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1.  Effect of Calcium Supplementation on Weight and Fat Loss in Women 
Data suggest that a diet deficient in calcium is associated with higher body weight and that augmenting calcium intake may reduce weight and fat gain or enhance loss. Our aim was to determine whether calcium supplementation during a weight loss intervention affects body fat or weight loss. Data were combined from three separate 25-wk randomized, double blind, placebo-controlled trials of 1000 mg/d calcium supplementation in 100 premenopausal and postmenopausal women. The primary outcome measures were change in body weight and fat mass adjusted for baseline values.
There were no significant differences in body weight or fat mass change between the placebo and the calcium-supplemented groups in the pooled analysis (adjusted mean ± SE; body weight, placebo –6.2 ± 0.7 vs. Ca –7.0 ± 0.7 kg; fat mass, placebo –4.5 ± 0.6 vs. Ca –5.5 ± 0.6 kg), and no significant interactions of calcium supplementation with menopausal/diet status. Analysis as separate trials also found no significant differences between the placebo and the calcium groups. Calcium supplementation did not significantly affect amount of weight or fat lost by women counseled to follow a moderately restricted diet for 25 wk. Nevertheless, the magnitude and direction of the differences for group means are consistent with a hypothesized small effect.
PMCID: PMC4010554  PMID: 14764774
2.  Clinical Utility and Reproducibility of Visceral Adipose Tissue Measurements Derived from Dual-energy X-ray Absorptiometry in White and African American Adults 
Obesity (Silver Spring, Md.)  2013;21(11):2221-2224.
Computed tomography and magnetic resonance imaging are currently used to measure abdominal visceral adipose tissue (VAT) in humans; however, more widely available and less costly dual-energy x-ray absorptiometry (DXA) also has the potential to measure VAT.
The purpose of this study was to determine reproducibility and clinical thresholds for DXA-derived VAT.
Design and Methods
The sample included 2317 white and African American adults 18–74 years of age. VAT areas (cm2) were measured using a Hologic DXA scanner equipped with APEX 4.0 software. Reproducibility was assessed using repeated measurements on 101 participants scanned 14 days apart. Receiver Operating Characteristic (ROC) curves were used to assess clinical utility and select thresholds that identified elevated cardiometabolic risk, defined as the presence of ≥2 risk factors.
Reproducibility of DXA-VAT was 8.1%. The areas under the ROC curves ranged from 0.754 in African American men to 0.807 in white women. The thresholds were higher in white men (154 cm2) and women (143 cm2) compared to African American men (101 cm2) and women (114 cm2).
The results demonstrate that DXA VAT is a useful clinical marker of cardiometabolic risk; however, further research is required to determine associations with health outcomes using longitudinal studies.
PMCID: PMC3819404  PMID: 23794256
imaging; abdominal obesity; ethnicity; race differences; risk factors
3.  Relationships between body roundness with body fat and visceral adipose tissue emerging from a new geometrical model 
Obesity (Silver Spring, Md.)  2013;21(11):2264-2271.
To develop a new geometrical index that combines height, waist circumference (WC), and hip circumference (HC) and relate this index to total and visceral body fat.
Design and Methods
Subject data were pooled from three databases that contained demographic, anthropometric, dual energy X-ray absorptiometry (DXA) measured fat mass, and magnetic resonance imaging measured visceral adipose tissue (VAT) volume. Two elliptical models of the human body were developed. Body roundness was calculated from the model using a well-established constant arising from the theory. Regression models based on eccentricity and other variables were used to predict % body fat and % VAT.
A body roundness index (BRI) was derived to quantify the individual body shape in a height-independent manner. Body roundness slightly improved predictions of % body fat and % VAT compared to the traditional metrics of body mass index (BMI), WC, or HC. On this basis, healthy body roundness ranges were established. An automated graphical program simulating study results was placed at
Body roundness index, a new shape measure, is a predictor of % body fat and % VAT and can be applied as a visual tool for health status evaluations.
PMCID: PMC3692604  PMID: 23519954
4.  A Simple Model Predicting Individual Weight Change in Humans 
Journal of biological dynamics  2011;5(6):579-599.
Excessive weight in adults is a national concern with over 2/3 of the US population deemed overweight. Because being overweight has been correlated to numerous diseases such as heart disease and type 2 diabetes, there is a need to understand mechanisms and predict outcomes of weight change and weight maintenance. A simple mathematical model that accurately predicts individual weight change offers opportunities to understand how individuals lose and gain weight and can be used to foster patient adherence to diets in clinical settings. For this purpose, we developed a one dimensional differential equation model of weight change based on the energy balance equation is paired to an algebraic relationship between fat free mass and fat mass derived from a large nationally representative sample of recently released data collected by the Centers for Disease Control. We validate the model's ability to predict individual participants’ weight change by comparing model estimates of final weight data from two recent underfeeding studies and one overfeeding study. Mean absolute error and standard deviation between model predictions and observed measurements of final weights are less than 1.8 ± 1.3 kg for the underfeeding studies and 2.5 ± 1.6 kg for the overfeeding study. Comparison of the model predictions to other one dimensional models of weight change shows improvement in mean absolute error, standard deviation of mean absolute error, and group mean predictions. The maximum absolute individual error decreased by approximately 60% substantiating reliability in individual weight change predictions. The model provides a viable method for estimating individual weight change as a result of changes in intake and determining individual dietary adherence during weight change studies.
PMCID: PMC3975626  PMID: 24707319
energy balance equation; metabolic adaptation; non-exercise activity thermogenesis; dietary adherence
6.  Assessing skeletal muscle mass: historical overview and state of the art 
Even though skeletal muscle (SM) is the largest body compartment in most adults and a key phenotypic marker of sarcopenia and cachexia, SM mass was until recently difficult and often impractical to quantify in vivo. This review traces the historical development of SM mass measurement methods and their evolution to advances that now promise to provide in-depth noninvasive measures of SM composition.
Key steps in the advancement of SM measurement methods and their application were obtained from historical records and widely cited publications over the past two centuries. Recent advances were established by collecting information on notable studies presented at scientific meetings and their related publications.
The year 1835 marks the discovery of creatine in meat by Chevreul, a finding that still resonates today in the D3-creatine method of measuring SM mass. Matiegka introduced an anthropometric approach for estimating SM mass in 1921 with the vision of creating a human “capacity” marker. The 1940s saw technological advances eventually leading up to the development of ultrasound and bioimpedance analysis methods of quantifying SM mass in vivo. Continuing to seek an elusive SM mass “reference” method, Burkinshaw and Cohn introduced the whole-body counting-neutron activation analysis method and provided some of the first detailed reports of cancer cachexia in the late 1970s. Three transformative breakthroughs leading to the current SM mass reference methods appeared in the 1970s and early 1980s as follows: the introduction of computed tomography (CT), photon absorptiometry, and magnetic resonance (MR) imaging. Each is advanced as an accurate and/or practical approach to quantifying whole-body and regional SM mass across the lifespan. These advances have led to a new understanding of fundamental body size-SM mass relationships that are now widely applied in the evaluation and monitoring of patients with sarcopenia and cachexia. An intermediate link between SM mass and function is SM composition. Advances in water-fat MR imaging, diffusion tensor imaging, MR elastography, imaging of connective tissue structures by ultra-short echo time MR, and other new MR approaches promise to close the gap that now exists between SM anatomy and function.
The global efforts of scientists over the past two centuries provides us with highly accurate means by which to measure SM mass across the lifespan with new advances promising to extend these efforts to noninvasive methods for quantifying SM composition.
PMCID: PMC3953319  PMID: 24532493
Body composition; Nutritional assessment; Sarcopenia; Cachexia
7.  Relationship between abdominal fat and bone mineral density in white and African American adults☆, ☆☆ 
Bone  2011;50(2):576-579.
Several studies have documented relationships between adipose tissue and bone mineral density (BMD); however, the degree to which there are racial differences in this relationship is not known. The purpose of this study was to examine the relationships between abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and BMD among white and African American adults. The sample included 330 white women, 328 African American women, 307 white men, and 116 African American men 18–74 years of age. Dual-energy X-ray absorptiometry scans were used to measure BMD and computed tomography scans were used to measure abdominal VAT and SAT. Linear regression was used to assess the relationships between abdominal adiposity and BMD and to explore possible sex and race differences in the associations. In the total sample as well as in all sex-by-race groups, VAT and SAT were negatively related to BMD, after adjustment for lean body mass (LBM) and several covariates. The VAT model (including covariates) explained 33.3% of the variance in BMD and the SAT model (including covariates) explained 32.7% of the variance in BMD. Being African American, being male, and having high LBM were all associated with higher BMD. Race and sex interactions were not significant, indicating that the relationships were similar across race and sex groups. In conclusion, BMD was inversely related to abdominal VAT and SAT in white and African American adults after adjustment for LBM.
PMCID: PMC3936414  PMID: 21549867
Obesity; Osteoporosis; Race/ethnicity; Gender; Adiposity
8.  Decreased limb muscle and increased central adiposity are associated with 5-year all-cause mortality in HIV infection 
AIDS (London, England)  2011;25(11):1405-1414.
Unintentional loss of weight and muscle due to aging and disease has been associated with increased mortality. Wasting and weight loss occur in HIV infection even in the modern era of effective antiretroviral therapy.
We determined the association of MRI-measured regional and total skeletal muscle and adipose tissue with 5-year, all-cause mortality in 922 HIV-infected persons in the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM).
After 5 years of follow-up, HIV-infected participants with arm skeletal muscle in the lowest tertile had a mortality rate of 23%, compared with 11 and 8% for those in the middle and highest tertiles. After multivariable adjustment for demographics, cardiovascular risk factors, HIV-related factors, inflammatory markers, and renal disease, we found that lower arm skeletal muscle, lower leg skeletal muscle and higher visceral adipose tissue (VAT) were each independently associated with increased mortality. Those in the lowest tertile of arm or leg skeletal muscle had higher odds of death [arm: odds ratio (OR)=2.0, 95% confidence interval (CI) 0.96–4.0; leg: OR=2.4, 95% CI 1.2–4.8] compared with the highest respective tertiles. Those in the highest tertile of VAT had 2.1-fold higher odds of death (95% CI 1.1–4.0) compared with the lowest VAT tertile.
Lower muscle mass and central adiposity appear to be important risk factors for mortality in HIV-infected individuals. A substantial proportion of this risk may be unrecognized because of the current reliance on body mass index in clinical practice.
PMCID: PMC3933309  PMID: 21572308
body composition; cachexia; fat redistribution; HIV infection; lipoatrophy; lipodystrophy; mortality; sarcopenia
9.  Evolving Concepts on Adjusting Human Resting Energy Expenditure Measurements for Body Size 
Establishing if an adult’s resting energy expenditure (REE) is high or low for their body size is a pervasive question in nutrition research. Early workers applied body mass and height as size measures and formulated the Surface Law and Kleiber’s Law, although each has limitations when adjusting REE. Body composition methods introduced during the mid-twentieth century provided a new opportunity to identify metabolically homogeneous “active” compartments. These compartments all show improved correlations with REE estimates over body mass-height approaches, but collectively share a common limitation: REE-body composition ratios are not “constant” but vary across men and women and with race, age, and body size. The now-accepted alternative to ratio-based norms is to adjust for predictors by applying regression models to calculate “residuals” that establish if a REE is relatively high or low. The distinguishing feature of statistical REE-body composition models is a “non-zero” intercept of unknown origin. The recent introduction of imaging methods has allowed development of physiological tissue-organ based REE prediction models. Herein we apply these imaging methods to provide a mechanistic explanation, supported by experimental data, for the non-zero intercept phenomenon and in that context propose future research directions for establishing between subject differences in relative energy metabolism.
PMCID: PMC3477241  PMID: 22863371
Energy Metabolism; Body Composition; Mathematical Model
10.  Anthropometric Markers of Obesity and Mortality in White and African American Adults: The Pennington Center Longitudinal Study 
Obesity (Silver Spring, Md.)  2013;21(5):1070-1075.
The purpose of this study was to determine the association between anthropometric measures of obesity and all-cause mortality in white and African American men and women. The sample included 14,343 adults 18 to 89 years of age. Height, weight, and waist and hip circumferences were measured, and the BMI (kg/m2), body adiposity index (BAI = ([hip circumference in centimeters]/[height in meters])1.5–18), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR) were computed. Vital status of the participants was determined from linkage with the National Death Index through 2009. Cox regression was used to assess the association between anthropometry and all1cause mortality, adjusting for age, sex, year of baseline examination, study code, smoking status, alcohol consumption and physical activity. Hazard ratios (HR) are expressed per standard deviation of each variable. A total of 438 deaths occurred during 120,637 person-years of follow-up. All anthropometric markers demonstrated significant associations with all-cause mortality in white subjects. In multivariable-adjusted models, BMI (HR 1.34; 95% CI: 1.19 - 1.50), waist circumference (1.41; 1.25 - 1.60), BAI (1.34; 1.17 - 1.53), WHtR (1.46; 1.28 - 1.65) and WHR (1.40; 1.23 - 1.61) all demonstrated significant relationships with mortality in white participants, but not in African Americans. In categorical analyses, there was a significant association between BMI status and mortality in whites but not African Americans. However, the risk associated with elevated waist circumference was almost identical in whites (1.49; 1.15 – 1.94) and African Americans (1.60; 1.06 – 2.40). In summary, this study has demonstrated race differences in the association between anthropometry and all-cause mortality.
PMCID: PMC3695407  PMID: 23784912
11.  Energy Content of Weight Loss: Kinetic Features During Voluntary Caloric Restriction 
Metabolism: clinical and experimental  2012;61(7):10.1016/j.metabol.2011.11.012.
The classic rule stating that restricting intake by 3500 kcal/wk will lead to a 1-lb/wk rate of weight loss has come under intense scrutiny. Generally not a component of most weight loss prediction models, the “early” rapid weight loss phase may represent a period during which the energy content of weight change (ΔEC/ΔW) is low and thus does not follow the classic “rule”. The current study tested this hypothesis.
Dynamic ΔEC/ΔW changes were examined in 23 CALERIE Study overweight men and women evaluated by dual-energy x-ray absorptiometry during weight loss at treatment weeks 4 to 24. Changes from baseline in body energy content were estimated from fat and fat-free mass. Repeated measures ANOVA was used to determine if ΔEC/ΔW changed significantly over time. The evaluation was expanded with addition of the Kiel 13-week weight loss study of 75 obese men and women to test with adequate power if there are sex differences in ΔEC/ΔW.
The ANOVA CALERIE time effect was significant (p <0.001) with post hoc tests indicating ΔEC/ΔW (kcal/kg) increased significantly from week 4 (X±SEM, 4, 858±388) to 6 (6, 041±376, p<0.01) and changed insignificantly thereafter; ΔEC/ΔW was significantly larger for Kiel women (6, 804±226) versus men (6, 119±240, p<0.05).
Sex-specific dynamic relative changes in body composition and related ΔEC/ΔW occur with weight loss initiation that extend one-month or more. These observations provide new information for developing energy balance models and further define limitations of the 3500 kcal energy deficit → 1 lb weight loss rule.
PMCID: PMC3810417  PMID: 22257646
Energy Balance; Body Composition; Weight Loss; Body Fat
12.  Dual-Energy X-Ray Absorptiometry Prediction of Adipose Tissue Depots in Children and Adolescents 
Pediatric research  2012;72(4):420-425.
The measurement of adipose tissue depots in-vivo requires expensive imaging methods not accessible to most clinicians and researchers. The study aim was to derive mathematical models to predict total adipose tissue (TAT) and sub-depots from total body fat derived from a dual energy x-ray absorptiometry (DXA) scan.
Models were developed to predict magnetic resonance imaging derived TAT and sub-depots subcutaneous (SAT), visceral (VAT), and intermuscular (IMAT) from DXA total body fat using cross-sectional data (T0) and validated results using 1 (T1) and 2 (T2) year follow-up data. Subjects were 176 multi-ethnic healthy children ages 5 to 17 years at T0. 22 were measured at T1 and T2. TAT was compared to fat.
At T0, TAT was greater than fat (12.5 ± 8.4 vs.12.0 ± 9.4 kg; p< 0.0001), with a quadratic relationship between TAT and fat which varied by sex. Predicted mean TAT’s were not different from measured TAT’s: T1: (9.84±4.45 kg vs. 9.50±4.37 kg; p=0.11) T2: (12.94±6.75 kg vs. 12.89±7.09 kg; p=0.76). The quadratic relationship was not influenced by race or age.
In general, the prediction equations for TAT and sub-depots were consistent with the measured values using T1 and T2 data.
PMCID: PMC3668789  PMID: 22821057
13.  Intermuscular Adipose Tissue and Metabolic Associations in HIV Infection 
Obesity (Silver Spring, Md.)  2010;19(2):283-291.
Intermuscular adipose tissue (IMAT) is associated with metabolic abnormalities similar to those associated with visceral adipose tissue (VAT). Increased IMAT has been found in obese human immunodeficiency virus (HIV)-infected women. We hypothesized that IMAT, like VAT, would be similar or increased in HIV-infected persons compared with healthy controls, despite decreases in subcutaneous adipose tissue (SAT) found in HIV infection. In the second FRAM (Study of Fat Redistribution and Metabolic Change in HIV infection) exam, we studied 425 HIV-infected subjects and 211 controls (from the Coronary Artery Risk Development in Young Adults study) who had regional AT and skeletal muscle (SM) measured by magnetic resonance imaging (MRI). Multivariable linear regression identified factors associated with IMAT and its association with metabolites. Total IMAT was 51% lower in HIV-infected participants compared with controls (P = 0.003). The HIV effect was attenuated after multivariable adjustment (to −28%, P < 0.0001 in men and −3.6%, P = 0.70 in women). Higher quantities of leg SAT, upper-trunk SAT, and VAT were associated with higher IMAT in HIV-infected participants, with weaker associations in controls. Stavudine use was associated with lower IMAT and SAT, but showed little relationship with VAT. In multivariable analyses, regional IMAT was associated with insulin resistance and triglycerides (TGs). Contrary to expectation, IMAT is not increased in HIV infection; after controlling for demographics, lifestyle, VAT, SAT, and SM, HIV+ men have lower IMAT compared with controls, whereas values for women are similar. Stavudine exposure is associated with both decreased IMAT and SAT, suggesting that IMAT shares cellular origins with SAT.
PMCID: PMC3731045  PMID: 20539305
14.  Myths, Presumptions, and Facts about Obesity 
The New England journal of medicine  2013;368(5):446-454.
Many beliefs about obesity persist in the absence of supporting scientific evidence (presumptions); some persist despite contradicting evidence (myths). The promulgation of unsupported beliefs may yield poorly informed policy decisions, inaccurate clinical and public health recommendations, and an unproductive allocation of research resources and may divert attention away from useful, evidence-based information.
Using Internet searches of popular media and scientific literature, we identified, reviewed, and classified obesity-related myths and presumptions. We also examined facts that are well supported by evidence, with an emphasis on those that have practical implications for public health, policy, or clinical recommendations.
We identified seven obesity-related myths concerning the effects of small sustained increases in energy intake or expenditure, establishment of realistic goals for weight loss, rapid weight loss, weight-loss readiness, physical-education classes, breast-feeding, and energy expended during sexual activity. We also identified six presumptions about the purported effects of regularly eating breakfast, early childhood experiences, eating fruits and vegetables, weight cycling, snacking, and the built (i.e., human-made) environment. Finally, we identified nine evidence-supported facts that are relevant for the formulation of sound public health, policy, or clinical recommendations.
False and scientifically unsupported beliefs about obesity are pervasive in both scientific literature and the popular press. (Funded by the National Institutes of Health.)
PMCID: PMC3606061  PMID: 23363498
15.  A Single MRI Slice Does Not Accurately Predict Visceral and Subcutaneous Adipose Tissue Changes During Weight Loss 
Obesity (Silver Spring, Md.)  2012;20(12):2458-2463.
Previous cross-sectional studies found that a single magnetic resonance imaging (MRI) slice predicts total visceral and subcutaneous adipose tissue (VAT and SAT) volumes well. We sought to investigate the accuracy of trunk single slice imaging in estimating changes of total VAT and SAT volume in 123 overweight and obese subjects who were enrolled in a 24-week CB-1R inverse agonist clinical trial (weight change, −7.7±5.3 kg; SAT change, −5.4±4.9 L, VAT change, −0.8±1.0 L). VAT and SAT volumes at baseline and 24 weeks were derived from whole body MRI images. The VAT area 5–10 cm above L4–L5 (A+5–10) (R2=0.59–0.70, P<0.001) best predicted changes in VAT volume but the strength of these correlations were significantly lower than those at baseline (R2=0.85–0.90, P<0.001). Furthermore, the L4–L5 slice poorly predicted VAT volume changes (R2=0.24–0.29, P<0.001). Studies will require 44–69% more subjects if (A+5–10) is used and 243–320% more subjects if the L4–L5 slice is used for equivalent power of multi slice total volume measurements of VAT changes. Similarly, single slice imaging predicts SAT loss less well than cross-sectional SAT (R2=0.31–0.49 vs. R2=0.52–0.68, p<0.05). Results stayed the same when examined in men and women separately. A single MRI slice 5–10 cm above L4–L5 is more powerful than the traditionally used L4–L5 slice in detecting VAT changes, but in general single slice imaging poorly predicts VAT and SAT changes during weight loss. For certain study designs, multi-slice imaging may be more cost effective than single slice imaging in detecting changes for VAT and SAT.
PMCID: PMC3466347  PMID: 22728693
Visceral adipose tissue; subcutaneous adipose tissue; clinical trial; magnetic resonance imaging; computed tomography; body composition
16.  The body adiposity index (hip circumference ÷ height1.5) is not a more accurate measure of adiposity than is BMI, waist circumference, or hip circumference 
Obesity (Silver Spring, Md.)  2012;20(12):2438-2444.
Based on cross-sectional analyses, it was suggested that hip circumference divided by height1.5 minus 18 (the body adiposity index, BAI), could directly estimate percent body fat without the need for further correction for sex or age. We compared the prediction of percent body fat, as assessed by dual-energy x-ray absorptiometry (PBFDXA), by BAI, BMI, and circumference (waist and hip) measurements among 1151 adults who had a total body scan by DXA and circumference measurements from 1993 through 2006. After accounting for sex, we found that PBFDXA was related similarly to BAI, BMI, waist circumference, and hip circumference. In general, BAI overestimated PBFDXA among men (3.9%) and underestimated PBFDXA among women (2.5%), but the magnitudes of these biases varied with the level of body fatness. The addition of covariates and quadratic terms for the body size measures in regression models substantially improved the prediction of PBFDXA, but none of the models based on BAI could more accurately predict PBFDXA than could those based on BMI or circumferences. We conclude that the use of BAI as an indicator of adiposity is likely to produce biased estimates of percent body fat, with the errors varying by sex and level of body fatness. Although regression models that account for the non-linear association, as well as the influence of sex, age and race, can yield more accurate estimates of PBFDXA, estimates based on BAI are not more accurate than those based on BMI, waist circumference, or hip circumference.
PMCID: PMC3477292  PMID: 22484365
17.  Greater Abdominal Fat Accumulation Is Associated with Higher Metabolic Risk in Chinese than in White People: An Ethnicity Study 
PLoS ONE  2013;8(3):e58688.
Chinese are reported to have a higher percent body fat (%BF) and a higher percent trunk fat (%TF) than whites for a given body mass index (BMI). However, the associations of these ethnic differences in body composition with metabolic risks remain unknown.
Methods and Procedures
A total of 1 029 Chinese from Hangzhou, China, and 207 whites from New York, NY, USA, were recruited in the present study. Body composition was measured using dual-energy X-ray absorptiometry (DXA). Analysis of covariance was used to assess the ethnic differences in fat, fat distribution, and metabolic risk factors.
After adjusting for BMI, age, and height, Chinese men had an average of 3.9% more %BF and 12.1% more %TF than white men; Chinese women had an average of 2.3% more %BF and 11.8% more %TF than white women. Compared with whites, higher metabolic risks were detected in Chinese for a given BMI after adjusting for age and height. Further adjustment for %BF did not change these ethnic disparities. However, after adjusting for %TF, the ethnic differences decreased and become insignificant in triglyceride, high-density lipoprotein cholesterol, and blood pressure (except for systolic blood pressure in men). For fasting plasma glucose, the ethnic differences persisted after adjustment for %BF, but decreased significantly from 0.910 to 0.686 mmol/L among men, and from 0.629 to 0.355 mmol/L among women, when the analyses were further controlled for %TF.
Chinese have both higher %BF and %TF than white people for a given BMI. However, only %TF could in part account for the higher metabolic risk observed in Chinese men and women.
PMCID: PMC3597722  PMID: 23516538
18.  MRI-measured pelvic bone marrow adipose tissue is inversely related to DXA-measured bone mineral in younger and older Adults 
Recent research has shown an inverse relationship between bone marrow adipose tissue (BMAT) and bone mineral density (BMD). There is a lack of evidence at the macro-imaging level to establish whether increased BMAT is a cause or effect of bone loss. This cross-sectional study compared the BMAT and BMD relationship between a younger adult group at or approaching peak bone mass (PBM) (age 18.0-39.9 yrs) and an older group with potential bone loss (PoBL) (age 40.0-88 yrs).
Pelvic BMAT was evaluated in 560 healthy men and women with T1-weighted whole body magnetic resonance imaging. BMD was measured using whole body dual-energy x-ray absorptiometry.
An inverse correlation was observed between pelvic BMAT and pelvic, total, and spine BMD in the younger PBM group (r=-0.419 to -0.461, P<0.001) and in the older PoBL group (r=-0.405 to -0.500, P<0.001). After adjusting for age, sex, ethnicity, menopausal status, total body fat, skeletal muscle, subcutaneous and visceral adipose tissue, neither subject group (younger PBM vs. older PoBL) nor its interaction with pelvic BMAT significantly contributed to the regression models with BMD as dependent variable and pelvic BMAT as independent variable (P=0.434 to 0.928).
Our findings indicate that an inverse relationship between pelvic BMAT and BMD is present both in younger subjects who have not yet experienced bone loss and also in older subjects. These results provide support at the macro-imaging level for the hypothesis that low BMD may be a result of preferential differentiation of mesenchymal stem cells from osteoblasts to adipocytes.
PMCID: PMC3396793  PMID: 22491495
body composition; bone marrow adipose tissue; bone mineral density; dual-energy X-ray absorptiometry; magnetic resonance imaging; aging
19.  Serum creatinine as a marker of muscle mass in chronic kidney disease: results of a cross-sectional study and review of literature 
Higher muscle mass is associated with better outcomes and longevity in patients with chronic disease states. Imaging studies such as dual-energy X-ray absorptiometry (DEXA) are among the gold standard methods for assessing body fat and lean body mass (LBM), approximately half of which is comprised of skeletal muscle mass. Elaborate imaging devices, however, are not commonly available in routine clinical practice and therefore easily accessible and cost-effective, but reliable muscle mass biomarkers are needed. One such marker is serum creatinine, derived from muscle-based creatine, which is inexpensive and ubiquitously available, and it can serve as a biomarker of skeletal muscle mass in human subjects.
Methods and results
In 118 hemodialysis patients, we found that the 3-month averaged serum creatinine concentration correlated well with DEXA-measured LBM. The recent literature regarding serum creatinine as a surrogate of muscle mass is summarized, as is the literature concerning the use of other measures of muscle mass, such as plasma gelsolin and actin, and urinary creatinine excretion. We have also reviewed the role of dietary meat intake in serum creatinine variability along with several biomarkers of dietary meat intake (creatine, carnitine, carnosine, ophidine, anserine, 3-methyl-l-histidine and 1-methylhistidine).
In summary, none of these biomarkers was studied in CKD patients. We advance the hypothesis that in both health and disease, under steady state, serum creatinine can serve as a reliable muscle mass biomarker if appropriate adjustment for full or residual kidney function and dietary meat intake is undertaken.
PMCID: PMC3581614  PMID: 22777757
Serum creatinine; Hemodialysis; Protein–energy wasting (PEW); Lean body mass (LBM); Nutritional status; Skeletal muscle mass
20.  Evaluation of Specific Metabolic Rates of Major Organs and Tissues: Comparison Between Nonobese and Obese Women 
Obesity (Silver Spring, Md.)  2011;20(1):95-100.
Elia (1992) identified the specific resting metabolic rates (Ki) of major organs and tissues in young adults with normal weight: 200 for liver, 240 for brain, 440 for heart and kidneys, 13 for skeletal muscle, 4.5 for adipose tissue and 12 for residual mass (all units in kcal/kg per day). The aim of the present study was to assess the applicability of Elia’s Ki values for obese adults. A sample of young women (n = 80) was divided into two groups, nonobese (BMI <29.9 kg/m2) and obese (BMI 30.0–43.2 kg/m2). This study was based on the mechanistic model: REE = Σ (Ki × Ti), where REE is whole-body resting energy expenditure measured by indirect calorimetry and Ti is the mass of individual organs and tissues measured by magnetic resonance imaging. For each organ/tissue, the corresponding Elia’s Ki value was analyzed respectively for nonobese and obese groups by using stepwise univariate regression analysis. Elia’s Ki values were within the range of 95% confidence intervals (CIs) in the nonobese group. However, Elia’s Ki values were outside the right boundaries of 95% CIs in the obese group and a corresponding obesity-adjusted coefficient was calculated as 0.98, indicating that Elia’s values overestimate Ki by 2.0% in obese adults. Obesity-adjusted Ki values were 196 for liver, 235 for brain, 431 for heart and kidneys, 12.7 for skeletal muscle, 4.4 for adipose tissue, and 11.8 for residual mass. In conclusion, although Elia’s Ki values were validated in nonobese women, obesity-adjustments are appropriate for application in obese women.
PMCID: PMC3319030  PMID: 21836642
21.  Rate of weight loss can be predicted by patient characteristics and intervention strategies 
Although dietary weight loss counseling usually employs a 500-1000 kcal/d energy deficit to induce weight loss of 0.5-1 kg/wk, this rate of weight loss is rarely achieved in research settings. Biological factors, such as changes in metabolic rate, are partly responsible but would account for a small deviation from expected weight loss. There must be other factors, behavioral or related to study design and implementation that affect the rate of weight loss observed.
To examine factors that influence the rate of weight loss obtained in clinical studies.
Thirty-five weight loss studies published between 1995 and 2009 were identified that used dietary counseling to induce weight loss in healthy subjects. Studies were included if they had a duration of at least 6 wk, used a strategy to counsel subjects to reduce free-living energy intakes, and reported weight loss data based on a completers analysis. Variables that were associated with the rate of weight loss among age, gender (% female subjects), initial body weight, frequency of dietary counseling, placebo use, exercise level, study length, and prescribed energy deficit were examined using linear regression analysis.
Study length was negatively related to the rate of weight loss (P<0.0001) whereas subject age (P<0.002), subject age squared (P=0.0073), initial body weight (P=0.0003), frequency of dietary counseling (P=0.0197), and prescribed energy deficit (P<0.0001) were positively related to the rate of weight loss observed in clinical studies.
These findings provide a tool for investigators and clinical dietitians to predict the rate of weight loss that can be expected within a population given the age, initial body weight, frequency of dietary counseling, and energy deficit prescription. These data, from clinical studies, suggest that the rate of weight loss is greater in older and heavier subjects and with higher contact frequency and caloric restriction.
PMCID: PMC3447534  PMID: 22717178
Obesity; duration; weight loss; caloric deficit; dietary counseling; diet
22.  Association of Increased Upper Trunk and Decreased Leg Fat With 2-h Glucose in Control and HIV-Infected Persons 
Diabetes Care  2011;34(11):2448-2453.
Changes in body fat distribution and abnormal glucose metabolism are common in HIV-infected patients. We hypothesized that HIV-infected participants would have a higher prevalence of impaired glucose tolerance (IGT) compared with control subjects.
A total of 491 HIV-infected and 187 control participants from the second examination of the Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) underwent glucose tolerance testing (GTT). Multivariable regression was used to identify factors associated with GTT parameters.
The prevalence of impaired fasting glucose (IFG) (>110 mg/dL) was similar in HIV-infected and control participants (21 vs. 25%, P = 0.23). In those without IFG, the prevalence of IGT was slightly higher in HIV-infected participants compared with control subjects (13.1 vs. 8.2%, P = 0.14) and in HIV+ participants with lipoatrophy versus without (18.1 vs. 11.5%, P = 0.084). Diabetes detected by GTT was rare (HIV subjects 1.3% and control subjects 0%, P = 0.65). Mean 2-h glucose levels were 7.6 mg/dL higher in the HIV-infected participants (P = 0.012). Increased upper trunk subcutaneous adipose tissue (SAT) and decreased leg SAT were associated with 2-h glucose and IGT in both HIV-infected and control participants. Adjusting for adipose tissue reduced the estimated effects of HIV. Exercise, alcohol use, and current tenofovir use were associated with lower 2-h glucose levels in HIV-infected participants.
In HIV infection, increased upper trunk SAT and decreased leg SAT are associated with higher 2-h glucose. These body fat characteristics may identify HIV-infected patients with normal fasting glucose but nonetheless at increased risk for diabetes.
PMCID: PMC3198295  PMID: 21926283
23.  Anthropometric Correlates of Total Body Fat, Abdominal Adiposity, and Cardiovascular Disease Risk Factors in a Biracial Sample of Men and Women 
Mayo Clinic Proceedings  2012;87(5):452-460.
To investigate associations between anthropometric measurements and total body fat, abdominal adipose tissue, and cardiovascular disease risk factors in a large biracial sample.
Patients and Methods
This study is limited to cross-sectional analyses of data from participants attending a baseline visit between January 26, 1996, and February 1, 2011. The sample included 2037 individuals aged 18 to 69 years: 488 African American women (24%), 686 white women (34%), 196 African American men (9%), and 667 white men (33%). Anthropometry included weight; hip circumference; waist circumference; waist-hip, waist-height, and weight-height ratios; body adiposity index; and body mass index. Body fat and percentage of fat were measured by dual-energy x-ray absorptiometry, and abdominal visceral and subcutaneous adipose tissue were measured by computed tomography. Bivariate correlations, logistic regression models, and receiver operator characteristic curves were used, and analyses were stratified by sex and race.
In each sex-by-race group, all anthropometric measures were highly correlated with percentage of fat, fat mass, and subcutaneous adipose tissue and moderately correlated with visceral adipose tissue, with the exception of the waist-hip ratio. The odds of having an elevated cardiometabolic risk were increased more than 2-fold per SD increase for most anthropometric variables, and the areas under the curve for each anthropometric measure were significantly greater than 0.5.
Several common anthropometric measures were moderately to highly correlated with total body fat, abdominal fat, and cardiovascular disease risk factors in a biracial sample of women and men. This comprehensive analysis provides evidence of the linkage between simple anthropometric measurements and the purported pathways between adiposity and health.
PMCID: PMC3498102  PMID: 22560524
AUC, area under the curve; BAI, body adiposity index; BMI, body mass index; CT, computed tomography; CVD, cardiovascular disease; DXA, dual-energy x-ray absorptiometry; HC, hip circumference; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; PCLS, Pennington Center Longitudinal Study; ROC, receiver operating characteristic; SAT, subcutaneous adipose tissue; VAT, visceral adipose tissue; WC, waist circumference
24.  Body Mass Index and the Risk of Dementia among Louisiana Low Income Diabetic Patients 
PLoS ONE  2012;7(9):e44537.
The association between obesity and dementia risk remains debatable and no studies have assessed this association among diabetic patients. The aim of our study was to investigate the association between body mass index (BMI) and dementia risk among middle and low income diabetic patients.
Methodology/Principal Findings
The sample included 44,660 diabetic patients (19,618 white and 25,042 African American) 30 to 96 years of age without a history of dementia in the Louisiana State University Hospital-Based Longitudinal Study. During a mean follow-up period of 3.9 years, 388 subjects developed incident dementia. The age- and sex-adjusted hazards ratios (HRs) for incident dementia at different levels of BMI (≤25, 25–26.9, 27–29.9, 30–34.9, and ≥35 kg/m2) were 1.00, 0.53 (95% CI 0.34–0.83), 0.29 (0.18–0.45), 0.37 (0.25–0.56), and 0.31 (0.21–0.48) (Ptrend<0.001) in white diabetic patients, and 1.00, 1.00 (95% CI 0.62–1.63), 0.62 (0.39–0.98), 0.56 (0.36–0.86), and 0.65 (0.43–1.01) (Ptrend = 0.029) in African American diabetic patients. Further adjustment for other confounding factors affected the results only slightly. There was a significant interaction between race and BMI on dementia risk (χ2 = 5.52, 1df, p<0.025), such that the association was stronger in white patients. In stratified analyses, the multivariate-adjusted inverse association between BMI and risk of dementia was present in subjects aged 55–64 years, 65–74 years, and ≥75 years, in men and women, in non-smokers and smokers, and in subjects with different types of health insurance.
Higher baseline BMI was associated with a lower risk of dementia among diabetic patients, and this association was stronger among white than among African American diabetic patients.
PMCID: PMC3434129  PMID: 22957079
25.  Effects of cell-type specific leptin receptor mutation on leptin transport across the BBB 
Peptides  2011;32(7):1392-1399.
The functions of leptin receptors (LRs) are cell-type specific. At the blood-brain barrier, LRs mediate leptin transport that is essential for its CNS actions, and both endothelial and astrocytic LRs may be involved. To test this, we generated endothelia specific LR knockout (ELKO) and astrocyte specific LR knockout (ALKO) mice. ELKO mice were derived from a cross of Tie2-cre recombinase mice with LR-floxed mice, whereas ALKO mice were generated by a cross of GFAP-cre with LR-floxed mice, yielding mutant transmembrane LRs without signaling functions in endothelial cells and astrocytes, respectively. The ELKO mutation did not affect leptin half-life in blood or apparent influx rate to the brain and spinal cord, though there was an increase of brain parenchymal uptake of leptin after in-situ brain perfusion. Similarly, the ALKO mutation did not affect blood-brain barrier permeation of leptin or its degradation in blood and brain. The results support our observation from cellular studies that membrane-bound truncated LRs are fully efficient in transporting leptin, and that basal levels of astrocytic LRs do not affect leptin transport across the endothelial monolayer. Nonetheless, the absence of leptin signaling at the BBB appears to enhance the availability of leptin to CNS parenchyma. The ELKO and ALKO mice provide new models to determine the dynamic regulation of leptin transport in metabolic and inflammatory disorders where cellular distribution of LRs is shifted.
PMCID: PMC3137692  PMID: 21616110
Leptin; BBB; Transport; Endothelial cells; Astrocytes; CNS effects

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