None listed
Conditions
Brief summary
Hydroxycitric acid (HCA), derived from the fruit Garcinia cambogia, reduces the rate of glucose absorption and decreases postprandial glycaemia in rodents, but its effects in humans are unknown. We aim to investigate the effects of small intestinal perfusion with HCA on glucose absorption, incretin (GIP and GLP-1) release and glycaemia in response to a subsequent intraduodenal glucose infusion in both health and type 2 diabetes. Healthy subjects and patients with type 2 diabetes will received an intraduodenal infusion of HCA (2800mg in water) or control (water alone) over 60min, followed by 60g glucose infused over 120min, in a double blind randomized crossover design. In the healthy subjects, 5g 3-O-methylglucose (3-OMG) will be co-infused with glucose as a marker of glucose absorption. Blood will be sampled frequently for subsequent assays.
Interventions
Subjects will be studied twice in crossover fashion, with at least 5 days between study days. On each day, the subject will arrive at the Royal Adelaide Hospital at approximately 0830. An intraduodenal catheter (diameter 3.5 mm; Dentsleeve, Ontario, Canada) will be inserted through an anaesthetised nostril and allowed to pass through the stomach and into the duodenum by peristalsis. The assembly will contain an infusion channel, located about 12 cm distally from the pylorus. The correct position
Subjects will be studied twice in crossover fashion, with at least 5 days between study days. On each day, the subject will arrive at the Royal Adelaide Hospital at approximately 0830. An intraduodenal catheter (diameter 3.5 mm; Dentsleeve, Ontario, Canada) will be inserted through an anaesthetised nostril and allowed to pass through the stomach and into the duodenum by peristalsis. The assembly will contain an infusion channel, located about 12 cm distally from the pylorus. The correct positioning of the catheter will be maintained by continuous measurement of the transmucosal potential difference (TMPD) from manometry side holes in the antrum and duodenum. For this purpose, a cannula filled with sterile saline will be placed subcutaneously in the left forearm and used as a reference electrode. The antral and duodenal channels will be perfused with degassed 0.9 % saline at 0.15 ml/minute. An intravenous cannula will be also be inserted to facilitate subsequent blood sampling. At T = -60, 4667mg of SuperCitriMax (Registered Trademark, InterHealth Nutraceuticals Incorporated) containing 2800mg of HCA, dissolved in 420 ml water or placebo (saline matched for osmolality) will be administered intraduodenally over 60 minutes. Then, at T = 0, intraduodenal glucose will be administered at a rate of 2 ml/min of 25% glucose (2 kcal/minute) for 120 minutes along with (in healthy subjects only) 5 g of 3-O-methylglcuose to facilitate measurement of exogenous glucose absorption.
Sponsors
University of Adelaide
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
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy subjects: - Males or females aged 18 – 70 years - Body mass index (BMI) 19 - 30 kg/m2 Type 2 diabetes patients: Patients with type 2 diabetes - Patients with a diagnosis of type 2 diabetes by WHO criteria (plasma glucose greater than or equal to 7 mmol/L fasting, or greater than or equal to 11.1 mmol/L two hours after a glucose challenge) or with a history of HbA1c greater than or equal to 6.5%. - Managed by diet alone. - HbA1c between 6.0 and 8.5% - Body mass index (BMI) 20 - 35 kg/m2 - Age 18 – 70 years
Exclusion criteria
- Use of any medication that may influence gastrointestinal motor function within 48 hours or 5 half lives of the study, specifically: opiates, anticholinergics, levodopa, calcium-channel antagonists, beta blockers, clonidine, nitrates, tricyclic antidepressants, selective serotonin re-uptake inhibitors, phosphodiesterase type 5 inhibitors, sumatriptan, metoclopramide, domperidone, cisapride, tegaserod, erythromycin - Intake of >20 g alcohol on a daily basis, or >10 cigarettes per day - History of gastrointestinal disease, including significant upper or lower gastrointestinal symptoms, or previous gastrointestinal surgery (other than uncomplicated appendicectomy) - Impaired renal or liver function (as assessed by calculated creatinine clearance < 90 mL/min or abnormal liver function tests) - Donation of blood within the previous 3 months - Participation of other studies within the previous 3 months
Outcome results
None listed