Effect of Abdominal Obesity on Heart Metabolism and Function
| Status: | Completed |
|---|---|
| Conditions: | Obesity Weight Loss, Diabetes |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 45 |
| Updated: | 4/2/2016 |
| Start Date: | June 2003 |
| End Date: | December 2011 |
| Contact: | Debi Delano, MSN |
| Email: | delanod@mir.wustl.edu |
| Phone: | 314-747-3876 |
Altered Myocardial Fatty Acid Metabolism In Obesity
Obesity is one of the most widespread health problems of today, with more than 61 million
adult Americans considered obese. Abdominal obesity (AO), in particular, is associated with
an increased chance of cardiac diseases, such as coronary artery disease, and related risk
factors, such as high blood pressure and type 2 diabetes mellitus (T2DM). Despite the known
association between AO and cardiac disease, the mechanisms responsible for this relationship
are still not well understood. Recent obesity studies have indicated that increased delivery
of fats to the heart may play a role in heart function impairments. This study will evaluate
the impact of AO on the human heart's use of fats for energy and on heart function.
adult Americans considered obese. Abdominal obesity (AO), in particular, is associated with
an increased chance of cardiac diseases, such as coronary artery disease, and related risk
factors, such as high blood pressure and type 2 diabetes mellitus (T2DM). Despite the known
association between AO and cardiac disease, the mechanisms responsible for this relationship
are still not well understood. Recent obesity studies have indicated that increased delivery
of fats to the heart may play a role in heart function impairments. This study will evaluate
the impact of AO on the human heart's use of fats for energy and on heart function.
Obesity is defined as having a high amount of excess body fat. Millions of people worldwide
meet the criteria for obesity, making it one of the most pressing current health issues. The
more body fat a person has, the more susceptible that person is to a number of life
threatening diseases, including heart disease, type 2 diabetes, gallstones, certain cancers,
and high blood pressure. A variety of factors can lead to obesity. These factors include
family history and genetics, physical inactivity, metabolism, hormone imbalance, and
environment. Past research suggests that an increased availability of fats in the body leads
to increased fat uptake by the heart. The heart only needs a certain amount of fat for
energy, which leaves the remaining fat in the heart tissue, possibly impairing proper heart
function. However, more information on the mechanisms behind the effects of fats on heart
metabolism is needed. This study will evaluate the impact of AO on the human heart's use of
fats for energy and on heart function.
This study will enroll both overweight and lean participants who will attend 4 to 7 study
visits. Visit 1 will consist of various screening tests, including a medical history,
physical exam, pregnancy test if applicable, routine blood test, and an echocardiogram
(ECHO) performed before and during exercise.
Visit 2 will consist of an abdominal fat and insulin sensitivity study. This will entail a
magnetic resonance imaging (MRI) test to image the heart and stomach, a dual energy x-ray
absorptiometry (DEXA) scan to measure total body fat and muscle content, and an insulin
sensitivity test to measure how well the hormone insulin controls blood sugar. The latter
test will require multiple blood draws over a 3-hour period.
Visits 3 and 4 will occur over a 2-week period. Both visits will consist of an overnight
stay at the General Clinical Research Center (GCRC) followed by a day of imaging studies.
During Visit 3, participants will first undergo a 4-hour whole body metabolism study, which
will include injection of a nonradioactive tracer through previously placed IVs, blood
draws, and breathing into a machine for approximately 15 minutes. Participants will then
undergo a positron emission tomographic (PET) heart metabolism study, which will also
involve tracer injections and blood draws. A resting ECHO test will also be done during the
PET study. Participants will be asked for permission to store a sample of their blood for a
period of up to 10 years to be used in future research studies on the heart. During Visit 4,
participants will undergo repeat tests from the third visit, except the PET study will
evaluate the heart's ability to use sugars instead of fats. This will complete the study
visits for all lean participants and some overweight participants and will entail 4 weeks of
participation.
Overweight participants may be asked to attend an additional three study visits during an
8-month weight management program at Washington University School of Medicine. Participants
will aim to lose 10% of their body weight over a 6-month period and to maintain that weight
loss for another 1- to 2-month stabilization period. At the end of the stabilization period,
participants will undergo repeat abdominal fat and insulin sensitivity studies during Visit
5, repeat whole body metabolism and heart metabolism studies during Visit 6, and repeat
whole body metabolism and glucose heart metabolism studies during Visit 7.
meet the criteria for obesity, making it one of the most pressing current health issues. The
more body fat a person has, the more susceptible that person is to a number of life
threatening diseases, including heart disease, type 2 diabetes, gallstones, certain cancers,
and high blood pressure. A variety of factors can lead to obesity. These factors include
family history and genetics, physical inactivity, metabolism, hormone imbalance, and
environment. Past research suggests that an increased availability of fats in the body leads
to increased fat uptake by the heart. The heart only needs a certain amount of fat for
energy, which leaves the remaining fat in the heart tissue, possibly impairing proper heart
function. However, more information on the mechanisms behind the effects of fats on heart
metabolism is needed. This study will evaluate the impact of AO on the human heart's use of
fats for energy and on heart function.
This study will enroll both overweight and lean participants who will attend 4 to 7 study
visits. Visit 1 will consist of various screening tests, including a medical history,
physical exam, pregnancy test if applicable, routine blood test, and an echocardiogram
(ECHO) performed before and during exercise.
Visit 2 will consist of an abdominal fat and insulin sensitivity study. This will entail a
magnetic resonance imaging (MRI) test to image the heart and stomach, a dual energy x-ray
absorptiometry (DEXA) scan to measure total body fat and muscle content, and an insulin
sensitivity test to measure how well the hormone insulin controls blood sugar. The latter
test will require multiple blood draws over a 3-hour period.
Visits 3 and 4 will occur over a 2-week period. Both visits will consist of an overnight
stay at the General Clinical Research Center (GCRC) followed by a day of imaging studies.
During Visit 3, participants will first undergo a 4-hour whole body metabolism study, which
will include injection of a nonradioactive tracer through previously placed IVs, blood
draws, and breathing into a machine for approximately 15 minutes. Participants will then
undergo a positron emission tomographic (PET) heart metabolism study, which will also
involve tracer injections and blood draws. A resting ECHO test will also be done during the
PET study. Participants will be asked for permission to store a sample of their blood for a
period of up to 10 years to be used in future research studies on the heart. During Visit 4,
participants will undergo repeat tests from the third visit, except the PET study will
evaluate the heart's ability to use sugars instead of fats. This will complete the study
visits for all lean participants and some overweight participants and will entail 4 weeks of
participation.
Overweight participants may be asked to attend an additional three study visits during an
8-month weight management program at Washington University School of Medicine. Participants
will aim to lose 10% of their body weight over a 6-month period and to maintain that weight
loss for another 1- to 2-month stabilization period. At the end of the stabilization period,
participants will undergo repeat abdominal fat and insulin sensitivity studies during Visit
5, repeat whole body metabolism and heart metabolism studies during Visit 6, and repeat
whole body metabolism and glucose heart metabolism studies during Visit 7.
Inclusion Criteria:
- Class II abdominal obesity body mass index (BMI) between 35 kg/m2 and 39.9 kg/m2;
waist circumference of greater than 90 cm in women and greater than 105 cm in men
- Diagnosis of type 2 diabetes
- Sedentary lifestyle
Exclusion Criteria:
- History of cardiovascular disease
- Regular exerciser
- Occupy a strenuously active job
- No evidence of inducible myocardial ischemia on resting/stress ECHO
- No risk factors of coronary artery disease, heart valve disease, or left ventricular
dysfunction
- Left ventricular hypertrophy (based on measure in left ventricular mass index)
- No evidence of coronary artery disease based on clinical parameters or on rest/stress
ECHO
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