Effect of Weight Loss on Myocardial Metabolism and Cardiac Relaxation in Obese Adults

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Obesity	Behavioral: Diet; Procedure: Gastric bypass surgery	Not Applicable

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')).

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	51 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Basic Science
Official Title:	Effect of Weight Loss on Myocardial Oxygen Consumption and Left Ventricular Relaxation in Obese Adults
Study Start Date :	June 2003
Actual Primary Completion Date :	June 2014
Actual Study Completion Date :	June 2014

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Diet; Participants who received counseling and instruction about weight loss through diet and exercise	Behavioral: Diet; 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.
Experimental: Gastric bypass surgery; Participants who received gastric bypass surgery	Procedure: Gastric 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.

Outcome Measures

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Primary Outcome Measures :

1. Total Myocardial Oxygen Consumption (MVO2) [ Time Frame: 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.
2. Total Myocardial Fatty Acid (FA) Utilization [ Time Frame: 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.
3. Total Myocardial Fatty Acid (FA) Oxidation [ Time Frame: 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 Outcome Measures :

1. Left Ventricular (LV) Relaxation (E') [ Time Frame: 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.
2. Septal Ratio (E/E') [ Time Frame: 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.
3. Left Ventricular (LV) Mass [ Time Frame: 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.
4. Mean Heart Rate [ Time Frame: 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.
5. Mean Arterial Pressure [ Time Frame: 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.
6. Mean Body Mass Index [ Time Frame: 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.
7. Mean Total Serum Cholesterol and Triglycerides [ Time Frame: 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).
8. Mean Homeostasis Model Assessment of Insulin Resistance [ Time Frame: 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.

Eligibility Criteria

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Ages Eligible for Study:	21 Years to 50 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Missouri
Washington University Medical School
Saint Louis, Missouri, United States, 63110

Sponsors and Collaborators

Washington University School of Medicine

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:	Robert Gropler, MD	Washington University Medical School

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications of Results:

Lin CH, Kurup S, Herrero P, Schechtman KB, Eagon JC, Klein S, Dávila-Román VG, Stein RI, Dorn GW 2nd, Gropler RJ, Waggoner AD, Peterson LR. Myocardial oxygen consumption change predicts left ventricular relaxation improvement in obese humans after weight loss. Obesity (Silver Spring). 2011 Sep;19(9):1804-12. doi: 10.1038/oby.2011.186. Epub 2011 Jul 7.

Other Publications:

Allison DB, Fontaine KR, Manson JE, Stevens J, VanItallie TB. Annual deaths attributable to obesity in the United States. JAMA. 1999 Oct 27;282(16):1530-8.

Hu FB, Stampfer MJ, Manson JE, Grodstein F, Colditz GA, Speizer FE, Willett WC. Trends in the incidence of coronary heart disease and changes in diet and lifestyle in women. N Engl J Med. 2000 Aug 24;343(8):530-7.

Folsom AR, Prineas RJ, Kaye SA, Munger RG. Incidence of hypertension and stroke in relation to body fat distribution and other risk factors in older women. Stroke. 1990 May;21(5):701-6.

Carey VJ, Walters EE, Colditz GA, Solomon CG, Willett WC, Rosner BA, Speizer FE, Manson JE. Body fat distribution and risk of non-insulin-dependent diabetes mellitus in women. The Nurses' Health Study. Am J Epidemiol. 1997 Apr 1;145(7):614-9.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Peterson LR, Saeed IM, McGill JB, Herrero P, Schechtman KB, Gunawardena R, Recklein CL, Coggan AR, DeMoss AJ, Dence CS, Gropler RJ. Sex and type 2 diabetes: obesity-independent effects on left ventricular substrate metabolism and relaxation in humans. Obesity (Silver Spring). 2012 Apr;20(4):802-10. doi: 10.1038/oby.2011.208. Epub 2011 Aug 4.

Responsible Party:	Washington University School of Medicine
ClinicalTrials.gov Identifier:	NCT00572624 History of Changes
Other Study ID Numbers:	05-0523 (201105066); P01HL013851-43 ( U.S. NIH Grant/Contract )
First Posted:	December 13, 2007
Results First Posted:	May 15, 2017
Last Update Posted:	May 15, 2017
Last Verified:	May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Washington University School of Medicine:

Heart Metabolism; Obesity; Weight loss; Gastric bypass surgery; Diet and exercise

Additional relevant MeSH terms:

Weight Loss; Body Weight Changes; Body Weight; Signs and Symptoms