the role of pregnancy-induced gallbladder dysmotility in the pathophysiology of gestational diabetes mellitus

Conditions: Gestational Diabetes Mellitus

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).

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

Keywords: gestational diabetes mellitus gallbladder motility glp-1 pregnancy