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PAPER Measurement of Total Energy Expenditure in Grossly Obese Women International Journal of Obesity (2003) 27, 641–647 & 2003 Nature Publishing Group All rights reserved 0307-0565/03 $25.00 www.nature.com/ijo PAPER Measurement of total energy expenditure in grossly obese women: comparison of the bicarbonate–urea method with whole-body calorimetry and free-living doubly labelled water ER Gibney1, P Murgatroyd2, A Wright3, S Jebb3 and M Elia4* 1Department of Biochemistry, Trinity College Dublin, Dublin, Ireland; 2Wellcome Trust Clinical Research Facility, Addenbrookes Hospital, Hills Road, Cambridge, UK; 3MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK; and 4Institute of Human Nutrition, Southampton General Hospital, Southampton, UK OBJECTIVE: To establish validity of the bicarbonate–urea (BU) method against direct measurements of gaseous exchange (GE) in a whole-body indirect calorimeter and to compare BU and doubly labelled water (DLW) measurements in free-living conditions in the same group of grossly obese women. DESIGN: Energy expenditure (EE) was estimated by the BU method over 24 h concurrently with whole-body indirect calorimetry and subsequently over 5 consecutive days at home concurrently with 14 day DLW. Six women, body mass index (BMI) 52.4710.4 kg/m2 (s.d.), were studied. RESULTS: Total energy expenditure (TEE) measurements by BU and GE within the metabolic chamber were not significantly different (BU ¼ 11.7971.89 MJ/day and GE ¼ 11.6471.86 MJ/day; mean difference, 0.2570.49 MJ/day, P40.05). Free-living TEE derived from BU and DLW was also similar (13.2871.86 and 13.8672.25 MJ/day, respectively; mean difference 0.1771.33 MJ/day, Po0.05). The measured physical activity level (PAL) in these very obese subjects was within the range reported in other free-living studies in less obese individuals (1.6270.14 using DLW and 1.5670.20 using BU). The BU method was well tolerated by the subjects. CONCLUSIONS: This study in grossly obese subjects, heavier than those participating in previous studies involving tracer methods, demonstrates validity of the BU against GE under controlled metabolic conditions, and the equivalence between BU and DLW under free-living conditions. The results suggest that both tracer methods are valid in this population group. This study also demonstrates the practicalities of using the BU method over 5 days, the longest application of the method so far. International Journal of Obesity (2003) 27, 641–647. doi:10.1038/sj.ijo.0802302 Keywords: energy expenditure; bicarbonate urea; indirect calorimetry; doubly labelled water; validation; free living Introduction on inferring intake from measurements of free-living total Obesity is one of the most important public health problems energy expenditure (TEE) using tracer methods, particularly facing both developed and developing countries.1 An the doubly labelled water (DLW) method. important aspect of the study of obesity is the assessment The DLW water method is an isotopic dilution method, of energy balance and intake. However, the accurate where energy expenditure is calculated from endogenous assessment of energy intake (EI) is difficult, especially in CO2 production, which is derived by the differential obese individuals, because of considerable under-report- elimination of the isotopes 2H and 18O from the body water ing,2,3 and hence, considerable emphasis has been placed pool.4 The DLW method has been validated against both gaseous exchange (GE) (considered to be the gold standard for the estimation of energy expenditure (EE)),5–9 and energy *Correspondence: Professor M Elia, Institute of Human Nutrition, South- balance studies.10,11 Some variation has been reported ampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. between the results of validation studies, which has been E-mail: [email protected] Received 18 March 2002; revised 27 January 2003; attributed to the different physiological states of the accepted 3 February 2003 individuals and errors associated with different analytical Measurement of total energy expenditure in obese women ER Gibney et al 642 methods undertaken by each laboratory.12–14 However, the rate. The two methods are thus complementary to each overall precision of estimating EE using the DLW is estimated other. to be within 73–6%.7,11,12,15–19 Therefore, the DLW method The BU method has been validated against respiratory is considered to be a valid method for estimation of free- gas exchange in both healthy lean individuals34 and living TEE, and has been applied to a range of population patients with lung cancer.35 The method has also been groups including the elderly,20 infants,18,21,22 sick22–29 applied to free-living healthy subjects,34 patients with undernourished30 and obese.15,31 lung cancer,35 meliodosis,36 HIV infection37 and chronic One validation study of particular interest is that of obstructive pulmonary (airway) disease (COPD).38 An analy- Ravussin et al,15 who compared DLW to GE in a whole-body sis of published data show that BU method underestimated metabolic chamber in a group of individuals with differing EE obtained by GE by only 0.0570.31 MJ/day, and is body mass index (BMI). The study reported an under- unrelated to the amount of body fat (r ¼ 0.05 using pooled estimation of EE by DLW that was related to fat mass data based on two studies in which total body fat ranged (r ¼À0.81, Po0.002) and percent body fat (r ¼À0.68, from 5 to 36 kg and BMI from 21 to 33 kg/m2 34,35.) However, Po0.02). The magnitude of this effect, À0.285 MJ/day for the majority of subjects in these studies were not obese and each additional 10 kg of fat, is certainly sufficient to be of span a limited range of body fat. The first element of the concern if the population is particularly obese, has wide current study, within the whole-body calorimeter, was variability in adiposity, or shows substantial changes in body designed to extend these validations to a grossly obese weight. The authors suggested that the underestimation population. could be because of larger sequestration of deuterium during The second elements is that this study tests the practicality fat synthesis in the obese subjects. However, Haggarty et al32 of the BU method under free-living conditions, provides the estimated the whole-body fatty acid and cholesterol synth- first direct comparison of the BU and DLW techniques in esis in weight-stable adults and demonstrated little evidence obese subjects, and provides long-term concurrent measure- of error on DLW-derived CO2 production, with a mean ments of CO2 production by two methods with differing underestimation of À0.5% CO2 production, suggesting that metabolic dependencies from which the observations of the DLW method is unlikely to be seriously affected. No Ravussin et al15 may be further explored. study has investigated the validity of DLW in an obese group since that of Ravussin et al,15 and other studies yielding individual subject data have not supported a relation Subjects and methods 6–10 between adiposity and error in DLW-estimated TEE. Six women with a long history of morbid obesity were There is now a pressing need to re-examine Ravussin’s recruited from a hospital outpatient clinic (Table 1). Their observations and, if they are confirmed, to explore further body weight had varied by less than 2 kg in the 4 weeks prior the mechanisms by which they may occur. to the start of the study. Apart from their obesity, all subjects The bicarbonate–urea (BU) method provides an alternative were considered to be in satisfactory health. Complete to DLW for measurement of free-living CO2 production, medical history, physical examinations and routine blood from which (EE) is then calculated using appropriate measurements were performed. None of the subjects had 33,34 factors. The BU method is based on the principle of diabetes, but some had arthralgias (subject 3 had some isotopic dilution of infused labelled bicarbonate, and the symptoms of osteoarthritis) and a certain degree of exer- assumption that the specific activity of urinary urea (formed tional dyspnoea. The study took place at the MRC Dunn from CO2 in the liver) is an indicator of CO2 production Clinical Nutrition Centre, Cambridge, UK. The study was within the body. The extent of isotopic dilution depends on approved by Medical Research Council (MRC) Dunn Nutri- the rate of entry of labelled CO2, infused as bicarbonate, tion Unit and Addenbrooke’s Hospital Ethics committees. relative to the rate of endogenous CO2 production. When Informed consent was obtained in writing from the volun- CO2 production is high, the enrichment or specific activity teers before beginning the study. 14 of CO2 in urinary urea is low, and the converse. The C-BU method is relatively less expensive than the DLW and can provide estimates of EE over periods from 12–24 h to several 14C bicarbonate administration days. In contrast, the DLW typically provides an integrated The 14C bicarbonate was administered as a primed constant estimate of EE over 10–20 days in adults. Both methods infusion. The prime was given on the day prior to (GE) estimate net CO2 production, and require conversion of CO2 measurement (day 0) and the infusion commenced. The production to EE. However, the techniques are influenced by infusion (24  106 dpm/day) was administered using the different physical and metabolic processes. For example, the Graseby minipump (Graseby variable-speed driver MS26; DLW is affected by fractionation of isotopes at body surfaces Graseby Medical, Watford, UK) and a bolus urea prime (see and potential sequestration into organic substances,19 while Elia39 for calculation of dose). Details of procedures for the BU method is potentially subject to carbon fixation, inserting the subcutaneous canulla are presented else- 34 14 variable recovery of labelled CO2 through variable equilibra- where.
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