None listed
Conditions
Brief summary
This research is likely to provide ‘proof of principle’ for a novel, ‘nutrient-based’ strategy – oral calcium supplementation – to reduce postprandial glycaemia in people with T2D by slowing gastric emptying, known to be integral to reductions in postprandial glycaemic excursions. The outcomes, if positive, will have major implications for the development of a novel, accessible, safe and cost-effective approach to the prevention and management of T2D.
Interventions
Each participant will be studied on three occasions, separated by at least 7 days in a double-blind, randomised, cross-over fashion. They will be instructed to discontinue oral anti-diabetic medications (e.g. metformin) for 48 h, avoid vigorous physical activity and alcohol for 24 hours, and to consume a standardised meal (beef lasagne; energy content: 602 kcal; McCain Food, Wendouree, Victoria, Australia) by 7 pm the night prior to each study visit. No additional food or drink will be permitted
Each participant will be studied on three occasions, separated by at least 7 days in a double-blind, randomised, cross-over fashion. They will be instructed to discontinue oral anti-diabetic medications (e.g. metformin) for 48 h, avoid vigorous physical activity and alcohol for 24 hours, and to consume a standardised meal (beef lasagne; energy content: 602 kcal; McCain Food, Wendouree, Victoria, Australia) by 7 pm the night prior to each study visit. No additional food or drink will be permitted after 7 pm, except for water, which can be consumed until 9:30 pm to ensure hydration. Each participant will arrive at the Adelaide University Clinical Research Facility by 8 am. Premenopausal female participants will undergo a pregnancy test using a urine sample before each study visit. Upon arrival and confirmation that the participant had fasted as required, they will then be seated, and an intravenous cannula will be placed into a forearm vein for blood sampling. A baseline blood sample (9 mL) to measure fasting plasma concentrations of glucose and hormones (e.g. insulin, glucagon, glucagon-like peptide-1), and a visual analogue scale questionnaire to assess gastrointestinal symptoms and appetite perceptions, will be collected. Then, a blood pressure cuff will be placed around their opposite arm connected to an automated DINAMAP machine, and blood pressure and heart rate measurements will be taken at baseline and at 15-minute intervals over the subsequent hour. At t=-60 min, participants will consume enteric-coated capsules containing either 0 (placebo; cellulose), 500, or 1000 mg of calcium (in the form of calcium citrate tetrahydrate), prepared at the Royal Adelaide Hospital pharmacy. Immediately before the ingestion of a nutrient drink, 3 consecutive blood pressure and heart rate measurements will be taken every 3 min to define the average baseline systolic blood pressure (i.e. t=-9, -6, -3 min). Then at t=-1 min, they will consume, within 1 min, a mixed-nutrient drink (Resource Plus, Nestle; 325 ml, 500 kcal, 74 g carbohydrates, 18 g protein and 15 g fat, plus 25 mL water), labelled with 100 mg sodium acetate-1-13C for measurement of gastric emptying by non-invasive breath sampling. The timing of calcium administration is based on previous studies indicating the maximum effects of intraduodenal calcium on plasma hormones and pyloric pressures. Further blood pressure and heart rate measurements will be recorded at 5-minute intervals from t=0 to t=180 min. Breath samples will be collected in sealed bags at baseline (prior to the mixed-nutrient drink) and at regular intervals (every 5 min for the first hour and then 15 min for the subsequent two hours) between t=0 to t=180 min, for analysis of 13CO2. Visual analogue scale scores and 9-mL blood samples will be collected every 30 min after the mixed-nutrient drink (at t=30, 60, 90, 120, 150, 180 min) to assess postprandial effects. At t=180 min, the final blood pressure and heart rate measurements, blood and breath samples, and visual analogue scale scores, will be collected, the i.v. cannula will be removed (after making sure that blood glucose is >5 mmol/L), and the participant will then be allowed to leave the laboratory.
Sponsors
Dr Javad Anjom Shoae - Adelaide University
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
45 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
People with T2D (World Health Organisation criteria) and BMI > 25 kg/m2
Exclusion criteria
-Weight change of more than ±5.0% during the three months prior to screening -History of ketoacidosis or hyperosmolar state/coma -History of severe hypoglycaemia resulting in seizure/unconsciousness/coma or hospitalisation for diabetic ketoacidosis in the last 3 months before screening. -Hypoglycaemia unawareness -Have a known clinically significant gastric emptying abnormality (e.g., severe diabetic gastroparesis or gastric outlet obstruction). -Significant GI symptoms, disease or surgery, current gallbladder or pancreatic disease, cardiovascular or respiratory diseases, or any other illness, including chronic conditions not explicitly listed, as assessed by the investigator -Use of prescribed or non-prescribed medications, including vitamins and herbal supplements which may affect energy metabolism, GI function, body weight or appetite (e.g. domperidone, cisapride, anticholinergic drugs (e.g. atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St John’s wort, etc.) -Individuals with low ferritin levels (females less than 15 ng/mL, males less than 30 ng/mL) -Estimated glomerular filtration rate (eGFR) less than 45 mL/min, used as a measure of kidney function -History of / or current active liver disease (other than non-alcoholic hepatic steatosis), primary biliary cirrhosis, or active symptomatic gallbladder disease -History of any clinically significant disease or disorder that may either put the volunteer at risk because of participation in the study, or influence the results or the ability of the volunteer to participate in the study -Baseline SBP less than or equal to 100mmHg -Current tobacco smokers (e.g. cigarettes, cigars, pipes, sheesha, chewing, vaping, etc.) -Recreational drug use (e.g. marijuana) or current intake of any illicit substance -Current intake of greater than 2 standard drinks on > 5 days per week -Lactose intolerance/other food allergy(ies) -Vegetarians -High-performance athletes -Inability to comprehend study protocol -In female participants, pregnancy, lactation or surgical sterilisation (a pregnancy test will be performed in premenopausal female volunteers, using a urine sample, prior to each study day) -Autonomic nerve function will be evaluated using standardised cardiovascular reflex tests. Patients will be excluded from the study if autonomic nerve damage is diagnosed, i.e. if they achieve a score greater than or equal to 3. -Donated blood in the past 3 months
Outcome results
None listed