None listed
Conditions
Brief summary
Emerging evidence of preclinical studies suggests that bitter substances in the gut can reduce appetite and slow the emptying of meals from the stomach, by stimulating gut hormone release. The proposed project will evaluate the hypotheses that, in patients with T2DM, activation of gastrointestinal bitter taste receptors(BTRs) substantially slows gastric emptying and reduces postprandial glycaemia after a standardized meal (Part A), and suppresses energy intake at an ad libitum buffet meal (Part B), in association with augmented secretion of glucagon-like peptide-1 (GLP-1)), peptide YY (PYY), cholecystokinin (CCK) and insulin, and suppression of ghrelin and glucagon. We will stimulate BTRs, as previously, using denatonium benzoate, the most potent BTR agonist known, to which humans are reproducibly sensitive.
Interventions
Following a screening visit, each subject will be studied on 4 occasions including 2 experimental settings: Parts A and B, 2 conditions each, separated by at least 7 days, in a double-blinded randomised order.
On each study day, a cannula will be inserted in an antecubital vein for regular blood sampling. Subjects will then consume a gelatin capsule containing either 30 mg denatonium benzoate (DB) or 30 mg sodium chloride (control) with 150 mL water (we will monitor adherence to the interventio
Following a screening visit, each subject will be studied on 4 occasions including 2 experimental settings: Parts A and B, 2 conditions each, separated by at least 7 days, in a double-blinded randomised order. On each study day, a cannula will be inserted in an antecubital vein for regular blood sampling. Subjects will then consume a gelatin capsule containing either 30 mg denatonium benzoate (DB) or 30 mg sodium chloride (control) with 150 mL water (we will monitor adherence to the intervention by mouth check). 30 min after taking the capsule, they will have a standardised test meal comprising 65 g powdered potato and 20 g glucose reconstituted with 200 mL water labelled with 100 mg 13C-octanoic acid for evaluation of gastric emptying and postprandial glycaemia (Part A: the first two of the 4 visits), or a standardised ad libitum buffet meal for evaluation of energy intake (Part B: the last two of the 4 visits).
Sponsors
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
50 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Type 2 diabetes (World Health Organisation (WHO) criteria), managed by diet or metformin only Body mass index (BMI) from 20 to 40 kg/m2 Age from 50 to 75 years Males and post-menopausal females Glycated haemoglobin (HbA1c) equal to 8.5% Haemoglobin above the lower limit of the normal range (ie. greater than 135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (ie. more than 30ng/mL for men and greater than 20mg/mL for women)
Exclusion criteria
Use of any medication that may influence gastrointestinal motor function within 48 hours or 5 half-lives of the study, specifically: opiates, anticholinergics, levodopa, beta-blockers, clonidine, nitrates, phosphodiesterase type 5 inhibitors, sumatriptan, metoclopramide, domperidone, cisapride, tegaserod, or erythromycin Evidence of drug abuse, or consumption of more than 20 g alcohol or 10 cigarettes on a daily basis History of gastrointestinal disease, including significant upper or lower gastrointestinal symptoms, pancreatitis, or previous gastrointestinal surgery (other than uncomplicated appendicectomy or cholecystectomy) Other significant illness, including epilepsy, cardiovascular or respiratory disease Impaired renal or liver function (as assessed by calculated creatinine clearance less than 90 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 Females who are pre-menopausal Inability to give informed consent Participants who do not eat beef Vegetarian diet
Outcome results
None listed