Recruiting

Vascular Insulin Sensitivity

Sponsor:

University of Virginia

Code:

NCT03894527

Conditions

Metabolic Syndrome

Obesity

Eligibility Criteria

Sex: All

Age: 40 - 70

Healthy Volunteers: Not accepted

Interventions

Single Bout of Exercise

Control Condition

Study Details

Brief summary:

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.

Conditions

Metabolic Syndrome

Obesity

Study ID

NCT03894527

Start date

Feb 18, 2019

Status verified date

Mar, 2019

Completion date

Jan 31, 2020

Anticipated

Primary completion date

Sep 30, 2019

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 40 - 70

Healthy Volunteers: Not accepted

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 Design

Enrollment

16 participants

Anticipated

Allocation

Non randomized

Intervention Model

Crossover

Primary purpose

Prevention

Interventions and Outcome Measures

Arms

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.

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.

Interventions

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.

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.

Primary outcome measure

  • Effect of single bout of exercise on FMD [ Time Frame: Baseline clamp study ]
  • Effect of single bout of exercise on CEU [ Time Frame: Baseline Clamp Study ]
  • Comparison of insulin stimulated FMD response [ Time Frame: Through study completion, up to about 4 weeks ]
  • Comparison of insulin stimulated CEU response [ Time Frame: Through study completion, up to about 4 weeks ]

Central Contacts and Locations

Central contacts

Emily Heiston, M.Ed.

434-243-8677emh5bh@virginia.edu

Locations

University of Virginia

Recruiting

Charlottesville, Virginia, United States, 22904

Contacts

Emily Heiston, M.Ed.

434-243-8677emh5bh@virginia.edu

Stephanie Miller, M.Ed.

434-243-8677slm4ps@virginia.edu

More Information

Sponsor

University of Virginia

Last update posted

Mar 28, 2019

Last verified

Mar, 2019

Keywords

  • Acute Exercise
  • Endothelial Function
  • Simple Obesity
  • Metabolic Syndrome

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Virginia on 2019-03-28.