Type 2 Diabetes MellitusSHELLNCT00766298
Skeletal Muscle Lipid and Insulin Resistance: Effects of Physical Activity and Weight Loss
A study testing Exercise, Weight Loss and Exercise and weight loss in people with Type 2 Diabetes Mellitus, run by University of Pittsburgh at 1 site in United States.
Trial summary
102 late- life adults at risk for developing type 2 diabetes mellitus, will be randomized to one of three interventions designed to improve insulin sensitivity thereby potentially preventing future progression of type 2 diabetes. Read more about this study
- Who is it for?
- Ages 60 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- Exercise, Weight Loss and Exercise and weight loss
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2004to Aug 2011
- 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 60 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 60-75 years of age
- Stable weight (No Gain/Loss of > 10 lbs in 6 months)
- Impaired Glucose Tolerance or Newly, untreated, undiagnosed type 2 diabetes
- Sedentary
- Non-smoker
- BMI 25.0-38.0 KG/M2
Show all 10Show fewer
- Resting Blood Pressure ≤ 150mmHg systolic and ≤ 95 mmHg diastolic
- IGT: Fasting Glucose > 100, < 126 2-Hour OGTT > 140 but < 200
- T2D: Fasting Glucose > 126 < 2000 2-Hour OGTT > 200
- Note from PCP/Cardiologist for exercise clearance if positive stress test symptoms were observed from GXT
Who cannot join
- Clinically significant CVD including h/o MI
- Peripheral Vascular Disease
- Hepatic, renal, muscular/neuromuscular, or active hematologic/oncologic disease
- Clinically diminished pulse
- Presence of bruits in lower extremities
- Previous history of pulmonary emboli
Show all 26Show fewer
- Peripheral Neuropathy
- Currently not engaged in a regular program and have a VO2 max pre-training value > 55 ml/kg-fat free mass-min., indicative of moderate fitness.
- Anemia (Hematocrit < 34%)
- Any contraindications to moderate exercise (Please specify)
- Inability and/ or unwillingness to comply with the protocol as written
- Active alcohol or substance abuse (Past 5 Years)
- Total cholesterol > 300 mg/dL
- Triglyceride > 350 mg/dL
- ALT > 80, AST > 80, Alk Phos > 240
- Proteinuria (defined as >1 + on routine dipstick), hypothyroidism (sTSH>8)
- Therapeutic Doses of Nicotinic Acid
- Oral glucocorticoids
- Females currently on hormone replacement therapy (HRT) less than 6 months
- Claustrophobia
- Previous difficulty with lidocaine or other local anesthetic
- Stress test symptoms:
- Positive ECG (> 2mm ST segment depression) without PCP cardiologist permission to participate
- Signs or symptoms of cardiovascular decomposition (hypotensive response to exercise)
- Onset of angina or angina like symptoms, shortness of breath, change in heart rhythm, signs of poor perfusion (light-headedness), tightness,
- Hypotension
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
102 late- life adults at risk for developing type 2 diabetes mellitus, will be randomized to one of three interventions designed to improve insulin sensitivity thereby potentially preventing future progression of type 2 diabetes. The investigators predict that insulin sensitivity will improve equally following either weight loss or exercise, while there will be additive effects from combined intervention.
The investigators hypothesize that weight loss will decrease intermuscular adipose tissue, intramyocellular lipid, and visceral abdominal adipose tissue.
Read the detailed description
The primary objective of this project will be to examine the role of skeletal muscle lipid and capacity for fat oxidation in insulin resistance in older adults who either are at high risk for the development of type 2 diabetes mellitus (T2DM) or who are untreated newly diagnosed T2DM. A randomized intervention trial will be conducted to examine the effects of physical activity and weight loss, alone or in combination, on intramyocellular lipid (IMCL), intermuscular adipose tissue (IMAT) and abdominal AT (adipose tissue), oxidative capacity and insulin resistance.
The first aim is to examine the effects of weight loss without exercise on AT distribution, intramyocellular lipid (IMCL) and oxidative capacity of skeletal muscle in conjunction with improvements in insulin sensitivity. We will test the hypotheses that weight loss without exercise will: 1) Improve insulin sensitivity, decrease the lipid interspersed within muscle (intermuscular AT), intramyocellular lipid (IMCL), as well as visceral abdominal AT (VAT); and 2) Will have no effects on either skeletal muscle oxidative capacity determined in vitro or in vivo.
A second aim is to examine the effects of exercise without weight loss on AT, IMCL, oxidative capacity and insulin resistance. We will test the hypotheses that exercise without weight loss will: 1) Increase the oxidative enzyme capacity of muscle; 2) Increase IMCL despite having little effect on AT distribution within muscle (intermuscular AT) or visceral AT; 3) Improve insulin sensitivity to a similar degree as weight loss without exercise.
A third aim will be to examine the combined effects of exercise and weight loss on insulin resistance. Our third hypotheses are that combining weight loss and exercise will 1) Decrease IMAT, VAT and have little overall effect on IMCL 2) Improve the oxidative capacity of skeletal muscle; 3) Confer synergistic improvements in insulin sensitivity through the combined actions on AT and skeletal muscle capacity for oxidation.
A fourth aim will be to examine the combined effects of exercise and weight loss on subjects with newly diagnosed but untreated T2DM. Our final hypotheses are that exercise and weight loss will have similar effects in subjects with newly diagnosed T2DM compared to those at risk for developing T2DM with regards to improved insulin sensitivity, body composition and oxidative capacity of skeletal muscle.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- Exercise, Weight Loss, Exercise and weight loss
- Keywords
- Exercise, Weight Loss, Physical Activity, Type 2 Diabetes Mellitus
- Medical subject headings
- Diabetes Mellitus, Type 2, Motor Activity, Weight Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExerciseBehavioural
16 week intervention; 6 exercise sessions weekly w 3 supervised exercise sessions weekly utilizing cycling or walking/jogging. Participants maintain exercise diaries: wks 1-4; 30 minutes at 60-70% MHR, wks 5-8; 40 minutes at 60-70% MHR, weeks 9-16; 40 minutes at 75% MHR
Weight LossBehavioural
The reduction of kcal/day through implementation of low fat diet
Exercise and weight lossBehavioural
Exercise: 16 week intervention; 6 exercise sessions weekly w 3 supervised exercise sessions weekly utilizing cycling or walking/jogging. Participants maintain exercise diaries: wks 1-4; 30 minutes at 60-70% MHR, wks 5-8; 40 minutes at 60-70% MHR, weeks 9-16; 40 minutes at 75% MHR.
Weight Loss: Reduction of kcal/day through implementation of a low fat diet.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Weight Loss Receives: Behavioral: Weight Loss |
| 2 | Experimental | Exercise Receives: Behavioral: Exercise |
| 3 | Experimental | Exercise and Weight Loss Receives: Behavioral: Exercise and weight loss |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effects of physical activity and weight loss, alone or in combination, on intramyocellular lipid, intermuscular adipose tissue and abdominal AT, oxidative capacity and insulin resistance.
Measured: 16 weeks
Secondary outcomes (1)
Assess the mechanisms by which these interventions may prevent the development of diabetes
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2008 (estimated)
- Study startJun 2004
- Primary completionAug 2011
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- American Diabetes Association
- Responsible party
- Principal investigator, Bret Goodpaster, University of Pittsburgh
- Investigators
- Bret H Goodpaster, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00766298
- Sponsor's protocol ID
- 0406003
- Acronym
- SHELL
- Status last verified
- Jul 2017
- First submitted
- 2 Oct 2008
- Last updated
- 31 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Amati F, Dube JJ, Coen PM, Stefanovic-Racic M, Toledo FG, Goodpaster BH. Physical inactivity and obesity underlie the insulin resistance of aging. Diabetes Care. 2009 Aug;32(8):1547-9. doi: 10.2337/dc09-0267. Epub 2009 Apr 28.
PubMed 19401446Amati F, Dube JJ, Shay C, Goodpaster BH. Separate and combined effects of exercise training and weight loss on exercise efficiency and substrate oxidation. J Appl Physiol (1985). 2008 Sep;105(3):825-31. doi: 10.1152/japplphysiol.90384.2008. Epub 2008 Jul 10.
PubMed 18617627Amati F, Dube JJ, Stefanovic-Racic M, Toledo FG, Goodpaster BH. Improvements in insulin sensitivity are blunted by subclinical hypothyroidism. Med Sci Sports Exerc. 2009 Feb;41(2):265-9. doi: 10.1249/MSS.0b013e318187c010.
PubMed 19127201Amati F, Pennant M, Azuma K, Dube JJ, Toledo FG, Rossi AP, Kelley DE, Goodpaster BH. Lower thigh subcutaneous and higher visceral abdominal adipose tissue content both contribute to insulin resistance. Obesity (Silver Spring). 2012 May;20(5):1115-7. doi: 10.1038/oby.2011.401. Epub 2012 Jan 19.
PubMed 22262160Menshikova EV, Ritov VB, Fairfull L, Ferrell RE, Kelley DE, Goodpaster BH. Effects of exercise on mitochondrial content and function in aging human skeletal muscle. J Gerontol A Biol Sci Med Sci. 2006 Jun;61(6):534-40. doi: 10.1093/gerona/61.6.534.
PubMed 16799133Dube JJ, Amati F, Toledo FG, Stefanovic-Racic M, Rossi A, Coen P, Goodpaster BH. Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide. Diabetologia. 2011 May;54(5):1147-56. doi: 10.1007/s00125-011-2065-0. Epub 2011 Feb 17.
PubMed 21327867
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Skeletal Muscle Lipid and Insulin Resistance: Effects of Physical Activity and Weight Loss
- ClinicalTrials.gov ID
- NCT00766298
- Acronym / sponsor ID
- SHELL / 0406003
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- Exercise, Weight Loss, Physical Activity, Type 2 Diabetes Mellitus
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- American Diabetes Association
- Study start
- Jun 2004
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 3 Oct 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.
102 late- life adults at risk for developing type 2 diabetes mellitus, will be randomized to one of three interventions designed to improve insulin sensitivity thereby potentially preventing future progression of type 2 diabetes. The investigators predict that insulin sensitivity will improve equally following either weight loss or exercise, while there will be additive effects from combined intervention.
The investigators hypothesize that weight loss will decrease intermuscular adipose tissue, intramyocellular lipid, and visceral abdominal adipose tissue.
Detailed description
The primary objective of this project will be to examine the role of skeletal muscle lipid and capacity for fat oxidation in insulin resistance in older adults who either are at high risk for the development of type 2 diabetes mellitus (T2DM) or who are untreated newly diagnosed T2DM. A randomized intervention trial will be conducted to examine the effects of physical activity and weight loss, alone or in combination, on intramyocellular lipid (IMCL), intermuscular adipose tissue (IMAT) and abdominal AT (adipose tissue), oxidative capacity and insulin resistance.
The first aim is to examine the effects of weight loss without exercise on AT distribution, intramyocellular lipid (IMCL) and oxidative capacity of skeletal muscle in conjunction with improvements in insulin sensitivity. We will test the hypotheses that weight loss without exercise will: 1) Improve insulin sensitivity, decrease the lipid interspersed within muscle (intermuscular AT), intramyocellular lipid (IMCL), as well as visceral abdominal AT (VAT); and 2) Will have no effects on either skeletal muscle oxidative capacity determined in vitro or in vivo.
A second aim is to examine the effects of exercise without weight loss on AT, IMCL, oxidative capacity and insulin resistance. We will test the hypotheses that exercise without weight loss will: 1) Increase the oxidative enzyme capacity of muscle; 2) Increase IMCL despite having little effect on AT distribution within muscle (intermuscular AT) or visceral AT; 3) Improve insulin sensitivity to a similar degree as weight loss without exercise.
A third aim will be to examine the combined effects of exercise and weight loss on insulin resistance. Our third hypotheses are that combining weight loss and exercise will 1) Decrease IMAT, VAT and have little overall effect on IMCL 2) Improve the oxidative capacity of skeletal muscle; 3) Confer synergistic improvements in insulin sensitivity through the combined actions on AT and skeletal muscle capacity for oxidation.
A fourth aim will be to examine the combined effects of exercise and weight loss on subjects with newly diagnosed but untreated T2DM. Our final hypotheses are that exercise and weight loss will have similar effects in subjects with newly diagnosed T2DM compared to those at risk for developing T2DM with regards to improved insulin sensitivity, body composition and oxidative capacity of skeletal muscle.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Behavioral: Weight LossWeight Loss |
| 2 | Experimental | Behavioral: ExerciseExercise |
| 3 | Experimental | Behavioral: Exercise and weight lossExercise and Weight Loss |
Who may qualify
- Ages
- 60 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 60-75 years of age
- Stable weight (No Gain/Loss of > 10 lbs in 6 months)
- Impaired Glucose Tolerance or Newly, untreated, undiagnosed type 2 diabetes
- Sedentary
- Non-smoker
Key exclusion criteria (26 listed)
- Clinically significant CVD including h/o MI
- Peripheral Vascular Disease
- Hepatic, renal, muscular/neuromuscular, or active hematologic/oncologic disease
- Clinically diminished pulse
- Presence of bruits in lower extremities
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 |
|---|---|---|
| Exercise16 week intervention; 6 exercise sessions weekly w 3 supervised exercise sessions weekly utilizing cycling or walking/jogging. Participants maintain exercise diaries: wks 1-4; 30 minutes at 60-70% MHR, wks 5-8; 40 minutes at 60-70% MHR, weeks 9-16; 40 minutes at 75% MHR | Behavioural | 2 |
| Weight LossThe reduction of kcal/day through implementation of low fat diet | Behavioural | 1 |
| Exercise and weight lossExercise: 16 week intervention; 6 exercise sessions weekly w 3 supervised exercise sessions weekly utilizing cycling or walking/jogging. Participants maintain exercise diaries: wks 1-4; 30 minutes at 60-70% MHR, wks 5-8; 40 minutes at 60-70% MHR, weeks 9-16; 40 minutes at 75% MHR. Weight Loss: Reduction of kcal/day through implementation of a low fat diet. | Behavioural | 3 |
Primary outcome
Effects of physical activity and weight loss, alone or in combination, on intramyocellular lipid, intermuscular adipose tissue and abdominal AT, oxidative capacity and insulin resistance.
Time frame: 16 weeks
1 secondary outcome
Assess the mechanisms by which these interventions may prevent the development of diabetes
Time frame: 16 weeks
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 31 Jul 2017.
- Results publication: PubMed 19401446Amati F, Dube JJ, Coen PM, Stefanovic-Racic M, Toledo FG, Goodpaster BH. Physical inactivity and obesity underlie the insulin resistance of aging. Diabetes Care. 2009 Aug;32(8):1547-9. doi: 10.2337/dc09-0267. Epub 2009 Apr 28.
- Results publication: PubMed 18617627Amati F, Dube JJ, Shay C, Goodpaster BH. Separate and combined effects of exercise training and weight loss on exercise efficiency and substrate oxidation. J Appl Physiol (1985). 2008 Sep;105(3):825-31. doi: 10.1152/japplphysiol.90384.2008. Epub 2008 Jul 10.
- Results publication: PubMed 19127201Amati F, Dube JJ, Stefanovic-Racic M, Toledo FG, Goodpaster BH. Improvements in insulin sensitivity are blunted by subclinical hypothyroidism. Med Sci Sports Exerc. 2009 Feb;41(2):265-9. doi: 10.1249/MSS.0b013e318187c010.
- Results publication: PubMed 22262160Amati F, Pennant M, Azuma K, Dube JJ, Toledo FG, Rossi AP, Kelley DE, Goodpaster BH. Lower thigh subcutaneous and higher visceral abdominal adipose tissue content both contribute to insulin resistance. Obesity (Silver Spring). 2012 May;20(5):1115-7. doi: 10.1038/oby.2011.401. Epub 2012 Jan 19.
- Results publication: PubMed 16799133Menshikova EV, Ritov VB, Fairfull L, Ferrell RE, Kelley DE, Goodpaster BH. Effects of exercise on mitochondrial content and function in aging human skeletal muscle. J Gerontol A Biol Sci Med Sci. 2006 Jun;61(6):534-40. doi: 10.1093/gerona/61.6.534.
- Derived from this study: PubMed 21327867Dube JJ, Amati F, Toledo FG, Stefanovic-Racic M, Rossi A, Coen P, Goodpaster BH. Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide. Diabetologia. 2011 May;54(5):1147-56. doi: 10.1007/s00125-011-2065-0. Epub 2011 Feb 17.
- Individual participant dataSharing planned: No
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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.
Bret H Goodpaster, PhD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exercise, Weight Loss and Exercise and weight loss in people with Type 2 Diabetes Mellitus, run by University of Pittsburgh 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 10 inclusion and 26 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 31 Jul 2017. 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?
Effects of physical activity and weight loss, alone or in combination, on intramyocellular lipid, intermuscular adipose tissue and abdominal AT, oxidative capacity and insulin resistance. (time frame: 16 weeks). 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 NCT00766298, which also lists 6 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 31 Jul 2017.