Clinical trial NCT03945435: Mechanisms of Exercise Resistance in Metabolic Disease
Official title: Mechanisms of Exercise Resistance in Metabolic Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Impaired Glucose Tolerance
Keywords: Exercise
Cardiorespiratory Fitness
Skeletal Muscle
Angiogenesis
Lead sponsor: Joslin Diabetes Center
Sponsor class: OTHER
First posted: 2019-05-10
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study population will be men and women from the Boston area

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.

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

Primary outcomes:
measure: VO2peak
timeFrame: One week
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
Study officials:
affiliation: Joslin Diabetes Center
name: Sarah Lessard, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: