Clinical trial NCT04108065: The Role of Pregnancy-induced Gallbladder Dysmotility in the Pathophysiology of Gestational Diabetes Mellitus
Official title: The Role of Pregnancy-induced Gallbladder Dysmotility in the Pathophysiology of Gestational Diabetes Mellitus
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Gestational Diabetes Mellitus
Keywords: gestational diabetes mellitus
gallbladder motility
glp-1
pregnancy
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
First posted: 2019-09-27
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 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. Only pregnant women who have been tested for gestational diabetes mellitus will be enrolled in the study.

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.

Eligibility criteria: 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

Primary outcomes:
measure: GLP-1 response
timeFrame: 240 minutes
measure: Gallbladder emptying
timeFrame: 240 minutes
Secondary outcomes:
measure: Responses of glucose, insulin, C-peptide, glucagon, GIP
timeFrame: 240 minutes
measure: Gastric emptying
timeFrame: 240 minutes
measure: Bile acid and gallbladder physiology
timeFrame: 240 minutes
measure: Oxytocin
timeFrame: 240 minutes
measure: GDF15
timeFrame: 240 minutes
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen
Study officials:
References: