The Role of Pregnancy-induced Gallbladder Dysmotility in the Pathophysiology of Gestational Diabetes Mellitus

Gestational Diabetes Mellitus Clinical Trial

Official title:

The Role of Pregnancy-induced Gallbladder Dysmotility in the Pathophysiology of Gestational Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04108065
• Other study ID #: H-19036095
• Status: Completed
• Start date: October 2, 2019
• Est. completion date: October 30, 2020

Study information

• Verified date: December 2020
• Source: University Hospital, Gentofte, Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The primary aim of the study is to evaluate postprandial gallbladder emptying and plasma concentrations of the glucose-lowering and satiety-promoting gut hormone glucagon-like peptide 1 (GLP-1) during third trimester of pregnancy in women with gestational diabetes mellitus (GDM) compared with age and body mass index (BMI)-matched pregnant control women with normal glucose tolerance (NGT).

Description:

Gestational diabetes mellitus (GDM) defined as glucose intolerance first detected during pregnancy is a strong predictor of future type 2 diabetes. Patients with GDM exhibit severely reduced postprandial responses of the insulinotropic and satiety-promoting gut hormone glucagon-like peptide 1 (GLP-1), which normalise alongside remission of GDM after delivery. Ingested nutrients and bile acids constitute potent stimulators of GLP-1 secretion. Reduced postprandial GLP-1 responses likely contribute to the pathophysiology of GDM, but the mechanisms are unknown. Based on previous studies studying gallbladder emptying during pregnancy, we hypothesize that reduced postprandial GLP-1 responses in GDM is due to incomplete gallbladder emptying during third trimester. If our hypothesis proves right, reduced gallbladder emptying and ensuing attenuation of postprandial GLP-1 secretion will constitute an obvious and druggable target for the treatment of GDM.

Fifteen women with gestational diabetes mellitus and 15 age and body mass index (BMI)-matched pregnant women with normal glucose tolerance will be enrolled in the study. For each subject, the study encompasses one screening visit and two experimental days; one during third trimester of pregnancy and one 3-9 months post partum. On experimental days, a standardised liquid mixed meal test (added 1.5 g of paracetamol for evaluation of gastric emptying according to paracetamol absorption) with repeated ultrasonographic gallbladder scans and blood samples will be performed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: October 30, 2020
• Est. primary completion date: October 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion criteria - women with gestational diabetes mellitus (GDM):

• GDM diagnosed according to current Danish guidelines (plasma glucose (PG) concentration at 120 min after a 75 g oral glucose tolerance test (OGTT) =9.0 mM)

• Caucasian ethnicity

• Age >18 years

• Pre-pregnancy BMI <30 kg/m2 and third trimester BMI <35 kg/m2

• Informed oral and written consent

Exclusion criteria - women with gestational diabetes:

• Anaemia (haemoglobin <7.5 mM)

• Previous preeclampsia, HELLP syndrome (haemolysis, elevated liver enzymes and low platelets) and/or pregnancy-induced intrahepatic cholestasis

• Gastrointestinal disease, previous gastric or intestinal resection, cholecystectomy and/or any major intra-abdominal surgery

• Previous pancreatic disease and/or neoplasia

• Postpartum use of hormonal contraception including intrauterine device

• Any condition the investigator group suspect would interfere with trial participation

Inclusion criteria - control group:

• Normal glucose tolerance (fasting plasma glucose (PG) concentration =6.0 mM and PG concentration at 120 min after a 75 g-OGTT <7.8 mM)

• Caucasian ethnicity

• Age >18 years

• Pre-pregnancy BMI <30 kg/m2 and third trimester BMI <35 kg/m2

• Informed oral and written consent

Exclusion criteria - control group:

• Anaemia (haemoglobin <7.5 mM)

• Previous preeclampsia, HELLP syndrome (haemolysis, elevated liver enzymes and low platelets) and/or pregnancy induced intrahepatic cholestasis

• Gastrointestinal disease, previous gastric or intestinal resection, cholecystectomy and/or any major intra-abdominal surgery

• Previous pancreatic disease and/or neoplasia

• Postpartum use of hormonal contraception including intrauterine device

• Verified prior GDM

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes, Gestational
• Gestational Diabetes Mellitus

Locations

Country	Name	City	State
Denmark	Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen	Hellerup

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	GLP-1 response	Postprandial GLP-1 response (as assessed by area under curve (AUC) within 240 minutes after meal ingestion) during third trimester compared to 3-9 months postpartum.	240 minutes
Primary	Gallbladder emptying	Postprandial gallbladder emptying (evaluated as repeated measures of gallbladder volumes using bed-side ultrasonography within 240 minutes after meal ingestion) during third trimester compared to 3-9 months postpartum.	240 minutes
Secondary	Responses of glucose, insulin, C-peptide, glucagon, GIP	Postprandial responses of glucose, insulin, C-peptide, glucagon (as assessed by area under curve (AUC) during third trimester compared to 3-9 months postpartum.	240 minutes
Secondary	Gastric emptying	Postprandial responses of paracetamol (as assessed by area under curve (AUC) during third trimester compared to 3-9 months postpartum.	240 minutes
Secondary	Bile acid and gallbladder physiology	Postprandial responses of GLP-2, CCK, total bile acids, C4 and FGF-19 (as assessed by area under curve (AUC) during third trimester compared to 3-9 months postpartum.	240 minutes
Secondary	Oxytocin	Postprandial responses of oxytocin (as assessed by area under curve (AUC) during third trimester compared to 3-9 months postpartum.	240 minutes
Secondary	GDF15	Postprandial responses of GDF-15 (as assessed by area under curve (AUC) during third trimester compared to 3-9 months postpartum.	240 minutes