Development and Validation of a Measurement System for ...

Development and Validation of a Measurement System for Assessment of Energy Expenditure and Physical Activity in Prader-Willi Syndrome Kong Y. Chen, * Ming Sun, * Merlin G. Butler, f Travis Thompson,$ and Michael G. Carlson *, f Abstract CHEN, KONG Y., MING SUN, MERLIN G. BUTLER, TRAVIS THOMPSON, AND MICHAEL G. CARLSON. Development and validation of a measurement system for assessment of energy expenditure and physical activity in Prader-Willi syndrome. Obes Res. 1999;7:387-394. Objective: The morbid obesity associated with Prader-Willi syndrome (PWS) may result from either excessive energy intake or reduced energy expenditure (EE). In this report, we describe the development and validation of an ActivityEnergy Measurement System (AEMS) to measure EE and physical activity components in an environment approximating free-living conditions. Research Methods and Procedures: The AEMS consists of a live-in, whole-room indirect calorimeter equipped with a novel force platform floor system to enable simultaneous measurements of EE, physical activity, and work efficiency during spontaneous activities and standardized exercises. Free-living physical activity and estimated free-living EE are measured using portable triaxial accelerometers individually calibrated in each subject during their stay in the AEMS. Results: Representative data from two PWS patients and two matched control (CTR) subjects displayed EE during their inactive lifestyles. Discussion: This combination of methods will allow the quantification of daily EE and its components, the amount and energy cost of physical activity, and the relationships between body composition and EE, in order to determine Submitted for publication November 18, 1998. Accepted for publication in final form April 13, 1999. From the *Departments of Medicine and ?Pediatrics and $John F. Kennedy Center, Vanderbilt University. Nashville, TN 372324453, Address correspondence to Kong Y. Chen, C2104 MCN, I161 Garland Ave.. Nashville, TN 37232-2279. FAX: (615)-343-6229. E-mail: kong.chen@mcmail. vanderbilt.edu Copyright 0 1999 NAASO.

their roles in the development and maintenance of the morbid obesity in PWS.

Key words: mental retardation, behavior, energy metabolism

Introduction The morbid obesity associated with Prader-Willi syndrome (PWS) is the result of chronic imbalance between energy intake and energy expenditure (EE). However, it is difficult to obtain quantitative information regarding these two components of energy balance in PWS patients due to the mental and physical status of the patients. It is essential to understand the cause of obesity in PWS in order to determine rational treatment options. Although the abnormal eating behaviors and excessive energy intake are welldocumented (l), there is limited information available regarding EE in PWS patients. Techniques for measuring EE and physical activity in individuals with PWS may be major limiting factors due to the special requirements dictated by the behavioral, cognitive, and functional limitations in PWS. Several previous studies have attempted to measure EE in PWS patients. In one study (2), total daily EE was 47% lower in PWS compared to controls, but this difference was reduced to 14% when allowances were made for differences in fat-free mass (FFM). Basal or resting EE, corrected for FFM, was similar in PWS patients compared to obese controls, suggesting that the low daily EE in PWS patients was mainly a result of a reduced FFM, and possibly a lower level of physical activity, although there was no direct assessment of the latter. In another study (3), daily EE measured in a whole-room calorimeter was also lower in PWS patients compared to obese controls. However, no information was available on differences in FFM, which may have accounted for a large part of this difference. Hill et al. (4) reported that OBESITY RESEARCH Vol. 7 No. 4 July 1999 387

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the tight relationship usually observed between resting EE and FFM differed in children with PWS compared to lean or obese controls. The difference suggested initial low rates of EE in subjects with PWS, independent of FFM, but once patients gained a large amount of weight, this relationship normalized. Reduced physical activity in PWS subjects may be the major cause of their decreased energy requirements, as highlighted by Schoeller et al. (2). PWS patients are characterized by hypotonia during infancy, which decreases during the first 2 to 3 years of life, leaving a residual amount thereafter. This low muscle tone and lack of coordination may favor a sedentary lifestyle (5). However, few studies have attempted to quantify levels of physical activity in PWS. It has been reported that children with PWS are less physically active during play compared to normal children (5). Nardella et al. (6) attempted to assess physical activity in PWS subjects and controls at a summer camp over a 2-week period using actometers and pedometers. They reported a wide range of activity levels in subjects with PWS and slightly higher physical activity compared to normal children. These results were inconclusive with respect to physical activity in PWS and furthermore do not address the situation in a normal home environment. Because physical activity is an important component of daily EE, even in relatively sedentary lifestyles, this factor needs further examination. In this report, we describe a novel activity-energy measurement system (AEMS) that allows simultaneous measurement of EE and physical activity (7, 8) in PWS patients and obese controls under close to free-living conditions. Using the AEMS, studies are underway to examine the relationships between EE, physical activity, and body composition in PWS patients and their controls.

Methods AEMS The AEMS at Vanderbilt University combines a wholeroom indirect calorimeter with a large force platform floor system (7), as shown in Figure 1. Equipped with a desk, chair, toilet, sink, telephone, T V N C R , audio-system, and fold-down bed, the AEMS is designed to bridge the differences between laboratory and free-living conditions. The room calorimeter is an airtight environmental room measuring 2.6x3.4x2.4 m3 and contains 19,500 L in net volume. Temperature inside the calorimeter is precisely controlled (22.5kO.2"C). Oxygen consumption (VO,), carbon-dioxide production (VCO,), air flow rate, temperature (inside and ambient), barometric pressure, and humidity are sampled 60 times per second and integrated at the end of each minute to calculate EE (9). To ensure homogeneity of the air in the calorimeter, a special multi-channel air sampling system is incorporated (8). The oxygen (Magnos 4G) and carbon dioxide (Uras 3G) analyzers (both by Hartman and Braun) are 388 OBESITY RESEARCH Vol. 7 No. 4 July 1999

Figure I: A schematic of the activity-energy measurement system (AEMS).

calibrated before each test with reference gas, and on a regular basis with mixtures of pure gases by a precision mixing pump. The accuracy of the calorimeter is frequently validated by burning pure propane or ethyl alcohol at a variable rate inside the room (8). By comparing the EE measured by the calorimetry system and EE calculated from the rate of combustion, the system error of the AEMS is controlled under 1% for 24-hour recordings (8). The force platform, measuring 2.5x2.5 m2, covers the entire living area inside the whole-room indirect calorimeter and is supported by multiple precision force transducers (7). The force platform allows computer-aided measurement (60 times per second) of body position, displacement, and mechanical forces with an accuracy of 97% or higher (7). An electronic monitoring/sensing system in the calorimetric chamber consists of sensors and switches installed inside the T V N C R , underneath the sleeping mattress, inside the chair, and at the airlock door where the participant receives food to record patterns of physical activity. Eight additional event buttons are used by the subject to signal periods of sleeping, eating, and exercising. Therefore, the combination of the force platform, sensors, and event buttons provides the accurate determination of the nature, duration, and frequency of physical activities at each minute. Activity records are also kept by the observing research staff due to the limited abilities of some participants to operate the event button system. A member of the research staff stays in the anteroom outside of the AEMS during the entire study period, monitors the participants behavior though a glass window, communicates directly with the participant through an intercom, and instructs the participant to perform certain tasks, including standardized exercises. In addition, a VHS video camera provides continuous monitoring by nursing staff to ensure the safety of subjects with special needs (i.e., children, physically or mentally handicapped adults).

Measurement of EE and Its Components by AEMS A major advantage of the AEMS is the continuous measurements of EE and other physical activity parameters

A Unique Whole-Room Calorimeter System, Chen et al.

30

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Net efficiency =

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Figure 2: Minute-by-minute energy expenditure (EE) and mechanical work (MW) measurements and the calculation of net efficiency (a representative data from the male control participant, CTRm, age 1 I , weight 102.1 kg).

over extended periods of time (hours to days), from which some important components of EE can be identified and studied individually. EE is usually expressed as the absolute rate (e.g., kUminute), or it can be expressed as a ratio with respect to basal EE (e.g., metabolic equivalents, or METs). Resting EE (REE) is measured during the 30-minute period when the participant initially enters the AEMS after an overnight sleep and fast, while the participant is sitting in the chair with minimum body movement. Any periods of body motion detected by the force platform are automatically removed from the REE analysis. EE during sitting (EESIT) is the average EE during which the participant sits in the chair and without significant body motion. Periods of sitting are detected via the sensors in the chair and through the participant's center of gravity on the force platform. EE during physical activity (EEACT) is defined as the increase in EE above the REE during body movements such as walking or other spontaneous physical activities. The sudden change in mechanical work measured by the force platform marks the starting and ending times of each activity. EEACT is calculated using an automated computer program by integrating the area under the EE/time curve and subtracting REE (Figure 2). Total EE (TEE) during the entire study period is obtained by summing the EE of each minute over the entire study period during which the participant stayed in the AEMS. TEE can also be expressed as the average rate of EE during the stay (kJ/minute). EE during the stay in the AEMS can also be divided into different intensity categories in order to study the patterns and distributions. Measurement of Physical Activities by AEMS Another important advantage of the AEMS over other existing methods is that the force platform can precisely

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7:30AM 8:30AM 9:30AM 10:30AM11:30AM 1230PM 1:30PM 2:30PM

Clock Time Figure 3: Measured energy expenditure (EE), respiratory quotient (RQ), body displacement (DP), horizontal mechanical work (HMW), and vertical mechanical work (VMW) during one study period for a study participant (CTRm).

determine variation in participant's physical movement, thus obtaining quantitative measures of external mechanical work performed during various physical activities. Body motion in terms of the cumulative distance a subject travels over time (rate of displacement, DP, or speed) was measured by the force platform in the AEMS. This design of the AEMS is believed to be the first to give an accurate measure of the distance and speed in which the participant has traveled inside the room (7). Mechanical Work (MW) is obtained by calculating force, acceleration in x-, y-, and z-axes (time derivative from speed), and body mass. As shown in Figure 3, the measurements include both horizontal and vertical MW components (7). Horizontal work (HMW) is produced when the body's center of gravity moves horizontally such as during walking, while vertical work (VMW) typically relates to posture changes, such as changes between sitting and standing. During periods of exercise, net efficiency is calculated as the MW performed divided by the associated EEAc, (7,8), e.g., MW / EE,, (Figure 2). Net efficiency of other OBESITY RESEARCH Vol. 7 No. 4 July 1999 389

A Unique Whole-Room Calorimeter System, Chen et al.

pontaneous physical activities can also be expressed as the ratio of total MW and total EE,,. Thus, using this combination of the whole-room indirect calorimeter and the force platform, net efficiency of different types of physical activity and exercise is determined for each participant in one system.

Measurement of Free-Living EE and Physical Activity by Triaxial Accelerometers A triaxial piezoelectric accelerometer (Tritrac-R3D activity monitor; Hemokinetics, Inc., Madison, WI) is used to record minute-by-minute physical activities in the form of acceleration measurements in three dimensions (x or antero-posterior axis, y or medial-lateral axis, and z or vertical axis). The monitor, weighing 170 grams and measuring 1 1. Ix6.7x3.2 cm, is worn on the right hip in a nylon pouch secured to a belt at the waistline during all activities in the AEMS. The accelerometer output is expressed as integrated acceleration over each minute in the three axes. The subject’s physical characteristics (gender, age, height, and weight) are entered upon initializing the monitor. This information is used to calculate an individual’s resting EE based on established predictive equations (shown in equations l and 2) (10).The prediction of EE during all physical activities is calculated internally using a regression equation from the vector magnitude of the acceleration registrations in the x-, y-, and z-axes. To model EE from body acceleration data measured by the Tritrac-R3D monitor, a two-component power model was used (equation 3). In brief, body motion in the horizontal plane (x- and y-axes) was combined as one component (denoted H), and acceleration in the vertical plane (zaxis) as the other component (denoted V). Each component was modeled by a linear and a nonlinear power parameters to model individual EE,,. Detailed description of this model has been published previously (10). Subjects Representative experiments were carried out in two PWS patients and two controls of similar age, gender, weight, adiposity and mental capacity (Table I). All volunteers are non-smokers, non-diabetic, and have normal renal, hepatic, and thyroid function as judged from routine laboratory tests. The diagnosis of PWS was established according to the criteria of Holm (1 I ) and confirmed by genetic analysis. Height was recorded to the nearest 0.5 cm, and weight was measured to the nearest 0.1 kg using a digital scale. Body composition was determined by dual-energy X-ray absorptiometry (1 2-14). Experimental Protocol Informed consent was obtained prior to participation from each subject, and when appropriate from a parent or a legal guardian. The study protocol was reviewed and ap390 OBESITY RESEARCH Vol. 7 No. 4 July 1999

Table 1. Subject characteristics PWS Male Female ~

Age (years.month) Weight (kg) Height (cm) BMI (kg/m2) Body fat (%) FFM (kg) ~~

~

Controls Male Female

~~~

16.2 101.4 151.1 44.5 49.0 51.6

~

34.7 54.4 147.3 25.2 35.2 35.4

11.0 102.1 167.5 36.4 53.2 48.0

23.5 46.7 147.3 21.6 20.1 37.4

~

PWS, Prader-Willi syndrome; BMI, body mass index; FFM, fatfree mass. Body composition was determined by dual-energy Xray absorptiometry.

proved by the Institutional Review Board of the Vanderbilt University. The participant is admitted to the AEMS at 07: 15 a.m. after an overnight fast. EE and physical activity were measured continuously from 7:30 a.m.-3:30 p.m. During the entire measuring period, the participant is monitored and given instructions by a member of the research staff who stays in the anteroom next to the AEMS. The study protocol in the AEMS is as follows. Upon entering the AEMS, the participant rests in the chair for 20-30 minutes for REE measurement. Meals are served at 8:OO a.m. and 12:OO p.m. In addition, light snacks are provided at approximately 1O:OO a.m. and 2:OO p.m. The amount and the macronutrient content of the food are designed to reflect their normal energy intake, estimated from a 7-day diet recall by the subjects or their parent or guardian. The participants are instructed to walk during 2 exercise sessions (10-minutes each, with a 10-minute break between them) during the morning (9:30-1O:OO) and two exercise sessions in the afternoon (2:30-3:OO). At 3:30 p.m., the participant is escorted out of the AEMS at the conclusion of the 8-hour measurement period. Each participant also wears the portable accelerometer during the entire stay in the AEMS and at least 3 days following for measurement of free-living physical activity and EE as described above.

Statistical Analysis The data were expressed as means k Standard Deviation. Relationships between variables were determined using the Pearson product-moment correlation coefficients ( r ) . Analysis of variance (ANOVA) was used to compare the differences between measured and estimated EE values. p value of 0.05 was used as the threshold. All data processing and analyses were performed by either MATLAB (version 5 , Mathworks Inc., Natick, MA) or SPSS for Windows (version 7, SPSS Inc., Chicago, IL) software packages.

A Unique Whole-Room Calorimeter System, Chen et al

Results The physical characteristics of the study participants are listed in Table 1. Representative examples of energy expenditure (EE) and physical activity (PA) measurements are illustrated in describing the data measurements and processing (Figures 2 and 3). The measurement period in the AEMS averaged 46826 minutes (range, 462472 minutes). In all participants, the AEMS detected a large percentage of the study periods was spent in sedentary PA, including 66210% of the entire time in sitting (either resting, watching TV, or performing other non-weight-baring PA). The MW measured by force platform was used to determine the exact duration of walking exercise periods, averaging 41k23 min (range, 10-63 minutes) for these participants. Also, by using the force platform of the AEMS, measured total DP varied from 3 1.1 to 69.0 meters/8 hours; total mechanical work (MW) averaged 147.221 10.2 kJ/8 hours; and the horizontal and vertical MW averaged 42.5k33.9 and 104.7279.7 kJ/8 hours, respectively. Additional parameters of PA are shown in Table 2. EE measurements using the indirect calorimeter of the AEMS are summarized in Table 3. For these participants, total EE averaged 341221147 kJ/8 hours. The rate of EE remained 5 1 .5 METs for 80%-95% of the 8-hour measurement period. EE during spontaneous physical activity (SPA) and during walking exercise periods increased to 6.822 1.94 and 10.9124.62 kJ/minute, respectively. The ratio of total to resting EE was 1.3920.11 (vary between 1.26 and 1S3). Net efficiency was calculated by using the ratio of MW and EE,,, averaging 13.8+6.9% during SPA and 17.5k5.3% during walking exercise (Table 3) for the entire group. Net efficiency tended to be reduced in PWS subjects during both SPA (8.0% vs. 19.6%) and walking exercise (13.1% vs. 2 1.9%) as compared to their controls. During the 8-hour measurement period in the AEMS, body acceleration counts recorded each minute by the triaxial accelerometers (Tritrac) were significantly correlated with the simultaneous force platform measurements of body displacement ( r = 0.79k0.17, p