Effect of GLP-1 on Microvascular Insulin Responses in Type 1 Diabetes

Early Phase 1WithdrawnNCT04133922

University of Virginia

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Conditions

Type 1 Diabetes Insulin Sensitivity/Resistance

Interventions

GLP-1DRUG

glucagon-like peptide 1

InsulinDRUG

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

Dextrose 20 % in WaterDRUG

We are using Dextrose to maintain Euglycemia during the insulin clamp

Eligibility

Sex: ALLMin age: 18 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

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 \-

Locations (1)

University of Virginia

Charlottesville, Virginia, United States