None listed
Conditions
Brief summary
Some people over the age of 65 years experience a substantial fall in BP after eating, so-called, postprandial hypotension. Recent, compelling, evidence indicates that the gut hormones, GLP-1 and GIP, modulate BP after a meal. Unlike GLP-1, GIP does not slow stomach emptying and may accelerate it. While the role of endogenous GIP in the regulation of postprandial blood glucose and BP remains uncertain, due to the lack of a specific GIP antagonist, our recent studies strongly support the concept that GIP regulates BP and gut blood flow. Colleagues in Copenhagen have recently developed an effective GIP antagonist in humans. We will use the GIP antagonist to define the roles of GIP, in the blood glucose, BP, gut blood flow flow and stomach emptying responses to a glucose drink in healthy older people..
Interventions
Each participant will be studied on 3 separate occasions, separated by an intervals of at least 7 days. Participants will be given an intravenous (iv) injection of GIP (1.5 pmol/kg/min), GIP antagonist (800 pmol/kg/min) or 0.9% saline (placebo) at approximately 9.00am (t = -30 min). Thirty minutes after the iv dose, the participant will be given a drink (t = 0 min) comprising 75g glucose and 5g 3-Ortho-Methyl-glucose labelled with 20 MBq 99mTc-calcium phytate, made up to 300ml water. 3-OMG is
Each participant will be studied on 3 separate occasions, separated by an intervals of at least 7 days. Participants will be given an intravenous (iv) injection of GIP (1.5 pmol/kg/min), GIP antagonist (800 pmol/kg/min) or 0.9% saline (placebo) at approximately 9.00am (t = -30 min). Thirty minutes after the iv dose, the participant will be given a drink (t = 0 min) comprising 75g glucose and 5g 3-Ortho-Methyl-glucose labelled with 20 MBq 99mTc-calcium phytate, made up to 300ml water. 3-OMG is a non-metabolisable glucose analogue and plasma levels can be used to assess glucose absorption. Gastric emptying, plasma glucose, plasma insulin, blood pressure (BP), heart rate (HR), superior mesenteric artery (SMA) flow and appetite will be monitored for 180 minutes after ingestion of the drink. At t = 180 min, the participants will be presented with a cold, buffet-style meal and be allowed 30 minutes to freely consume food until they are comfortably full. The weight of the food will be recorded before and after it is offered to the subjects and energy intake and macronutrient composition calculated subsequently using commercially available software. At least one member of the research team will be present at all times to monitor participants and to ensure adherence to the intervention.
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
65 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
• Male or female healthy participants • Body Mass Index (BMI) 19 - 35 kg/m²
Exclusion criteria
• Participants with diabetes, a history of severe respiratory, cardiovascular, hepatic and/or renal disease (severe in that the social or physical manifestation of the disease, or living with the condition, impact negatively and significantly on the individuals’ ability to lead a normal day to day life), chronic alcohol abuse or epilepsy (excluded by history) or if iron status, or liver function tests are outside the following ranges: • Alanine aminotransferase (ALT) 0 - 55 U/L • Alkaline phosphatase 30 - 110 U/L • Aspartate transaminase 0 - 45 U/L • Amylase and/or lipase >3 x ULN • Bilirubin 6 - 24 mmol/L • Ferritin 15 – 200 ng/mL (Females) 30 – 300 ng/mL (Males) • Haemoglobin 115 - 155 g/L (Females) 135 – 172 g/L (Males) • Participants with a creatinine clearance cut-off of < 50 ml/min Calculated creatinine clearance will be determined as follows (29): Cr clearance = [140 - age (years) x weight (kg)] / [0.814 x serum creatinine (µmol/L)] (For female subjects, multiply Cr clearance x 0.85) • Participants requiring medication likely to influence BP or gastrointestinal function • Participants with a past history of gastrointestinal disease, including known gastroparesis, significant upper gastrointestinal symptoms and previous gastric surgery • Participants with a history of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, • Participants with a current or prior history of c-cell carcinoma • Smoking > 10 cigarettes/day • Alcohol consumption > 20 g/day • Participants who have donated blood in the previous 12 weeks
Outcome results
None listed