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

NCT03174288

NAINTERVENTIONAL

University of Virginia

32 participants

Started 2015-08 · Completed 2019-05-22

Status: Completed (as of 12-23-2025)

Conditions

Type 1 Diabetes

Interventions

OTHER: Exercise DRUG: Spironolactone

Linked Papers (from SciSciNet-V2)

Total Papers58

Background

11

Result

0

Derived

0

Unknown

47

View on ClinicalTrials.gov

Total Citations Per Year

Brief 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.

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Background Papers22

Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance.

1,695 citations

Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance.

1,695 citations

Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release.

1,200 citations

Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release.

1,200 citations

Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance.

Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance.

Insulin-mediated skeletal muscle vasodilation contributes to both insulin sensitivity and responsiveness in lean humans.

Insulin-mediated skeletal muscle vasodilation contributes to both insulin sensitivity and responsiveness in lean humans.

The vascular actions of insulin control its delivery to muscle and regulate the rate-limiting step in skeletal muscle insulin action

The vascular actions of insulin control its delivery to muscle and regulate the rate-limiting step in skeletal muscle insulin action

Insulin Resistance, Defective Insulin-Mediated Fatty Acid Suppression, and Coronary Artery Calcification in Subjects With and Without Type 1 Diabetes

Insulin Resistance, Defective Insulin-Mediated Fatty Acid Suppression, and Coronary Artery Calcification in Subjects With and Without Type 1 Diabetes

Insulin regulates its own delivery to skeletal muscle by feed-forward actions on the vasculature

Insulin regulates its own delivery to skeletal muscle by feed-forward actions on the vasculature

Obesity Blunts Microvascular Recruitment in Human Forearm Muscle After a Mixed Meal

Obesity Blunts Microvascular Recruitment in Human Forearm Muscle After a Mixed Meal

Arterial Stiffness Is Increased in Patients With Type 1 Diabetes Without Cardiovascular Disease

Arterial Stiffness Is Increased in Patients With Type 1 Diabetes Without Cardiovascular Disease

Salsalate Attenuates Free Fatty Acid–Induced Microvascular and Metabolic Insulin Resistance in Humans

Salsalate Attenuates Free Fatty Acid–Induced Microvascular and Metabolic Insulin Resistance in Humans

Muscle microvascular recruitment predicts insulin sensitivity in middle-aged patients with type 1 diabetes mellitus

Muscle microvascular recruitment predicts insulin sensitivity in middle-aged patients with type 1 diabetes mellitus

Result Papers0

No result papers linked

Derived Papers0

No derived papers linked

Unknown Papers47

The L-Arginine-Nitric Oxide Pathway

6,737 citations

Markers of Inflammation and Cardiovascular Disease

6,067 citations

Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery

4,535 citations

Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial

3,776 citations

Aortic Stiffness Is an Independent Predictor of Primary Coronary Events in Hypertensive Patients

1,728 citations

The clinical implications of endothelial dysfunction

1,709 citations

Nitric Oxide Is Responsible for Flow-Dependent Dilatation of Human Peripheral Conduit Arteries In Vivo

1,632 citations

Assessment of Arterial Distensibility by Automatic Pulse Wave Velocity Measurement

1,354 citations

Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus.

1,102 citations

New Markers of Inflammation and Endothelial Cell Activation

Magnitude and determinants of coronary artery disease in juvenile-onset, insulin-dependent diabetes mellitus

Hemodynamic actions of insulin

Endothelial Function Testing as a Biomarker of Vascular Disease

Endothelial function

Microvascular Recruitment Is an Early Insulin Effect That Regulates Skeletal Muscle Glucose Uptake In Vivo

Impaired vascular reactivity in insulin-dependent diabetes mellitus is related to disease duration and low density lipoprotein cholesterol levels

Microvascular Function Predicts Cardiovascular Events in Primary Prevention

Nitric oxide functions as an inhibitor of platelet adhesion under flow conditions.

Plasma concentration of C-reactive protein is increased in Type I diabetic patients without clinical macroangiopathy and correlates with markers of endothelial dysfunction: evidence for chronic inflammation

Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin

Obesity Blunts Insulin-Mediated Microvascular Recruitment in Human Forearm Muscle

Markers of inflammation are cross-sectionally associated with microvascular complications and cardiovascular disease in type 1 diabetes?the EURODIAB Prospective Complications Study

Report of the National Heart, Lung, and Blood Institute-National Institute of Diabetes and Digestive and Kidney Diseases Working Group on Cardiovascular Complications of Type 1 Diabetes Mellitus

Physiologic Hyperinsulinemia Enhances Human Skeletal Muscle Perfusion by Capillary Recruitment

All-cause mortality rates in patients with type 1 diabetes mellitus compared with a non-diabetic population from the UK general practice research database, 1992–1999

Skeletal Muscle Microvascular Recruitment by Physiological Hyperinsulinemia Precedes Increases in Total Blood Flow

Mixed meal and light exercise each recruit muscle capillaries in healthy humans

Insulin Sensitivity of Muscle Capillary Recruitment In Vivo

Postprandial Myocardial Perfusion in Healthy Subjects and in Type 2 Diabetic Patients

Plasma concentrations of VCAM‐1 and ICAM‐1 are elevated in patients with Type 1 diabetes mellitus with microalbuminuria and overt nephropathy

C-Reactive Protein Inhibits Endothelium-Dependent NO-Mediated Dilation in Coronary Arterioles by Activating p38 Kinase and NAD(P)H Oxidase

Elevated C-Reactive Protein Associates With Early-Stage Carotid Atherosclerosis in Young Subjects With Type 1 Diabetes

Acute vasoconstriction-induced insulin resistance in rat muscle in vivo.

Physical Activity Duration, Intensity, and Arterial Stiffening in Postmenopausal Women

Serum Interleukin-6 Correlates With Endothelial Dysfunction in Healthy Men Independently of Insulin Sensitivity

Hyperinsulinemia Rapidly Increases Human Muscle Microvascular Perfusion but Fails to Increase Muscle Insulin Clearance

Skeletal muscle capillary responses to insulin are abnormal in late-stage diabetes and are restored by angiogensin-converting enzyme inhibition

Contraction Stimulates Nitric Oxide–Independent Microvascular Recruitment and Increases Muscle Insulin Uptake

Endothelial-Dependent Vasodilation and Incidence of Type 2 Diabetes in a Population of Healthy Postmenopausal Women

Effect of Weight Reduction with Dietary Intervention on Arterial Distensibility and Endothelial Function in Obese Men

C-Reactive Protein Inhibits Endothelium-Dependent Nitric Oxide-Mediated Dilation of Retinal Arterioles via Enhanced Superoxide Production

Insulin stimulates laser Doppler signal by rat muscle in vivo, consistent with nutritive flow recruitment

Insulin-Induced Decrease in Large Artery Stiffness Is Impaired in Uncomplicated Type 1 Diabetes Mellitus

Association Between Elevated Serum C-Reactive Protein and Triglyceride Levels in Young Subjects With Type 1 Diabetes

Impaired flow-mediated dilatation response in uncomplicated Type 1 diabetes mellitus: influence of shear stress and microvascular reactivity

High-sensitivity C-reactive protein and impaired coronary vasoreactivity in young men with uncomplicated type 1 diabetes

Can augmentation index substitute aortic pulse wave velocity in the assessment of central arterial stiffness in type 1 diabetes?