Gestational Diabetes Mellitus
Conditions
Keywords
gestational diabetes mellitus, gallbladder motility, glp-1, pregnancy
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.
Interventions
None listed
Sponsors
University Hospital, Gentofte, Copenhagen
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| Gastric emptying | 240 minutes | Postprandial responses of paracetamol (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. |
Countries
Denmark
Outcome results
None listed