None listed
Conditions
Brief summary
The purpose of this trial is to investigate the dose-related effects of intraduodenal administration of the bitter agonist, quinine, a non-nutritive (calorie-free) compound, on gastric emptying, gut and gluco-regulatory hormone, postprandial blood glucose and gastrointestinal symptoms in people with type 2 diabetes. The relationship between outcomes and the ability to detect bitter in the oral cavity will also be investigated. We have found previously that specific dietary nutrients, when given into the small intestine in small amounts (and so not contributing significantly to overall energy intake) have the unique ability to substantially stimulate gastrointestinal functions leading to marked improvements in postprandial blood glucose. There has been an increasing interest in the effects of bitter compounds, some of which also occur in the diet, including thio-urea compounds in certain vegetables or fruit, or quinine in tonic water, with reported effects on gut functions.
Interventions
Participants will receive in randomised, double-blind fashion, a 10-ml bolus of either (i) 600 mg quinine or (ii) 300 mg quinine, or (iii) water (control) intraduodenally on 3 separate visits. Each visit will be ~5hrs in duration, and separated by 3-7 days. Visits will be carried out at the Clinical Research Facility, Adelaide Medical School, University of Adelaide, by staff and students trained in the required clinical research techniques.
Participants will consume a standardised dinner meal,
Participants will receive in randomised, double-blind fashion, a 10-ml bolus of either (i) 600 mg quinine or (ii) 300 mg quinine, or (iii) water (control) intraduodenally on 3 separate visits. Each visit will be ~5hrs in duration, and separated by 3-7 days. Visits will be carried out at the Clinical Research Facility, Adelaide Medical School, University of Adelaide, by staff and students trained in the required clinical research techniques. Participants will consume a standardised dinner meal, (400g McCain's beef lasagne), the night before each study visit by no later than 7pm. After fasting for 14 hours overnight and refraining from alcohol and exercise for 24 hours, participants will arrive at the Clinical Research Facility by 8:30am. Upon arrival, participants will be intubated with a 17-channel manometric catheter (Dentsleeve, Mui Scientific) that will be inserted through an anaesthetised nostril and allowed to pass through the stomach and into the duodenum by peristalsis. The infusion port will be positioned ~ 14 cm distal to the pylorus. The correct positioning of the catheter will be monitored continuously by measurement of the transmucosal potential difference in the stomach (~ -40 mV) and the duodenum (~ 0 mV). Once the catheter has been positioned correctly, an intravenous cannula will be placed into a forearm vein for regular blood sampling to measure plasma hormone concentrations, and a baseline venous blood sample (10 mL) and Visual analogue Scale (VAS) questionnaire, to assess gastrointestinal symptoms (nausea and bloating), will be collected. Immediately thereafter (t = -31 min), participants will receive a 10-ml bolus of either (i) 600 mg quinine or (ii) 300 mg quinine, or (iii) water into the duodenum, after which the catheter will be removed and blood samples and VAS taken every 10 minutes. 30 min later (at t = -1 min), participants will consume, within 1 minute, 350ml (500 kcal) of a mixed-nutrient drink (Resource Plus) labelled with 100mg of 13C-acetate for measurement of gastric emptying by breath sampling and and 3 g 3-O-methyl-glucose (3-OMG) for the measurement of glucose absorption using plasma samples. Further venous blood samples and VAS will be taken every 10 min over the first 30 min after ingestion of the drink (t = 0 – 30 min) and then at 15-min intervals (t = 30 – 60 min), 30-min intervals (t = 60 – 120 min), and at t = 180 min. In addition, gastric emptying will be evaluated using breath test and 2D ultrasound (measuring antral area) at baseline and every 5 min after ingestion of the drink (t = 0 – 60 min) and then at 15-min intervals (t = 60 – 180 min). At t=180 min, after final blood and breath samples, ultrasound and VAS measurements, participants will be served a light lunch, after which they will be allowed to leave the laboratory.
Sponsors
Professor Christine Feinle-Bisset
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
Male
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Male participants with type 2 diabetes mellitus (T2DM), (aged 18-70 years BMI, 28-37 kg/m2, waist circumference <102 cm), will be included in the study. T2DM diagnosis will be based on WHO criteria. HbA1c will be >=6.5 - <=7.9% at screening. T2DM patients will need to be diet-controlled, with or without blood glucose medications (<2 g/d). Blood glucose medications will be withheld for 48 hours prior to each study day. All participants will be required to be weight-stable (ie <5% fluctuation) at study entry, which will be ascertained by a stable body weight in the preceding 4 weeks.
Exclusion criteria
Significant gastrointestinal symptoms, disease or surgery; Use of prescribed or non-prescribed medications (including vitamins and herbal supplements) which may affect energy metabolism, gastrointestinal function, body weight or appetite (eg domperidone and cisapride, anticholinergic drugs (eg atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St Johns Wort etc.); Lactose intolerance/other food allergy(ies); Current gallbladder or pancreatic disease; Cardiovascular or respiratory diseases; Individuals with low ferritin levels (less than 30 ng/mL), or who have donated blood in the 12 weeks prior to taking part in the study; Any other illnesses as assessed by the investigator (including chronic illnesses not explicitly listed above); High performance athletes; Current intake of greater than 2 standard drinks on greater than 5 days per week; Current smokers of cigarettes/cigars/marijuana; Current intake of any illicit substance; Vegetarians; Inability to comprehend study protocol; HbA1c <6.5% - >7.9%; Any patient whose medication cannot be withheld for 48 hours for medical reasons; Estimated glomerular filtration rate <45 ml/min;
Outcome results
None listed