Mechanisms of Exercise Resistance in Metabolic Disease

Study Overview
=================
Brief Summary
-----------------
This project will determine exercise capacity and molecular markers of the response to acute exercise in human subjects with impaired or normal glucose tolerance.

Detailed Description
-----------------
Low exercise capacity is an early clinical marker of metabolic impairment that predicts type 2 diabetes (T2D) risk, as well as future co-morbidities and complications. Aerobic exercise training is the only effective treatment to increase exercise capacity and reduce metabolic risk. However, despite maintaining similar levels of physical activity, exercise capacity remains lower in people with impaired glucose tolerance and T2D, compared to those with normal glucose tolerance, suggesting exercise resistance. The mechanisms of exercise resistance in metabolic disease are unknown. In preclinical studies, exercise-induced increases in circulating angiogenic markers and skeletal muscle capillary density predict improved exercise capacity with training. Furthermore, it was demonstrated that impaired glucose tolerance precedes exercise resistance and impaired exercise-induce angiogenesis in muscle. Based on these data, it was hypothesized that exercise resistance in human T2D is caused by an impaired angiogenic response to exercise, secondary to impaired glycemic control. This study will determine whether the angiogenic response to a single bout of exercise in human subjects is blunted in patients with impaired glucose tolerance (IGT), compared to those with normal glucose tolerance (NGT). Angiogenic potential will be measured using a novel in vitro assay developed to assess endothelial tube-formation induced by circulating serum angiogenic regulators following exercise. In addition, a novel exercise-activated signaling pathway in skeletal muscle that is predictive of exercise resistance in animal models was identified. A second aim of the proposed investigation is to determine the effect of impaired glucose tolerance on molecular signaling in response to exercise in skeletal muscle. This investigation represents a critical step in determining the mechanisms that contribute to low exercise capacity in individuals at risk for diabetes.

Official Title
-----------------
Mechanisms of Exercise Resistance in Metabolic Disease

Conditions
-----------------
Impaired Glucose Tolerance

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18-45, BMI 26-32 kg/m2, Sedentary Lifestyle Exclusion Criteria: Type 1 or Type 2 diabetes, heart or lung disease, hypertension, contraindications to exercise testing, pregnancy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Normal Glucose Tolerance<br>Blood glucose level of less than 140 mg/dL at the 2 hour timepoint. | |
| Impaired Glucose Tolerance<br>Blood glucose level of greater or equal to 140 mg/dL at the 2 hour timepoint. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VO2peak | Cardiorespiratory Fitness | One week | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Exercise, Cardiorespiratory Fitness, Skeletal Muscle, Angiogenesis