Impact of Acute Exercise on Vascular Insulin Sensitivity in Metabolic Syndrome

March 26, 2019 updated by: Steven K. Malin, PhD, University of Virginia
Obesity is an independent risk factor for type 2 diabetes and cardiovascular disease. The increased prevalence of obesity worldwide is a major concern among the scientific and medical communities. Insulin resistance is a common factor associated with obesity, metabolic syndrome, hypertension, and type 2 diabetes. Individuals affected by these conditions often experience endothelial dysfunction as well. Insulin resistance provides a key link between metabolic syndrome risk factors and vascular disease. Development of strategies aimed at preventing vascular dysfunction and future disease caused by metabolic disturbances is needed. Although the relationship between obesity and various diseases is well known, the acute effects of insulin on vascular function in obese individuals have yet to be fully determined. Additionally, the effects of acute exercise on insulin-stimulated endothelial function are unknown. Exercise may be an effective and potent treatment that protects against endothelial dysfunction, insulin resistance, and future cardiometabolic disease commonly present with obesity. However, less attention has been placed on vascular insulin sensitivity. The purpose of this study is to test the hypothesis that a single bout of exercise increases insulin-stimulated blood flow at the macro- and micro-vasculature level in obese individuals with metabolic syndrome to similar levels as healthy obese control. Our laboratory has available non-invasive methods to quantify vascular function and the gold-standard technique for assessing insulin sensitivity (euglycemic-hyperinsulinemic clamp). The investigators will assess vascular function (flow-mediated dilation, post-ischemic flow velocity and contrast-enhanced ultrasound) as well as arterial stiffness (augmentation index and pulse wave velocity) before and at the end of the clamp protocol performed the morning following a bout of exercise and a control (no-exercise) condition in 1) metabolic syndrome and 2) obese adults. If our hypothesis is sustained, it will suggest that a key role of the vasculature exists in regulating insulin following exercise and will provide insight into the link between the vasculature, obesity, metabolic syndrome and cardiovascular disease and may confer decreased risk for cardiometabolic disease.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

16

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Virginia
      • Charlottesville, Virginia, United States, 22904
        • Recruiting
        • University of Virginia
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Males and females, ages 40-70 years
  • Never diagnosed with type 2 diabetes and/or cardiovascular disease
  • Not currently engaged in > 60 min/wk of exercise

  • Inclusion criteria specific to health obese vs. metabolic syndrome potential participants:

    • Healthy Obese: (BMI ≥ 30 kg/m2 but ≤ 45 kg/m2) and no other metabolic syndrome risk factors, excluding waist circumference.
    • Metabolic Syndrome: (BMI ≥ 30 kg/m2 but ≤ 45 kg/m2) and must meet at least 3 out of 5 National Cholesterol Education Adult Treatment Panel III Metabolic Syndrome Criteria:

Increased waist circumference (≥102 cm in men; ≥88 cm in women) Elevated triglycerides (≥150 mg/dl) or currently taking medication (Rx) Reduced HDL-cholesterol (<40mg/dl in men, <50 mg/dl in women) or currently taking medication (Rx) High blood pressure (≥130 mmHg systolic or ≥85mmHg diastolic) or currently taking medication (Rx) Elevated fasting glucose (≥100 mg/dl)

Subject may participate if on the following drugs:

  • Diuretics, ace-inhibitors and ARBs for treatment of hypertension
  • Statins

Exclusion Criteria:

  • Morbidly obese patients (BMI >45 kg/m2) and overweight/lean patients (BMI <30 kg/m2).
  • Subjects who have not been weight stable (>2kg weight change in past 3 months).
  • Currently participating in a regular exercise training program ( >30 min. of physical activity per day, >2 days/week)
  • Medication or food supplement that is known to affect insulin sensitivity or endothelial function (TZDs, sulfonylureas, biguanides, alpha-glucosidase inhibitors, phosphodiesterase inhibitors, beta-blockers, alpha-blockers, fibrates, glucocorticoids, fish oil, allopurinol)
  • Subjects with abnormal estimated glomerular filtration rate (eGFR).
  • Hypertriglyceridemic (>400 mg/dl) subjects.
  • Hypertensive (>160/100 mmHg)
  • Subjects taking vasoactive medications also known to affect heart rate and rhythm (i.e. Ca++ channel blockers, nitrates, alpha- or beta-blockers).
  • Subjects with a history of significant metabolic, cardiac, congestive heart failure, cerebrovascular, hematological, pulmonary, gastrointestinal, liver, renal, or endocrine disease or cancer that in the investigator's opinion would interfere with or alter the outcome measures, or impact subject safety.
  • Smoking presently or in the past 1 year.
  • HbA1c ≥ 6.5
  • Subjects currently taking Metformin or any active weight suppression medication (e.g. phentermine, orlistat, lorcaserin, naltrexone-bupropion in combination, liraglutide, benzphetamine, diethylpropion, phendimetrazine)
  • Pregnant (as evidenced by positive pregnancy test) or breastfeeding
  • Subjects with contraindications to participation in an exercise program
  • Known hypersensitivity to perflutren (contained in Definity)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Control

Subjects with simple obesity will complete 2 different testing conditions in a counterbalanced order with at least one week between conditions.

10-12 hrs post test condition the subject will report for a Euglycemic-Hyperinsulinemic clamp study, where Flow Mediated Dilation (FMD) and Contrast Enhanced Ultrasound (CEU) will be performed.
Behavioral: Single Bout of Exercise
An exercise condition, which will be walking at a moderate intensity (~70% VO2peak). Time will vary based upon individual fitness levels to burn ~400kcals (estimated 0.5 - 1hr). Oxygen consumption will be measured during exercise via a metabolic cart to confirm energy expenditure. Participants will then rest following the exercise procedure for 20 minutes. Between 20 and 45 minutes following exercise, oxygen consumption will be measured to understand and capture excess post-exercise oxygen consumption (EPOC). Following this, participants will be provided with a standardize dinner and snack to consume in the AMP lab.
Behavioral: Control Condition
A control (no-exercise) condition. Participants will report to the AMP lab to rest for the same duration as the exercise bout and consume the standardized dinner and snack.
Active Comparator: Metabolic Syndrome

Subjects with metabolic syndrome will complete 2 different testing conditions in a counterbalanced order with at least one week between conditions.

10-12 hrs post test condition the subject will report for a Euglycemic-Hyperinsulinemic clamp study, where Flow Mediated Dilation (FMD) and Contrast Enhanced Ultrasound (CEU) will be performed.
Behavioral: Single Bout of Exercise
An exercise condition, which will be walking at a moderate intensity (~70% VO2peak). Time will vary based upon individual fitness levels to burn ~400kcals (estimated 0.5 - 1hr). Oxygen consumption will be measured during exercise via a metabolic cart to confirm energy expenditure. Participants will then rest following the exercise procedure for 20 minutes. Between 20 and 45 minutes following exercise, oxygen consumption will be measured to understand and capture excess post-exercise oxygen consumption (EPOC). Following this, participants will be provided with a standardize dinner and snack to consume in the AMP lab.
Behavioral: Control Condition
A control (no-exercise) condition. Participants will report to the AMP lab to rest for the same duration as the exercise bout and consume the standardized dinner and snack.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of single bout of exercise on FMD
Time Frame: Baseline clamp study
Flow Mediated Dilation (FMD) as a percentage
Baseline clamp study
Effect of single bout of exercise on CEU
Time Frame: Baseline Clamp Study
Contrast Enhanced Ultrasound (CEU) as a percentage
Baseline Clamp Study
Comparison of insulin stimulated FMD response
Time Frame: Through study completion, up to about 4 weeks
Flow mediated dilation as a percentage of fasting values
Through study completion, up to about 4 weeks
Comparison of insulin stimulated CEU response
Time Frame: Through study completion, up to about 4 weeks
Contrast Enhanced Ultrasound (CEU) as a percentage of fasting values
Through study completion, up to about 4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Systemic Arterial stiffness
Time Frame: Through study completion, up to about 4 weeks
Augmentation Index as a percentage
Through study completion, up to about 4 weeks
Central Arterial Stiffness
Time Frame: Through study completion, up to about 4 weeks
Pulse wave velocity in m/s
Through study completion, up to about 4 weeks
Metabolic Flexibility
Time Frame: Through study completion, up to about 4 weeks
Respiratory gases in fasted and insulin-stimulated states in arbitrary units
Through study completion, up to about 4 weeks
Fasting glucose
Time Frame: Through study completion, up to about 4 weeks
Comparison of glucose collected at baseline in mg/dl
Through study completion, up to about 4 weeks
Fasting insulin
Time Frame: Through study completion, up to about 4 weeks
Comparison of insulin collected at baseline in uU/ml
Through study completion, up to about 4 weeks
Free Fatty Acids
Time Frame: Through study completion, up to about 4 weeks
Comparison of free fatty acids collected at baseline in mEq/L
Through study completion, up to about 4 weeks
Adiponectin
Time Frame: Through study completion, up to about 4 weeks
Comparison of inflammatory in ng/ml
Through study completion, up to about 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Virginia

Collaborators

American College of Sports Medicine

Investigators

  • Principal Investigator: Steve Malin, PhD, University of Virginia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 18, 2019

Primary Completion (Anticipated)

September 30, 2019

Study Completion (Anticipated)

January 31, 2020

Study Registration Dates

First Submitted

March 5, 2019

First Submitted That Met QC Criteria

March 26, 2019

First Posted (Actual)

March 28, 2019

Study Record Updates

Last Update Posted (Actual)

March 28, 2019

Last Update Submitted That Met QC Criteria

March 26, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 19060

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Obesity

Clinical Trials on Single Bout of Exercise

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Hungary

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe