Resistance Training and Cardiometabolic Health

April 14, 2021 updated by: Siddhartha Angadi, Arizona State University
This study will investigate the relationship between resistance training load and repetitions on cardiometabolic outcomes. The primary objective of this clinical trial is to determine whether high load or low load resistance exercise training affects arterial stiffness in overweight or obese men and women. Our secondary objectives are to investigate the effects of high and low load RT on vascular function, cardiac structure, and markers of insulin sensitivity. Finally, we are going to preliminarily explore the effects of resistance training on intestinal bacteria.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

While it has been firmly established that aerobic exercise training is an effective modality for managing cardiometabolic disease risk, the influence of resistance training (RT) is not as well characterized. It is well established that RT improves muscular strength, size, cross sectional area, and bone mineral density. Alterations in muscle fiber type, glycolytic and oxidative enzyme profile, skeletal muscle proteins, and rates of protein synthesis also occur in response to RT and are obtained from skeletal muscle biopsies. Data from quasi-experimental studies suggest that moderate-to-high repetition RT with lower training loads may positively affect skeletal muscle proteins (Glucose Transporter Type 4 (GLUT4), Hexokinase 2 (HK2), and Adenylate kinase 2 (AK2) involved in insulin signaling in non-diabetic, obese men. However, data on high load, low rep RT on these variables is lacking. Thus, we will collect skeletal muscle biopsies to determine if changes in insulin signaling skeletal muscle proteins are present in response to both training with both high and low training loads. There is also a body of evidence suggesting that RT may improve VO2peak values in individuals with low baseline VO2peak values via a possible increase in capillary density, however, results are currently mixed. Low VO2peak values in overweight and obese individuals are positively associated with high risk of cardiovascular and all-cause mortality. Thus, we will measure VO2peak values to determine if (A) starting previously untrained obese individuals with RT can also improve VO2peak and (B) potential changes in VO2peak are load dependent. RT has also been reported to improve insulin sensitivity and central pressure. Additionally, aerobic exercise training may positively influence alterations in the intestinal microbiome, with no currently available evidence on the effects of RT, Although RT has been shown to be beneficial for improving arterial stiffness and insulin sensitivity, most of the available literature is based on protocols prescribing moderate-to-high repetitions and thus lower training loads. Thus, the effects of prescribing higher training loads on the aforementioned variables are not fully understood.

Increased arterial stiffness (as characterized by carotid-femoral pulse wave velocity (PWV) and augmentation index) is a clinical marker for cardiovascular disease and an independent risk factor for adverse cardiovascular events and all-cause mortality. Increased arterial stiffness has is positively associated with insulin resistance and type II diabetes. In the early stages of insulin resistance, peripheral insulin action, which occurs primarily in the skeletal muscle is impaired. This leads to a compensatory increase in insulin release in order to maintain glucose homeostasis, thus leading to hypertrophy of the pancreatic β cells. During the early stages of insulin resistance, fasting glucose levels will remain normal, with hyperglycemia manifesting in the later stages. Chronic hyperinsulinemia and hyperglycemia in turn cause increases in the renin-angiotensin aldosterone system as well expression of the angiotensin type I receptor in vascular tissue, thus stimulating VSMC proliferation, which leads to an increase in arterial stiffness. Chronic hyperglycemia and/or type II diabetes can lead to an increase in the production of advanced glycation end products (AGEs), which are proteins or lipids that become glycated due to exposure to glucose. Excessive production of AGEs can lead to an increase in collagen cross linking in the vascular walls, which thus leads to an increase in arterial stiffness.

Thus, it appears that increases in arterial stiffness occur due to perturbations in pulsatile shear and flow, which leads to abnormal turnover of scaffolding proteins, specifically excessive collagen production, and the proliferation of VSMCs, which results in a stiffer vasculature. This is exacerbated by the insulin resistant and/or hyperglycemic state due to an increase in local activity of the RAAS and expression of angiotensin I receptor activation in the vascular wall and an increase in age production, which leads to an increase in VSMCs and collagen cross-linking, respectively, thus further contributing to the development of a stiffer vasculature. These structural changes can have deleterious downstream consequences that include ischemic heart disease, myocardial infarction, and heart failure.

Current studies on the effects of RT on arterial stiffness have reported mixed results. It has been suggested that training with higher loads may cause greater increases in stiffness than training with lower loads due to greater acute elevations in blood pressure that occur with high load RT. Case control studies have reported that resistance trained young and middle aged non obese men demonstrated higher levels of arterial stiffness when compared to their aged-matched counterparts. Alternative cross-sectional studies reported that muscular strength was inversely related with arterial stiffness. Follow-up randomized control trials (RCT) investigated changes in arterial stiffness after several months of RT in non-obese, resistance training naïve adults. Improvements in central pressure, in the absence of changes in PWV, have been reported in non-diabetic obese adults after 12 weeks of RT but the study lacked an effective control group. Additionally, improvements in insulin sensitivity in non-diabetic obese males after 12 weeks of RT but was not a randomized controlled trial (RCT). Improvements in endothelial function has also been reported after six months of progressive RT that included both moderate and high training loads. This is significant because endothelial dysfunction is a downstream consequence of increased arterial stiffness, and thus an improvement in endothelial function, as measured by relative flow mediated dilation (%FMD), in response to RT is a reflects an improvement in vascular function, which is unlikely to occur in conjunction with an increase in vascular stiffness. To our knowledge, there are no current published RCTs on the effects of high load RT that have measured both arterial stiffness and endothelial function. This study will follow up on previous studies by comparing the effects of two distinct RT protocols (high load vs low load) on arterial stiffness as, measured by PWV and augmentation index, and endothelial function, as measured by %FMD, to a nonexercising control group.

A body of literature exists to suggest that morphological changes of the left ventricle take place in response to resistance training. Case control studies have reported that elite resistance trained athletes demonstrate evidence of left ventricular wall thickening. The increase in left ventricular wall thickness is referred to as concentric hypertrophy, which occurs in response to a chronic increase in afterload. This occurs in the presence of increased arterial stiffness, uncontrolled hypertension, and aortic stenosis, all of which can lead to heart failure (HF). RT induced concentric hypertrophy appears to be a physiological training adaptation, similar to the eccentric hypertrophy that takes place in response to aerobic training, and thus does not appear to be deleterious. Furthermore, current RCTs on the effects of RT on morphological changes of the LV suggest that this adaptation does not always occur or may occur in response to specific training volumes, frequencies, intensities, and/or over a longer training duration. Since the main outcome of this study is arterial stiffness, which is a precursor for concentric hypertrophy of the LV, we will also measure left ventricular wall thickness to see if A) morphological changes in the LV take place and B) if LV morphological changes are influenced by training load.

Thus, it appears that moderate training loads are shown to improve insulin sensitivity in obese individuals. This is significant because insulin resistance is a precursor to increases in arterial stiffness. However, the effects of training with higher loads on insulin sensitivity is a current gap in the literature. It has been previously proposed that high load RT may reduce arterial compliance and/or lead to concentric hypertrophy of the left ventricular walls. However, current evidence suggests that both moderate and high training loads improve endothelial function, without negatively affecting the left ventricular wall. Since endothelial dysfunction is a negative downstream consequence of an increase in arterial stiffness, it is unlikely that it would improve in conjunction with an increase in stiffness. Thus, this study will be the first to measure all of these variables to determine if and how they are influenced by training load.

The intestinal human microbiome is a recent target of interest due to its role in metabolic disease risk. Current evidence reports a link between cardiometabolic diseases and changes in the intestinal microbiota. The effects of exercise training on changes in the intestinal microbiome is also currently under investigation. Evidence in rat models currently suggest that voluntary and controlled aerobic exercise training is associated with favorable changes in the gut microbiome. However, human studies on the effects of exercise on the intestinal microbiome are currently lacking. .

The purpose of this study is to investigate the effects and potential differences between high load and low load RT on arterial stiffness. Based on the above described gaps in the literature the current study will serve as a follow up RCT to previous studies and will further explore the link between RT, arterial stiffness, and insulin sensitivity. From an exploratory stand-point we will examine changes if any in the gut microbiome following resistance training versus control. The proposed study will serve as a follow up RCT to investigate the differences between high load and low load RT on markers of arterial stiffness and insulin sensitivity. This study will also serve as the first RCT to investigate the long-term effects of RT in the intestinal microbiome. Studies investigating the effects of high load/low repetition RT on cardiometabolic biomarkers are currently lacking, with the current body of literature focusing on the effects of moderate and low loads and high repetitions, with limited data on the effects of high load RT.

Study Type

Interventional

Enrollment (Actual)

62

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 Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85004
        • Arizona State University

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

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male and female
  • 18-55 years of age
  • BMI 25-40
  • No recent history of starting a structured exercise program or diet in the last 3 months

Exclusion Criteria:

  • Current smoker and/or recreational drug user
  • Answers "yes" to one or more questions on the Physical Activity Readiness Questionnaire
  • Diagnosed diabetes, heart disease
  • History of anabolic steroid use in the past six months
  • Taking medications for treatment of diabetes, heart disease, and hypertension.
  • Orthopedic or musculoskeletal contraindications to resistance training
  • Unwilling to follow any aspect of the study protocol including blood sampling and weight training

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Resistance Training 1
Participants will perform resistance training with high training loads and low repetitions (high load/low rep resistance training).
Other: High Load/Low Rep Resistance Training
Participants will be prescribed High Load/Low Rep resistance training.
Experimental: Resistance Training 2
Participants will perform resistance training with low training loads and high repetitions (Low load/high rep resistance training).
Other: Low Load/High Rep Resistance Training
Participants will be prescribed Low Load/High Rep resistance training.
No Intervention: Wait-list control
This group will be offered the option of participating in either experimental group after the study is completed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Arterial Stiffness
Time Frame: Change from Baseline Pulse Wave Velocity at 12 weeks
Measured via pulse wave velocity
Change from Baseline Pulse Wave Velocity at 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Insulin Sensitivity
Time Frame: Change from Baseline Matsuda Index at 12 weeks
Measured via oral glucose tolerance testing (OGTT)
Change from Baseline Matsuda Index at 12 weeks
Endothelial Function
Time Frame: Change from Baseline %FMD at 12 weeks
Measured via flow mediated dilation (FMD)
Change from Baseline %FMD at 12 weeks
Cardiac echocardiography
Time Frame: Changes in systolic and diastolic parameters from baseline to 12 weeks
Measured using ultrasound
Changes in systolic and diastolic parameters from baseline to 12 weeks
Isokinetic Strength
Time Frame: Change from Baseline isokinetic strength at 12 weeks
Measured via dynamometry
Change from Baseline isokinetic strength at 12 weeks
Isometric Strength
Time Frame: Change from Baseline Isometric strength at 12 weeks
Measured via dynamometry
Change from Baseline Isometric strength at 12 weeks
Hexokinase
Time Frame: Change from Baseline in insulin signalling proteins at 12 weeks
Measured via skeletal muscle biopsies
Change from Baseline in insulin signalling proteins at 12 weeks
Insulin signaling proteins
Time Frame: Change from Baseline in insulin signaling proteins at 12 weeks
Measured via skeletal muscle biopsies
Change from Baseline in insulin signaling proteins at 12 weeks
Muscle Volume
Time Frame: Change from Baseline Muscle Volume at 12 weeks
Measured via ultrasonography
Change from Baseline Muscle Volume at 12 weeks
Body Composition
Time Frame: Change from Baseline body composition at 12 weeks
Measured via Dual X-Ray Absorptiometry (DXA)
Change from Baseline body composition at 12 weeks
Central Systolic Pressure
Time Frame: Change from Baseline Central Systolic Pressure at 12 weeks
Measured via Pulse Wave Analysis
Change from Baseline Central Systolic Pressure at 12 weeks
Central Diastolic Pressure
Time Frame: Change from Baseline Central Systolic Pressure at 12 weeks
Measured via Pulse Wave Analysis
Change from Baseline Central Systolic Pressure at 12 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximal Oxygen Consumption
Time Frame: Change from Baseline VO2peak at 12 weeks
Measured via VO2peak testing using an integrated metabolic system.
Change from Baseline VO2peak at 12 weeks

Collaborators and Investigators

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

Sponsor

Arizona State University

Investigators

  • Principal Investigator: Siddhartha S Angadi, PhD, Arizona State University

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)

September 21, 2017

Primary Completion (Actual)

August 31, 2020

Study Completion (Actual)

August 31, 2020

Study Registration Dates

First Submitted

October 13, 2017

First Submitted That Met QC Criteria

October 25, 2017

First Posted (Actual)

October 30, 2017

Study Record Updates

Last Update Posted (Actual)

April 19, 2021

Last Update Submitted That Met QC Criteria

April 14, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00006617

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

This data will be used primarily for a doctoral dissertation project as well as manuscript publication.

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.

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