None listed
Conditions
Brief summary
Despite increasing use of non-caloric sweeteners in western diets, it is not known whether habitual high intake alters glucose absorption in healthy subjects. This is critical knowledge, as an increased risk of developing type 2 diabetes may occur in regular, heavy consumers of non-caloric sweeteners, potentially due to increased uptake of glucose in the intestine. The outcome of this diet supplementation study will, accordingly, be of enormous public health interest as it determines whether intestinal sensors for sugars and artificial sweeteners (intestinal sweet taste receptors) set absorptive capacity in humans.
Interventions
Healthy subjects will be screened then undergo 2 study day visits in a randomised, double-blinded manner. Study day 1 will occur prior to diet supplementation, with study day 2 immediately following 2 weeks of diet supplementation with placebo capsules or capsules containing a combination of non-caloric sweeteners (sucralose, 92 mg + acesulfame K, 52 mg). Single capsules will be consumed immediately prior to meals, three times daily. Adherence to the intervention will be monitored by capsule re
Healthy subjects will be screened then undergo 2 study day visits in a randomised, double-blinded manner. Study day 1 will occur prior to diet supplementation, with study day 2 immediately following 2 weeks of diet supplementation with placebo capsules or capsules containing a combination of non-caloric sweeteners (sucralose, 92 mg + acesulfame K, 52 mg). Single capsules will be consumed immediately prior to meals, three times daily. Adherence to the intervention will be monitored by capsule return. On each study day, fasted unsedated subjects will have an intravenous cannula inserted into a forearm vein in one arm for blood sampling and a small diameter (5.3 mm) video endoscope placed in position in the second part of the duodenum via an anaesthetised nostril. Five mucosal biopsies will be collected via endoscope forceps, then an intraduodenal glucose infusion commenced for 30 min via the endoscope channel (30 g glucose, together with 3 g of the non-metabolisable glucose analogue 3-O-methy-glucose (3-OMG) dissolved in water to a total volume of 150 mL, infused at 5 mL/min; 4 kcal/min). An additional 5 biopsies will be collected post-infusion; bloods will be collected regularly over 2 hours.
Sponsors
Royal Adelaide Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Non-diabetic, healthy volunteers matched as closely as possible for sex and body mass index; Body mass index 20-30 kg/m2; HbA1c less than or equal to 7.0%
Exclusion criteria
Significant illness including impairment to cardiovascular or respiratory function that would limit a subject’s activity and therefore would represent a risk to undertaking endoscopy safely (American Society of Anaesthesiologists Grade 3 or more); History of gastrointestinal disease, including significant upper gastrointestinal symptoms (assessed by a validated gastrointestinal symptom questionnaire), pancreatitis, or previous gastrointestinal surgery (other than uncomplicated appendectomy or cholecystectomy); Diffuse mucosal disease involving the upper gastrointestinal tract, including Crohn’s disease, coeliac disease, or ischaemic changes, evident either macroscopically or on histopathological examination of mucosal biopsies; Haemoglobin below the lower limit of the normal range (ie. below 135g/L for men and 115g/L for women), and ferritin below the lower limit of normal (below 20ng/mL for women and 30ng/mL for men); Impaired renal or liver function (as assessed by calculated creatinine clearance < 90 mL/min or abnormal liver function tests, > 2 times upper limit of normal); Body mass index > 30 kg/m2 or < 20 kg/m2; Donation of blood within the previous 3 months; Participation in any other research studies within the previous 3 months; Subjects requiring the use of anticoagulant drugs, antiplatelet agents or NSAIDS; Subjects with known coagulopathy; Presence of mucosal abnormalities at endoscopy; Subjects requiring medication that may influence gastrointestinal function; Evidence of drug abuse, consumption of more than 20 g alcohol or 10 cigarettes per day; Female patients not using appropriate contraceptive method (ie oral contraceptive pill, diaphragm, DepoProvera hormonal contraceptive injection, intrauterine device (IUD), Norplant method); Vegetarian, lactation or pregnancy (verified by urine testing in women of reproductive age; in these subjects, study will be completed during the follicular phase of the menstrual cycle); habitual consumption of >500 mL of artificially sweetened drink, or food equivalent
Outcome results
None listed