None listed
Conditions
Brief summary
The proposed study is designed to determine, in patients with type 2 diabetes, (i) whether blood glucose, incretin hormone (ie. glucagonlike peptide1 (GLP1) and glucosedependent insulinotropic polypeptide (GIP)), insulin, glucagon, and fibroblast growth factor19 (FGF19) concentrations in response to a small intestinal glucose infusion (2 kcal/min) are modified by intrajejunal infusion of taurocholic acid (TCA), (ii) the effect of TCA on small intestinal glucose absorption, and (iii) the relative contribution of the actions of GLP1 to the lowering of glycaemia by TCA, using the specific antagonist, exendin (939). Additionally, changes in blood pressure (BP), heart rate (HR) and superior mesenteric artery (SMA) blood flow in response to intrajejunal glucose infusion will be evaluated, in the presence and absence of intrajejunal TCA and intravenous exendin (939).
Interventions
Following an overnight fast, each subject will receive the following four treatments, separated by at least 7 days, in a double-blind, randomised fashion:
(1) intrajejunal infusion of saline (+ i.v. saline)
(2) intrajejunal infusion of taurocholic acid (TCA) (+ i.v. saline)
(3) intrajejunal infusion of saline (+ i.v. exendin (9-39))
(4) intrajejunal infusion of TCA (+ i.v. exendin (9-39))
An intravenous infusion of exendin (9-39) (Bachem, Clinalfa products, L?ufelfingen, Switzerland) at 600 pmo
Following an overnight fast, each subject will receive the following four treatments, separated by at least 7 days, in a double-blind, randomised fashion: (1) intrajejunal infusion of saline (+ i.v. saline) (2) intrajejunal infusion of taurocholic acid (TCA) (+ i.v. saline) (3) intrajejunal infusion of saline (+ i.v. exendin (9-39)) (4) intrajejunal infusion of TCA (+ i.v. exendin (9-39)) An intravenous infusion of exendin (9-39) (Bachem, Clinalfa products, L?ufelfingen, Switzerland) at 600 pmol/kg/min (a rate known to be well tolerated and to block >95% of the actions of endogenous GLP-1 in humans), or 0.9% saline, will be commenced at T = -60 min, and maintained until T = 120 min. Intrajejunal infusion of either TCA (4g TCA dissolved in 240 mL 0.9% saline), or 0.9% saline, will be commenced at the rate of 240 mL/hour during T -30-0 min, and reduced to the rate of 60 mL/hour during T = 0-120 min. At T = 0 min, subjects will also receive a small intestinal infusion consisting of 60 g glucose with 5 g 3-O-methylglucose (3-OMG) dissolved in water to a total volume of 240 mL, infused over 120 minutes (2 mL/min, and 2 kcal/min).
Sponsors
Royal Adelaide Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes (World Health Organisation (WHO) criteria), managed by diet or metformin only * Body mass index (BMI) 20 - 40 kg/m2 * Age 18 - 75 years * Males and post-menopausal females * Glycated haemoglobin (HbA1c) less than or equal to 8.5% * Haemoglobin above the lower limit of the normal range (ie. >135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (ie. >30ng/mL for men and >20mg/mL for women)
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, beta blockers, clonidine, nitrates, tricyclic antidepressants, selective serotonin re-uptake inhibitors, phosphodiesterase type 5 inhibitors, sumatriptan, metoclopramide, domperidone, cisapride, tegaserod, or erythromycin * Evidence of drug abuse, or consumption of more than 20 g alcohol or 10 cigarettes on a daily basis * History of gastrointestinal disease, including significant upper or lower gastrointestinal symptoms, pancreatitis, or previous gastrointestinal surgery (other than uncomplicated appendicectomy or cholecystectomy) * Other significant illness, including epilepsy, cardiovascular or respiratory disease * 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 range)) * Donation of blood within the previous 3 months * Participation in any other research studies within the previous 3 months * Females who are pre-menopausal * Inability to give informed consent * Participants who do not eat beef * Vegetarian diet
Outcome results
None listed