Type 2 Diabetes MellitusNCT03419195
Cardiovascular Mechanisms of Exercise Intolerance in Diabetes and the Role of Sex
A study testing Cardiovascular exercise training in people with Type 2 Diabetes Mellitus and Healthy, run by University of Colorado, Denver at 1 site in United States.
Trial summary
This study will define the relationship of cardiac, vascular function and skeletal muscle blood flow (individually and together) to cardiovascular exercise capacity in in men and women with and without type 2 diabetes (T2DM). Read more about this study
- Who is it for?
- Ages 30 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes Mellitus, Healthy, Overweight
- What is being tested?
- Cardiovascular exercise training
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 124 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Feb 2018to 20 Mar 2023
- 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 30 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men and women with and without type 2 diabetes
- BMI 25-40
- Sedentary subjects not participating in a regular exercise program (<one bout of exercise/week)
Who cannot join
- Documented cardiovascular disease
- Uncontrolled hypertension: disease systolic blood pressure (SBP) > 150, diastolic blood pressure (DBP)> 110
- Obstructive pulmonary disease or asthma
- Peripheral neuropathy
- Physical impairment that would limit exercise ability
- Subjects taking beta blockers, calcium channel blockers, insulin, or Thiazolidinediones (TZD)
Show all 15Show fewer
- Current or past smoking within the last 1 years
- Current tobacco use
- Anemia
- Control HbA1c > 5.7, T2DM HbA1c > 9
- Pregnant, nursing or hormonal therapy (other than contraceptives)
- Peri or post-menopausal women
- Type 1 diabetes
- Hepatic or renal disease.
- Peptic ulcer disease.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado, Anschutz Medical Campus
Aurora, Colorado, 80045
About this study
This study will define the relationship of cardiac, vascular function and skeletal muscle blood flow (individually and together) to cardiovascular exercise capacity in in men and women with and without type 2 diabetes (T2DM). Identification of differences in the effects of exercise training on the integrated cardiovascular system and metabolism in men and women with and without T2DM will reveal specific adaptive responses to exercise.This study will evaluate \& compare exercise function in a total of 60 subjects from the Denver area (30 people with T2DM and 30 overweight control subjects).
Specific Aim 1: To test the hypothesis that the integration of cardiac function, macrovascular function, and microvascular function is impaired in T2D and correlates with cardiovascular exercise capacity (CVEC) impairment.
Read more
Specific Aim 2: To test the hypothesis that exercise training will elicit adaptive responses in cardiac and vascular function, muscle perfusion and metabolism with differences by T2D status.
Differences between the exercise responses in people with T2DM and healthy people will help further identify the disease process of T2DM and direct future research of treatments and interventions.
Read the detailed description
It is well established that functional exercise capacity and peak oxygen uptake (VO2) are reduced in patients with type 2 diabetes mellitus (T2DM) compared with healthy counterparts. The mechanisms underlying the exercise deficit in T2DM remain largely unknown, but previous work has suggested that reduced exercise blood flow and impaired submaximal VO2 may be contributing factors. Both of these findings are consistent with a peripheral impairment of skeletal muscle oxygen delivery, oxygen utilization, or both. Indeed, dysfunction of skeletal muscle metabolism plays a key role in the pathophysiology of T2DM, and considerable work has described abnormalities of oxidative function in the skeletal muscle of people with T2DM. Given this, it is likely that the causes of exercise intolerance in T2DM may relate to specific defects at the level of the skeletal muscle, particularly given that skeletal muscle blood flow and oxidative capacity are impaired in diabetes. However, to the knowledge of the investigators, no one has related these peripheral muscle abnormalities to the diminished exercise function in this patient group.
The overarching hypothesis for the proposed research is that impaired CVEC in T2DM is the result of preclinical cardiac, vascular dysfunction and skeletal muscle perfusion abnormalities. Exercise training will improve CVEC and will reveal specific reversible therapeutic aspects of this pathology. The investigators will first determine the impairments and then evaluate responses to an established cardiac rehabilitation exercise training program, established to improve fitness in people with and without diabetes. Given the greater CVEC abnormalities observed in women, sex differences will be evaluated for each aim.
- Being tested
- Cardiovascular exercise training
- Keywords
- Type 2 Diabetes, Overweight, Exercise Training, Exercise Impairment, Healthy Control, Veteran, Blood Flow
- Medical subject headings
- Diabetes Mellitus, Type 2, Overweight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiovascular exercise trainingOther
Also called Exercise Training
Following the completion of baseline testing, both subject groups will undergo supervised cardiovascular exercise training 3 times per week for 3 months (plus a 3 week ramp-up). Exercise training will take place on a treadmill, stationary bicycle, elliptical, rowing machine, or combination of machines. Each session will last 1 hour, which includes a 5 minute warm-up, 50 minutes of exercise, and a 5 minute cool down.
| Study group | Role | What they receive |
|---|---|---|
| Type 2 diabetes | Experimental | Men and women between the ages of 30-55 with well controlled type 2 diabetes (A1C <9%). Receives: Other: Cardiovascular exercise training |
| Healthy overweight controls | Experimental | Men and women between the ages of 30-55 with BMI 25-40 and limited immediate family history of type 2 diabetes. Receives: Other: Cardiovascular exercise training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in peak oxygen consumption (VO2peak)
Subjects' peak oxygen consumption will be tested on a stationary bike before and after 3 months of exercise
Measured: Through study completion, approximately 4 months
Change in insulin sensitivity
The investigators will evaluate the changes in insulin sensitivity utilizing a euglycemic insulin clamp
Measured: Through study completion, approximately 4 months
Change in muscular mitochondrial function
The investigators will examine mitochondrial function using magnetic resistance (MR) spectroscopy during single leg calf exercise
Measured: Through study completion, approximately 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2018
- Study start7 Feb 2018
- Primary completion20 Mar 2023
- Study completion20 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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 Colorado, DenverThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 124 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- VA Eastern Colorado Health Care System
- Responsible party
- Sponsor
- Investigators
- Judy Regensteiner, PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03419195
- Sponsor's protocol ID
- 17-0356
- Status last verified
- Jul 2023
- First submitted
- 18 Jan 2018
- Last updated
- 12 Jul 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Park S, Englund EK, Fujiwara T, Enge D, Schafer M, Gerstner Saucedo J, Clark EW, Abushamat LA, Scalzo RL, Fonseca B, Hunter KS, Sammel MD, Regensteiner JG, Reusch JEB, Barker AJ. Comprehensive CMR evaluation including 4D flow-derived E/A vorticity ratio in overweight adults with and without type 2 diabetes mellitus. Cardiovasc Diabetol. 2025 Dec 8;25(1):7. doi: 10.1186/s12933-025-02999-9.
PubMed 41361416Abushamat LA, Enge D, Fujiwara T, Schafer M, Clark EW, Englund EK, Scalzo RL, Johnston A, Rafferty D, Schauer IE, Whipple MO, Hunter K, Huebschmann AG, Nadeau KJ, Jarvis K, Barker AJ, Regensteiner JG, Reusch JEB. Obesity dominates early effects on cardiac structure and arterial stiffness in people with type 2 diabetes. J Hypertens. 2023 Nov 1;41(11):1775-1784. doi: 10.1097/HJH.0000000000003534. Epub 2023 Aug 17.
PubMed 37589719
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiovascular Mechanisms of Exercise Intolerance in Diabetes and the Role of Sex
- ClinicalTrials.gov ID
- NCT03419195
- Acronym / sponsor ID
- 17-0356
- Keywords
- Type 2 Diabetes, Overweight, Exercise Training, Exercise Impairment, Healthy Control, Veteran, Blood Flow
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 124 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- VA Eastern Colorado Health Care System
- Study start
- 7 Feb 2018 (actual)
- Primary completion
- 20 Mar 2023 (actual)
- Study completion
- 20 Mar 2023 (actual)
- First posted
- 1 Feb 2018 (actual)
- 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.
This study will define the relationship of cardiac, vascular function and skeletal muscle blood flow (individually and together) to cardiovascular exercise capacity in in men and women with and without type 2 diabetes (T2DM). Identification of differences in the effects of exercise training on the integrated cardiovascular system and metabolism in men and women with and without T2DM will reveal specific adaptive responses to exercise.This study will evaluate \& compare exercise function in a total of 60 subjects from the Denver area (30 people with T2DM and 30 overweight control subjects).
Specific Aim 1: To test the hypothesis that the integration of cardiac function, macrovascular function, and microvascular function is impaired in T2D and correlates with cardiovascular exercise capacity (CVEC) impairment.
Specific Aim 2: To test the hypothesis that exercise training will elicit adaptive responses in cardiac and vascular function, muscle perfusion and metabolism with differences by T2D status.
Differences between the exercise responses in people with T2DM and healthy people will help further identify the disease process of T2DM and direct future research of treatments and interventions.
Detailed description
It is well established that functional exercise capacity and peak oxygen uptake (VO2) are reduced in patients with type 2 diabetes mellitus (T2DM) compared with healthy counterparts. The mechanisms underlying the exercise deficit in T2DM remain largely unknown, but previous work has suggested that reduced exercise blood flow and impaired submaximal VO2 may be contributing factors. Both of these findings are consistent with a peripheral impairment of skeletal muscle oxygen delivery, oxygen utilization, or both. Indeed, dysfunction of skeletal muscle metabolism plays a key role in the pathophysiology of T2DM, and considerable work has described abnormalities of oxidative function in the skeletal muscle of people with T2DM. Given this, it is likely that the causes of exercise intolerance in T2DM may relate to specific defects at the level of the skeletal muscle, particularly given that skeletal muscle blood flow and oxidative capacity are impaired in diabetes. However, to the knowledge of the investigators, no one has related these peripheral muscle abnormalities to the diminished exercise function in this patient group.
The overarching hypothesis for the proposed research is that impaired CVEC in T2DM is the result of preclinical cardiac, vascular dysfunction and skeletal muscle perfusion abnormalities. Exercise training will improve CVEC and will reveal specific reversible therapeutic aspects of this pathology. The investigators will first determine the impairments and then evaluate responses to an established cardiac rehabilitation exercise training program, established to improve fitness in people with and without diabetes. Given the greater CVEC abnormalities observed in women, sex differences will be evaluated for each aim.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Type 2 diabetes | Experimental | Other: Cardiovascular exercise trainingMen and women between the ages of 30-55 with well controlled type 2 diabetes (A1C <9%). |
| Healthy overweight controls | Experimental | Other: Cardiovascular exercise trainingMen and women between the ages of 30-55 with BMI 25-40 and limited immediate family history of type 2 diabetes. |
Who may qualify
- Ages
- 30 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Men and women with and without type 2 diabetes
- BMI 25-40
- Sedentary subjects not participating in a regular exercise program (<one bout of exercise/week)
Key exclusion criteria (15 listed)
- Documented cardiovascular disease
- Uncontrolled hypertension: disease systolic blood pressure (SBP) > 150, diastolic blood pressure (DBP)> 110
- Obstructive pulmonary disease or asthma
- Peripheral neuropathy
- Physical impairment that would limit exercise ability
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 |
|---|---|---|
| Cardiovascular exercise trainingAlso: Exercise TrainingFollowing the completion of baseline testing, both subject groups will undergo supervised cardiovascular exercise training 3 times per week for 3 months (plus a 3 week ramp-up). Exercise training will take place on a treadmill, stationary bicycle, elliptical, rowing machine, or combination of machines. Each session will last 1 hour, which includes a 5 minute warm-up, 50 minutes of exercise, and a 5 minute cool down. | Other | Healthy overweight controls, Type 2 diabetes |
Primary outcome
Change in peak oxygen consumption (VO2peak)
Time frame: Through study completion, approximately 4 months
Subjects' peak oxygen consumption will be tested on a stationary bike before and after 3 months of exercise
Change in insulin sensitivity
Time frame: Through study completion, approximately 4 months
The investigators will evaluate the changes in insulin sensitivity utilizing a euglycemic insulin clamp
Change in muscular mitochondrial function
Time frame: Through study completion, approximately 4 months
The investigators will examine mitochondrial function using magnetic resistance (MR) spectroscopy during single leg calf exercise
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 12 Jul 2023.
- Derived from this study: PubMed 41361416Park S, Englund EK, Fujiwara T, Enge D, Schafer M, Gerstner Saucedo J, Clark EW, Abushamat LA, Scalzo RL, Fonseca B, Hunter KS, Sammel MD, Regensteiner JG, Reusch JEB, Barker AJ. Comprehensive CMR evaluation including 4D flow-derived E/A vorticity ratio in overweight adults with and without type 2 diabetes mellitus. Cardiovasc Diabetol. 2025 Dec 8;25(1):7. doi: 10.1186/s12933-025-02999-9.
- Derived from this study: PubMed 37589719Abushamat LA, Enge D, Fujiwara T, Schafer M, Clark EW, Englund EK, Scalzo RL, Johnston A, Rafferty D, Schauer IE, Whipple MO, Hunter K, Huebschmann AG, Nadeau KJ, Jarvis K, Barker AJ, Regensteiner JG, Reusch JEB. Obesity dominates early effects on cardiac structure and arterial stiffness in people with type 2 diabetes. J Hypertens. 2023 Nov 1;41(11):1775-1784. doi: 10.1097/HJH.0000000000003534. Epub 2023 Aug 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.
Judy Regensteiner, PhD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cardiovascular exercise training in people with Type 2 Diabetes Mellitus and Healthy, run by University of Colorado, Denver 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 3 inclusion and 15 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 12 Jul 2023. 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?
Change in peak oxygen consumption (VO2peak) (time frame: Through study completion, approximately 4 months). The study lists 3 primary outcomes in all. 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 NCT03419195, which also lists 2 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 12 Jul 2023.