Mechanisms by Which Strength Training Ameliorates the Metabolic Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by East Tennessee State University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Charles A. Stuart, East Tennessee State University
ClinicalTrials.gov Identifier:
NCT00727779
First received: July 31, 2008
Last updated: February 25, 2013
Last verified: February 2013
  Purpose

Prevention and treatment strategies for diabetes use exercise as the cornerstone. Even though endurance training and strength training both improve insulin resistance, strength training may be better suited for persons at risk for type 2 diabetes. We will expand our pilot studies of muscle adaptation induced by resistance exercise training to determine the biochemical mechanisms that will cause people with the Metabolic Syndrome to secure major benefit from intense strength training.


Condition Intervention
Metabolic Syndrome
Behavioral: strength training

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Mechanisms by Which Strength Training Ameliorates the Metabolic Syndrome

Resource links provided by NLM:


Further study details as provided by East Tennessee State University:

Primary Outcome Measures:
  • euglycemic clamp steady state glucose infusion rate (clamp GIR) [ Time Frame: pre- post- intervention ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • GLUT4 content of muscle [ Time Frame: pre- post- intervention ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: January 2008
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: metabolic syndrome
intervention is to undergo eight weeks of progressive strength training; metabolic syndrome subjects will have baseline and post-intervention assessments including muscle biopsies and insulin clamps
Behavioral: strength training
eight weeks of progressively increasing resistance training will be done in both groups side-by-side
Active Comparator: control subjects
intervention is to undergo eight weeks of progressive strength training; non-obese sedentary subjects will have the same assessments as the metabolic syndrome subjects and exercise training simultaneously.
Behavioral: strength training
eight weeks of progressively increasing resistance training will be done in both groups side-by-side

Detailed Description:

Life style alterations can be powerful deterrents to developing type 2 diabetes and are cornerstones of the treatment of this condition. Both aerobic and resistance exercise improve diabetes blood glucose control and insulin resistance. These two types of exercise appear to exert their effects on different muscle fiber types - red for endurance and white for strength. Similar to the effects of endurance exercise training, strength training increases muscle glucose transporter isoform 4 (GLUT4), but in contrast, mitochondria numbers do not increase. We hypothesize (1) that strength training in persons with pre-diabetes may be effective in reversing insulin resistance by novel mechanisms that are distinct from the endurance training-induced mitochondrial biogenesis. We further hypothesize (2) that resistance exercise training enhances whole body insulin action primarily by increasing the white fiber size via the protein kinase mammalian target of rapamycin (mTOR) and improves insulin-stimulated glucose uptake by increased GLUT4 expression primarily in white fibers of the trained muscles. In this proposal, we will perform eight weeks of progressive strength training on ten subjects with the Metabolic Syndrome who are at high risk for developing type 2 diabetes and on ten sedentary control subjects. This project builds on our experience with a study of focused resistance training whose results are presented in this application. In this pilot study, subjects exercised on stationary bicycles for six weeks causing muscle GLUT4 and phopho-mTOR to increase substantially, but maximal oxygen uptake (VO2max), phospho-AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ co-activator (PGC-1α), and mitochondrial markers did not change. Our hypotheses will be tested by two Specific Aims. (1) Subjects at high risk for diabetes will undergo progressively increasing intensity resistance exercise training and increased strength and improved insulin responsiveness will both be quantified to demonstrate significant benefit, and (2) quantify the effect of resistance exercise training on anatomic and functional adaptation in muscle. We will characterize fiber type, fiber size, fiber-specific changes in mitochondrial DNA and enzymes, fiber-specific changes in the principle glucose transporters in muscle (GLUT4, GLUT5, and GLUT12), and evaluate changes in two distinct intramuscular pathways (AMPK, mTOR) and regulatory factors (PGC-1α, PPARγ, PPARδ) using immunoblots of muscle subcellular fractions and immunohistochemical techniques. These evaluations of molecular mechanisms will also include assessing changes in full human Affymetrix gene array data that may move us to new potential resistance training-regulated gene targets. It is the long-term goal of this team of investigators to understand the interplay between life style changes and pharmacological agents in the prevention and treatment of diabetes. Our results will facilitate the development of more effective clinical options to turn back the epidemic of obesity and diabetes in the United States.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

obese family history of diabetes

Exclusion Criteria:

non-obese diabetes

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00727779

Contacts
Contact: Charles A Stuart, MD 423-439-6282 stuartc@etsu.edu
Contact: Susan Whitaker, RN 423-439-6282 whitakersa@etsu.edu

Locations
United States, Tennessee
East Tennessee State Univ Recruiting
Johnson City, Tennessee, United States, 37614
Contact: Charles A Stuart, MD         
Contact: Mary Ward, MSN, RN         
Sub-Investigator: Michael H Stone, Ph.D.         
Sub-Investigator: Michael W Ramsey, Ph.D.         
Sponsors and Collaborators
East Tennessee State University
Investigators
Principal Investigator: Charles A Stuart, MD East Tennessee State University, Johnson City, TN
  More Information

Publications:

Responsible Party: Charles A. Stuart, Professor, Internal Medicine, East Tennessee State University
ClinicalTrials.gov Identifier: NCT00727779     History of Changes
Other Study ID Numbers: R15 DK80488, R15DK080488
Study First Received: July 31, 2008
Last Updated: February 25, 2013
Health Authority: United States: Federal Government

Keywords provided by East Tennessee State University:
diabetes, metabolic syndrome, type 2 diabetes

Additional relevant MeSH terms:
Metabolic Syndrome X
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on July 20, 2014