Mechanisms of Exercise Resistance in Metabolic Disease

NCT ID: NCT03945435

Last Updated: 2019-08-19

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 29 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-07-01
• Study Completion Date: 2019-04-11

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.

Conditions

Impaired Glucose Tolerance

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Normal Glucose Tolerance

Blood glucose level of less than 140 mg/dL at the 2 hour timepoint.

No interventions assigned to this group

Impaired Glucose Tolerance

Blood glucose level of greater or equal to 140 mg/dL at the 2 hour timepoint.

No interventions assigned to this group

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Joslin Diabetes Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sarah Lessard, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Joslin Diabetes Center

Locations

Joslin Diabetes Center

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

2017-09

Identifier Type: -

Identifier Source: org_study_id