Mechanisms of Exercise Resistance in Metabolic Disease

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Study Design

Related Conditions & MeSH terms

Clinical Trial Details

NCT number	NCT03945435
Study type	Observational
Source	Joslin Diabetes Center
Contact
Status	Completed
Phase
Start date	July 1, 2018
Completion date	April 11, 2019

View Details

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Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.