Metabolic SyndromeNCT00727779
Mechanisms by Which Strength Training Ameliorates the Metabolic Syndrome
A study testing strength training in people with Metabolic Syndrome, run by East Tennessee State University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Metabolic Syndrome
- What is being tested?
- strength training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2008to Jun 2013
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- obese family history of diabetes
Who cannot join
- non-obese diabetes
Trial locations and contacts
1 site in 1 country.
United States1 site
East Tennessee State Univ
Johnson City, Tennessee, 37614
About this study
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.
Read the 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.
- Conditions
- Metabolic Syndrome
- Being tested
- strength training
- Keywords
- diabetes, metabolic syndrome, type 2 diabetes
- Medical subject headings
- Metabolic Syndrome, Diabetes Mellitus, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
strength trainingBehavioural
eight weeks of progressively increasing resistance training will be done in both groups side-by-side
| Study group | Role | What they receive |
|---|---|---|
| metabolic syndrome | Experimental | 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 Receives: Behavioral: strength training |
| control subjects | Active comparator | 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. Receives: Behavioral: strength training |
What is being measured
The primary outcome is the main question the study is designed to answer.
euglycemic clamp steady state glucose infusion rate (clamp GIR)
Measured: pre- post- intervention
Secondary outcomes (1)
GLUT4 content of muscle
Measured: pre- post- intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2008 (estimated)
- Study startJan 2008
- Primary completionJun 2013
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Metabolic SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- East Tennessee State University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Charles A. Stuart, East Tennessee State University
- Investigators
- Charles A Stuart, MD, Principal investigator, East Tennessee State University, Johnson City, TN
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00727779
- Sponsor's protocol ID
- R15DK080488
- Other IDs
- R15DK080488
- Status last verified
- Feb 2015
- First submitted
- 31 Jul 2008
- Last updated
- 16 Feb 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Stuart CA, Yin D, Howell ME, Dykes RJ, Laffan JJ, Ferrando AA. Hexose transporter mRNAs for GLUT4, GLUT5, and GLUT12 predominate in human muscle. Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E1067-73. doi: 10.1152/ajpendo.00250.2006. Epub 2006 Jun 27.
PubMed 16803853Reeds DN, Stuart CA, Perez O, Klein S. Adipose tissue, hepatic, and skeletal muscle insulin sensitivity in extremely obese subjects with acanthosis nigricans. Metabolism. 2006 Dec;55(12):1658-63. doi: 10.1016/j.metabol.2006.08.006.
PubMed 17142140Stuart CA, Howell ME, Yin D. Overexpression of GLUT5 in diabetic muscle is reversed by pioglitazone. Diabetes Care. 2007 Apr;30(4):925-31. doi: 10.2337/dc06-1788. Epub 2007 Jan 24.
PubMed 17251278Moorman J, Zhang Y, Liu B, LeSage G, Chen Y, Stuart C, Prayther D, Yin D. HIV-1 gp120 primes lymphocytes for opioid-induced, beta-arrestin 2-dependent apoptosis. Biochim Biophys Acta. 2009 Aug;1793(8):1366-71. doi: 10.1016/j.bbamcr.2009.05.007. Epub 2009 May 27.
PubMed 19477204Copland JA, Pardini AW, Wood TG, Yin D, Green A, Bodenburg YH, Urban RJ, Stuart CA. IGF-1 controls GLUT3 expression in muscle via the transcriptional factor Sp1. Biochim Biophys Acta. 2007 Nov-Dec;1769(11-12):631-40. doi: 10.1016/j.bbaexp.2007.08.002. Epub 2007 Sep 4.
PubMed 17920708Layne AS, Nasrallah S, South MA, Howell ME, McCurry MP, Ramsey MW, Stone MH, Stuart CA. Impaired muscle AMPK activation in the metabolic syndrome may attenuate improved insulin action after exercise training. J Clin Endocrinol Metab. 2011 Jun;96(6):1815-26. doi: 10.1210/jc.2010-2532. Epub 2011 Apr 20.
PubMed 21508135Stuart CA, Ross IR, Howell ME, McCurry MP, Wood TG, Ceci JD, Kennel SJ, Wall J. Brain glucose transporter (Glut3) haploinsufficiency does not impair mouse brain glucose uptake. Brain Res. 2011 Apr 12;1384:15-22. doi: 10.1016/j.brainres.2011.02.014.
PubMed 21316350Stuart CA, Howell ME, Cartwright BM, McCurry MP, Lee ML, Ramsey MW, Stone MH. Insulin resistance and muscle insulin receptor substrate-1 serine hyperphosphorylation. Physiol Rep. 2014 Dec 3;2(12):e12236. doi: 10.14814/phy2.12236. Print 2014 Dec 1.
PubMed 25472611Stuart CA, South MA, Lee ML, McCurry MP, Howell ME, Ramsey MW, Stone MH. Insulin responsiveness in metabolic syndrome after eight weeks of cycle training. Med Sci Sports Exerc. 2013 Nov;45(11):2021-9. doi: 10.1249/MSS.0b013e31829a6ce8.
PubMed 23669880Stuart CA, McCurry MP, Marino A, South MA, Howell ME, Layne AS, Ramsey MW, Stone MH. Slow-twitch fiber proportion in skeletal muscle correlates with insulin responsiveness. J Clin Endocrinol Metab. 2013 May;98(5):2027-36. doi: 10.1210/jc.2012-3876. Epub 2013 Mar 20.
PubMed 23515448
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms by Which Strength Training Ameliorates the Metabolic Syndrome
- ClinicalTrials.gov ID
- NCT00727779
- Acronym / sponsor ID
- R15DK080488
- Conditions
- Metabolic Syndrome
- Keywords
- diabetes, metabolic syndrome, type 2 diabetes
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- East Tennessee State UniversityUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Jan 2008
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 4 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| metabolic syndrome | Experimental | Behavioral: strength trainingintervention 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 |
| control subjects | Active comparator | Behavioral: strength trainingintervention 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- obese family history of diabetes
Key exclusion criteria (1 listed)
- non-obese diabetes
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| strength trainingeight weeks of progressively increasing resistance training will be done in both groups side-by-side | Behavioural | control subjects, metabolic syndrome |
Primary outcome
euglycemic clamp steady state glucose infusion rate (clamp GIR)
Time frame: pre- post- intervention
1 secondary outcome
GLUT4 content of muscle
Time frame: pre- post- intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2015.
- Background: PubMed 16803853Stuart CA, Yin D, Howell ME, Dykes RJ, Laffan JJ, Ferrando AA. Hexose transporter mRNAs for GLUT4, GLUT5, and GLUT12 predominate in human muscle. Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E1067-73. doi: 10.1152/ajpendo.00250.2006. Epub 2006 Jun 27.
- Background: PubMed 17142140Reeds DN, Stuart CA, Perez O, Klein S. Adipose tissue, hepatic, and skeletal muscle insulin sensitivity in extremely obese subjects with acanthosis nigricans. Metabolism. 2006 Dec;55(12):1658-63. doi: 10.1016/j.metabol.2006.08.006.
- Background: PubMed 17251278Stuart CA, Howell ME, Yin D. Overexpression of GLUT5 in diabetic muscle is reversed by pioglitazone. Diabetes Care. 2007 Apr;30(4):925-31. doi: 10.2337/dc06-1788. Epub 2007 Jan 24.
- Background: PubMed 19477204Moorman J, Zhang Y, Liu B, LeSage G, Chen Y, Stuart C, Prayther D, Yin D. HIV-1 gp120 primes lymphocytes for opioid-induced, beta-arrestin 2-dependent apoptosis. Biochim Biophys Acta. 2009 Aug;1793(8):1366-71. doi: 10.1016/j.bbamcr.2009.05.007. Epub 2009 May 27.
- Results publication: PubMed 17920708Copland JA, Pardini AW, Wood TG, Yin D, Green A, Bodenburg YH, Urban RJ, Stuart CA. IGF-1 controls GLUT3 expression in muscle via the transcriptional factor Sp1. Biochim Biophys Acta. 2007 Nov-Dec;1769(11-12):631-40. doi: 10.1016/j.bbaexp.2007.08.002. Epub 2007 Sep 4.
- Results publication: PubMed 21508135Layne AS, Nasrallah S, South MA, Howell ME, McCurry MP, Ramsey MW, Stone MH, Stuart CA. Impaired muscle AMPK activation in the metabolic syndrome may attenuate improved insulin action after exercise training. J Clin Endocrinol Metab. 2011 Jun;96(6):1815-26. doi: 10.1210/jc.2010-2532. Epub 2011 Apr 20.
- Results publication: PubMed 21316350Stuart CA, Ross IR, Howell ME, McCurry MP, Wood TG, Ceci JD, Kennel SJ, Wall J. Brain glucose transporter (Glut3) haploinsufficiency does not impair mouse brain glucose uptake. Brain Res. 2011 Apr 12;1384:15-22. doi: 10.1016/j.brainres.2011.02.014.
- Results publication: PubMed 25472611Stuart CA, Howell ME, Cartwright BM, McCurry MP, Lee ML, Ramsey MW, Stone MH. Insulin resistance and muscle insulin receptor substrate-1 serine hyperphosphorylation. Physiol Rep. 2014 Dec 3;2(12):e12236. doi: 10.14814/phy2.12236. Print 2014 Dec 1.
- Results publication: PubMed 23669880Stuart CA, South MA, Lee ML, McCurry MP, Howell ME, Ramsey MW, Stone MH. Insulin responsiveness in metabolic syndrome after eight weeks of cycle training. Med Sci Sports Exerc. 2013 Nov;45(11):2021-9. doi: 10.1249/MSS.0b013e31829a6ce8.
- Results publication: PubMed 23515448Stuart CA, McCurry MP, Marino A, South MA, Howell ME, Layne AS, Ramsey MW, Stone MH. Slow-twitch fiber proportion in skeletal muscle correlates with insulin responsiveness. J Clin Endocrinol Metab. 2013 May;98(5):2027-36. doi: 10.1210/jc.2012-3876. Epub 2013 Mar 20.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charles A Stuart, MD principal investigator
East Tennessee State University, Johnson City, TN
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing strength training in people with Metabolic Syndrome, run by East Tennessee State University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
euglycemic clamp steady state glucose infusion rate (clamp GIR) (time frame: pre- post- intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00727779, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2015.