点击显示 收起
1 From the Gastrointestinal Division, the Weight Control Unit and the Body Composition Unit, the Department of Medicine, St Luke's–Roosevelt Hospital Center, Columbia University of Physicians and Surgeons, New York (SA, ESE, DA, JW, SBH, and DPK), and the Taipei Medical University, Taipei, Taiwan (SJJL).
2 Supported by the NIH (DK 42618 and DK 37352) and the Community Research Initiative on AIDS, New York. 3 Reprints not available. Address correspondence to DP Kotler, GI Division/S&R 1301, St Luke's– Roosevelt Hospital Center, 1111 Amsterdam Avenue, New York, NY 10025. E-mail: dpkotler{at}aol.com.
ABSTRACT
Background: HIV-infected individuals may develop malnutrition or lipodystrophy, leading to losses of subcutaneous adipose tissue (SAT).
Objective: We compared the ability of a Durnin-Womersley formula for total adipose tissue (TAT) to estimate change in SAT with the use of whole-body magnetic resonance imaging (MRI) as a criterion measure.
Design: We analyzed data from 2 clinical trials: a prospective randomized trial of protein supplements, progressive resistance training, or combined treatment in 29 malnourished, HIV-positive women, and a prospective open-label trial of recombinant human growth hormone in 25 HIV-infected subjects with visceral adipose tissue (VAT) accumulation. Changes in fat by the Durnin-Womersley formula and in SAT, TAT, and VAT by MRI were compared by linear regression, and Bland-Altman analyses were used to assess the agreement between the prediction and criterion methods. The repeatability of the Durnin-Womersley measurement was evaluated in 14 weight-stable, healthy adults studied twice within 1 y.
Results: At baseline, Durnin-Womersley fat was significantly associated with SAT (r2 = 0.75, P < 0.001) and TAT (r2 = 0.79, P < 0.001) but not with VAT. Change in Durnin-Womersley fat was significantly associated with change in SAT (r2 = 0.66, P < 0.001) and in TAT (r2 = 0.57, P < 0.001) but not in VAT. The limits of agreement for the Durnin-Womersley estimation of change in SAT were -3.4 to 2.6 kg and the SEE was 1.5 kg. The SEE for repeated measures of SAT in healthy control subjects was 0.84.
Conclusions: The Durnin-Womersley formula can be used to predict change in SAT. The limits of agreement and the SEE for predicting change in SAT by MRI are approximately twice as great as the error of repeated Durnin-Womersley measures in control subjects.
Key Words: Durnin-Womersley formula • subcutaneous fat • HIV • body composition • magnetic resonance imaging • MRI • adipose tissue • recombinant human growth hormone
INTRODUCTION
Nutritional alterations in HIV infection include undernutrition and fat redistribution. Although early studies of undernutrition concentrated on depletion of body cell mass (1), depletion of fat was also seen. The prevalence of undernutrition has decreased significantly since the introduction of highly active antiretroviral therapy. However, a substantial proportion of HIV-infected men, women, and children undergo body fat redistribution, characterized by depletion of subcutaneous adipose tissue (SAT) or accumulation of adipose tissue in the visceral compartment (visceral adipose tissue, or VAT) and other upper-body regions without changes in lean mass (2–7). The redistribution of body fat is variably associated with metabolic alterations, namely, hyperlipidemia and insulin resistance. The etiology and pathogenesis of these changes are uncertain. There is great concern that these changes are associated with accelerated atherogenesis, as they are in non-HIV conditions (8). It is important to recognize that both undernutrition and fat redistribution are characterized by a loss in SAT. Thus, accurate measurement of regional fat contents is of interest to physicians treating HIV infection.
Numerous methods, varying considerably in sophistication and expense, have been used to estimate body fat content. Cross-sectional imaging techniques such as magnetic resonance imaging (MRI) and computed tomography are the most precise of the available measures, allow differentiation of SAT and VAT, and can measure changes in these compartments (9, 10). However, expense, the requirement for experienced technicians, and machine availability limit the use of these methods. Dual-energy X-ray absorptiometry may also reflect regional body composition, especially in the limbs (11), whereas bioelectrical impedance analysis, probe dilution for measuring total body water, hydrodensitometry, and other techniques are used mainly to estimate total body adipose tissue (TAT).
Anthropometric measurements are inexpensive, easily performed techniques for estimating total body and regional fat contents. Measurements such as the waist-to-hip ratio have been widely used in epidemiologic studies (8, 12), although the application of such methods in clinical settings has been limited. Most studies involved cross-sectional measurements and few validated anthropometry for estimating change in regional fat contents.
Using hydrodensitometry as the criterion method, Durnin and Womersley (13) derived several equations of various complexity to estimate total body fat in men and women in large study groups. Their equations have been widely used in epidemiologic research. In the present study, we use their estimate of fat based on the log sum of 4 skinfold thicknesses (triceps, biceps, subscapular, and suprailiac). Logically, it would appear that skinfold thicknesses reflect SAT rather than TAT because skinfold thicknesses should be unaffected by changes in VAT. Although the difference is small in healthy adults because most body fat is in the SAT compartment, errors in measurement may occur in HIV-infected individuals or in uninfected individuals with fat redistribution, in whom VAT may account for as much as 50% of TAT (5). Thus, the relative ability of these formulas to estimate changes in SAT and TAT is uncertain.
The purpose of this study was to evaluate the ability of the Durnin-Womersley formula to estimate the sizes of the regional fat compartments, especially SAT, in HIV-infected subjects, and the changes in these compartments as a result of specific interventions. The results of the anthropometric estimations were compared with measurements made by a criterion method, whole-body MRI scanning. Formal evaluation included estimations of bias and determinations of the limits of agreement and their precision. Because the actual error of a prediction equation is related to the inherent variability of both the measurements and the prediction model itself, we also determined the repeatability of measuring fat content by use of the Durnin-Womersley formula in the absence of intervention in a data set of repeated anthropometric measurements made in healthy adults.
SUBJECTS AND METHODS
Subjects and study design
This was a retrospective analysis of the results of body-composition studies performed in 2 groups of HIV-infected individuals and in 1 group of healthy control subjects. Data from 2 clinical trials of interventions for HIV-associated nutritional alterations, conducted between 1997 and 1999 and in which both MRI and anthropometry were performed, were pooled and analyzed. One trial was a prospective randomized trial comparing 14 wk of therapy with protein supplements, progressive resistance training, or combined treatment in 29 HIV-infected women with a body cell mass/height 90% of race-sex reference values (14). The other trial was a prospective open-label trial of recombinant human growth hormone (6 mg/d given subcutaneously) in 25 HIV-infected subjects with VAT accumulation (15). For the purpose of this study, we analyzed only the first 12 wk of therapy. The 2 groups of HIV-infected subjects had a mean age of 42 y (range: 28–67 y). Twenty-six of the subjects were white, 22 were African American, and 6 were Hispanic. In addition, we analyzed repeated anthropometric measurements made within 1 y in 14 healthy, weight-stable adults. The repeatability of measurements of weight, body cell mass, fat-free mass, and body fat content in stable subjects was published previously (16). The Institutional Review Board of St Luke's–Roosevelt Institute for Health Sciences approved the studies, and the subjects gave signed, informed consent.
Body-composition measurements
Subjects were positioned supine on a 1.5T scanner (6X Horizon; General Electric, Milwaukee) platform with their arms fully extended above their heads. About 40 axial images of 10-mm thickness were obtained with 40-mm interslice intervals from head to toe, as described previously (5). All MRI scans were analyzed manually with VECT image analysis software (Martel Inc, Montreal) on a Silicon Graphics workstation (Mountain View, CA) to identify and quantify SAT and VAT compartments. Cross-sectional areas on each image were integrated to provide volume estimates for the whole body and the compartments. The error of the estimate of TAT and SAT on repeated measurements has been estimated at 2–10% in different studies (9, 17). The difference in results on repeated readings of a single, whole MRI measurement averages 1% for TAT and SAT and 6% for VAT in our laboratory.
Anthropometric measurements were made by 1 of 3 observers, per the Airlie Consensus Report (18), using Lange calipers (Cambridge Scientific Instruments, Cambridge, MD). The specific skinfold thicknesses measured were the biceps, triceps, subscapular, and suprailiac, and they were measured 3 times each. The observers were supervised by a single trainer, and the variation in the individual measurements with repeated testing and between observers was kept to <10%.
Statistical analysis
The Durnin-Womersley formula for men and women was applied to calculate total body fat in all 54 HIV-infected subjects. Adipose tissue values obtained from MRI readings were converted to fat in kilograms by using the factor 0.833 (19). The assumptions underlying the conversion are that adipose tissue contains 11% extracellular water and that adipose tissue cell mass is 94% lipid by weight. The conversion was necessary because the quantification of errors in prediction requires that the measured and predicted variables be expressed in the same units. Whereas the Durnin-Womersley formula measures fat as a percentage of body weight, MRI measures the volume of adipose tissue, which has a different mass-to-volume relation (density) than does lean tissue and also includes some nonlipid extracellular and intracellular mass.
Simple linear regression was used to analyze the relation between total fat obtained by the Durnin-Womersley method and SAT, TAT, and VAT obtained from MRI scans at both baseline and follow-up. Additionally, linear regression was used to measure the association of change (difference between follow-up and baseline) in Durnin-Womersley fat and change in SAT, TAT, and VAT.
We followed the Bland-Altman (20) model to assess the agreement between the calculated Durnin-Womersley fat and MRI measures of SAT, TAT, and VAT. We calculated the mean of the fat estimates obtained from the 2 measures and their differences. A graph of the difference between methods against the mean was plotted. This method normalizes the distribution of the sample and decreases its variation. The limits of agreement for the 2 methods, essentially the 95% CI for the prediction, were calculated, as was the precision of those limits. In addition, the SEE was calculated. This latter value represents the average expected error, as opposed to the maximum error, represented by the limits of agreement and is a more practical reflection of the utility of the prediction.
The actual error of a predictive model for estimating change in SAT by Durnin-Womersley includes the inherent variability of the anthropometric measures. To test the repeatability of the estimation of body fat by Durnin, we analyzed a data set of 14 weight-stable healthy adults who were studied twice within 1 y. With use of the second measurement as a predictor of the first, the correlation coefficient, limits of agreement, and SEE were determined. All analyzes were performed with SAS (version 7; SAS Institute Inc, Cary, NC).
RESULTS
Cross-sectional studies
Durnin-Womersley fat was significantly associated with MRI-measured SAT (r2 = 0.75 and 0.73 at baseline and follow-up, respectively, P < 0.001; Figure 1) and with MRI-measured TAT (r2 = 0.79, P < 0.001 for both baseline and follow-up; data not shown). MRI-measured SAT and VAT were also strongly associated (r2 = 0.96 and 0.95 at baseline and follow-up, respectively, P < 0.001; data not shown). In contrast, Durnin-Womersley fat was of no value in predicting MRI-measured VAT either at baseline or at follow up. At baseline, mean (±SD) TAT was 17.2 ± 0.8 kg, SAT was 14.5 ± 0.8 kg, VAT was 2.7 ± 0.3 kg, and Durnin-Womersley fat was 16.4 ± 0.8 kg.
FIGURE 1. . Relation between subcutaneous adipose tissue (SAT) as measured by magnetic resonance imaging (MRI) and total body fat as estimated with use of the Durnin-Womersley formula at baseline (n = 54). y = 0.7711x + 0.5018 (r2 = 0.75, P < 0.001).
The difference between the cross-sectional Durnin-Womersley and MRI estimates for SAT as well as the average of the estimates were calculated as described in Subjects and Methods. The relation was not significant; ie, the slope of the regression lines was not significantly different from zero (Figure 2). The limits of agreement for SAT ranged from -8.7 to 2.3 kg. The precision of the lower limit ranged from -9.5 to -8.0 kg; the precision of the upper limit ranged from 1.5 to 3.0 kg.
FIGURE 2. . Bland-Altman model for predicting subcutaneous adipose tissue. The y axis represents the difference between the Durnin-Womersley and magnetic resonance imaging measurements, and the x axis represents the average of the 2 measurements. The middle line represents the mean difference between the measurements, whereas the upper and lower lines are the upper and lower limits of agreements, respectively (n = 54).
Longitudinal studies
The change in SAT in the HIV study group as a result of intervention ranged from -5.9 to 7.0. kg. The change in TAT ranged from -8.7 to 7.2 kg, and the change in VAT ranged from -5.1 to 1.2 kg. The change in Durnin-Womersley fat from baseline to follow-up was significantly associated with the change in MRI-measured SAT (Figure 3). Change in Durnin-Womersley fat was also significantly related to change in TAT (r2 = 0.57, P < 0.001; data not shown). In contrast, change in Durnin-Womersley fat was of no value in predicting change in VAT. The SEE for the prediction of change in SAT was 1.5 kg, whereas the SEE for the prediction of change in TAT was 2.0 kg.
FIGURE 3. . Relation between change in subcutaneous adipose tissue (SAT) as measured by magnetic resonance imaging (MRI) and change in total body fat as estimated with use of the Durnin-Womersley formula (n = 54). y = 0.7309x - 0.408 (r2 = 0.66, P < 0.001).
We then applied the Bland-Altman model to assess the agreement between anthropometry and MRI for determining changes in SAT. The difference between Durnin-Womersley and MRI estimates of change in SAT were plotted as a function of the average change estimated by the 2 methods; the slope of the resulting regression line was not significantly different from zero (Figure 4). The limits of agreement for change in SAT as estimated by Durnin-Womersley fat were from -3.4 to 2.6 kg, respectively. The precision of the lower limit for change in SAT ranged from -3.9 to -3.1 kg; the precision of the upper limit ranged from 2.2 to 3.1 kg.
FIGURE 4. . Bland-Altman model for predicting change in subcutaneous adipose tissue. The y axis represents the difference between the Durnin-Womersley and magnetic resonance imaging measurements, and the x axis represents the average of the 2 measurements. The middle line represents the mean difference between the measurements, whereas the upper and lower lines are the upper and lower limits of agreements, respectively (n = 54).
The repeatability of the Durnin-Womersley formula was assessed in 14 healthy adults in whom 2 anthropometric measures had been taken. The repeat measure was plotted as a function of the initial measurement, and the resulting r2 was 0.99. The limits of agreement for repeated Durnin-Womersley measurements in healthy control subjects ranged from -1.6 to 1.8 kg and the SEE was 0.84 kg.
DISCUSSION
The need for a simple yet reliable method of estimating regional fat has become critical in the nutritional assessment of individuals. The criterion methods, cross-sectional imaging by computed tomography or MRI, have been used only as research tools. Other techniques, including anthropometry, have been used mainly in epidemiologic studies. No anthropometric technique has been validated for clinical use and applied in a widespread manner.
This study evaluated the ability of a Durnin-Womersley formula to estimate change in SAT over a range of changes that might be seen in a clinical setting. This is the first study, to our knowledge, to use the Durnin-Womersley formulas to study regional fat content. Overall, we found a strong relation between fat estimated by the Durnin-Womersley formula and MRI measurements of SAT. There was a great deal of covariance between change in TAT and in SAT.
Interestingly, the accuracy of the Durnin-Womersley formula was greater than its precision. Although Durnin and Womersley derived the relation between the log sum of the skinfold thicknesses against fat as determined by hydrodensitometry, we found that the actual values predicted by the Durnin-Womersley formula were equally related to MRI-measured values of SAT and TAT. In addition, the limits of agreement in estimating change in SAT were lower than the average errors in predicting a single measurement.
Ultimately, the clinical utility of the Durnin-Womersley formulas or any other anthropometric relation is a matter of judgment. The results of this study show that the direction of change in SAT as determined by MRI is along that of the Durnin-Womersley estimate of fat (Figure 3), so that there is categorical agreement between the measures. The limits of agreement for change in SAT are ±3 kg compared with the observed changes of ±6 kg. These limits of agreement should be considered as maximum errors. The SEE, which is the average expected error, was 1.5 kg for the prediction of change in SAT in the HIV group.
The observed prediction error includes the error in the Durnin-Womersley model as well as the inherent repeatability of the anthropometric and MRI measurements. We did not study repeated MRI measurements, although repeated readings of the same measurement usually are within 1%. The limits of agreement in repeated Durnin-Womersley measurements in healthy control subjects ranged from -1.6 to 1.8 kg and the SEE was 0.84. Thus, about one-half of the observed error in predicting change in SAT may be ascribed to the inherent variability of the Durnin-Womersley measurement.
Other investigators have added more measurements to the Durnin-Womersley formulas and increased the correlation coefficients for the cross-sectional prediction of total fat (21–23). These studies used hydrodensitometry as the criterion method and assessed only total body fat. None of these studies addressed changes in regional fat components. In general, the addition of more variables to a predictive equation must be balanced against the propagation of error.
In summary, the Durnin-Womersley formulas for estimating body fat content can be applied to the estimation of change in SAT. Although the relations are sufficiently strong for use in epidemiologic studies and other clinical investigations, the relatively broad limits of agreement suggest that some caution be used in clinical application. The development of prediction equations based on criterion measurements of SAT might improve the predictability of anthropometry for estimating regional fat content and its change.
REFERENCES