Therapeutic Strategies for Microvascular Dysfunction in Type 1 Diabetes
- Conditions
- Diabetes Mellitus, Type 1Endothelial Dysfunction
- Interventions
- Registration Number
- NCT05478707
- Lead Sponsor
- University of Virginia
- Brief Summary
The investigators will test the hypothesis that, in adults with type 1 diabetes (T1D), glucagon-like peptide-1 receptor agonism (GLP-1RA, i.e. dulaglutide) and exercise training each enhance insulin-mediated skeletal muscle microvascular perfusion via attenuating endothelial oxidative stress and thereby improving endothelial function.
- Detailed Description
In this study, 64 (n=48 needed to complete) adult participants with type 1 diabetes will be randomized (1:1:1) to 14-weeks of one of 3 interventions: 1) dulaglutide, 2) placebo, or 3) exercise training.
Participants will undergo two study admissions at baseline and 14 weeks. Prior to each admission, participants will wear a continuous glucose monitor (Dexcom G6 Professional) for 10 days to assess glycemic variability (GV). Prior to admissions, they will undergo cardiorespiratory fitness testing. On study admission days, participants will undergo an antecubital vein endothelial cell biopsy prior to commencing vascular testing. From the harvested endothelial cells, the investigators will quantify endothelial cell reactive oxygen species (ROS) and protein expression relevant to insulin-mediated endothelial function. Vascular testing will include contrast enhanced ultrasound of quadriceps muscle to determine microvascular blood volume (MBV). The investigators will also measure brachial artery flow mediated dilation (FMD). Quadriceps skeletal muscle oxygenation (HHb) will also be measured. These vascular and muscle oxygenation measurements will be conducted before and after a 120-minute euglycemic insulin clamp which will measure insulin sensitivity based on glucose infusion rate (GIR).
This randomized, placebo-controlled study will assess whether GLP-1 receptor agonism with dulaglutide or exercise training improves insulin-mediated skeletal muscle microvascular perfusion. The investigators will assess for predictive relationships between microvascular perfusion and cardiorespiratory fitness (VO2max), insulin sensitivity (GIR), endothelial reactive oxygen species (ROS), and glycemic variability (GV).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 64
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Exercise training exercise training Supervised high intensity interval training on a stationary bicycle will be conducted 3 days per week for 14 weeks. Participants will warm up at low intensity for 3 min then repeat 1-min bouts of 100% peak power output followed by 1-min recovery at 50 W. Training will start with 6 intervals per session, increasing by 2 intervals every 2 weeks. Sessions will end with a 10-min cool-down. Placebo Placebo Saline subcutaneous injection, volume matched to dulaglutide, i.e. 0.5 mL weekly for 14 weeks Dulaglutide Dulaglutide Dulaglutide (0.75 mg/0.5 mL weekly for 2 weeks, then 1.5 mg/0.5 mL weekly for 12 weeks) subcutaneous injection
- Primary Outcome Measures
Name Time Method Microvascular blood volume (MBV) At baseline and after 14 weeks of treatment. Insulin mediated change in muscle microvascular blood volume (MBV). A measure of microvascular nitric oxide dependent endothelial function
- Secondary Outcome Measures
Name Time Method Brachial artery flow mediated dilation (FMD) At baseline and after 14 weeks of treatment Post-occlusive percent (%) change in diameter. A measure of conduit artery nitric oxide-dependent endothelial function.
Glucose infusion rate (GIR) At baseline and after 14 weeks of treatment Mean GIR over the final 30 minutes of euglycemic insulin clamp; a measure of insulin sensitivity
Cardiorespiratory fitness, maximum consumption of oxygen (VO2max) At baseline and after 14 weeks of treatment Assessed by cycle ergometer exercise testing.
Skeletal muscle oxygenation, deoxyhemoglobin (HHb) At baseline and after 14 weeks of treatment. Measured before and after insulin clamp. Assessed by frequency domain multi-distance near-infrared spectroscopy (NIRS) monitor at the quadriceps muscle
Trial Locations
- Locations (1)
University of Virginia
🇺🇸Charlottesville, Virginia, United States