Mechanisms of Exercise Resistance in Metabolic Disease

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

Study Overview

• Status: Completed
• Conditions: Impaired 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.

• Study Type: Observational
• Enrollment (Actual): 29

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Joslin Diabetes Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Study population will be men and women from the Boston area

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Normal Glucose Tolerance; Blood glucose level of less than 140 mg/dL at the 2 hour timepoint.
Impaired Glucose Tolerance; 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

Collaborators and Investigators

• Sponsor: Joslin Diabetes Center
• Investigators: Principal Investigator: Sarah Lessard, Ph.D., Joslin Diabetes Center

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Actual): April 11, 2019
• Study Completion (Actual): April 11, 2019

Study Registration Dates

• First Submitted: May 23, 2018
• First Submitted That Met QC Criteria: May 8, 2019
• First Posted (Actual): May 10, 2019

Study Record Updates

• Last Update Posted (Actual): August 19, 2019
• Last Update Submitted That Met QC Criteria: August 15, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Exercise; Angiogenesis; Cardiorespiratory Fitness; Skeletal Muscle
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Hyperglycemia; Glucose Intolerance; Metabolic Diseases
• Other Study ID Numbers: 2017-09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No