The Impact of Fitness and Mineralocorticoid Receptor Blockade on Vascular Dysfunction in Adults With Type 1 Diabetes

• Status: Completed
• Trial end date: 2019-05-22
• Target enrollment: 0
• Participant gender: All

Summary

In this protocol, 60 subjects with DM1 will be studied at baseline, after 12 weeks of MCR blockade or 12 weeks of exercise, and again after an additional 12 weeks of MCR blockade, exercise or the combination of both interventions. The investigators will assess function in conduit (pulse wave velocity-PWV, flow-mediated dilation-FMD and augmentation index-AI), resistance (post-ischemic flow velocity-PIFV) and heart and skeletal muscle microvascular (contrast enhanced ultrasound-CEU) vessels before and after 2 hrs of a euglycemic insulin clamp.

We hypothesize that compared to healthy controls, both baseline and insulin-responsive vascular function are impaired throughout the arterial vasculature by DM1 and that exercise training and/or mineralocorticoid receptor (MCR) blockade will improve both baseline and insulin-responsive pan-arterial function.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Virginia
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Treatments: Mineralocorticoids; Spironolactone

Criteria

Inclusion Criteria:

• Age 18-50 years

• BMI ≤30

• No clinically significant lab values other than those consistent with DM1

• Subjects will have been on insulin for at least 5 years and HbA1c <9

Exclusion Criteria:

• Smoking presently or in the past 6 months

• Medications that affect the vasculature (except ACE or ARB , although they will need to be off these drugs for 2 weeks prior to study).

• Elevated LDL cholesterol > 160

• BP <100/60 or >160/90

• Pulse oximetry <90%

• Pregnant or breastfeeding

• History of cardiovascular disease, cerebral vascular disease, peripheral vascular disease, liver disease

• Presence of an intracardiac or intrapulmonary shunt (we will screen for this by auscultation during the physical exam).

• Known hypersensitivity to perflutren (contained in Definity)

• Serum Potassium ≥5.0

• HbA1c ≥ 9

• Retinopathy

• Ketoacidosis within the past year.