Cardiovascular Mechanisms of Exercise Intolerance in Diabetes and the Role of Sex
Condition: Type 2 Diabetes Mellitus; Healthy; Overweight; Cardiovascular Risk Factor
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Overweight
Study type: Interventional

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). 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.
    

Intervention name(s): Cardiovascular exercise training
Intervention type(s): Other
Intervention description(s): 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.
Other intervention name(s): Exercise Training
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Type 2 Diabetes; Overweight; Exercise Training; Exercise Impairment; Healthy Control; Veteran; Blood Flow