Clinical trial NCT04133922: Effect of GLP-1 on Microvascular Insulin Responses in Type 1 Diabetes
Official title: Effect of GLP-1 on Microvascular Insulin Responses in Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Type 1 Diabetes
Insulin Sensitivity/Resistance
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: American Diabetes Association
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2019-10-21
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Each subject is studied 3 times in randomized order
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

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Primary outcomes:
measure: change in microvascular blood volume between baseline and 2 hour insulin clamp
timeFrame: baseline and after 2 hour insulin clamp
measure: change in insulin sensitivity between baseline and 2 hour insulin clamp
timeFrame: baseline and after 2 hour insulin clamp
Secondary outcomes:
measure: change in augmentation index between baseline and 2 hour insulin clamp
timeFrame: baseline and after 2 hour insulin clamp
measure: change in flow-mediated dilation between baseline and 2 hour insulin clamp
timeFrame: baseline and after 2 hour insulin clamp
measure: change in pulse wave velocity between baseline and 2 hour insulin clamp
timeFrame: baseline and after 2 hour insulin clamp
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: Department of Endocrinology, University of Virginia
name: Zhenqi Liu, MD
role: PRINCIPAL_INVESTIGATOR
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