Reversing Glucose and Lipid-mediated Vascular Dysfunction (REGAL)
University of Kansas Medical Center
Summary
The purpose of our study is to understand the extent to which the blood vessels are affected by glucose and fat (lipids) in lean healthy adults and if these changes in the blood vessels contribute to the development of high blood pressure.
Description
Hypertension, obesity, and insulin resistance are associated with elevated muscle sympathetic nerve activity (MSNA), which is important for blood pressure regulation. The measurement of MSNA is safely performed in humans using the microneurographic technique that involves recording sympathetic nerve activity projecting to skeletal muscle using a small microelectrode at the peroneal nerve near the knee. The health of your blood vessels will be tested in this study, in addition to the activity of the nerves that control the blood vessels. The function of the nerves and blood vessels can be dimi…
Eligibility
- Age range
- 18–79 years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: * Lean: BMI \< 25 kg/m * Normal insulin sensitivity: (calculation based on fasting glucose and insulin concentrations in blood) * Middle-aged: 18-79 years * Blood pressure: \< 140 (systolic) and \< 90 mmHg (diastolic * Weight stable (+/- 5 lbs) for the previous 3 months * Participants must be willing and able to discontinue taking any vitamin C or E supplements or omega-3 fatty acids beginning 2 weeks prior. * Able and willing to provide written informed consent Exclusion Criteria: * Diabetes mellitus Type I or Type II: fasting glucose \< 126 mg/dL and/or HbA1c \< 6.5% *…
Interventions
- DrugDextrose 20 % in 500 ML Injection
Dextrose (20% intravenous solution) will be obtained from the Investigational Pharmacy located in the KU Clinical Research Center where studies take place. After fasting for at least 8 hours, dextrose will be administered via antecubital vein at a standard rate of 4 mg/kg/min for 2 hours.
- DrugIntralipid
Intralipid ® 20% will be obtained from the Investigational Pharmacy located in the KU Clinical Research Center where studies take place. After fasting for at least 8 hours, Intralipid ® 20% will be administered via antecubital vein at 0.75 mL/min for 2 hours Increases in circulating markers of oxidative stress peak within 2 hours of Intralipid ® 20% infusion in healthy adults (42). An initial heparin bolus of 1000 UL followed by 200 U/hr infusion will be included to activate endothelial lipoprotein lipase and accelerate hydrolysis of fatty acids.
- DrugSaline
Saline will be obtained from the Investigational Pharmacy located in the KU Clinical Research Center where studies take place. Will be administered via antecubital vein at 75 to 150 mL/hour for 2 hours.
- DrugAscorbic acid
(ASCOR) will be obtained from the KU Investigational Pharmacy located in the KU Clinical Research Center where studies will take place. A priming bolus of 0.06 g ascorbic acid/kg fat free mass (FFM) dissolved in 100 mL of saline will be infused intravenously at 5 mL/min for 20 minutes, followed immediately by a "drip-infusion" of 0.02 g/kg FFM dissolved in 30 mL of saline administered over 2 hours at 0.5 mL/min. The KU Investigational Pharmacy will randomize ascorbic acid or placebo (saline) for each participant.
Location
- University of Kansas Medical CenterKansas City, Kansas