symptom score during the GE study (r = -0.46, P = 0.003) and lipid infusion (r = -0.47, P < 0.01). GE and symptoms during GE study accounted for 40% and 32%, respectively, of the variance in daily symptom severity and quality of life.

Conclusions: In DM gastroenteropathy, GE and symptoms during a GE study explain daily symptoms. Symptoms during enteral lipid infusion were borderline increased but not reduced by a GLP-1 antagonist.

Trial registration: ClinicalTrials.gov NCT02170870.

Copyright © 2019 Endocrine Society.

Figures

Figure 1.

Study design. (A) GE scintigraphy, (B, C) enteral lipid infusion at a variable rate, and (E) GI endoscopy were performed over 3 days. (D) Symptoms during the GE study and lipid infusion were assessed with VAS scales. Thereafter, participants recorded their symptoms daily for 2 weeks. Used with permission of Mayo Foundation for Medical Education and Research. All rights reserved.

Figure 2.

Consolidated Standards of Reporting Trials flow diagram.

Figure 3.

Comparison of symptoms during enteral lipid infusion in controls and patients with DM.

Figure 4.

Changes in plasma hormone (CCK, GLP-1, ghrelin, and PYY) levels measured during enteral lipid infusion. Values are mean ± SEM.

Figure 5.

Relationship between nausea during lipid infusion and plasma hormones.

Figure 6.

Comparison of HbA1c with symptoms during GE study (left panel) and enteral lipid infusion (right panel).