None listed
Conditions
Brief summary
Intestinal sweet taste receptors (STRs) sense all sweet stimuli to coordinate the absorption and metabolism of glucose. We have shown that a defect in intestinal STRs in patients with type 2 diabetes (T2D), as well as supplementation of low-calorie sweeteners in non-diabetic subjects, both accelerate glucose absorption and worsen glycaemic control. We now propose to block intestinal STRs in patients with T2D to evaluate the potential glycaemic benefits of this potential 'next generation' diabetes therapy.
Interventions
Patients with Type 2 Diabetes Mellitus will be screened then undergo two study day visits in a randomised, double-blinded manner. Study day one will occur prior to diet supplementation, with study day two immediately following four weeks of diet supplementation with placebo capsules or capsules containing the sweet taste blocker, lactisole (300mg). Single capsules will be consumed immediately prior to meals, three times daily. Adherence to intervention will be monitored by capsule return and pat
Patients with Type 2 Diabetes Mellitus will be screened then undergo two study day visits in a randomised, double-blinded manner. Study day one will occur prior to diet supplementation, with study day two immediately following four weeks of diet supplementation with placebo capsules or capsules containing the sweet taste blocker, lactisole (300mg). Single capsules will be consumed immediately prior to meals, three times daily. Adherence to intervention will be monitored by capsule return and patient diary. 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 silicone rubber nasoenteral catheter positioned into the second part of the duodenum via an anaesthetised nostril as confirmed by transmucosal potential difference. An intraduodenal glucose infusion will be commenced for 30 min via the catheter (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). Bloods will be collected regularly over 2 hours; stool will be collected pre and post study for microbiome analyses.
Sponsors
Royal Adelaide Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
40 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
i) Volunteers with Type 2 Diabetes Mellitus (American Diabetes Association criteria) managed by metformin alone (morning dose of metformin will be withheld until after study day lunch on each visit, to reduce effects on gut hormone responses) ii) HbA1c less than or equal to 8.5% iii) Body mass index (BMI) 25 - 35 kg/m2 iv) Haemoglobin above the lower limit of the normal range (i.e. above 135g/L for men and above 115g/L for women), and ferritin above the lower limit of normal (above 20ng/mL for women and above 30ng/mL for men) v) Consumption of more than one low-calorie sweetener (LCS) containing beverage per day, or equivalent
Exclusion criteria
i) Significant illness, other than type 2 diabetes, including impairment to cardiovascular or respiratory function that limits a participant’s activity and represents a risk to safe placement of a nasoenteral catheter. ii) History of gastrointestinal disease, including significant upper gastrointestinal symptoms (assessed by validated gastrointestinal symptom questionnaire), pancreatitis, or previous gastrointestinal surgery (other than uncomplicated appendectomy or cholecystectomy) iii) Impaired renal or liver function (as assessed by calculated creatinine clearance less than or equal to 90 mL/min or abnormal liver function tests (greater than or equal to 2 times upper limit of normal)) iv) Participants medicated with anti-diabetics other than metformin v) Participants unable to self-monitor blood glucose levels vi) Volunteers with body mass index greater than or equal to 20 kg/m2 or less than or equal to 35 kg/m2 vii) Donation of blood within the previous 3 months viii) Participation in any other research studies within the previous 3 months ix) Participants medicated with opiates, anticholinergics, levodopa, clonidine, nitrates, phosphodiesterase type 5 inhibitors, sumatriptan, metoclopramide, domperidone, cisapride, prucalopride, or erythromycin x) Evidence of drug abuse, daily consumption of more than 20 g alcohol or 10 cigarettes xi) Female patients not using appropriate contraceptive method (i.e. oral contraceptive pill, diaphragm, DepoProvera hormonal contraceptive injection, intrauterine device, Norplant method) xii) Vegetarian, lactation, or pregnancy
Outcome results
None listed