None listed
Conditions
Brief summary
Despite increasing use of low calorie sweeteners (LCS) in western diets, and an association between regular, heavy consumption of LCS containing beverages and an increased risk of developing Type 2 Diabetes Mellitus (T2DM), it has only been recently established by our group that LCS supplementation impairs glycaemic control in healthy subjects ACTRN12615000866505. This occurs via augmented intestinal glucose uptake and is likely to involve negative changes in gut microbiota that impair host control of glycaemia. Patients with T2DM are intuitively likely to be at higher risk of these changes due to higher consumption of LCS, defective control of intestinal sweet taste sensors, and augmented glucose uptake, but whether this is the case, and the degree of increased risk, is yet to be determined.
Interventions
Patients with Type 2 Diabetes Mellitus 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 low-calorie sweeteners (sucralose, 92 mg, acesulfame K, 52 mg). Single capsules will be consumed immediately prior to meals, three times daily. Adherence to intervention will be monitor
Patients with Type 2 Diabetes Mellitus 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 low-calorie sweeteners (sucralose, 92 mg, acesulfame K, 52 mg). 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 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
Diabetes Australia
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
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Volunteers with Type 2 Diabetes Mellitus (American Diabetes Association criteria) managed by diet alone or metformin. In patients treated with metformin, this drug will be withheld for 48 h prior to each study visit, since it has the capacity to stimulate GLP-1 secretion
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 undertaking endoscopy safely. ii) 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) iii) 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. iv) Haemoglobin below the lower limit of the normal range (ie. <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) v) Significant history of migraine vi) 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)) vii) Participants medicated with anti-diabetics other than metformin viii) Participants unable to self-monitor blood glucose levels ix) Volunteers with body mass index less than 20 kg/m2 x) Donation of blood within the previous 3 months xi) Participation in any other research studies within the previous 3 months xii) Participants medicated with opiates, anticholinergics, levodopa, clonidine, nitrates, phosphodiesterase type 5 inhibitors, sumatriptan, metoclopramide, domperidone, cisapride, tegaserod, or erythromycin xiii) Participants with known coagulopathy, or treated with any antiplatelet or anticoagulant medication xiv) Presence of mucosal abnormalities at endoscopy xv) Evidence of drug abuse, consumption of more than 20 g alcohol or 10 cigarettes per day xvi) Female patients not using appropriate contraceptive method (ie oral contraceptive pill, diaphragm, DepoProvera hormonal contraceptive injection, intrauterine device (IUD), Norplant method) xvii) Vegetarian, lactation, or pregnancy (verified by urine testing in women of reproductive age; in these participants, the study will be completed during the follicular phase of the menstrual cycle)
Outcome results
None listed