Metabolic Adaptations in Response to High Intensity Interval Training in Obese Adults

Study Overview
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Brief Summary
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The overall objectives are to: Assess mechanisms underlying HIIT-induced improvements in insulin resistance at the whole-body, tissue, and cellular levels. Systematically compare different HIIT regimens to help identify effective doses of HIIT that may be optimal for improving metabolic health in obese adults. Assess the ability/willingness of obese subjects to adhere to a long-term HIIT program. Findings from these studies will greatly expand knowledge about the effects of HIIT on metabolic health, and will provide valuable information for development of programs aimed at maximizing key metabolic benefits of exercise.

Detailed Description
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If subjects are eligible for the study, they will be randomized into one of four different exercise training groups. Before training (and twice after 3 months of training) subjects will participate in a clinical study in which they will be required to stay overnight in the hospital. During the clinical study, the research team will perform a series of metabolic tests. Before and after the 3 months of training, the research team will assess subjects free-living 24h blood sugar control using a Continuous Glucose Monitor (CGM). The research team will measure several other relevant clinical markers (e.g., whole body and regional body fat assessments [Dual Energy X-ray Absorptiometry (DEXA) and Magnetic Resonance Imager (MRI)], hepatic lipid accumulation [MRI analysis], blood lipid profile, resting metabolic rate, glycated hemoglobin [hemoglobin A1c]). After the first 3 months of training, adherence to the subjects assigned training program will be tracked for the next 9 months (1 year of training in total). One year after initiating a training program, subjects will be asked to return to the clinic for a quick follow-up visit where the research team will complete some standard clinical assessments (e.g., body weight, body composition, blood pressure, and a blood sample).

Official Title
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Metabolic Adaptations in Response to High Intensity Interval Training in Obese Adults

Conditions
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Glucose Intolerance

Intervention / Treatment
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* Other: High Intensity Interval Training #1
* Other: Moderate intensity continuous training
* Other: High Intensity Interval Training #2
* Other: High Intensity Interval Training #3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-40 Body Mass Index: 30-40 kg/m2 Waist circumference: 88-98cm for women and 100-110cm for men Glucose intolerant (i.e., 2h glucose concentration during a screening oral glucose tolerance test (OGTT)= 140-199mg/dl No regularly planned exercise/physical activity Women must have regularly occurring menses and must be premenopausal Exclusion Criteria: EKG abnormalities as assessed by the cardiologist on the research team Evidence/history of cardiovascular or metabolic disease Medications known to affect lipid or glucose metabolism Pregnant or lactating Tobacco or e-cigarette use

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: High Intensity Interval Training #1<br>Obese adults with impaired glucose tolerance will be randomized into one of four different exercise training groups for a 3 month exercise intervention. | Other: High Intensity Interval Training #1<br>* (HIIT#1) 10 x 1 min. at  90%HRmax - with low intensity warm-up, recovery, and cool down - total of 25 min/session .<br>|
| Other: Moderate intensity continuous training<br>Obese adults with impaired glucose tolerance will be randomized into one of four different exercise training groups for a 3 month exercise intervention. | Other: Moderate intensity continuous training<br>* Moderate-intensity continuous training (MICT) = steady-state exercise at 60-70%HRmax for 45min. Representing a commonly prescribed exercise program.<br>|
| Other: High Intensity Interval Training #2<br>Obese adults with impaired glucose tolerance will be randomized into one of four different exercise training groups for a 3 month exercise intervention. | Other: High Intensity Interval Training #2<br>* (HIIT #2) 5 x 1 min at 90%HRmax + 10 min steady-state exercise at 70%HRmax [25min;  150kcals; 4d/wk]<br>|
| Other: High Intensity Interval Training #3<br>Obese adults with impaired glucose tolerance will be randomized into one of four different exercise training groups for a 3 month exercise intervention. | Other: High Intensity Interval Training #3<br>* (HIIT #3) 5 x 1 min at 90%HRmax [15min;  90kcals; 4d/wk]<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Sensitivity | A hyperinsulinemic-euglycemic clamp will be used to assess peripheral insulin sensitivity | Change from Baseline at 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Continuous Glucose Monitoring |  | Change from Baseline at 3 months | 
| Resting Metabolic Rate |  | baseline and 3 months | 
| Muscle Biopsy | To measure Mitochondrial Proteins | Change from Baseline at 3 months | 
| Adipose Tissue Biopsy | To measure cytokines | Change from Baseline at 3 months |