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

Subhankar Chakraborty, Magnus Halland, Duane Burton, Anshuman Desai, Bridget Neja, Phillip Anson Low, Wolfgang Singer, Michael Camilleri, Alan R. Zinsmeister, Adil Eddie Bharucha

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1967-1977
Number of pages11
JournalThe Journal of clinical endocrinology and metabolism
Volume104
Issue number6
DOIs
StatePublished - Jun 1 2019

Fingerprint

Gastric Emptying
Lipids
Peptides
Small Intestine
Medical problems
Diabetes Mellitus
Glycosylated Hemoglobin A
Gastroparesis
Symptom Assessment
Tertiary Care Centers
Randomized Controlled Trials
Placebos
Quality of Life

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

GI Dysfunctions in Diabetic Gastroenteropathy, Their Relationships With Symptoms, and Effects of a GLP-1 Antagonist. / Chakraborty, Subhankar; Halland, Magnus; Burton, Duane; Desai, Anshuman; Neja, Bridget; Low, Phillip Anson; Singer, Wolfgang; Camilleri, Michael; Zinsmeister, Alan R.; Bharucha, Adil Eddie.

In: The Journal of clinical endocrinology and metabolism, Vol. 104, No. 6, 01.06.2019, p. 1967-1977.

Research output: Contribution to journalArticle

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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.",
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AU - Chakraborty, Subhankar

AU - Halland, Magnus

AU - Burton, Duane

AU - Desai, Anshuman

AU - Neja, Bridget

AU - Low, Phillip Anson

AU - Singer, Wolfgang

AU - Camilleri, Michael

AU - Zinsmeister, Alan R.

AU - Bharucha, Adil Eddie

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N2 - 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.

AB - 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.

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