Insulin Sensitivity/Resistance, Type 1 Diabetes
Conditions
Brief summary
GLP-1 increases skeletal and cardiac microvascular perfusion and improves insulin's microvascular responses in human subjects with T1DM, leading to improved metabolic insulin responses, endothelial function, and increased muscle oxygenation
Detailed description
The proposed study will determine the effect of GLP-1 infusion on microvascular perfusion and microvascular insulin responses in both skeletal and cardiac muscle microvasculature in humans with T1DM. The investigators will study 20 participants with T1DM using a state-of-the-art technology, contrast enhanced ultrasound (CEU), to assess whether GLP-1 augments skeletal and cardiac microvascular blood flow (MBF) as a representation of microvascular perfusion, flow-mediated dilation (FMD) as a measurement of endothelial function, and augmentation index (AI) and pulse wave velocity (PWV) as surrogates for large vessel compliance. The investigators will use the combined CEU and euglycemic-hyperinsulinemic clamp approach to determine if microvascular and metabolic IR improves as a result.
Interventions
DRUGGLP-1
glucagon-like peptide 1
DRUGInsulin
we are using to replace basal insulin and to raise insulin concentrations during the insulin clamp
We are using Dextrose to maintain Euglycemia during the insulin clamp
Sponsors
American Diabetes Association
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Each subject is studied 3 times in randomized order
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1. History of type 1 diabetes, duration \> 1 year 2. Age 18-40 years 3. HbA1c \< 8.5% 4. BMI \>/=18, \<30 kg/m2 5. Using insulin for diabetes treatment only 6. On stable regimen of non-diabetic medications for the last 6 months, excluding oral contraceptives (OCP) 7. All screening labs within normal limits or not clinical significant
Exclusion criteria
1\) Pregnancy or currently breastfeeding 2) Smoking history within 6 months 3) History of microvascular (microalbuminuria, retinopathy, neuropathy) or macrovascular diabetes complications (coronary artery disease, stroke, peripheral vascular disease) 4) Taking vasoactive medications (i.e. calcium channel blockers, angiotensin-converting enzyme or renin inhibitors, angiotensin-receptor blockers, nitrates, alpha-blockers) 5) OCP use within 3 months or 1 month if menses has subsequently occurred 6) Known hypersensitivity to perflutren (contained in Definity© contrast) 7) Screening O2 saturation\<90% 8) Anemia (hemoglobin \<12 g/dL in women, hemoglobin \<13 g/dL in men) 9) Diabetic ketoacidosis (DKA) on presentation to screening visits or study admission days \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| change in microvascular blood volume between baseline and 2 hour insulin clamp | baseline and after 2 hour insulin clamp | vascular measurement |
| change in insulin sensitivity between baseline and 2 hour insulin clamp | baseline and after 2 hour insulin clamp | vascular measurement |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| change in augmentation index between baseline and 2 hour insulin clamp | baseline and after 2 hour insulin clamp | vascular measurement |
| change in flow-mediated dilation between baseline and 2 hour insulin clamp | baseline and after 2 hour insulin clamp | vascular measurement |
| change in pulse wave velocity between baseline and 2 hour insulin clamp | baseline and after 2 hour insulin clamp | vascular measurement |
Countries
United States
Outcome results
None listed