Effects of combined administration of L-tryptophan and lauric acid on gut functions, and blood glucose control in humans with type 2 diabetes

INTERVENTION: 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 s CONDITION: Diet and Nutrition ‐ Obesity Metabolic and Endocrine ‐ Diabetes Type 2 diabetes;Obesity; ; Type 2 diabetes ; Obesity PRIMARY OUTCOME: Changes in C‐peptide, and other gut hormone concentrations, including cholecystokinin, GLP‐1 and GIP, This outcome is of an exploratory nature so that other gut hormones to be measured may be decided upon based on the effects of this intervention on plasma glucose, and other outcomes.[Plasma will be obtained from blood samples taken at t = ‐31, ‐15, 0, 10, 20, 30, 45, 60, 90, 120, 180 min, where t = ‐31 is just prior to infusion commencement and t = 180 is 180 mins following ingestion of the mixed‐nutrient drink.] Changes in plasma glucose concentration[Plasma will be obtained from blood samples taken at t = ‐31, ‐15, 0, 10, 20, 30, 45, 60, 90, 120, 180 min, where t = ‐31 is just prior to infusion commencement and t = 180 is 180 mins following ingestion of the mixed‐nutrient drink.; ] Gastric emptying will be measured using a 13C‐acetate breath test, measuring; 13CO2 concentrations in exhaled air of end‐expiratory breath samples.[Breath samples will be collected at t = ‐31, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180 min,, where t = ‐31 is just prior to infusion commencement and t = 180 is 180 mins following ingestion of the mixed‐nutrient drink.] SECONDARY OUTCOME: Appetite ratings (hunger, fullness, desire to eat, and prospective consumption), GI symptoms (nausea and bloating) and drowsiness will be assessed using a 100mm visual analogue scale (VAS) questionnaire. This VAS has been extensively employed in published studies conducted by the investigators. This outcome is of an exploratory nature so that specific parameters to be measured may be decided upon based on the effect of the intervention on this and other outcomes, therefore, this is a composite outcome.[VAS questionnaires will be completed at t = ‐31, ‐15, 0, 10, 20, 30, 45, 60, 75, 90, 105, 120, 150, 180 min, where t = ‐31 is just prior to infusion commencement and t = 180 is 180 mins following ingestion of the mixed‐nutrient drink.] 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.