Insulin Sensitivity, Vascular Stiffness
Conditions
Brief summary
The investigators are studying the effects of Hyperglycemia on vascular function and insulin sensitivity on healthy adults
Detailed description
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.
Interventions
DRUGOctreotide
we are using it to block insulin secretion from the pancreas
DRUGInsulin
we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp
DRUGDextrose 20% solution
We are using dextrose to maintain glycemia level
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Each subject is studied 4 times in a randomized sequential order
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Flow Mediated Dilation (FMD) Between Baseline and After 2 Hour Insulin Clamp | 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 . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Augmentation Index Between Baseline and After 2 Hour Insulin Clamp | 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. |
| Change in Pulse Wave Velocity (PWV) Between Baseline and After 2 Hour Insulin Clamp | 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 |
Countries
United States
Participant flow
Recruitment details
20 potential study participants were screened for eligibility
Pre-assignment details
15 participants were ultimately enrolled. Five potential subjects failed to meet inclusion criteria and were subsequently excluded from the study.
Participants by arm
| Arm | Count |
|---|---|
| All Participants all participants who completed the study | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age, Continuous | 24 years STANDARD_DEVIATION 1 |
| Race/Ethnicity, Customized african american | 1 Participants |
| Race/Ethnicity, Customized asian | 1 Participants |
| Race/Ethnicity, Customized caucasian | 13 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 14 | 0 / 10 | 0 / 12 |
| other Total, other adverse events | 0 / 13 | 0 / 14 | 0 / 10 | 0 / 12 |
| serious Total, serious adverse events | 0 / 13 | 0 / 14 | 0 / 10 | 0 / 12 |
Outcome results
Primary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Octreotide- Euglycemia | Change in Flow Mediated Dilation (FMD) Between Baseline and After 2 Hour Insulin Clamp | 11.8 % change | Standard Deviation 4.4 |
| Octreotide - Euglycemia- Insulin Clamp | Change in Flow Mediated Dilation (FMD) Between Baseline and After 2 Hour Insulin Clamp | 11.8 % change | Standard Deviation 4 |
| Octreotide- Hyperglycemia | Change in Flow Mediated Dilation (FMD) Between Baseline and After 2 Hour Insulin Clamp | 8.9 % change | Standard Deviation 4.3 |
| Octreotide- Hyperglycemia - Insulin Clamp | Change in Flow Mediated Dilation (FMD) Between Baseline and After 2 Hour Insulin Clamp | 8.95 % change | Standard Deviation 4.5 |
Secondary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Octreotide- Euglycemia | Change in Augmentation Index Between Baseline and After 2 Hour Insulin Clamp | -4.15 percentage | Standard Deviation 11.72 |
| Octreotide - Euglycemia- Insulin Clamp | Change in Augmentation Index Between Baseline and After 2 Hour Insulin Clamp | -2.23 percentage | Standard Deviation 12.33 |
| Octreotide- Hyperglycemia | Change in Augmentation Index Between Baseline and After 2 Hour Insulin Clamp | -4.80 percentage | Standard Deviation 12.13 |
| Octreotide- Hyperglycemia - Insulin Clamp | Change in Augmentation Index Between Baseline and After 2 Hour Insulin Clamp | -8.45 percentage | Standard Deviation 9.16 |
Secondary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Octreotide- Euglycemia | Change in Pulse Wave Velocity (PWV) Between Baseline and After 2 Hour Insulin Clamp | 5.21 m/sec | Standard Deviation 0.64 |
| Octreotide - Euglycemia- Insulin Clamp | Change in Pulse Wave Velocity (PWV) Between Baseline and After 2 Hour Insulin Clamp | 5.06 m/sec | Standard Deviation 0.76 |
| Octreotide- Hyperglycemia | Change in Pulse Wave Velocity (PWV) Between Baseline and After 2 Hour Insulin Clamp | 4.79 m/sec | Standard Deviation 0.79 |
| Octreotide- Hyperglycemia - Insulin Clamp | Change in Pulse Wave Velocity (PWV) Between Baseline and After 2 Hour Insulin Clamp | 5.07 m/sec | Standard Deviation 0.67 |