None listed
Conditions
Brief summary
Bile acids, released into the intestine after the meals, have long been regarded as simple ‘intestinal detergents’ to aid fat digestion. Recent evidence suggests that bile acids are also capable of regulating the blood sugar levels after meals, by releasing of a hormone from the intestines called glucagon-like peptide-1 (GLP-1). We recently showed that a bitter tasting substance, denatonium benzoate, could enhance the release of GLP-1. We now want to test whether combining a bile acid (taurocholic acid) with denatonium benzoate in capsules taken by mouth will improve blood glucose control after a meal in people with type 2 diabetes.
Interventions
Following enrolment, each participant will be studied on 5 occasions, separated by at least 7 days, in a double-blinded, randomised, crossover design. On the evening preceding the study day (~1900h), participants will be given a standardised evening meal. Following this meal, participants will be asked to fast from solids and liquids until the following morning (except that water will be allowed until 10 pm), when they will attend the Clinical Research Facility (CRF) of the Adelaide Health and M
Following enrolment, each participant will be studied on 5 occasions, separated by at least 7 days, in a double-blinded, randomised, crossover design. On the evening preceding the study day (~1900h), participants will be given a standardised evening meal. Following this meal, participants will be asked to fast from solids and liquids until the following morning (except that water will be allowed until 10 pm), when they will attend the Clinical Research Facility (CRF) of the Adelaide Health and Medical Science (AHMS) building at ~0800h. The participant will receive a text message the evening before the study day to remind them to have the standardised meal and stay fasting until the following morning. On each study day, participants will be instructed to defer any morning dose of prescribed medications until the end of the investigation. Upon arrival, an intravenous cannula will be placed into a vein on the dorsum of the hand, which will be kept warm with a heat pad to allow sampling of “arterialised” blood. Then participants will ingest 4 double-shell DRcaps® Capsules (Capsugel, NJ, USA), each containing either (i) placebo (cellulose only); (ii) 0.5 g taurocholic acid (TCA) - total dose 2 g TCA; (iii) 0.25 g TCA + 7.5 mg denatonium benzoate (DB) - total dose 1 g TCA + 30 mg DB; (iv) 0.5 g TCA + 7.5 mg DB - total dose 2 g TCA + 30 mg DB; or (v) 1 g TCA + 7.5 mg DB - total dose 4 g TCA + 30 mg DB, with 150 mL water (t = -60 min). At t = 0 min, participants will consume a mashed potato meal comprising 65 g powdered potato (Continental, Epping, NSW), 20 g glucose and 20 g margarine reconstituted with 200 mL boiling water and one egg yolk containing 100 uL 13C-octanioc acid (between t = -5 to 0 min). Breath samples will be collected every 5 min in the first 30 min and every 15 min between t = 30-240 min for the measurement of gastric emptying. “Arterialised” venous blood will be sampled at t = -60, 0, 30, 60, 90, 120, 180 and 240 min for measurement of plasma glucose, glucagon-like peptide-1 (GLP-1), fibroblast growth factor 19 (FGF-19), Serotonin (5-hydroxytryptamine, 5-HT), insulin, C-peptide, glucagon and bile acid profiles. Blood pressure will be monitored every 15 min between t = -60-240 min. The volume of the gallbladder will be measured by 3D ultrasound at t = -60, 0, 30, 60, 90, 120, 150, 180, 210 and 240 min. Gastrointestinal symptoms (e.g. nausea) and appetite sensations (e.g. hunger, fullness) will assessed every 30 min using the standardised visual analogue scales. After a final blood sample is collected (t = 240 min), an ad libitum buffet meal will be provided from which subjects will be free to eat as much as they wish for 30 min (t = 240 to 300), and from which energy intake will be quantified. Blood glucose concentration will be monitored after the meal. Once blood glucose has stabilised above 5 mmol/L, they will be free to leave the laboratory. The total amount of blood drawn during the screening and 5 study visits will be 410 mL.
Sponsors
The University of Adelaide
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
• Type 2 diabetes (American Diabetes Association criteria) treated by diet and/or metformin alone • Body mass index (BMI) from 20 to 40 kg/m2 • Males and females, aged from 18 to 79 years • Glycated haemoglobin (HbA1c) from 6.0% to 8.5% • Haemoglobin above the lower limit of the normal range (ie. above 135 g/L for men and 115 g/L for women), and ferritin above the lower limit of normal (ie. above 30 ng/mL for men and 20 mg/mL for women)
Exclusion criteria
• Use of any medication that may influence gastrointestinal motor function, body weight or appetite (opiates, anticholinergics, levodopa, clonidine, nitrates, tricyclic antidepressants, selective serotonin re-uptake inhibitors, phosphodiesterase type 5 inhibitors, sumatriptan, metoclopramide, domperidone, cisapride, prucalopride, or erythromycin) • History of gastrointestinal disease, including significant upper or lower gastrointestinal symptoms, pancreatitis, or previous gastrointestinal surgery (other than uncomplicated appendicectomy), or coagulation abnormalities • Evidence of drug abuse, consumption of more than 20 g alcohol or 10 cigarettes on a daily basis • History of any form of heart disease or symptoms of syncope or pre-syncope (including feeling lightheaded or dizzy, feeling unsteady when standing, unexplained falls, fainting, unexplained changes in vision, such as blurring or tunnel vision) • Other significant illness, including epilepsy, cardiovascular or respiratory disease • Impaired renal or liver function (as assessed by calculated creatinine clearance less than 60 mL/min or abnormal liver function tests (more than 2 times upper limit of normal range)) • Donation of blood within the previous 3 months • Participation in any other research studies within the previous 3 months • Vegan/vegetarian • Inability to give informed consent
Outcome results
None listed