Track topics on Twitter Track topics that are important to you
Exenatide acutely inhibits intestinal lipoprotein particle production. We are unable to speculate whether exenatide affects hepatic lipoprotein production in humans since there is currently no evidence from animal models or in vitro studies that have demonstrated an effect
Subjects will receive an infusion of stable isotope enriched acetate, leucine and a bolus of glycerol in order to measure the rates of fatty acid synthesis, apolipoprotein and triglyceride turnover respectively. This in vivo stable isotope enrichment methodology has been widely established and used by investigators around the world for more than 30 years to examine the metabolism of various metabolites in humans.
Following an overnight fast, at approximately 9am on day 1 of the study the subject will be admitted to hospital and will have a 30ml fasting blood sample drawn for analysis of plasma glucose, total plasma cholesterol, LDL-cholesterol, HDL cholesterol, triglycerides (TG), free fatty acids (FFA), insulin, GLP-1, growth hormone, glucagon, stable isotope enrichment and a more detailed analysis of triglyceride rich lipoprotein (TRL) composition (lipid and apolipoprotein content). A radio-opaque polyvinyl feeding tube (Entriflex NG Tube 55'' [140cm] 10fr Item # 8884721055, Kendall Products, Tyco Healthcare, Toronto, ON) will be inserted through the nose into the stomach, with enough length provided for migration of the tip into the duodenum. The subject will be administered 10 mg metoclopramide orally to facilitate transport of the tip of the tube into the duodenum. The subject will be allowed to eat regular meals during the day but will fast overnight after 7pm and will remain fasting for the duration of the study. Water ad lib will be allowed. At approximately 3pm on day 1 an abdominal X-Ray will confirm the position of the tube in the duodenum. At 4pm 2 iv's will be inserted into a superficial vein in each forearm, one for infusion and one for sampling. An infusion of 1-13C acetate (15 gm in a bag of ½ N saline at 32ml/hr) will begin after the iv's have been inserted and will be infused for the remainder of the study, which is 27 hours.
Starting at 4am a synthetic triglyceride emulsion, Intralipid (20% solution, Baxter Canada) , will be infused through the feeding tube into the duodenum at a rate of 40 ml/hr for the duration of the experiment (ie until 7pm that evening). This will provide a steady state fed state for the subsequent assessment of lipoprotein turnover kinetics.
The subjects will receive, in random order, either exenatide 10 mg or equivalent volume of saline subcutaneously at 7am on day 2 of the hospitalization (i.e. at -2hr) during the first of the two studies. The pancreatic clamp will begin at 7am (-2hr), immediately following administration of either exenatide or saline and continue throughout the subsequent 12 hours (until 7pm). . During the pancreatic clamp the subjects will receive an iv infusion of glucagon (0.65ng/kg/min), growth hormone (Humatrope, 3.0 ng/kg/min), somatostatin (sandostatin, 25 µg/hr) and insulin (Novolin R, 0.05 mU/kg/min).
At 9 am (we will refer to this time point as 0hr of the lipoprotein turnover study), the lipoprotein turnover study will begin. An iv bolus of deuterated-glycerol (d5-glycerol, 75 mmol/kg) will be administered, followed by a primed-constant infusion of deuterated leucine; d3-leucine, (10 mmol/kg bolus followed by 10 mmol/kg/hr for 10 hours). Blood samples will be collected prior to and at regular time intervals for 10 hours after the iv bolus of d3-glycerol and start of the constant infusion of d3-leucine (for assessment of lipoprotein kinetics). Blood samples will be collected prior to (30ml at -2hr, 10ml at -1hr and 30ml at 0hr) and 5min and 15min (10ml each) and then 30ml each at 30min, 1hr, 2hr, 3hr, 4hr, 5hr, 6hr (only 10ml),7hr, 8hr, 9hr and 10hr after administration of d5-glycerol and start of d3-leucine infusion.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science
Toronto General Hospital,
Not yet recruiting
University Health Network, Toronto
Published on BioPortfolio: 2014-08-27T03:16:22-0400
The primary purpose of this study is to assess the anti-exenatide-antibody response to exenatide re-exposure as measured by anti-exenatide antibodies and incidence of treatment-emergent al...
The purpose of this substudy is to obtain CGM data from individuals taking exenatide. The CGM measurements gathered before starting and during treatment with exenatide IR and/or exenatide ...
Exenatide is the first in a new class of drugs for the treatment of type 2 diabetes mellitus called incretin mimetics. Exenatide resembles a gut hormone, which increases the insulin secret...
The purpose of this study is the examine the effect of taking exenatide on the blood levels (pharmacokinetics) of orally-administered contraceptives.
The purpose of this study is to find out how exenatide causes weight loss. Specifically, the study is assessing how exenatide may change how people take in energy (energy intake), as well...
Diabetic retinopathy (DR) is one of the most common complications of diabetes and the leading cause of acquired blindness in adults. In diabetic patients hyperglycemia induces complex metabolic abnorm...
Exenatide, a glucagon-like peptide-1 agonist and a licensed treatment for Type 2 diabetes significantly reduced deterioration in motor symptoms in patients with Parkinson's disease in a randomised, pl...
A Randomized Controlled Trial of Dapagliflozin Plus Once-Weekly Exenatide Versus Placebo in Individuals with Obesity and Without Diabetes: Metabolic Effects and Markers Associated with Bodyweight Loss.
The sodium-glucose cotransporter 2 inhibitor dapagliflozin and the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide reduce bodyweight via differing and complementary mechanisms. This post ho...
The prevalence of hyperlipidemia is increasing rapidly. The role of Coreopsis tinctoria (CT) in amending lipid metabolism in hyperlipidemia patients has not been reported. This study aims to evaluate ...
Hyperlipidemia is a risk factor for various cardiovascular and metabolic disorders. And it is tightly related to chronic inflammation. Interleukin-38 (IL-38) represents a new member of anti-inflammato...
Common occlusive arterial disease which is caused by ATHEROSCLEROSIS. It is characterized by lesions in the innermost layer (ARTERIAL INTIMA) of arteries including the AORTA and its branches to the extremities. Risk factors include smoking, HYPERLIPIDEMIA, and HYPERTENSION.
A type of familial lipid metabolism disorder characterized by a variable pattern of elevated plasma CHOLESTEROL and/or TRIGLYCERIDES. Multiple genes on different chromosomes may be involved, such as the major late transcription factor (UPSTREAM STIMULATORY FACTORS) on CHROMOSOME 1.
Rare and often fatal drug complication which affects patients undergoing long-term treatment with high doses of PROPOFOL. It is characterized by METABOLIC ACIDOSIS; HYPERLIPIDEMIA; RHABDOMYOLYSIS; cardiovascular CIRCULATORY COLLAPSE; CARDIAC FAILURE; and KIDNEY FAILURE.
A severe type of hyperlipidemia, sometimes familial, that it is characterized by the elevation of both plasma CHYLOMICRONS and TRIGLYCERIDES contained in VERY-LOW-DENSITY LIPOPROTEINS. Type V hyperlipoproteinemia is often associated with DIABETES MELLITUS and is not caused by reduced LIPOPROTEIN LIPASE activity as in HYPERLIPOPROTEINEMIA TYPE I .
An autosomal recessive disease in which gene expression of glucose-6-phosphatase is absent, resulting in hypoglycemia due to lack of glucose production. Accumulation of glycogen in liver and kidney leads to organomegaly, particularly massive hepatomegaly. Increased concentrations of lactic acid and hyperlipidemia appear in the plasma. Clinical gout often appears in early childhood.
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...