Fuel Utilization, Diet Composition, and Exercise in African American Women
Condition: Obesity; Diabetes; Insulin Resistance
MeSH terms: Insulin Resistance
Study type: Interventional

Summary: 
      African American women have a high prevalence of obesity and type 2 diabetes and do not
      optimally burn fat and carbohydrates in response to changes in these nutrients in their
      diets. This research project seek to determine if high intensity interval training (HIIT)
      exercise training can help healthy, but inactive, premenopausal, non-diabetic women increase
      their bodies' use of fat and carbohydrates when provided with a high fat or low fat diets. In
      this study, investigators will measure the rate at which fat is burned in response to weight
      maintaining low-fat and high-fat diets and how exercise may affect these responses.
    

Detailed description: 
      African Americans have the highest age-adjusted death rate for heart disease and diabetes in
      the United States. Obesity, a significant risk factor for these conditions, is highly
      prevalent in African Americans, particularly women, leading to increased co-morbidities.
      Cardiovascular risk and incidence were reported to be higher in African American women than
      in both white women and African American men. Ethnic differences in lifestyle behaviors and
      economic disadvantage account for some of this disparity but genetic/molecular factors may
      play a role. The study team has shown that more pre-menopausal, non-diabetic, African
      American women do not increase post-absorptive lipid oxidation in response to a eucaloric
      increase in dietary fat than white women counterparts. African American women were also shown
      to have increased rates of low aerobic capacity (VO2peak) and insulin resistance.

      A lack of increasing fuel utilization in response to an increase in fuel availability,
      particularly fat, is associated with obesity and insulin resistance and is attributed to a
      decrease in the oxidative capacity of the skeletal muscle. An eucaloric increase in dietary
      fat leads to increased post-absorptive lipid utilization through hormonal changes that affect
      the mitochondria and a decrease in this response is postulated to reflect a decrease in the
      mitochondria/oxidative capacity. Lipid utilization in response to an increase in dietary fat
      is enhanced by acute exercise. Aerobic training could also improve aerobic capacity and
      insulin resistance and increases the oxidative capacity/mitochondrial activity in the
      skeletal muscle, measured in vitro. The degree to which training affects aerobic capacity and
      metabolism differs with the type, intensity and duration of training and with the population
      studied. High-intensity interval training (HIIT) programs improved aerobic fitness and
      insulin resistance in cardiac, sedentary and obese individuals and rapidly increased markers
      of lipid oxidation and mitochondrial activity in skeletal muscle, measured in vitro. A great
      appeal of HIIT is that lesser time per week spent exercising may be needed to produce these
      effects. There have been a paucity of effective exercise training studies in African American
      women; none have employed HIIT which appears uniquely suited given their metabolic profile
      and none have examined the impact of training on the metabolic response to an increase in
      dietary fat.

      Therefore the Aims of this study are to determine, in overweight and obese, sedentary,
      pre-menopausal, non-diabetic African American women, whether a 14-week of a HIIT exercise
      program will:

      I. Increase systemic post-absorptive lipid oxidation in response to a higher fat diet (50%
      fat, 35% CHO, 15% protein). The study team hypothesizes that the women who successfully
      complete training will have significantly higher post-absorptive lipid oxidation in response
      to the higher fat diet compared to the sedentary controls on a similar diet.

      II. Improve aerobic endurance capacity. The study team hypothesizes that VO2peak will be
      significantly higher in the women who successfully complete training compared to the
      sedentary controls.

      III. Improve insulin sensitivity. The study team hypothesizes that insulin sensitivity will
      be significantly higher in the women who successfully complete training compared to the
      sedentary controls.

      Te secondary aims are to determine whether: 1) the exercise training favorably changes muscle
      adipose tissue distribution and lipid accumulation and 2) these changes correlate with an
      improvement in insulin sensitivity.

      To test these hypotheses The study team will conduct a clinical trial in 48 pre-menopausal,
      healthy, sedentary, overweight and obese African American women. All women will be challenged
      with a 10-day eucaloric higher fat diet. Then, half of the women will be randomized to
      participate in a 14-week HIIT program designed to significantly increase their aerobic
      endurance and half will maintain baseline physical activity. Throughout the follow period all
      women will be counseled to follow the same, weight-maintaining, heart-healthy diet. After 14
      weeks the higher fat dietary challenges will be repeated, at weight stability ensured with
      the use of the whole-body calorimeter (metabolic chamber). Post-absorptive lipid oxidation,
      insulin sensitivity and muscle-associated fat will be measured at the end of each of the
      higher fat diet periods, before and after the 14 weeks of exercise raining, in the sedentary
      and exercising women, 2 days after the last bout of acute exercise.

      HIIT has a greater potential for translation into clinical practice as the shorter exercise
      time may improve compliance which is the biggest deterrent for the success of exercise
      training programs. Prevention of obesity and reversal of decreased aerobic capacity and
      insulin resistance in younger individuals such as African American women of child-bearing age
      (pre-menopausal) could be crucial to decrease the worrisome trends of obesity-related
      illnesses in African Americans.
    

Intervention name(s): High Intensity Interval Training (HIIT)
Intervention type(s): Other
Intervention description(s): HIIT involves exercising in blocks of time (typically 4-5 minutes) where a small percentage of the time (typically 1 minute) is spent above the anaerobic (lactate) threshold (the "work interval") followed by the remainder of the time at a sub-anaerobic threshold ("active recovery").
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: The study team will conduct a randomized clinical trial in 48 healthy pre-menopausal sedentary overweight and obese African American women. The women will be randomized to two groups: a) half of the women in each diet group will be training (EX) and b) half of the women in each diet group will be sedentary (C). Each woman will participate over a 5 months period, through 4 menstrual cycles so that baseline and post-intervention measurements are done during the follicular phase of the menstrual cycle. The baseline and post-intervention measurements will be done after a 10-day period of controlled eucaloric High-Fat feeding. On Days 9-11 of the 10 -day period they will be in-patients in the CRR and they will all be sedentary. On Day 9 they will be admitted to the Metabolic Chamber and have 24-hour energy expenditure measurements as previously described which will be used for the diet on subsequent days in the CRR. On Day 10 they will be fed the same amount of calories they bu
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Obesity; Prediabetes; metabolic flexibility; insulin sensitivity; high-intensity interval training; exercise tolerance