Effects of Exercise Training Intensity on Fitness and Insulin Sensitivity in African Americans

Study Overview
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Brief Summary
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African Americans are at a substantially greater type 2 diabetes risk compared to Caucasians; however, very little data are available on the effects of exercise training on type 2 diabetes risk factors in at risk African Americans. The present proposal will evaluate the effects of 6 months of moderate versus vigorous intensity aerobic exercise training on fitness, insulin sensitivity, mitochondrial capacity, skeletal muscle oxidative/insulin sensitivity markers, adiposity, and quality of life in African Americans.

Detailed Description
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African Americans have a much greater risk of type 2 diabetes compared to Caucasians in the United States. Similarly, recent evidence has emerged that fitness level, a major risk factor for type 2 diabetes also tends to be lower in African Americans. Many scientific studies have shown that exercise training has a beneficial impact on fitness levels and a variety of other type 2 diabetes risk factors such as the reduction of glucose/insulin levels, and body fat Importantly, studies performed in mostly Caucasian populations suggest that exercise training at a vigorous intensity may promote greater improvements in type 2 diabetes risk factors compared to moderate intensity exercise, which may suggest that it has greater promise in reducing type 2 diabetes risk. However, few exercise training studies compare the health benefits of different exercise training programs (such as exercise intensity) in African Americans, which is clinically important due to their greater type 2 diabetes risk, and that fact that they are less likely to meet public health recommendations for physical activity compared to their Caucasian counterparts. The High Intensity exercise to Promote Accelerated improvements in CardiorEspiratory fitness (HI-PACE) study will evaluate the effect of exercise intensity on cardiorespiratory fitness (CRF) and insulin sensitivity in obese (BMI: 30-45) African Americans (40-65 yrs.) with at least 1 additional T2D risk factor. Participants (n=60) will be recruited in collaboration with the ECU Center for Health Disparities, and subsequently randomized to moderate intensity (MOD-INT, n=20) or high intensity (HIGH-INT, n=20) aerobic exercise training, or to a control group (CON, n=20) for 24 weeks. Supervised exercise training will be performed at a heart rate associated with  50% and  75% of VO2 max in the MOD-INT and the HIGH-INT groups, respectively at the same exercise volume of 600 MET-minutes per week (consistent with public health recommendations). The primary outcome is the change in CRF, which will be assessed at baseline, mid-intervention, and follow-up. Insulin sensitivity will be measured via an intravenous glucose tolerance test at baseline and follow-up. Other secondary measures include mitochondrial oxidative capacity using infrared and measurements on muscle biopsies (PGC-1α and other indices of mitochondrial content), the expression of a protein involved with insulin action (GLUT-4 expression) in skeletal muscle as well as systemic inflammation, adiposity, quality of life and exercise enjoyment measures.

Official Title
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The High Intensity Exercise to Promote Accelerated Improvements in CardiorEspiratory Fitness (HI-PACE) Study

Conditions
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Obesity, Insulin Resistance, Sedentary Lifestyle

Intervention / Treatment
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* Behavioral: Moderate intensity exercise training (MOD-INT)
* Behavioral: High Intensity exercise training (HI-INT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: African American Body mass index 30-45 kg/m2 sedentary/low active (step count ≤ 6,500 step/day) capable and willing to give written informed consent and understand exclusion criteria willingness to accept group assignment from randomization No resistance training and no structured aerobic exercise for > 20 minutes per day, 3+ days per week, for the last 6 months conditions that are contraindicated for exercise training Exclusion Criteria: Resting blood pressure > 180 mm Hg systolic and/or >100 mm Hg diastolic; individuals on blood pressure medications meeting the blood pressure criteria are eligible Diagnosis of type 1 or 2 diabetes, and/or fasting glucose >125 mg/dL Medication for the treatment of type 1 or type 2 diabetes Bariatric surgery including gastric banding or bypass (potential effects on energy intake) Factors that may limit adherence to intervention or affect conduct of the trial Unable or unwilling to communicate with staff Failure to complete run-in or baseline testing Hospitalization for depression or severe mental illness in the last 6 months Not physically capable of performing the exercise required of the study protocol Consuming more than 14 alcoholic beverages per week Plan to be away from the Pitt County area more than 3 weeks in the next 3 months Lack support from a primary health care provider or family members Significant weight loss in the past year (> 20 pounds) or are currently using weight loss medications. Current diagnosis of schizophrenia, other psychotic disorders, or bipolar disorder Another member of the household who is currently a participant or staff member of this study Other temporary intervening event, such as sick spouse, or bereavement Other medical, psychiatric, or behavioral limitations that may interfere with study participation or the ability to follow the intervention protocol Underlying diseases or conditions likely to limit lifespan and/or affect the safety of the intervention Cancer requiring treatment in the past 5 years with anything but excellent prognosis Self-reported HIV, tuberculosis, Hepatitis B, or Hepatitis C History or evidence of serious arrhythmias, cardiomyopathy, congestive heart failure, aortic aneurism, myocardial infarction or heart transplantation Renal disease: urine protein > 100 mg/dl, serum creatinine ≥ 1.5 mg/dl or currently receiving dialysis. Auto-immune diseases (such as Lupus, Multiple Sclerosis, Graves' disease, or Rheumatoid arthritis) Chronic obstructive lung disease, peripheral vascular disease or angina that limits ability to follow exercise protocol History of stroke or transient ischemic attack History of vascular aneurysms History of bleeding disorders Pregnancy or plans to become pregnant Dieting or plans to diet, or in a weight loss program Any other medical condition or disease that is life threatening or that can interfere with or be aggravated by exercise.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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 |
| --- | --- |
| No Intervention: Control<br>This group does not change physical activity during the intervention period, but will receive exercise training after the study is complete | |
| Experimental: MOD-INT<br>The Moderate intensity exercise training (MOD-INT) group will exercise at a moderate aerobic exercise intensity for 24 weeks | Behavioral: Moderate intensity exercise training (MOD-INT)<br>* Participants in the MOD-INT group will exercise at the heart rate associated with 45-55% VO2 max. The exercise volume will be 600 MET-minutes per week, which is consistent with current public health guidelines (500-1,000 MET-minutes)<br>|
| Experimental: HIGH-INT<br>High Intensity exercise training (HI-INT) group will exercise at a high aerobic intensity for 24 weeks | Behavioral: High Intensity exercise training (HI-INT)<br>* Participants in the HI-INT group will exercise at the heart rate associated with 70-80% VO2 max (heart rate ranges will be updated at mid-intervention CRF assessment). The exercise volume will be 600 MET-minutes per week, which is consistent with current public health guidelines (500-1,000 MET-minutes)3<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cardiorespiratory fitness | Fitness will be measured using a modified Balke protocol on a treadmill. Participants will walk at an initial speed of 2.0 mph with 0% grade for the first 3 minutes after which the treadmill speed will increase to 3.0 mph for the next 3 minutes. The treadmill grade will be increased by 2.5% every 3 minutes until volitional exhaustion. Respiratory gases (VO2, CO2) and ventilation will be measured continuously using a True Max 2400 Metabolic Measurement Cart (Parvomedics, Salt Lake City Utah). | Baseline and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body composition | Dual-energy X-ray absorptiometry will be used to measure changes in fat and lean mass. | Baseline and 24 weeks | 
| Change in body weight | Weight will be measured using a calibrated scale | Baseline and 24 weeks | 
| Change in waist circumference | Waist circumference will be measured at the natural waist (midway between the inferior border of the rib cage and the superior aspect of the iliac crest) with a Gulick tape measure. Both landmarks (the inferior border of the ribcage and the superior aspect of the iliac crest) will be marked and the distance will be measured to determine the appropriate measurement site. Staff will confirm that: 1) the measurement tape remains horizontal; 2) the tape touches the entire circumference of the participant; 3) abdominal tissue is not compressed; 3) the tape measure is not within abdominal folds; 4) the measurement is taken at the end of normal respiration. The measurement will be repeated an additional time, and the reported value will be the average of these measurements. Both measurements must be within 0.5 cm to be considered acceptable for data purposes. | Baseline and 24 weeks | 
| Changes in physical activity levels | Participants will wear an ActivPal accelerometer for seven consecutive days, 24-hrs/day. The amount of time spent sitting and standing and steps will be calculated | Baseline and 24 Weeks | 
| Change in dietary composition | Food Frequency Questionnaire (FFQ) contains approximately 105 items grouped by categories and is completed for both frequency of consumption as well as portion size selections by the individual. The questionnaire, upon completion, provides estimated daily intake values for selected nutrients (kilocalories, macronutrients, and micronutrients) and provides information on food group servings. | Baseline and 24 weeks | 
| Changes in blood lipids concentrations | Low density lipoproteins, high density lipoproteins, total cholesterol, and triglycerides will be measured from baseline and 24 weeks from blood samples by Labcorp Inc. | Baseline and 24 weeks | 
| Change in systemic inflammation | High sensitivity c-reactive protein will be measured at baseline and follow-up | Baseline and 24 weeks | 
| Change in insulin sensitivity | Insulin sensitivity will be measured using an intravenous glucose tolerance test | Baseline and 24 weeks | 
| Change in arterial stiffness | Arterial stiffness will be measured using pulse wave velocity. | Baseline and 24 weeks | 
| Change in quality of life | Quality of life (QOL) will be measured by the short form health survey (SF-36) | Baseline and 24 weeks | 
| Change in mitochondrial enzymes and protein content | Mitochondrial enzymes (citrate synthase, COX IV, GLUT-4, CPT-1) protein content (COX IV, GLUT-4 CPT-1 and PGC-1 alpha) | Baseline and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exercise, insulin resistance, mitochondrial function, arterial stiffness, exercise intensity, fitness