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

NCT ID: NCT04108065

Last Updated: 2020-12-21

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-10-02
• Study Completion Date: 2020-10-30

Brief 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).

Detailed 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.

Conditions

Gestational Diabetes Mellitus

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients 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)

No interventions assigned to this group

Pregnant women with normal glucose tolerance (control group)

Pregnant women with 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)

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Gentofte, Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Filip Krag Knop

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen

Hellerup, , Denmark

Countries

Denmark

Other Identifiers

H-19036095

Identifier Type: -

Identifier Source: org_study_id