None listed
Conditions
Brief summary
Recent studies have demonstrated that specific nutrients, including lauric acid and L-tryptophan, have energy intake-suppressant and blood glucose-regulatory effects via several pathways, including stimulation of gut hormones and motility, and the slowing of gastric emptying, in healthy individuals. We aim to investigate the hypothesis that the combined intraduodenal administration of lauric acid and tryptophan, compared with the individual nutrients, will more potently stimulate gut functions, including gut hormones, and gastric emptying, associated with reduced postprandial blood glucose in people with type 2 diabetes.
Interventions
Participants will receive in a randomised, double-blind fashion, a 45-min intraduodenal infusion of either (i) L-tryptophan at 0.10 kcal/min (1.1 g/45 min), (ii) lauric acid at 0.3 kcal/min (1.5 g/45 min), (iii) combination of (i) and (ii), or (iv) saline (control) on 4 separate visits. The total duration of each study visit will be 4.5-6 hours, and will be separated by 3-7 days. To ensure adherence to the intervention, research staff will closely supervise the participants throughout the study
Participants will receive in a randomised, double-blind fashion, a 45-min intraduodenal infusion of either (i) L-tryptophan at 0.10 kcal/min (1.1 g/45 min), (ii) lauric acid at 0.3 kcal/min (1.5 g/45 min), (iii) combination of (i) and (ii), or (iv) saline (control) on 4 separate visits. The total duration of each study visit will be 4.5-6 hours, and will be separated by 3-7 days. To ensure adherence to the intervention, research staff will closely supervise the participants throughout the study visit. Study visits will be performed in the Clinical Research Facility of the Adelaide Medical School, by University of Adelaide staff and students trained in the required techniques. Participants will consume a standardised dinner meal, (400g McCain's beef lasagne), the night before each study visit between 6:30 to 7 pm. After being fasted for 13.5 to 14 hrs overnight and refraining from any exercise and alcohol intake for 24 hrs, participants will arrive at the laboratory at 8:30 am. Upon arrival, participants will be intubated with a 17-channel manometric catheter that will be inserted through an anaesthetised nostril and allowed to pass through the stomach and into the duodenum by peristalsis. The manometric catheter consists of 16 side holes spaced at 1.5 cm intervals and an additional channel (with the side hole positioned approx. 14 cm distal to the pylorus when the catheter is in the correct position) is used for intraduodenal infusions. The correct positioning of the catheter will be maintained by continuous measurement of the transmucosal potential difference (TMPD) between the most distal antral channel and the most proximal duodenal channel. Once the catheter has been positioned correctly, an intravenous cannula will be placed into a forearm vein for blood sampling. At t = -31 min, a baseline blood sample and breath sample will be taken, and participants will complete a visual analogue scale (VAS) questionnaire. Immediately thereafter (t = -30 min), one of the infusions will commence, and continue until t = 15 min. At t = -1 min, participants will be given a mixed-nutrient drink (containing 500 kcal, 74 g carbohydrates) to consume within 2 min, which will be marked with carbon-13 acetate to facilitate the measurement of gastric emptying using 13C-breath test. Blood samples, VAS ratings and breath samples will be obtained at regular intervals until t = 180 min. Participants will then be served a light lunch, consisting of a sandwich, fruit/muesli bar, and water, and then allowed to leave the laboratory.
Sponsors
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 75 Years
Healthy volunteers
No
Inclusion criteria
Male participants with type 2 diabetes mellitus (T2DM), (aged 18-75 years BMI: 28-38 kg/m2), will be included in the study. T2DM diagnosis will be based on WHO criteria. HbA1c will be >=6.5 - <=7.9% at screening. Blood glucose medications will be required to 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 GI symptoms, or history of GI disease or surgery Current gallbladder or pancreatic disease Cardiovascular or respiratory diseases Any other illnesses (except type 2 diabetes) as assessed by the investigator (including chronic illnesses not explicitly listed above) Use of prescribed or non-prescribed medications (including vitamins and herbal supplements) which may affect energy metabolism, GI function, bodyweight or appetite (e.g. domperidone, cisapride, anticholinergic drugs (e.g. atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St Johns Wort etc.) Lactose intolerance/other food allergy(ies) Individuals with low ferritin levels (<30 ng/mL), or who have donated blood in the 12 weeks prior to taking part in the study High performance athletes Current intake of > 2 standard drinks on > 5 days per week (>140g/week) Current smokers of tobacco (cigarettes, cigars, pipes, sheesha, chewing, vaping etc.) Current use of recreational drugs, e.g. marijuana Current intake of any illicit substance Vegetarians Inability to tolerate nasoduodenal tube Inability to comprehend study protocol HbA1c <6% or >7.9% Estimated glomerular filtration rate <45 ml/min Any patient whose medication cannot be withheld for 48 hours for medical reasons
Outcome results
None listed