Type 2 Diabetes and Exercise Function in Single Leg Exercises

Role of Vascular Function: Oxygen Delivery vs Oxygen Utilization in the Exercise Impairment in Type 2 Diabetes

This study plans to learn more about the effects of type 2 diabetes (T2DM) on exercise blood flow and muscle oxygen uptake. This study will evaluate & compare exercise function during single leg plantar flexion exercise in a total of 45 subjects from the Denver area (15 lean controls, 15 people with T2DM, and 15 overweight control subjects). 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 our knowledge, 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 both a failure to adequately increase muscle oxygen delivery following the onset of exercise and reduced oxidative function of skeletal muscle contribute to the acute oxygen deficit and diminished exercise tolerance that has been observed in patients with T2DM.

Supervised single leg, exercise training of the index (dominant) calf muscle 5 days per week for two weeks - alternating weight-bearing single leg calf raises and single leg calf extensions by endurance resistance training (weight machine apparatus).

Following the completion of baseline testing, all 3 subject groups will undergo supervised single leg, exercise training of the index (dominant) calf muscle 5 days per week for two weeks - alternating weight-bearing single leg calf raises and single leg calf extensions by endurance resistance training (weight machine apparatus).

The investigators evaluated the dynamics of muscle deoxygenation (O2 extraction) using near infrared spectroscopy (NIRS) during single leg plantar flexion exercise to identify the predominant mechanisms of oxygen delivery versus oxygen utilization abnormalities in the muscle of T2DM during the transition from rest to exercise. These measurements were gathered continuously for 2-5 minutes of multiple exercise bouts within two visits, one prior to the exercise intervention period and one post exercise intervention.

Inclusion Criteria: Men and women with and without type 2 diabetes 30-70 years of age Lean and overweight Sedentary subjects not participating in a regular exercise program (<one bout of exercise/week) Exclusion Criteria: Documented cardiovascular disease Uncontrolled hypertension: systolic blood pressure (SBP) > 150, diastolic blood pressure (DBP)> 110 Obstructive pulmonary disease or asthma Peripheral neuropathy Subjects taking beta blockers, insulin, or Thiazolidinediones (TZD) Current or past smoking within the last 2 years Anemia Control HbA1c > 6, T2DM HbA1c > 10 Type 1 diabetes Any implanted metal in subject's body