MEASUREMENT OF AGREEMENT OF RESTING METABOLIC RATE BETWEEN INDIRECT CALORIMETERY AND MULTIPLE ESTIMATION MODELS IN ADULTS USING AIR DISPLACEMENT PLETHYSMOGRAPHY A Thesis Presented to The Graduate Faculty of The University of Akron In Partial Fulfillment Of the Requirements for the Degree Master of Science Brian Miller December, 2013 MEASUREMENT OF AGREEMENT OF RESTING METABOLIC RATE BETWEEN INDIRECT CALORIMETERY AND MULTIPLE ESTIMATION MODELS IN ADULTS USING AIR DISPLACEMENT PLETHYSMOGRAPHY Brian Miller Thesis Approved: Accepted: _______________________________ Advisor Dr. Ronald Otterstetter ____________________________ Department Chair Dr. Victor Pinheiro _______________________________ Committee Member Mrs. Michelle Boltz ____________________________ Interim Dean of the College Dr. Susan G. Clark _______________________________ Committee Member Dr. Mark Fridline ____________________________ Dean of the Graduate School Dr. George R. Newkome ______________________________ Date ii ABSTRACT PURPOSE: Air displacement plethysmography (ADP) is a well validated method for estimating body composition. Similarly, predictive equations derived from regression techniques based on large samples are extensively utilized in estimating resting metabolic rate (RMR). The Cos Med BOD POD System®, which operates via ADP, utilizes a predictive equation to estimate RMR based on the Nelson (1992) model. However, the agreement of this predictive model with indirect calorimetery (IC) has come into question. The aim of this study is to investigate the agreement of RMR estimation models using ADP measures against a gas exchange IC system in addition to other predictive RMR models. METHODS: Sixty-six apparently healthy subjects (25 men, 41 women) participated in and completed the study. RMR measurements were obtained from the Parvomedics TrueOne 2400 System® and The Cos Med BOD POD System® within 10 minutes of one another. IC RMR estimates were tested against nine other validated models using ADP measures via ANOVA techniques with multiple comparisons testing and Bland Altman analysis. RESULTS: The Nelson (1992) model under-predicted RMR compared to IC (P<0.001). The Dore et al. (1982) model was the best predictor of RMR compared to the IC measures (p=0.907). However, by sex, the Dore et al. (1982) model significantly underpredicted RMR for men and over-predicted for women when compared to the IC measure (men: -231±87kcal, p<0.014 and women: 150±43kcal, p <0.001, respectively). iii CONCLUSIONS: The current RMR estimation model using ADP measures underpredicts total caloric needs. The Dore et al. (1982) model more accurately predicted RMR in the entire sample but significantly varied when split by sex. iv DEDICATION This manuscript is dedicated to the Memory of my late grandmother, Rita M. Janke (March 31, 1930 – September 12, 2013 R.I.P.). v ACKNOWLEDGEMENTS I would like to thank my mentors from The University of Akron including Dr. Deborah Marino and Mrs. Michelle Boltz from nutrition, Dr. Ronald Otterstetter from exercise physiology, and Dr. Mark Fridline from statistics. Without their devotion and friendship, this journey would have been impossible. I would have not been able to complete this thesis without the love and support from my wife Elise, my mother-in-law Denise, and my Basset Hound, Sprinkles. vi TABLE OF CONTENTS Page LIST OF TABLES ............................................................................................ ix LIST OF FIGURES ........................................................................................... x CHAPTER I. INTRODUCTION .................................................................................... 1 II. BACKGROUND OF THE STUDY ......................................................... 3 Air Displacement Plethysmography ................................................... 3 Estimation of Resting Metabolic Rate ................................................ 6 Indirect Calorimetery .......................................................................... 9 Agreement between Estimation Methods ......................................... 10 III METHODOLOGY ................................................................................. 13 Hypothesis and Statement of Objectives .......................................... 13 Subjects and Inclusion Criteria ......................................................... 13 Testing Procedure ............................................................................. 14 Statistical Analysis ............................................................................ 15 IV. RESULTS ............................................................................................... 16 V. DISCUSSION ......................................................................................... 21 vii Limitations ........................................................................................ 24 VI. CONCLUSION ...................................................................................... 25 REFERENCES ................................................................................................ 26 APPENDICES ................................................................................................. 29 APPENDIX A: LETTER OF INFORMED CONSENT ........................ 30 APPENDIX B: IRB LETTER OF APPROVAL .................................... 32 viii LIST OF TABLES Table Page 1 RMR Estimation Models and Derivation Specifics ................................8 2 Sample Characteristics ...........................................................................16 3 Agreement between Estimation Models and RMR-C ............................17 4 Results of Repeated Measures ANOVA ................................................18 5 Paired Sample t-test and Limits of Agreement .......................................20 ix LIST OF FIGURES Figure 1 Page Box Plots of Estimated RMR by Model .................................................19 x CHAPTER I INTRODUCTION Accurate resting metabolic rate (RMR) measurements are necessary for professionals to provide appropriate nutrition and exercise recommendations. These measurements are an important component of clinical and professional settings to provide important information regarding energy requirements and macronutrient utilization at rest (Cooper et al., 2009). Inaccurate measurements of RMR can lead to negative consequences of the resulting malnutrition. RMR is the amount of energy (kcal) a person uses per day to sustain metabolism at rest (Mifflin, St Jeor, Hill, Scott, Daugherty & Koh, 1990). Resting metabolic rate can be measured via indirect calorimetery (IC) or estimated by predictive equations. Portable indirect calorimeters that measure gas exchange provide accurate readouts within 5% of direct calorimetery. IC is a reliable and well documented method of estimating a person’s metabolic demands by analyzing the ratio of carbon dioxide and oxygen throughout respiration (Cooper et al., 2009). However, predictive equations are most often utilized due to their ease of use and low cost. In many cases these equations employ surrogate variables acquired from other anthropometric measurement methods. Consequently, large variances are possible based on which method that measurement was acquired from. Here, many of the predictive models used to estimate RMR are not derived using body composition measurements 1 from air displacement plethysmography (ADP) (Nelson, Weinsier, Long & Schutz, 1992). ADP determines body volume on the basis of the pressure/volume relationship in tandem with models that estimate body composition based on body density. The Cos Med BOD POD System® (BOD POD) estimates RMR via ADP (Life Measurement Inc. [LMI], 2004). The majority of research in ADP is based on the accuracy of determining body composition measures, including fat mass (FM) and fat-free mass (FFM) rather than applicability of these measures in estimating RMR. Thus, limited research has been conducted regarding the BOD POD’s accuracy in determining RMR. The BOD POD employs the RMR estimation model derived by Nelson et al. (1992) (LMI, 2004). The Nelson equation is a validated and cross-validated model that includes both FM and FFM (Nelson, Weinsier, Long & Schutz, 1992). However, this model might present with large variances that might not optimally predict RMR for a total population or when split by sex. Furthermore, the derivation of this model is not based on measures obtained from the BOD POD. The central hypothesis states that the current methodology of estimating RMR using the measurements obtained from ADP will result in large variances that are inappropriate for patient recommendations. The aim of this study is to compare the agreement between multiple RMR estimation models using body composition measures obtained from an ADP against IC via metabolic cart. 2 CHAPTER II BACKGROUND OF THE STUDY Air Displacement Plethysmography Air displacement plethysmography (ADP) uses the principle of whole body densitometry to estimate the amount of fat and lean tissue in the body. ADP was an instrument created in cooperation with the National Institute of Health designed to replace the gold standard measure of hydro-densitometry. In addition to ADP, body composition can be estimated by a variety of methods including skin folds, bioelectric impedance, hydro-densitometry, and dual energy x-ray absorptiometry (DEXA). However, each of these methods has potential physical and financial limitations such as the user bias, invasiveness, and discomfort of hydro-densitometry and the cost of the DEXA (Hoffman & Hilderbrant, 2001). ADP has been shown to be equivocal to hydrostatic weighing and DEXA techniques in estimating body composition (Fields, Goran, & McCroy, 2002). This technique is a two-compartment estimation method that analyzes the components of the body including fat mass and fat free mass (water, bone, non-bone mineral, and protein). The universal density of fat and fat-free compartments based on cadaver analysis is 0.9g/cc and 1.1g/cc, respectively. ADP employs the use of multiple body composition estimation equations using body density (LMI, 2004). 3 Here, body density is determined by the relationship of the density of an object proportional to it mass divided by its volume (Density = Mass/Volume). First, a subject is weighed. Then the subject’s volume is determined from pressure exerted by that body in a closed chamber. Here, the test chamber pressure (Ptest) and volume (Vtest) are compared to a reference pressure (Preference) and volume (Vreference) using Boyle’s Gas Law illustrated below (LMI, 2004). The Cos Med BOD POD System® (BOD POD) is beneficial for the exercise specialist and/or dietitian in that it can: measure the amount of lean and body fat tissue, measure the effectiveness of a lifestyle modification, provide motivational feedback for clients, and discourage the use of rapid weight loss programs that result in depletion of metabolically active tissue rather than body fat (Hoffman & Hilderbrant, 2001). The BOD POD is comprised of a cabin, integrated computer system with data interface board and monitor, software, scale, and calibration standard. The subject is prompted to wear a tight-fitting synthetic swimsuit and cap to prevent and/or reduce erroneous air displacement. Air displacement is then measured by the movement of a mounted diaphragm within the cabin as air is pumped into the cabin equal to the volume of the empty cabin. A pressure gradient is created with the addition of a subject’s displacement that causes outward movement of the diaphragm. This displacement is compared against a volume standard to determine the subject’s total volume. Body density is determined from the division of the subject’s weight by their volume. Body composition is then determined using one of multiple body composition estimation equations using body density. The default model is based on the Siri 1961 equation, 4 illustrated below, which is designed for body fat percentage estimation in the general population (Hoffman & Hilderbrant, 2001; LMI, 2004). Body Fat % = The BOD POD system is designed to correct for the isothermal effect, the variance in body mass from hair, lung volume, clothing, and body surface area. Thoracic lung gas volume is a critical component to the variance in predicted body density. If left uncorrected the estimated lung volume can vary by up to 40% of the actual lung volume. The thoracic lung volume correction factor is a built in function derived from the Crapo Equation that estimates lung volume as the sum of forced reserve capacity and half of the tidal volume (LMI, 2004). The BOD POD employs the RMR estimation model derived by Nelson et al. 1992 (LMI, 2004). The Nelson equation is a validated and cross-validated model that includes both FM and FFM (Nelson, Weinsier, Long & Schutz, 1992). However, this model might present with large variances that might not optimally predict RMR for a total population or when split by sex. Predictive equations, including Nelson et al. (1992) are most often utilized due to their ease of use and low cost. In many cases these equations employ surrogate variables acquired from other anthropometric measurement methods. Consequently, large variances are possible based on which method each measurement is acquired from. Here, many of the predictive models used to estimate RMR are not derived using body composition measurements from ADP (Nelson, Weinsier, Long & Schutz, 1992). Due to the strict protocol and technical difficulties associated with obtaining an accurate measurement of RMR, prediction equations have been developed to estimate 5 RMR based on parameters more easily measured. BOD POD uses prediction equations which account for both FM and FFM to provide the most accurate estimates of RMR (LMI, 2004). Therefore the equation of Nelson (1992), which includes measured FM and FFM as its predictors, should, in theory, provide a reliable and accurate assessment of RMR in tandem with changes that occur in body composition (Nelson, Weinsier, Long & Schutz, 1992). Although the Nelson (1992) model was chosen based on its inclusion of the FM and FFM as its predictive variables for estimating RMR (LMI, 2004) the derivation of the Nelson (1992) model was not based on measurements made directly from the BOD POD system or an ADP method (Nelson, Weinsier, Long & Schutz, 1992). Estimation of Resting Metabolic Rate RMR is the energy requirement to sustain vital functions during rest or physical inactivity expressed as kcal/day (Hasson, Howe, Jones & Freedson, 2011). Total energy expenditure is comprised of four components: the sleeping metabolic rate, the energy cost of arousal, the thermic effect of food, and the energy cost of physical activity. RMR is the summation of the sleeping metabolic rate and the energy cost of arousal which is equivocal to the minimum rate of energy expenditure in an awake, relaxed person in a supine position in a thermo-neutral environment (Ravussin & Bogardus, 1989). RMR accounts for the largest proportion of total energy expenditure except for individuals that are involved in high-energy physical activity (Li, Tereskowski, Edwards, Simpson & Buchholz, 2010). Because of its important role in regulating body weight and composition there is an increased need in providing patients with their baseline metabolic requirements. 6 However, providing patients with an inaccurate RMR might have adverse consequences (Hasson, Howe, Jones & Freedson, 2011). Inaccurate assessment of body composition can lead to body dysmorphism and relative disorders such as anorexia and obesity in tandem with their individual clinical implications (Fields, Wilson, Gladdens, Hunter & Pascoe, 2001). Concurrently, estimations of RMR based off of estimated body composition measures might have similar consequences. Thus, the accurate prediction of RMR has many useful applications in the weight management of both normal-weight and obese individuals. Dieting is a common practice in the United States. Many diet regimes create weight loss through depletion of muscle mass and body water rather than body fat as a consequence of inappropriate nutrition (Hoffman & Hilderbrant, 2001). Clients might find difficulty in monitoring progress in a weight management program through diet and exercise when the weight remains constant while ratio of body fat to lean muscle mass changes (Hoffman & Hilderbrant, 2001). It is unfortunate that many of these individuals are unaware of their energy requirements to maintain an optimal metabolism (Mifflin et al., 1990). Therefore it is of the upmost importance to establishing an accurate method of predicting resting metabolic requirements. Table one illustrates multiple RMR estimation models and their population specifics. Many attempts have been made over the past century to establish estimation models to predict RMR in humans. Today, predictive equations are most often utilized in clinical practice to predict a subject’s RMR for prescribing daily dietary-energy 7 requirements due to their ease of use and low cost (Frakenfield, Rowe, Smith & Cooney, 2003). Table 1: RMR Estimation Models and Derivation Specifics N1 Reference Equation Cunningham (1980) 223 502 + 21.6(FFM) Dore et al. (1982) 140 712+8.24(wt)+0.02(FFM)-3.25(age) Bernstein et al. (1983) 185 251 + 22(FFM) + 6.4(FM) - 2.1(age) Garrow & Weber (1985) 104 310 + 24.2(FFM) + 5.8(%fat) Ravussin et al. (1986) 249 392 + 21.8(FFM) Owen (1988) 104 186 + 23.6(FFM) Kashiwazaki (1988) 134 304 + 24.5(FFM) Mifflin et al. (1989) 483 413 + 19.7(FFM) Nelson (1992) 213 25.8(FFM) + 4.04(FM) 1 Sample size used for derivation 2 Sex: M = Male; F = Female 3 Body Type: L = Lean; O = Obese Sex2 M/F F M/F F M/F M/F M/F M/F M/F Body3 L/O L/O O L/O L/O L/O L/O L/O L/O In addition to use in practice, many body composition analysis devices utilize these predictive equations to provide an RMR estimation feature. Many predictive models are built upon measures from a general sample thus the applicability of the model to subjects that fall outside of the norm might not be appropriate. Frakenfield, Rowe, Smith & Cooney (2003) explored the agreement of predictive models to estimate RMR. Here, models based on general samples had a tendency to over-predict RMR in obese subjects when compared to a weight adjustment method (Frakenfield, Rowe, Smith & Cooney, 2003). Multiple factors can influence RMR including: time of day, anxiety, diurnal variation, the thermic effect of food, elevated post-exercise oxygen consumption, stimulants, and pharmaceuticals. Therefore standard conditions for establishing a RMR are necessary including: 8-12hr fasting for food and ergometric agents and a 12hr 8 abstinence from exercise (Haugen, Melanson, Tran, Kearney & Hill, 2003). Haugen et al. (2003) found within-subject variances for repeated RMR measures between morning measurements of 4.5%, afternoon measurements of 2.8%, and 4.6% between morning and afternoon measurements (Haugen, Melanson, Tran, Kearney & Hill, 2003). Many of the predictive models used to estimate RMR are not derived using body composition measurements from ADP (Nelson, Weinsier, Long & Schutz, 1992). Hasson, Howe, Jones & Freedson, (2011) compared the accuracy of four resting metabolic rate regression models compared to a measured RMR when stratified by sex, ethnicity, and BMI (Hasson, Howe, Jones & Freedson, 2011). Here, the accuracy of each model compared to the measured RMR greatly varied when stratified by each parameter. When employing a regression based model, clinicians and practitioners need to consider what sample that model was derived on to assess whether its estimation is appropriate (Hasson, Howe, Jones & Freedson, 2011). Ravussin and Bogardus (1989) found a strong positive correlation between FFM and RMR. However, the obese person required less energy per unit body mass than there lean controls. This suggests that energy preservation efficiency increases with an increase in fat mass. Thus RMR requirements decrease with increased FM (Ravussin & Bogardus, 1989). Indirect Calorimetery Accurate assessment of energy requirements is a necessary component in the formulation and evaluation of a nutrition focused plan. The metabolic rate can be measured via IC or estimated by predictive equations. Predictive equations are more often used due to their ease of use and low cost in many cases using surrogate variable 9 acquired for other anthropometric analysis which might result in significant variance from the actual metabolic rate. Portable indirect calorimeters that measure gas exchange provide accurate readouts within 5% of direct calorimetery. It is important for practitioners to understand the limitations of the predictive methods and to consider their applicability to their patients/clients (Frankenfield, Roth-Yousey & Compher, 2005). The statistical laws of model derivation from multivariate regression work best when applied to specific subsets of people rather than a general population. However, when applied to individual cases, large errors might occur when the subject does not match the sample that the model was derived upon including age, sex, and body composition. Frankenfield, Roth-Yousey & Compher (2005) identified an acceptable estimation of RMR within ±10% of the direct or indirect measure (Frankenfield, RothYousey & Compher, 2005). The Parvomedics TrueOne 2400 system® (CART) is a gas exchange measurement IC system that reliably measures minute ventilation, oxygen consumption, carbon dioxide production (Crouter, Antczak, Hudak, Valle & Haas, 2006). Crouter et al. (2006) explored the accuracy and reliability of the CART system when compared to Douglas Bag method which was considered the gold standard measure of gas exchange calorimetery. At rest, the CART system was not statistically different than the Douglas Bag method (p≥0.05; CV 4.7-5.7%) (Crouter, Antczak, Hudak, Valle & Haas, 2006). Therefore the interchangeability of CART is equivocal to the Douglas Bag Method. Agreement between Estimation Methods In clinical practice, professionals aim to have data based on direct measurement without adverse effect or influence which might be cumbersome, not practical, or 10 impossible. Thus these true values remain unknown. In lieu of direct measurement, indirect approaches are used where a new method has to be evaluated via comparison to a well established technique rather than a true quantity (i.e. IC compared to a predictive equation). If the new measurement technique agrees with the well established technique, the new method can be utilized interchangeably based on its practicality (Bland & Altman, 1986). Many scientific studies use the product-moment correlation coefficient (r) between measures as an indicator of the degree of agreement. The correlation statistic has a null hypothesis where two measures are not linearly related. However, the presence of a linear relationship between methods is not necessarily agreement between the two measures. Rather, it is the strength of their relationship along a straight line. Here, perfect correlation occurs where the points of measure are relative upon a straight line not necessarily a unit-to-unit relationship. Correlation does not take into account variations outside of a unit-to-unit relationship or scale. For example a situation where two units of change for the first measure are observed for every one unit change of the second measure can have a perfect correlation if this relationship remains constant upon a straight line. Furthermore, larger values of each measure carry greater weight than smaller values. Since most investigations look at comparisons of measures over large/whole ranges, a high or inflated correlation coefficient is likely (Bland & Altman, 1986). It is unlikely that two methods of measurement agree exactly. Therefore, the agreement method developed by Bland & Altman (1986) can be utilized to determine the amount of difference between each method. Prior to using this analysis, the maximum 11 allowable/practical difference between each RMR estimation method needs to be considered (Bland & Altman, 1986). Frakenfield, Rowe, Smith & Cooney (2003), found the practical difference between RMR estimation methods where the main outcomes of each subjects estimated RMR was less or equal to ±10% from the measured value (Frakenfield, Rowe, Smith & Cooney, 2003). Therefore the level agreement limit of RMR estimation measures is set at ten percent above and below the CART measure. The lack of agreement using this method is summarized by calculating the bias estimated via the mean difference and its sample standard deviation. In the case where a consistent bias is present, the mean difference can be subtracted from the new measure/method. Assuming a Normal (Gaussian) distribution, 95% of the averages will lie between two standard deviations above and below the mean difference (Bland & Altman, 1986). It is important to note that this measure of agreement is a point estimate for that sample. However, the agreement/bias of a second sample might be different. Albeit, the 95% confidence interval and mean difference with its standard errors can be used for applications to a whole population of similar characteristics where with 95% certainty the difference between measures will fall within the lower and upper limits represented as the following with mean difference (d) and sample standard deviation(S): Lower Limits of Agreement: d – 2S and Upper Limits of Agreement: d + 2S (Bland & Altman, 1986). 12 CHAPTER III METHODOLOGY Hypothesis and Statement of Objectives The current methodology of estimating resting metabolic rate using the measurements obtained from ADP via BOD POD will result in large variances from measures obtained from the gas exchange IC via CART. The main objective of this paper is to compare the agreement between multiple RMR estimation models using body composition measures obtained from an ADP against IC via CART. Subjects and Inclusion Criteria This is a cross-validation research study that requires all subjects to be tested by the Cos Med BOD POD System® and the Parvomedics TrueOne 2400 Indirect Calorimetery System®. The study population is comprised of a convenience sample of healthy college-aged adult men and women (18-30 years old) recruited from a Midwestern university and local surrounding community. Informed consent was provided by each subject and participation was voluntary with each subject able to terminate testing at any time (See appendix A for sample letter of informed consent). A total of 66 subjects (41 female and 25 male) participated in and completed the study with no dropouts. The current study was approved by The University of Akron’s Institutional Review Board (appendix B). 13 Testing Procedure Measurements collected for each participant from the BOD POD included RMR, FM, FFM, body fat percentage, and body volume and RMR from the CART (RMR-C). Prior to testing, subjects were required to: 1) Fast 12 hours prior to the test 2) Avoid strenuous exercise 24 hours prior to the test 3) Wear tight fitting clothing (including the provided skull cap) and 4) remove all jewelry. The testing protocol was broken into three phases. The first included collecting anthropometric measurements and subject specifics (height, weight, age, and declaration of fasting protocol). Anthropometric measurements, including height and weight, were measured via Detecto Digital Stadiometer®. The metabolic phase employs the use the ParvoMedics TrueOne 2400 Indirect Calorimetery System® calibrated to manufacturer specifications. The subject is required to lie in a supine position in a quiet room for a total of 60 minutes while attached to the CART via nasal/oral mask. The first 30 minutes of the test is discarded in order for the subject to reach steady state. RMR is represented as the average of last 15 minutes of cart measure extrapolated out to 24 hrs. The final phase employs the use of the Cos Med BOD POD System® calibrated to manufactures specifications using a vessel of a known volume (50L). The subject entered the chamber wearing tight fitting clothing and a Lycra cap. The door is closed sealing the chamber for testing to begin. Body fat percentage is estimated using the SIRI 1961 equation (LMI, 2004). A maximum of a ten minute period was allotted between CART and BOD POD measurements. 14 Statistical Analysis A repeated-measures one-way ANOVA with a Greenhouse-Geisser correction was performed comparing RMR estimation models accompanied by a Fisher’s Least Significant Difference (LSD) multiple comparisons test and 95% confidence intervals of models differences against RMR-C. Inter-quartile range box plots used to visually illustrate differences between methods and highlight outliers. Pearson correlations were performed between each parameter method compared to RMR-C. Tabulation was performed to sum the total proportion of subjects that varied greater than ±10% of the RMR-C value. Measures were performed for the total sample and split by sex. Sample characteristic expressed as mean ± standard deviation with model estimates expressed as mean ± standard error of the mean (S.E.M.) with significance set at p<0.05. Bland Altman measures of agreement were performed between RMR-C and Nelson (1992) and Dore et al. (1982). Values expressed as mean difference ± (S.E.M.), LLA (lower limits of agreement = mean difference - 2SD), and ULA (Upper limits of agreement = mean difference + 2SD). Paired sample t-tests were performed between the Nelson (1992) and Dore et al. (1982) estimation models and the RMR-C values. Significance was set at p<0.05. All statistical analysis was performed using Minitab Statistical software version 16 and SPSS version 20. 15 CHAPTER IV RESULTS Sample characteristics are illustrated in table 2 below. Based on the sample characteristics, the study sample was comprised of young men and women in their early twenties, who were within a normal BMI range and sex appropriate body fat percentages. Table 2: Sample Characteristics Parameter Total Male n = 66 n = 25 Age (yr) 23.0 ± 4.7 22.7 ± 4.4 Height (cm) 170.2 ± 9.4 178.6 ± 7.0 Weight (kg) 68.9 ± 4.1 82.4 ± 12.9 2) BMI (kg/m 23.8 ± 3.3 26.3 ± 3.3 1 FM (kg) 14.7 ± 6.0 14.6 ± 8.4 1 FFM (kg) 54.2 ± 12.6 67.8 ± 8.0 Body Fat %1 22.0 ± 7.7 17.9 ± 8.3 1 Density (kg/L) 1.0480 ± 0.0185 1.0580 ± 0.0199 Parameters expressed as Mean ± SD 1 Measured via BOD POD body composition estimates Female n = 41 23.2 ± 5.0 165.0 ± 6.6 61.1 ± 7.4 22.3 ± 2.3 14.8 ± 4.2 46.3 ± 6.7 24.5 ± 6.2 1.0419 ± 0.0156 Tabulation of RMR estimates that fell outside of ±10% of the cart measure are illustrated in table 3 below. Here, the Dore et al. 1982 model was that highest performing model with 41%, 44%, and 39% within range of the RMR-C estimates for total, males, and females, respectively. The Nelson (1992) model performed with 14%, 8%, and 17% within range of the RMR-C estimates for total, males, and females, respectively. Concurrently, no other model performed with greater than 10% of subjects within 10% of CART. 16 Table 3: Agreement between Estimation Models and RMR-C Model Total Male Female Cunningham (1990) 3% 4% 2% Dore et al. (1982) 41% 44% 39% Bernstein et al. (1983) 3% 4% 2% Garrow & Weber (1985) 2% 4% 0% Ravussin & Bogardus (1989) 3% 4% 2% Owen (1988) 3% 4% 2% Kashiwazaki (1988) 3% 4% 2% Mifflin et al. (1989) 5% 8% 2% Nelson (1992) 14% 8% 17% The above is represented as the percentage of subjects whose agreement between estimation model and RMR-C is less than ±10%. Box plots of the total sample and split by sex of RMR by model is represented in figure 1. It is notable that for the female sample, there we numerous outliers identified using the inter-quartile range method. The repeated measures one-way analysis of variance of estimated RMR by model reached significance for the total sample and when split by sex (total: F = 398.9, female: F = 210.0, male: F = 223.0; p <0.001). The multiple comparisons test revealed that the Dore et al. (1982) model did not significantly differ from the RMR-C measure (p = 0.907). However, when split by sex Dore et al. (1982) significantly over-predicted for females by 150±43 kcals (p < 0.001) and under-predicted for males 231±87 kcals (p = 0.014) when compared to RMR-C. Results of the repeated measures ANOVA is represented in table 4. 17 Table 4: Results of Repeated Measures ANOVA Model Dore et al. (1982) Sample Total Male Female d ± S.E.M. 6±48 -231±87 150±43 p-value 0.907 0.014 0.001 95% C.I. (-90, 101) (-411, -52) (63, 237) Nelson (1992) Total Male Female -436±44 -576±82 -351±46 <0.001 <0.001 <0.001 (-525, -348) (-746, -406) (-445, -258) Cunningham (1980) Total Male Female 1268±70 1216±97 1299±97 <0.001 <0.001 <0.001 (1128, 1407) (1015, 1416) (1104, 1495) Bernstein et al. (1983) Total Male Female 1253±73 1189±93 1291±103 <0.001 <0.001 <0.001 (1107, 1398) (997, 1381) (1083, 1499) Garrow & Weber (1985) Total Male Female 1524±76 1501±102 1538±106 <0.001 <0.001 <0.001 (1373, 1675) (1291, 1712) (1324, 1752) Ravussin & Bogardus (1989) Total Male Female 1182±71 1134±98 1212±97 <0.001 <0.001 <0.001 (1041, 1323) (933, 1336) (1015, 1409) Owen (1988) Total Male Female 1198±75 1187±102 1205±104 <0.001 <0.001 <0.001 (1049, 1348) (977, 1397) (995, 1415) Kashiwazaki (1988) Total Male Female 1427±77 1434±102 1423±107 <0.001 <0.001 <0.001 (1273, 1581) (1219, 1650) (1206, 1640) Mifflin et al. (1989) Total Male Female 944±66 853±93 1000±90 <0.001 <0.001 <0.001 (812, 1077) (661, 1045) (818, 1182) 1 d ± S.E.M represented Fisher’s LSD Multiple Comparisons Test, Significance (p <0.05) n = 66 (male 25; female 41) 2 18 Estimated RMR by Model (Total) RMR (kcal/day) 6000 5000 4000 3000 2000 1000 R RM C els N on m ha ing n n Cu re Do s in ter du te bs ar ns e r g r W Be d Bo an nd a w sin r ro us Ga v Ra O w en K hiw as i ak az lin iff M i ak az lin iff M i ak az lin iff M Estimated RMR by Model (Female) RMR (kcal/day) 6000 5000 4000 3000 2000 1000 R RM C els N on am gh n i nn Cu re Do r s in du s te s te ar eb rn g r e W B d Bo d an an w in r ro ss Ga vu a R O w en K a iw sh Estimated RMR by Model (Male) RMR (kcal/day) 5000 4000 3000 2000 1000 R RM C els N on m ha ing n n Cu re Do s in ter du te bs ar ns e r g r W Be d Bo d an n a w sin r ro us Ga v Ra Figure 1: Box Plots of Estimated RMR by Model 19 O w en K hiw as Table 5 illustrates the results of sample paired t-tests and Bland Altman Limits of Agreement of Nelson (1992) and Dore et al. (1982) compared to RMR-C values. As a whole the Nelson (1992) model significantly under-predicted RMR when compared to the RMR-C. The Dore et al. (1982) model was the best performing pre-existing model when considering a total sample. However when split by sex, a significance difference was detected with an over-prediction for female subjects and an under-prediction for male subjects. Considering the Bland Altman Limits of Agreement, each model performed outside of the ±10% acceptable limit when compared to mean RMR-C values. The Dore et al. (1982) model performed best for females and the Nelson (1992) model performed best for the male population. Table 5: Paired Sample t-test and Limits of Agreement d±S.E.M.1 LLA2 ULA3 p-value4 Model t-Statistic Nelson (1992) 436±44 -297 1139 0.001 9.88 Female 351±46 -230 933 0.001 7.58 Male 578±86 -245 1401 0.001 6.74 Dore et al. (1982) -6±48 -767 756 0.907 -0.12 Female -150±43 -688 338 0.001 -3.50 Male 229±91 -641 1100 0.019 2.53 Analysis based on Bland & Altman, 1986 with model comparison to RMR-C d±S.E.M, LLA, ULA represented as kcal/day 1 d = mean difference; expressed as RMR-C – Estimation Model 2 LLA = Bland Altman Lower Limits of Agreement d – 2S 3 ULA = Bland Altman Upper Limits of Agreement d + 2S 4 p-value: null hypothesis d ≠ 0 20 CHAPTER V DISCUSSION The aim of the current study was to investigate which RMR estimation model, using anthropometrics derived from ADP, had the best agreement when compared RMR estimated via gas exchange IC. There has been limited research concerning the applicability of predictive models in estimating RMR in young, healthy adults. Most studies have focused on critically ill, obese, and/or mental health patients (Li, Tereskowski, Edwards, Simpson & Buchholz, 2010). Dixon et al. (2005) compared ADP estimates to hydrostatic weighing estimates and found no statistical or practical difference in methods when using lean, young adult subjects (Dixon, Deitrick, Pierce, Cutrufello & Drapeau, 2005). IC measured via gas exchange has proven to be a powerful RMR measurement method in vivo. However, the applicability of this technique might not be cost effective or technically feasible for use by clinicians in everyday practice (Li, Tereskowski, Edwards, Simpson & Buchholz, 2010). Therefore in practice, many anthropometric measurement tools, including the Cos Med BOD POD System® use their body composition measurements in tandem with predictive models to estimate RMR without regard to which method was used to derive that model. 21 The BOD POD uses the Nelson (1992) model due to its inclusion of FFM (LMI, 2004). The Nelson (1992) model was formulated on a sample of obese and non-obese men and women (n=213; 86 male, 127 female) based upon the contribution of FM and FFM to RMR. The single best indicator of RMR in this model was FFM (r² =0.53-0.88 or proportion of variation in RMR accounted for by FFM) (Nelson, Weinsier, Long & Schutz, 1992). Similarly, Mifflin et al., (1990) found FFM as the best single predictor of RMR (r² = 0.64) when considering age, sex, height, weight, FM, and FFM. (Mifflin et al., 1990) However, the Nelson (1992) model was not derived using ADP but rather tradition densitometry and anthropometry via hydro-densitometry (Nelson, Weinsier, Long & Schutz, 1992). The previous statement might support the current study’s findings of low prediction of RMR-C by FFM (r² = 0.30) in tandem with the under-prediction of RMR-C. The ability to accurately assess body composition has a multitude of health consequences associated with level of fatness. Barreira et al. (2012) explored the anthropometric correlates of total and central body fat in relation to the development of cardiovascular disease risk factors in male and female adults. Here an increase in total body fatness was strongly correlated with increased cardiovascular risk (dyslipidemia and elevated blood pressure) in addition to elevated fasting plasma glucose (Barreira, Staiano, Harrington, Heymsfield & Smith, 2012). The results of the current study identify the Dore et al. (1982) model as having the best agreement with the RMR-C measurements. Dore et al. (1982) explored the metabolic demands of women with different degrees of obesity. Here, RMR was 4% higher than predicted in severely obese women. Following significant weight loss with a mean of 30kg, same subject RMR decreased to 1% higher than predicted. Here, a hyper-metabolic 22 state was not observed with increased weight loss. However the agreement of the predictive model to gas exchange IC, improved as BMI decreased to a normal range. The Dore et al. (1982) model was derived a sample of 140 women with varying degrees of obesity. Similar to the Nelson (1992) model, Dore et al. (1982) includes FFM as a predictor of RMR. This model did not employ ADP measurements in its derivation but rather total body potassium to estimate skeletal muscle mass used interchangeably as FFM (Doré, Hesp, Wilkins & Garrow, 1982). It is interesting that this model out performed a dual sex model considering it is based on primarily obese female subjects. Therefore based on the paired sample t-test results between the Nelson (1992) and Dore et al. (1982) models compared to RMR-C, the Dore et al. (1982) model is the best overall model when considering RMR estimation using ADP measurements. However, there was lack of agreement of the Dore et al. (1982) model compared to RMR-C when the sample was split by sex. The Bland Altman Limits of Agreement suggest that both Dore et al. (1982) and Nelson (1992) models performed similar for the overall population while Nelson (1992) best predicts for males and Dore et al. (1982) best predicts for females. This supports the notion that when employing a regression based model, clinicians/practitioners need to consider what sample the model was derived on to assess whether its estimation is appropriate (Hasson, Howe, Jones & Freedson, 2011). This study has highlighted that the Nelson (1992) model as a whole is inappropriate for RMR estimation using ADP measurements. The Dore et al. (1982) model might be a better option for use with this technique considering the study sample. RMR estimation models should be chosen based on the origins of measurements they employ. 23 Limitations The current study is designed around a convenience sample of young, physically active, lean adults. Therefore no true statistical consideration was given to sample size requirements for estimating model agreement and model derivation. Nor, was any consideration made for outliers. Additionally, this study does not consider the impact of lean versus obese or ethnic variations in metabolism. Further studies are warranted in validation of the derived model as well as studying the impact of increased body fatness or ethnicity when using any of the studied or derived models in the current study. Regression techniques were not appropriate for this study given sample size limitations, but should be explored in future studies. Furthermore, no control to indicate steady state RMR had been achieved was utilized beyond allowing 30 minutes to reach steady state before measurement. Future studies should investigate the threshold of the respiratory quotient (RQ) as an indicator of true RMR. 24 CHAPTER VI CONCLUSION The aim of the current study was to investigate the agreement of multiple preexisting RMR estimation models with gas exchange IC RMR measurements using body composition measures obtained from ADP. The Nelson (1992) model used for RMR estimation with ADP measures under-predicts total caloric needs for a total sample and when split by sex. Based on analysis of variance, paired sample t-test, and Bland Altman techniques, the Dore et al. (1982) model more accurately predicted RMR in the entire sample but significantly varied when separated by sex. Based on limits of agreement the total sample and the sample split by sex each had a different preferable model. It is imperative for practitioners to consider the sample by which an estimation model is derived and how and what anthropometric measures are used as its predictors to appropriately estimate RMR. The recommendations of this study suggest that the Dore et al. (1982) model might be more appropriate for estimation of RMR for young healthy adult men and women. 25 REFERENCES Barreira, T., Staiano, A., Harrington, D., Heymsfield, S., & Smith, S. (2012). Anthropometric correlates of total body fat, abdominal adiposity, and cardiovascular disease risk factors in a biracial sample of men and women. Mayo Clin Proc, 87(5), 452-460. Bland , J., & Altman, D. (1986). Statistical methods for assessing agreement between two methods of clinical measurement. Lancet, (i), 307-310. Crouter, S., Antczak, A., Hudak, J., Valle, D., & Haas, J. (2006). Accuracy and reliability of the Parvomedics TrueOne 2400 and Medgraphics VO2000 metabolic systems. Eur J Appl Pyhsiol, (98), 139-151. Cooper, J., Watras, A., OBrien, M., Luke, A., Dobratz, J., Earthman, C., & Schoeller, D. (2009). Assessing validity and reliability of resting metabolic rate in six gas analysis systems. JADA, (109), 128-132. Cunningham, J. (1991). Body composition as a determinant of energy expenditure: a synthetic review and a proposed general prediction equation. Am J Clin Nutr, (54), 963-969. Dixon, C., Deitrick, R., Pierce, J., Cutrufello, P., & Drapeau, L. (2005). Evaluation of the bod pod and leg-to-leg bioelectrical impedance analysis for estimating percent body fat in national collegiate athletic association division iii collegiate athletes. J Strength Cond Res,19(1), 85-91. Doré, C., Hesp, R., Wilkins, D., & Garrow, J. (1982). Prediction of energy requirements of obese patients after massive weight loss. Human Nutrition. Clinical Nutrition, 36C(1), 41-48. 26 Frankenfield, D., Roth-Yousey, L., & Compher, C. (2005). Comparison of predictive equations for resting metabolic rate in healthy nonobese and obese adults: A systematic review. JADA, 105(5), 775-789. Frakenfield, D., Rowe, W., Smith, S., & Cooney, R. (2003). Validation of several established equations for resting metabolic rate in obese and nonobese people. JADA 103(9), 1152-1159. Fields, D., Wilson, D., Gladdens, B., Hunter, G., & Pascoe, D. (2001). Comparison of the bod pod with the four-compartment model in adult females. Med Sci Sports Exerc, 33(9), 1605-1610. Fields, D., Goran, M., & McCroy, M. (2002). Body-composition assessment via airdisplacement plethysmography in adults and children: a review. Am J Clin Nutr, (75), 453-467. Hasson, R., Howe, C., Jones, B., & Freedson, P. (2011). Accuracy of four resting metabolic rate prediction equations: Effects of sex, body mass index, age, and race/ethnicity. J Sci Med Sport, (14), 344-351. Haugen, H., Melanson, E., Tran, Z., Kearney, J., & Hill, J. (2003). Variability of measured resting metabolic rate. Am J Clin Nutr, (78), 1141-1144. Hoffman, C., & Hilderbrant, L. (2001). Use of the air displacement plethysmography to monitor body composition: A beneficial tool for dietitians. JADA,101(9), 986988. Li, A., Tereskowski, C., Edwards, M., Simpson, J., & Buchholz, A. (2010). Published predictive equations overestimate measured resting metabolic rate in young, healthy females. J Am Col Nutr, 29(3), 222-227. Life Measurement Inc. (2004). Customer training: body composition tracking system. LMI Part # 2102948 Rev B. Maxwell, S., Kelley, K., & Rausch, J. (2008). Sample size planning for statistical power and accuracy in parameter estimation. Annu Rev Pyschol, (59), 537-563. Mifflin, M., St Jeor, S., Hill, L., Scott, B., Daugherty, S., & Koh, Y. (1990). A new predictive equation for resting energy expenditure in healthy individuals. Am J Clin Nutr, 51, 241-247. Nelson, K., Weinsier, R., Long, C., & Schutz, Y. (1992). Prediction of resting energy expenditure from fat-free mass and fat mass. Am J Clin Nutr, (56), 848-856. 27 Ravussin, E., & Bogardus, C. (1989). Relationship of genetics, age, and physical fitness to daily energy expenditure and fuel utilization. Am J Clin Nutr, (49), 968-975. 28 APPENDICES 29 APPENDIX A LETTER OF INFORMED CONSENT The Validity of Air Displacement Plethysmography in Measuring Resting Metabolic Rate in Young Adults DESCRIPTION: You are invited to participate in a research study investigating the accuracy of air displacement plethysmography (BOD POD) in measuring resting metabolic rate (RMR). From the information gathered in this study we hope to learn more about BOD POD, including its accuracy in measuring RMR. PROCEDURES: With your consent, we would like to perform a body composition test using the BOD POD and also measure your RMR using a metabolic cart. You will be required to fast for twelve hours including abstaining from taking ergometric substances (i.e. caffeine or smoking) and to wear tight-fitting clothing (i.e. spandex or lyca material) or swim apparel. The first measurement of your RMR will be measured by the metabolic cart. This will require you to lay down for 1 hr while the metabolic cart measures your RMR by collecting expired air using a face mask. Ten minutes after that measurement is taken, we will measure your RMR via the BOD POD. The BOD POD procedure measures your height, weight, body fat percentage, and resting metabolic rate. This is a non-invasive test which requires you to sit in an egg-like chamber for two or three 50 second cycles. RISKS: We do not expect any risks associated with the testing procedure. Since the BOD POD is an enclosed chamber you might have a feeling of claustrophobia. There is a window for you to view out of and we will stop the test if any discomfort is felt. BENEFITS: At the end of the testing you will receive a printed copy of the results from the BOD POD and from the metabolic cart. The information gathered can be used to get a better idea of where you stand with your body composition and resting metabolic rate. 30 I understand that if I have any questions about the research being conducted I may contact the chief researcher, Brian Miller, whose email address is listed below: Brian Miller [email protected] I also understand that participation is voluntary and may opt out of the research at any point without penalty. __________________________________________________________________ Print Name __________________________________________________________________ Signature Date 31 APPENDIX B IRB LETTER OF APPROVAL 32
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