Obesity
Conditions
Keywords
Heart Metabolism, Obesity, Weight loss, Gastric bypass surgery, Diet and exercise
Brief summary
Obesity adversely affects myocardial (muscular heart tissue) metabolism, efficiency, and diastolic function. The objective of this study was to determine if weight loss could improve obesity-related myocardial metabolism and efficiency and if these improvements were directly related to improved diastolic function.
Detailed description
This was a prospective, interventional study in obese adults ages 21 to 50 years of age to determine whether weight loss could improve obesity-related myocardial metabolism and efficiency. Two different mechanisms of weight loss were studied: diet and exercise and gastric bypass surgery. Positron emission tomography (PET) was used to quantitate myocardial oxygen consumption (MVO2) and myocardial fatty acid (FA) metabolism. Echocardiography with tissue Doppler imaging was used to quantify cardiac structure, systolic and diastolic function (left ventricular (LV) relaxation (E') and septal ratio (E/E')).
Interventions
BEHAVIORALDiet
Participants attended 20 group behavioral modification sessions led by a behaviorist, a registered dietician, and a physical therapist. The meal plans ranged from 1200 to 1500 kilocalories per day, depending on subject sex and BMI, and were designed to achieve ≤1% body weight loss/week. Participants completed daily food records, and were taught a variety of weight management skills. The exercise component included strength, flexibility, balance, and endurance instruction, gradually increasing to 30 minutes of exercise 5 days/week.
PROCEDUREGastric bypass surgery
The same surgeon performed all bypass procedures using standard techniques. A small (\ 20 ml) proximal gastric pouch was created by stapling the stomach, and a 75-cm Roux-en-Y limb was constructed by transecting the jejunum distal to the ligament of Treitz, and creating a jejunojejunostomy 75 cm distal to the transection.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Body mass index (BMI) \> 30 kg/m\^2 * Sedentary lifestyle
Exclusion criteria
* Body weight \>159 kg * Insulin-requiring diabetes * Heart failure * History of coronary artery disease * Chest pain * Untreated sleep apnea * Being an active smoker * Pregnant, lactating, or postmenopausal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Myocardial Oxygen Consumption (MVO2) | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | The evening before an imaging study, all participants were given a meal containing 12 kcal/kg adjusted body weight (=ideal body weight + ((actual body weight-ideal body weight) x 0.25)). Participants fasted until their imaging studies were completed. Myocardial oxygen consumption (MVO2) was measured using positron emission tomography (PET) following injection of 1-\^11C-acetate. Total MVO2 was calculated by multiplying the MVO2 measure by left ventricular weight. |
| Total Myocardial Fatty Acid (FA) Utilization | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | The evening before an imaging study, all participants were given a meal containing 12 kcal/kg adjusted body weight (=ideal body weight + ((actual body weight-ideal body weight) x 0.25)). Participants fasted until their imaging studies were completed. Myocardial blood flow was measured using positron emission tomography (PET) following injection of \^30O-water. Myocardial fatty acid (FA) utilization was measured using PET after injection of 1-\^11C-palmitate. The calculations that describe the relationship between the different measures of myocardial FA metabolism are: FA utilization/gram = blood flow/gram × FA uptake/gram × \[average plasma free FA at the time of the 1-11C-palmitate injection\]; FA utilization/gram = FA oxidation/gram + esterification/gram. Total fatty acid utilization was calculated by multiplying the fatty acid utilization rate by left ventricular weight. |
| Total Myocardial Fatty Acid (FA) Oxidation | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | The evening before an imaging study, all participants were given a meal containing 12 kcal/kg adjusted body weight (=ideal body weight + ((actual body weight-ideal body weight) x 0.25)). Participants fasted until their imaging studies were completed. Myocardial fatty acid utilization was measured using positron emission tomography (PET) after injecting 1-\^11C-palmitate. Total fatty acid oxidation was calculated by multiplying the fatty acid oxidation rate by left ventricular weight. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Heart Rate | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | Heart rate was measured at scheduled physical examinations. |
| Mean Arterial Pressure | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | Mean arterial pressure was measured at scheduled physical examinations. |
| Left Ventricular (LV) Relaxation (E') | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | Immediately following MVO2 measurement, complete two-dimensional, M-mode, and Doppler echocardiographic studies were performed using second harmonic imaging. Left ventricular relaxation (E') was measured at the lateral annulus. All reported measurements represent the average of three consecutive cardiac cycles. A single investigator blinded to all clinical parameters evaluated all echocardiograms. |
| Mean Total Serum Cholesterol and Triglycerides | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | Blood testing was conducted at scheduled times during the study. Serum cholesterol and triglycerides were measured by the enzymatic method (Roche Diagnostics). |
| Mean Homeostasis Model Assessment of Insulin Resistance | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | The homeostasis model assessment of insulin resistance (HOMA) was used to calculate insulin resistance using the first AM, fasting glucose and insulin levels. Plasma insulin levels were measured by radioimmunoassay, and glucose levels were measured by automated hexokinase assay. A HOMA score of \<3 represents normal insulin resistance, a score between 3 and 5 moderate insulin resistance, and a score of 5 or higher represents severe insulin resistance. |
| Mean Body Mass Index | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | Participant weight and height was measured at scheduled physical examinations. Body mass index was calculated as participant body weight in kilograms divided by their height in meters squared. |
| Septal Ratio (E/E') | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | Immediately following MVO2 measurement, complete two-dimensional, M-mode, and Doppler echocardiographic studies were performed using second harmonic imaging. The early diastolic (E) velocity was measured, left ventricular relaxation (E') was measured at the lateral mitral annulus, and the E/E'(septal) ratio was calculated. All reported measurements represent the average of three consecutive cardiac cycles. A single investigator blinded to all clinical parameters evaluated all echocardiograms. The normal septal ratio from the lateral mitral annulus is \<5, a ratio from 5 to 10 is indeterminate, and a ratio of \>10 indicates elevated left atrial pressure. |
| Left Ventricular (LV) Mass | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | Immediately following MVO2 measurement, complete two-dimensional, M-mode, and Doppler echocardiographic study were performed using second harmonic imaging. Left ventricular (LV) mass was measured using the area-length method. All reported measurements represent the average of three consecutive cardiac cycles. A single investigator blinded to all clinical parameters evaluated all echocardiograms. |
Countries
United States
Participant flow
Recruitment details
Gastric bypass surgery participants were recruited from the Barnes-Jewish Hospital bariatric surgery center. Diet and exercise participants were recruited from the Volunteer for Health office of Washington University School of Medicine.
Participants by arm
| Arm | Count |
|---|---|
| Diet Participants who received counseling and instruction about weight loss through diet and exercise | 20 |
| Gastric Bypass Surgery Participants who received gastric bypass surgery | 10 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Admitted to being a smoker | 1 | 0 |
| Overall Study | Health issues unrelated to the study | 1 | 0 |
| Overall Study | Lost to Follow-up | 10 | 4 |
| Overall Study | Medication change | 1 | 0 |
| Overall Study | Problem with vascular access | 1 | 0 |
| Overall Study | Refused to do the stress test | 1 | 0 |
| Overall Study | Started a new job-- no time for study | 1 | 0 |
| Overall Study | Wanted to do a different diet program | 1 | 0 |
Baseline characteristics
| Characteristic | Diet | Total | Gastric Bypass Surgery |
|---|---|---|---|
| Age, Customized ≥ 21 and ≤ 50 years of age | 20 Participants | 30 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 30 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 5 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 25 Participants | 10 Participants |
| Region of Enrollment United States | 20 participants | 30 participants | 10 participants |
| Sex: Female, Male Female | 12 Participants | 22 Participants | 10 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 37 | 0 / 14 |
| serious Total, serious adverse events | 0 / 37 | 0 / 14 |
Outcome results
Primary
Total Myocardial Fatty Acid (FA) Oxidation
The evening before an imaging study, all participants were given a meal containing 12 kcal/kg adjusted body weight (=ideal body weight + ((actual body weight-ideal body weight) x 0.25)). Participants fasted until their imaging studies were completed. Myocardial fatty acid utilization was measured using positron emission tomography (PET) after injecting 1-\^11C-palmitate. Total fatty acid oxidation was calculated by multiplying the fatty acid oxidation rate by left ventricular weight.
Time frame: Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Population: Participants who lost 5% of their body weight during the study and for whom data are available
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diet | Total Myocardial Fatty Acid (FA) Oxidation | Baseline | 134 nmol/g/min | Standard Deviation 37 |
| Diet | Total Myocardial Fatty Acid (FA) Oxidation | Post-intervention | 128 nmol/g/min | Standard Deviation 37 |
| Gastric Bypass Surgery | Total Myocardial Fatty Acid (FA) Oxidation | Baseline | 141 nmol/g/min | Standard Deviation 47 |
| Gastric Bypass Surgery | Total Myocardial Fatty Acid (FA) Oxidation | Post-intervention | 127 nmol/g/min | Standard Deviation 50 |
Primary
Total Myocardial Fatty Acid (FA) Utilization
The evening before an imaging study, all participants were given a meal containing 12 kcal/kg adjusted body weight (=ideal body weight + ((actual body weight-ideal body weight) x 0.25)). Participants fasted until their imaging studies were completed. Myocardial blood flow was measured using positron emission tomography (PET) following injection of \^30O-water. Myocardial fatty acid (FA) utilization was measured using PET after injection of 1-\^11C-palmitate. The calculations that describe the relationship between the different measures of myocardial FA metabolism are: FA utilization/gram = blood flow/gram × FA uptake/gram × \[average plasma free FA at the time of the 1-11C-palmitate injection\]; FA utilization/gram = FA oxidation/gram + esterification/gram. Total fatty acid utilization was calculated by multiplying the fatty acid utilization rate by left ventricular weight.
Time frame: Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Population: Participants who lost 5% of their body weight during the study and for whom data are available
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diet | Total Myocardial Fatty Acid (FA) Utilization | Baseline | 148 nmol/g/min | Standard Deviation 38 |
| Diet | Total Myocardial Fatty Acid (FA) Utilization | Post-intervention | 144 nmol/g/min | Standard Deviation 36 |
| Gastric Bypass Surgery | Total Myocardial Fatty Acid (FA) Utilization | Baseline | 166 nmol/g/min | Standard Deviation 48 |
| Gastric Bypass Surgery | Total Myocardial Fatty Acid (FA) Utilization | Post-intervention | 148 nmol/g/min | Standard Deviation 79 |
Primary
Total Myocardial Oxygen Consumption (MVO2)
The evening before an imaging study, all participants were given a meal containing 12 kcal/kg adjusted body weight (=ideal body weight + ((actual body weight-ideal body weight) x 0.25)). Participants fasted until their imaging studies were completed. Myocardial oxygen consumption (MVO2) was measured using positron emission tomography (PET) following injection of 1-\^11C-acetate. Total MVO2 was calculated by multiplying the MVO2 measure by left ventricular weight.
Time frame: Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Population: Participants who lost 5% of their body weight during the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diet | Total Myocardial Oxygen Consumption (MVO2) | Baseline | 1064 µmol/min | Standard Deviation 318 |
| Diet | Total Myocardial Oxygen Consumption (MVO2) | Post-intervention | 947 µmol/min | Standard Deviation 309 |
| Gastric Bypass Surgery | Total Myocardial Oxygen Consumption (MVO2) | Baseline | 1202 µmol/min | Standard Deviation 373 |
| Gastric Bypass Surgery | Total Myocardial Oxygen Consumption (MVO2) | Post-intervention | 835 µmol/min | Standard Deviation 232 |
Secondary
Left Ventricular (LV) Mass
Immediately following MVO2 measurement, complete two-dimensional, M-mode, and Doppler echocardiographic study were performed using second harmonic imaging. Left ventricular (LV) mass was measured using the area-length method. All reported measurements represent the average of three consecutive cardiac cycles. A single investigator blinded to all clinical parameters evaluated all echocardiograms.
Time frame: Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Population: Participants who lost 5% of their body weight during the study and for whom data are available
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diet | Left Ventricular (LV) Mass | Baseline | 186 grams | Standard Deviation 34 |
| Diet | Left Ventricular (LV) Mass | Post-intervention | 186 grams | Standard Deviation 32 |
| Gastric Bypass Surgery | Left Ventricular (LV) Mass | Baseline | 180 grams | Standard Deviation 24 |
| Gastric Bypass Surgery | Left Ventricular (LV) Mass | Post-intervention | 141 grams | Standard Deviation 20 |
Secondary
Left Ventricular (LV) Relaxation (E')
Immediately following MVO2 measurement, complete two-dimensional, M-mode, and Doppler echocardiographic studies were performed using second harmonic imaging. Left ventricular relaxation (E') was measured at the lateral annulus. All reported measurements represent the average of three consecutive cardiac cycles. A single investigator blinded to all clinical parameters evaluated all echocardiograms.
Time frame: Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Population: Participants who lost 5% of their body weight during the study and for whom data are available
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diet | Left Ventricular (LV) Relaxation (E') | Baseline | 14.0 cm/second | Standard Deviation 2.7 |
| Diet | Left Ventricular (LV) Relaxation (E') | Post-intervention | 14.1 cm/second | Standard Deviation 2.2 |
| Gastric Bypass Surgery | Left Ventricular (LV) Relaxation (E') | Baseline | 8.2 cm/second | Standard Deviation 1.2 |
| Gastric Bypass Surgery | Left Ventricular (LV) Relaxation (E') | Post-intervention | 10.4 cm/second | Standard Deviation 1.8 |
Secondary
Mean Arterial Pressure
Mean arterial pressure was measured at scheduled physical examinations.
Time frame: Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Population: Participants who lost 5% of their body weight during the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diet | Mean Arterial Pressure | Baseline | 89 mm Hg | Standard Deviation 9 |
| Diet | Mean Arterial Pressure | Post-intervention | 89 mm Hg | Standard Deviation 10 |
| Gastric Bypass Surgery | Mean Arterial Pressure | Baseline | 89 mm Hg | Standard Deviation 6 |
| Gastric Bypass Surgery | Mean Arterial Pressure | Post-intervention | 86 mm Hg | Standard Deviation 9 |
Secondary
Mean Body Mass Index
Participant weight and height was measured at scheduled physical examinations. Body mass index was calculated as participant body weight in kilograms divided by their height in meters squared.
Time frame: Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Population: Participants who lost 5% of their body weight during the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diet | Mean Body Mass Index | Post-intervention | 36 kg/m^2 | Standard Deviation 7 |
| Diet | Mean Body Mass Index | Baseline | 39 kg/m^2 | Standard Deviation 6 |
| Gastric Bypass Surgery | Mean Body Mass Index | Baseline | 44 kg/m^2 | Standard Deviation 7 |
| Gastric Bypass Surgery | Mean Body Mass Index | Post-intervention | 29 kg/m^2 | Standard Deviation 5 |
Secondary
Mean Heart Rate
Heart rate was measured at scheduled physical examinations.
Time frame: Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Population: Participants who lost 5% of their body weight during the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diet | Mean Heart Rate | Baseline | 69 beats per minute | Standard Deviation 11 |
| Diet | Mean Heart Rate | Post-intervention | 61 beats per minute | Standard Deviation 12 |
| Gastric Bypass Surgery | Mean Heart Rate | Baseline | 72 beats per minute | Standard Deviation 13 |
| Gastric Bypass Surgery | Mean Heart Rate | Post-intervention | 65 beats per minute | Standard Deviation 17 |
Secondary
Mean Homeostasis Model Assessment of Insulin Resistance
The homeostasis model assessment of insulin resistance (HOMA) was used to calculate insulin resistance using the first AM, fasting glucose and insulin levels. Plasma insulin levels were measured by radioimmunoassay, and glucose levels were measured by automated hexokinase assay. A HOMA score of \<3 represents normal insulin resistance, a score between 3 and 5 moderate insulin resistance, and a score of 5 or higher represents severe insulin resistance.
Time frame: Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Population: Participants who lost 5% of their body weight during the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diet | Mean Homeostasis Model Assessment of Insulin Resistance | Baseline | 3.8 units on a scale | Standard Deviation 2 |
| Diet | Mean Homeostasis Model Assessment of Insulin Resistance | Post-intervention | 2.7 units on a scale | Standard Deviation 1.5 |
| Gastric Bypass Surgery | Mean Homeostasis Model Assessment of Insulin Resistance | Baseline | 5.5 units on a scale | Standard Deviation 5.3 |
| Gastric Bypass Surgery | Mean Homeostasis Model Assessment of Insulin Resistance | Post-intervention | 0.9 units on a scale | Standard Deviation 0.4 |
Secondary
Mean Total Serum Cholesterol and Triglycerides
Blood testing was conducted at scheduled times during the study. Serum cholesterol and triglycerides were measured by the enzymatic method (Roche Diagnostics).
Time frame: Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Population: Participants who lost 5% of their body weight during the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diet | Mean Total Serum Cholesterol and Triglycerides | Total serum cholesterol, baseline | 182 mg/dl | Standard Deviation 38 |
| Diet | Mean Total Serum Cholesterol and Triglycerides | Total serum cholesterol, post-intervention | 153 mg/dl | Standard Deviation 35 |
| Diet | Mean Total Serum Cholesterol and Triglycerides | Serum triglycerides, post-intervention | 118 mg/dl | Standard Deviation 73 |
| Diet | Mean Total Serum Cholesterol and Triglycerides | Serum triglycerides, baseline | 153 mg/dl | Standard Deviation 112 |
| Gastric Bypass Surgery | Mean Total Serum Cholesterol and Triglycerides | Serum triglycerides, post-intervention | 72 mg/dl | Standard Deviation 21 |
| Gastric Bypass Surgery | Mean Total Serum Cholesterol and Triglycerides | Total serum cholesterol, baseline | 167 mg/dl | Standard Deviation 33 |
| Gastric Bypass Surgery | Mean Total Serum Cholesterol and Triglycerides | Total serum cholesterol, post-intervention | 136 mg/dl | Standard Deviation 27 |
| Gastric Bypass Surgery | Mean Total Serum Cholesterol and Triglycerides | Serum triglycerides, baseline | 168 mg/dl | Standard Deviation 90 |
Secondary
Septal Ratio (E/E')
Immediately following MVO2 measurement, complete two-dimensional, M-mode, and Doppler echocardiographic studies were performed using second harmonic imaging. The early diastolic (E) velocity was measured, left ventricular relaxation (E') was measured at the lateral mitral annulus, and the E/E'(septal) ratio was calculated. All reported measurements represent the average of three consecutive cardiac cycles. A single investigator blinded to all clinical parameters evaluated all echocardiograms. The normal septal ratio from the lateral mitral annulus is \<5, a ratio from 5 to 10 is indeterminate, and a ratio of \>10 indicates elevated left atrial pressure.
Time frame: Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Population: Participants who lost 5% of their body weight during the study and for whom data are available
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diet | Septal Ratio (E/E') | Baseline | 5.9 ratio | Standard Deviation 1.1 |
| Diet | Septal Ratio (E/E') | Post-intervention | 6.1 ratio | Standard Deviation 1.1 |
| Gastric Bypass Surgery | Septal Ratio (E/E') | Baseline | 12.5 ratio | Standard Deviation 2.1 |
| Gastric Bypass Surgery | Septal Ratio (E/E') | Post-intervention | 8.1 ratio | Standard Deviation 0.9 |