Effect of Hyperglycemia on Microvascular Perfusion in Healthy Adults (EJB050)

University of Virginia

Status and phase: Completed; Early Phase 1

Conditions: Vascular Stiffness; Insulin Sensitivity

Treatments: Drug: Insulin; Drug: Octreotide; Drug: Dextrose 20% solution

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03520569

19948

T32DK007646 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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

Full description

The investigators will study 22 healthy subjects (18-35 yrs) four times as follows:

Saline + Octreotide + euglycemia; Octreotide + hyperglycemia; Octreotide + hyperglycemia + insulin clamp and 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.

Enrollment: 15 patients

Sex: All

Ages: 18 to 35 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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15 participants in 4 patient groups

Octreotide- Euglycemia

Active Comparator group

Description:

octreotide is 30 ng/kg/min x 240 min insulin 0.15mU/kg/min x 240 min Dextrose 20% at variable rate to maintain euglycemia for 240 min

Treatment:

Drug: Dextrose 20% solution

Drug: Octreotide

Drug: Insulin

Octreotide - Euglycemia- insulin clamp

Active Comparator group

Description:

octreotide is 30 ng/kg/min x 330 min insulin 0.15mU/kg/min x 210 min insulin 1.0mU/kg/min x 120 min Dextrose 20% at variable rate to maintain euglycemia for 330 min

Treatment:

Drug: Dextrose 20% solution

Drug: Octreotide

Drug: Insulin

Octreotide- hyperglycemia

Active Comparator group

Description:

octreotide is 30 ng/kg/min x 330 min insulin 0.15mU/kg/min x 330 min Dextrose 20% at variable rate to maintain euglycemia for 90 min Dextrose 20% at variable rate to maintain hyperglycemia for 240 min

Treatment:

Drug: Dextrose 20% solution

Drug: Octreotide

Drug: Insulin

Octreotide- hyperglycemia - insulin clamp

Active Comparator group

Description:

octreotide is 30 ng/kg/min x 330 min insulin 0.15mU/kg/min x 210 min insulin 1.0mU/kg/min x 120 min Dextrose 20% at variable rate to maintain euglycemia for 90 min Dextrose 20% at variable rate to maintain hyperglycemia for 240 min

Treatment:

Drug: Dextrose 20% solution

Drug: Octreotide

Drug: Insulin