Effect of GLP-1 on Microvascular Insulin Responses in Type 1 Diabetes (KML001)

University of Virginia

Status and phase: Withdrawn; Early Phase 1

Conditions: Type 1 Diabetes; Insulin Sensitivity/Resistance

Treatments: Drug: Dextrose 20 % in Water; Drug: Insulin; Drug: GLP-1

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04133922

21590

5R01DK102359-03 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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

Full 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.

Sex: All

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 3 patient groups

GLP-1

Active Comparator group

Description:

GLP-1 infusion 1.2 pmol/kg/min for 150 min

Treatment:

Drug: GLP-1

GLP-1 + Insulin clamp

Active Comparator group

Description:

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

Treatment:

Drug: Insulin

Drug: Dextrose 20 % in Water

Drug: GLP-1

Saline + Insulin clamp

Active Comparator group

Description:

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.

Treatment:

Drug: Insulin

Drug: Dextrose 20 % in Water