Role of Microvascular Insulin Resistance and Cardiorespiratory Fitness Diabetes (REACH)

The goal of this two-site grant proposal is to determine the role of the decreased insulin-mediated muscle perfusion found in type 2 diabetes in contributing to the development of cardiac and skeletal muscle dysfunction and subsequent functional exercise impairment. In addition, it is also our goal to determine whether exercise training attenuates insulin resistance and restores insulin-mediated perfusion to the heart and to skeletal muscle, leading to improved cardiac function and exercise performance.

It is our goal to determine whether exercise training attenuates insulin resistance and restores insulin-mediated perfusion to the heart and to skeletal muscle, leading to improved cardiac function and exercise performance. Data from our two research teams suggest that the cardiac and skeletal muscle microvascular dysfunction present in people with type 2 diabetes contributes to limitations in cardiac and skeletal muscle function associated with impaired functional exercise capacity (a major predictor of CV and all-cause mortality). Insulin action is a potent predictor of the functional exercise capacity impairment in type 2 diabetes. The exact relationship between insulin action, cardiac and muscle dysfunction, cardiac and skeletal muscle perfusion and decreased functional exercise capacity in type 2 diabetes remains unclear.

Subjects' peak oxygen consumption will be tested on a stationary bike before and after 15 weeks of exercise

The investigators will evaluate the changes in insulin sensitivity utilizing a euglycemic insulin clamp

Inclusion Criteria: Sedentary (defined as less than 1 hour per week of physical activity) BMI: 25-40 Men and women with and without type 2 diabetes 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 > 9 Pregnant, nursing or hormonal therapy (other than contraceptives) Peri or post-menopausal women Type 1 diabetes Hepatic or renal disease.