The Role of Pregnancy-induced Gallbladder Dysmotility in the Pathophysiology of Gestational Diabetes Mellitus
- Conditions
- Gestational Diabetes Mellitus
- Registration Number
- NCT04108065
- Lead Sponsor
- University Hospital, Gentofte, Copenhagen
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method GLP-1 response 240 minutes 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.
Gallbladder emptying 240 minutes 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.
- Secondary Outcome Measures
Name Time Method Responses of glucose, insulin, C-peptide, glucagon, GIP 240 minutes Postprandial responses of glucose, insulin, C-peptide, glucagon (as assessed by area under curve (AUC) during third trimester compared to 3-9 months postpartum.
Oxytocin 240 minutes Postprandial responses of oxytocin (as assessed by area under curve (AUC) during third trimester compared to 3-9 months postpartum.
Gastric emptying 240 minutes Postprandial responses of paracetamol (as assessed by area under curve (AUC) during third trimester compared to 3-9 months postpartum.
Bile acid and gallbladder physiology 240 minutes 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.
GDF15 240 minutes Postprandial responses of GDF-15 (as assessed by area under curve (AUC) during third trimester compared to 3-9 months postpartum.
Trial Locations
- Locations (1)
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen
🇩🇰Hellerup, Denmark