Effect of Hyperglycemia on Microvascular Perfusion in Healthy Adults

Early Phase 1CompletedNCT03520569

University of Virginia15 enrolled

Overview

The investigators are studying the effects of Hyperglycemia on vascular function and insulin sensitivity on healthy adults

The investigators will study 22 healthy subjects (18-35 yrs) four times as follows: 1. Saline + Octreotide + euglycemia; 2. Octreotide + hyperglycemia; 3. Octreotide + hyperglycemia + insulin clamp and 4. Octreotide + Euglycemia + insulin clamp. The sequence of admissions will be assigned randomly. The investigators will assess function in conduit (pulse wave velocity-PWV, augmentation index-AI and flow-mediated dilation-FMD), resistance (post-ischemic flow velocity-PIFV) and heart and skeletal muscle microvascular (contrast enhanced ultrasound-CEU) vessels. This work will: a) identify whether vascular stiffness and indices of NO action are impaired throughout the arterial tree with hyperglycemia.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Vascular Stiffness Insulin Sensitivity

Interventions

OctreotideDRUG

we are using it to block insulin secretion from the pancreas

InsulinDRUG

we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp

Dextrose 20% solutionDRUG

We are using dextrose to maintain glycemia level

Eligibility

Sex: ALLMin age: 18 YearsMax age: 35 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy with no chronic illness * Age 18-35 * Normal BMI (18-25) * Normal screening labs or no clinically significant values Exclusion Criteria: * First degree relative with Type 2 Diabetes * Smoking presently or in the past 6 months * Medications that affect the vasculature * Overweight or other indications of insulin resistance * Elevated LDL cholesterol \> 160 * Elevated BP \> 140/90 * History of congestive heart failure, ischemic heart disease, severe pulmonary disease, liver or kidney disease, bleeding disorders * Any vascular disease such as myocardial infarction, stroke, peripheral vascular disease * Presence of an intracardiac or intrapulmonary shunt (we will screen for this by auscultation during the physical exam by PI). * Pregnant or breastfeeding. * Known hypersensitivity to perflutren (contained in Definity)

Locations (1)

University of Virginia

Charlottesville, Virginia, United States

Outcomes

Primary Outcomes

Change in Flow Mediated Dilation (FMD) Between Baseline and After 2 Hour Insulin Clamp

Flow mediated dilation measures the change in brachial diameter in response to 5 minutes of ischemia using B-mode ultrasound. It provides an index of nitric oxide generation by the endothelium .

Time frame: baseline and after 2 hour insulin clamp

Secondary Outcomes

Change in Augmentation Index Between Baseline and After 2 Hour Insulin Clamp

The augmentation index (AIx) measured at the radial artery is a measure of systemic arterial stiffness, and is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. Higher percentages indicate increased arterial stiffness.

Time frame: baseline and after 2 hour insulin clamp

Change in Pulse Wave Velocity (PWV) Between Baseline and After 2 Hour Insulin Clamp

The time required for a blood pressure wave to travel from the carotid to the femoral artery was measured in meter/sec. This is a measurement of central artery stiffness. Higher numbers indicate stiffer vessels

Time frame: baseline and after 2 hour insulin clamp

Data from ClinicalTrials.gov

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