Impact of Acute Exercise on Vascular Insulin Sensitivity in Metabolic Syndrome

NCT ID: NCT03894527

Last Updated: 2019-03-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-02-18

Study Completion Date

2020-01-31

Brief Summary

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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.

Detailed Description

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Conditions

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Metabolic Syndrome Obesity

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Single Bout of Exercise

Intervention Type BEHAVIORAL

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.

Control Condition

Intervention Type BEHAVIORAL

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.

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.

Group Type ACTIVE_COMPARATOR

Single Bout of Exercise

Intervention Type BEHAVIORAL

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.

Control Condition

Intervention Type BEHAVIORAL

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.

Interventions

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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.

Intervention Type 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.

Intervention Type BEHAVIORAL

Eligibility Criteria

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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

* 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)
Minimum Eligible Age

40 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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American College of Sports Medicine

OTHER

Sponsor Role collaborator

University of Virginia

OTHER

Sponsor Role lead

Responsible Party

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Steven K. Malin, PhD

Assitant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Steve Malin, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

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University of Virginia

Charlottesville, Virginia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Emily Heiston, M.Ed.

Role: CONTACT

434-243-8677

Facility Contacts

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Emily Heiston, M.Ed.

Role: primary

434-243-8677

Stephanie Miller, M.Ed.

Role: backup

434-243-8677

References

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Other Identifiers

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19060

Identifier Type: -

Identifier Source: org_study_id

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