Cardiovascular Mechanisms of Exercise Intolerance in Diabetes and the Role of Sex
| Status: | Recruiting |
|---|---|
| Conditions: | Healthy Studies, Obesity Weight Loss, Peripheral Vascular Disease, Diabetes, Diabetes |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Endocrinology, Other |
| Healthy: | No |
| Age Range: | 30 - 55 |
| Updated: | 2/24/2019 |
| Start Date: | February 7, 2018 |
| End Date: | December 31, 2021 |
| Contact: | Deirdre Rafferty, MS |
| Email: | deirdre.rafferty@ucdenver.edu |
| Phone: | 720-848-6688 |
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.
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.
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.
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.
Inclusion Criteria:
- Men and women with and without type 2 diabetes
- BMI 25-40
- Sedentary subjects not participating in a regular exercise program (
Exclusion Criteria:
- 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)
- Current or past smoking within the last 1 years
- Current tobacco use
- Anemia
- Control HbA1c > 5.7, T2DM HbA1c > 10
- Pregnant, nursing or hormonal therapy (other than contraceptives)
- Peri or post-menopausal women
- Type 1 diabetes
- Hepatic or renal disease.
- Peptic ulcer disease.
We found this trial at
1
site
13001 E 17th Pl
Aurora, Colorado 80045
Aurora, Colorado 80045
(303) 724-5000
Principal Investigator: Judy Regensteiner, PhD
Phone: 720-848-6688
University of Colorado Anschutz Medical Campus Located in the Denver metro area near the Rocky...
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