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

Early Phase 1

Withdrawn

• Conditions: Type 1 Diabetes; Insulin Sensitivity/Resistance
• Interventions: Drug: GLP-1; Drug: Insulin; Drug: Dextrose 20 % in Water

• Registration Number: NCT04133922
• Lead Sponsor: University of Virginia

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.

Study Timeline

• Study Start: 2019-10-14
• Study First Submitted: 2019-10-15
• Study First Submitted QC: 2019-10-17
• Study First Posted: 2019-10-21
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-07
• Last Update Posted: 2022-03-22
• Primary Completion: 2023-10
• Study Completion: 2024-10

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Saline + Insulin clamp	Dextrose 20 % in Water	Saline infusion at 30 ml/hr for 150 min and insulin 1 mU/kg/min + Dextrose 20% at variable rate to maintain euglycemia for 120 min.
GLP-1	GLP-1	GLP-1 infusion 1.2 pmol/kg/min for 150 min
GLP-1 + Insulin clamp	GLP-1	GLP-1 infusion 1.2 pmol/kg/min for 150 min and insulin 1 mU/kg/min + Dextrose 20% at variable rate to maintain euglycemia for 120 min
GLP-1 + Insulin clamp	Dextrose 20 % in Water	GLP-1 infusion 1.2 pmol/kg/min for 150 min and insulin 1 mU/kg/min + Dextrose 20% at variable rate to maintain euglycemia for 120 min
Saline + Insulin clamp	Insulin	Saline infusion at 30 ml/hr for 150 min and insulin 1 mU/kg/min + Dextrose 20% at variable rate to maintain euglycemia for 120 min.
GLP-1 + Insulin clamp	Insulin	GLP-1 infusion 1.2 pmol/kg/min for 150 min and insulin 1 mU/kg/min + Dextrose 20% at variable rate to maintain euglycemia for 120 min

Primary Outcome Measures

Name	Time	Method
change in insulin sensitivity between baseline and 2 hour insulin clamp	baseline and after 2 hour insulin clamp	vascular measurement
change in microvascular blood volume between baseline and 2 hour insulin clamp	baseline and after 2 hour insulin clamp	vascular measurement

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States