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1.  Adipokines, hormones related to body composition, and insulin resistance in HIV fat redistribution syndrome 
BMC Infectious Diseases  2014;14:347.
Lipodystrophies are characterized by adipose tissue redistribution, insulin resistance (IR) and metabolic complications. Adipokines and hormones related to body composition may play an important role linking these alterations. Our aim was to evaluate adipocyte-derived hormones (adiponectin, leptin, resistin, TNF-α, PAI-1) and ghrelin plasma levels and their relationship with IR in HIV-infected patients according to the presence of lipodystrophy and fat redistribution.
Anthropometric and metabolic parameters, HOMA-IR, body composition by DXA and CT, and adipokines were evaluated in 217 HIV-infected patients on cART and 74 controls. Fat mass ratio defined lipodystrophy (L-FMR) was defined as the ratio of the percentage of the trunk fat mass to the percentage of the lower limb fat mass by DXA. Patient’s fat redistribution was classified into 4 different groups according the presence or absence of either clinical lipoatrophy or abdominal prominence: no lipodystrophy, isolated central fat accumulation (ICFA), isolated lipoatrophy and mixed forms (MXF). The associations between adipokines levels and anthropometric, metabolic and body composition were estimated by Spearman correlation.
Leptin levels were lower in patients with FMR-L and isolated lipoatrophy, and higher in those with ICFA and MXF. Positive correlations were found between leptin and body fat (total, trunk, leg, arm fat evaluated by DXA, and total, visceral (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratio evaluated by CT) regardless of FMR-L, and with HOMA-IR only in patients with FMR-L. Adiponectin correlated negatively with VAT, and its mean levels were lower in patients with ICFA and higher in those with no lipodystrophy. Resistin was not correlated with adipose tissue but positively correlated with HOMA-IR in FMR-L patients. PAI-1 levels were higher in MXF-patients and their levels were positively correlated with VAT in those with FMR-L. Ghrelin was higher in HIV-infected patients than controls despite BMI-matching.
The overall body fat reduction in HIV lipoatrophy was associated with low leptin plasma levels, and visceral fat accumulation was mainly associated with decreased plasma levels of adiponectin.
PMCID: PMC4079215  PMID: 24958357
Lipodystrophy; HIV; Adipokines; Body composition; Insulin resistance
2.  Association of Upper Trunk and Visceral Adipose Tissue Volume With Insulin Resistance in Control and HIV-Infected Subjects in the FRAM Study 
Visceral obesity is associated with insulin resistance, but the association of other regional adipose depots with insulin resistance is not understood. In HIV infection, buffalo hump (upper trunk fat) is associated, but the association of upper trunk fat with insulin resistance has not been examined in controls. To determine the independent association of adipose depots other than visceral with insulin resistance, we performed a cross-sectional analysis of controls and HIV-infected subjects in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study, who had measurements of glucose, insulin, and adipose tissue volumes by whole-body magnetic resonance imaging. We studied 926 HIV-positive persons from 16 academic medical center clinics and trials units with demographic characteristics representative of US patients with HIV infection and 258 FRAM controls from the population-based Coronary Artery Risk Development in Young Adults study. We measured visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volume in the legs, arms, lower trunk (back and abdomen), and upper trunk (back and chest) and assessed their association with the homeostasis model of assessment (HOMA) and HOMA >4 by stepwise multivariable analysis. The prevalence of HOMA >4 as a marker of insulin resistance was 28% among controls compared with 37% among HIV-infected subjects (P = 0.005). Among controls, those in the highest tertile of upper trunk SAT volume had an odds ratio (OR) of 9.0 (95% confidence interval [CI]: 2.4 to 34; P = 0.001) for having HOMA >4 compared with the lowest tertile, whereas in HIV-positive subjects, the OR was lower (OR = 2.09, 95% CI: 1.36 to 3.19; P = 0.001). Among controls, the highest tertile of VAT volume had an OR of 12.1 (95% CI: 3.2 to 46; P = 0.0002) of having HOMA >4 compared with the lowest tertile, whereas in HIV-positive subjects, the OR was 3.12 (95% CI: 2.0 to 4.8; P < 0.0001). After adjusting for VAT and upper trunk SAT, the association of other SAT depots with HOMA >4 did not reach statistical significance. Thus, VAT and upper trunk SAT are independently associated with insulin resistance in controls and in HIV-infected persons.
PMCID: PMC3164883  PMID: 18167644
buffalo hump; fat distribution; insulin resistance; lipodystrophy; visceral obesity
3.  Fat Distribution in Men With HIV Infection 
Both peripheral fat loss and central fat gain have been reported in HIV infection. Which changes are specific to HIV were determined by comparison with control subjects and the associations among different adipose tissue depots were determined.
Cross-sectional analysis of HIV-positive and control men from the study of Fat Redistribution and Metabolic Change in HIV Infection. Lipoatrophy or lipohypertrophy was defined as concordance between participant report of change and examination. Regional adipose tissue volume was measured by magnetic resonance imaging (MRI).
HIV-positive men reported more fat loss than controls in all peripheral and most central depots. Peripheral lipoatrophy was more frequent in HIV-positive men than in controls (38.3% vs. 4.6%, P < 0.001), whereas central lipohypertrophy was less frequent (40.2% vs. 55.9%, P = 0.001). Among HIV-positive men, the presence of central lipohypertrophy was not positively associated with peripheral lipoatrophy (odds ratio = 0.71, CI: 0.47 to 1.06, P = 0.10). On MRI, HIV-positive men with clinical peripheral lipoatrophy had less subcutaneous adipose tissue (SAT) in peripheral and central sites and less visceral adipose tissue (VAT) than HIV-positive men without peripheral lipoatrophy. HIV-positive men both with and without lipoatrophy had less SAT than controls, with legs and lower trunk more affected than upper trunk. Use of the antiretroviral drugs stavudine or indinavir was associated with less leg SAT but did not appear to be associated with more VAT; nevirapine use was associated with less VAT.
Both peripheral and central subcutaneous lipoatrophy was found in HIV infection. Lipoatrophy in HIV-positive men is not associated with reciprocally increased VAT.
PMCID: PMC3166344  PMID: 16186728
HIV infection; lipodystrophy; lipoatrophy; lipohypertrophy; visceral obesity; fat redistribution; body composition
4.  The Associations of Regional Adipose Tissue with Lipid and Lipoprotein Levels in HIV-infected Men 
HIV infection and antiretroviral therapy are associated with dyslipidemia, but the association between regional adipose tissue depots and lipid levels is not defined.
The association of MRI-measured visceral (VAT) and regional subcutaneous adipose tissue (SAT) volume with fasting lipid parameters was analyzed by multivariable linear regression in 737 HIV-infected and 145 control men from the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM).
HIV-infected men had higher median triglycerides (TG) (170mg/dl vs. 107mg/dl, p<0.0001), lower high density lipoprotein (HDL-C) (38mg/dl vs. 46mg/dl, p<0.0001) and lower low density lipoprotein (LDL-C) (105mg/dl vs. 125mg/dl, p<0.0001) than controls. After adjustment, greater VAT was associated with higher TG and lower HDL-C in both HIV-infected and control men, while greater leg SAT was associated with lower TG in HIV-infected men with a similar trend in controls. More upper trunk SAT was associated with higher LDL-C and lower HDL-C in controls, while more lower trunk SAT was associated with higher TG in controls. After adjustment, HIV infection remained strongly associated (p<0.0001) with higher TG (+76%, CI: 53, 103), lower LDL-C (−19%, CI: −25,−12), and lower HDL-C (−18%, CI: −22,−12).
HIV-infected men are more likely than controls to have higher TG and lower HDL-C, which promote atherosclerosis, but also lower LDL-C. Less leg SAT and more VAT are important factors associated with high TG and low HDL-C in HIV-infected men. The reduced leg SAT in HIV-infected men with lipoatrophy places them at increased risk for pro-atherogenic dyslipidemia.
PMCID: PMC3156607  PMID: 18360291
5.  Fat Distribution in Women With HIV Infection 
Both peripheral fat loss and central fat gain have been reported in women with HIV infection. We determined the fat changes that are specific to HIV infection in women.
HIV-infected and control women from the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) were compared. Lipoatrophy or lipohypertrophy was defined as concordance between participant report of fat change and clinical examination. Whole-body magnetic resonance imaging measured regional adipose tissue volumes. The relationship among different adipose tissue depots was assessed. Factors associated with individual depots were analyzed using multivariate linear regression.
HIV-infected women reported more fat loss than controls in all peripheral and most central depots. Peripheral lipoatrophy was more frequent in HIV-infected women than controls (28% vs. 4%, P < 0.001), whereas central lipohypertrophy was similar (62% vs. 63%). Among HIV-infected women, those with central lipohypertrophy were less likely to have peripheral lipoatrophy (odds ratio, 0.39; 95% confidence interval, 0.20 to 0.75, P = 0.006) than those without central lipohypertrophy. On magnetic resonance imaging, HIV-infected women with clinical peripheral lipoatrophy had less subcutaneous adipose tissue (SAT) in peripheral and central sites and less visceral adipose tissue (VAT) than HIV-infected women without peripheral lipoatrophy. Compared with controls, HIV-infected women had less SAT in the legs, regardless of the presence or absence of lipoatrophy. However, those without lipoatrophy had more VAT and upper trunk SAT than controls. Use of the antiretroviral drug stavudine was associated with less leg SAT but was not associated with VAT. The use of highly active antiretroviral therapy, however, was associated with more VAT.
Peripheral lipoatrophy occurs commonly in HIV-infected women but is not associated with reciprocally increased VAT or trunk fat.
PMCID: PMC3166343  PMID: 16837863
HIV; lipodystrophy; lipoatrophy; lipohypertrophy; visceral obesity; fat redistribution; body composition
6.  The development of simple anthropometric measures to diagnose antiretroviral therapy-associated lipodystrophy in resource limited settings 
Lipohypertrophy does not appear to be an adverse ART reaction while lipoatrophy is clearly associated with the use of stavudine (d4T) and zidovudine (AZT). In low and middle income countries d4T has only recently been phased out and AZT is still widely being used. Several case definitions have been developed to diagnose lipodystrophy, but none of them are generalizable to sub-Saharan Africa where black women have less visceral adipose tissue and more subcutaneous adipose tissue than white women. We aimed to develop a simple, objective measure to define lipoatrophy and lipohypertrophy by comparing patient report to anthropometric and dual-energy X-ray absorptiometry (DXA) -derived variables.
DXA and anthropometric measures were obtained in a cross sectional sample of black HIV-infected South African men (n = 116) and women (n = 434) on ART. Self-reported information on fat gain or fat loss was collected using a standard questionnaire. Receiver operating characteristic (ROC) curves were used to describe the performance of anthropometric and DXA-derived variables using patient reported lipoatrophy and lipohypertrophy as the reference standard.
Lipoatrophy and lipohypertrophy were more common in women (25% and 33% respectively) than in men (10% and 13% respectively). There were insufficient numbers of men with DXA scans for meaningful analysis. The best predictors of lipoatrophy in women were the anthropometric variables tricep (AUC = 0.725) and thigh skinfold (AUC =0.720) thicknesses; and the DXA-derived variables percentage lower limb fat (AUC = 0.705) and percentage lower limb fat/height (AUC = 0.713). The best predictors of lipohypertrophy in women were the anthropometric variable waist/hip ratio (AUC = 0.645) and the DXA-derived variable percentage trunk fat/percentage limb fat (AUC = 0.647).
We were able to develop simple, anthropometric measures for defining lipoatrophy and lipohypertrophy, using a sample of black HIV-infected South African women with DXA scans. This is of particular relevance in resource limited settings, where health professionals need simple and inexpensive methods of diagnosing patients with lipoatrophy and lipohypertrophy.
PMCID: PMC4138415  PMID: 25143778
HIV; Lipoatrophy; Lipohypertrophy; Lipodystrophy; DXA; Anthropometry; Sub-Saharan africa; Antiretroviral therapy
7.  iDXA, Prodigy, and DPXL dual-energy X-ray absorptiometry whole-body scans: a cross-calibration study 
Total body fat, lean, and bone mineral content (BMC) in addition to regional fat and lean mass values for arms, legs, and trunk were compared across a pencil-beam (Lunar DPX-L) and two fan-beam (GE Lunar Prodigy and GE Lunar iDXA) dual energy x-ray absorptiometry (DXA) systems.
Subjects were a multi-ethnic sample of 99 healthy adult males (47%) and females (mean ± SD: age 46.3 ± 16.9 yrs; weight 73.4±16.6 kg; height 167.6±9.7 cm; BMI 26.0±5.2 kg/m2) who had whole-body scans performed within a 3 hour period on the three systems. Repeated measures ANOVA was used to test the null hypothesis that the mean values for the three systems were equal. Translation equations between the methods were derived using regression techniques.
BMC: For both genders, total BMC by iDXA was lower (P≤0.004) than the other systems. Lean: For males, iDXA was lower (P≤0.03) than the other systems for total, trunk and arms. For females, DPXL estimated higher (P<0.001) lean mass compared to the other systems for total, trunk and arms, but iDXA estimated greater legs lean mass. For both genders, all DPXL mean values were greater than Prodigy mean values (P<0.001).
Fat: In females, all 3 systems were different from each other for total, trunk, and legs (P≤0.04). For arms, DPXL and iDXA were higher than Prodigy (P<0.0004). For males, DPXL was less (P<0.001) for total body, trunk and legs compared to the other two systems and greater than Prodigy only for arms (P<0.0007). These data were used to derive translation equations between systems. For several measurements, the differences between systems were related to gender.
For estimation of BMC and body composition, there was high agreement between all DXA systems (R2=0.85 to 0.99). Even so, cross-calibration equations should be used to examine data across systems to avoid erroneous conclusions.
PMCID: PMC2661815  PMID: 19028125
DXA; cross-calibration; densitometry; body composition; pencil beam; fan beam; iDXA
8.  Asian women have greater abdominal and visceral adiposity than Caucasian women with similar body mass index 
Nutrition & Diabetes  2011;1(5):e6-.
In the Multiethnic Cohort Study, Japanese Americans (JA) have lower mean body mass index (BMI) compared with Caucasians, but show a higher waist-to-hip ratio at similar BMI values and a greater risk of diabetes and obesity-associated cancers.
We investigated the abdominal, visceral and hepatic fat distribution in these Asian and Caucasian Americans.
A cross-sectional sample of 60 female cohort participants (30 JA and 30 Caucasians), of ages 60–65 years and BMIs 18.5–40 kg m−2, underwent anthropometric measurements and a whole-body dual energy X-ray absorptiometry (DXA) scan: a subset of 48 women also had abdominal magnetic resonance imaging (MRI).
By design, JA women had similar BMIs (mean 26.5 kg m−2) to Caucasian women (27.1 kg m−2). JA women were found to have a significantly smaller hip circumference (96.9 vs 103.6 cm; P=0.007) but not a significantly lower DXA total fat mass (25.5 vs 28.8 kg; P=0.16). After adjusting for age and DXA total fat mass, JA women had a greater waist-to-hip ratio (0.97 vs 0.89; P<0.0001), DXA trunk fat (15.4 vs 13.9 kg; P=0.0004) and MRI % abdominal visceral fat (23.9 vs 18.5% P=0.01) and a lower DXA leg fat mass (8.2 vs 10.0 kg; P=<.0001). Their MRI % subcutaneous fat (33.4 vs 30.2% P=0.21) and % liver fat (5.8 vs 3.8% P=0.06) did not significantly differ from that of Caucasian women.
Our findings build on limited past evidence, suggesting that Asian women carry greater abdominal and visceral fat when compared with Caucasian women with similar overall adiposity. This may contribute to their elevated metabolic risk for obesity-related diseases.
PMCID: PMC3302135  PMID: 23449381
body composition; central obesity; liver fat; race/ethnicity; subcutaneous adipose tissue; visceral adipose tissue
9.  Regional fat deposition and cardiovascular risk in HIV infection: The FRAM study 
AIDS care  2011;23(8):929-938.
HIV-infected individuals are at increased risk for cardiovascular disease (CVD) and lipodystrophy, but the relationship between regional adipose tissue (AT) depots and CVD risk is not well-described. We determined regional AT volumes and CVD risk in an analysis of 586 HIV-infected and 280 control FRAM study subjects using whole-body magnetic resonance imaging (MRI) and the Framingham Risk Score (FRS). Median FRS and FRS >10% were higher in HIV than control men (4.7% vs. 3.7%, p=0.0002; 16% vs. 4%, p<0.0001). HIV and control women had similarly-low FRS (1.1% vs. 1.2%, p=0.91). In controls, total AT and all regional AT depots showed strong positive correlations with FRS (p<0.001) in men, and weaker positive correlations in women. Greater visceral AT (VAT) and lower leg subcutaneous AT (SAT) volumes were associated with elevated FRS in HIV subjects, with a trend for upper trunk SAT. Controls in the lowest quartile of leg SAT had the lowest FRS (1.5%), whereas HIV with similarly-low leg SAT had the highest FRS (4.0%, p<0.001 vs. controls). Increased VAT is associated with CVD risk, but the risk is higher in HIV-infected individuals relative to controls at every level of VAT. Peripheral lipoatrophy (as measured by leg SAT) is associated with striking increased CVD risk in HIV-infected patients, even after controlling for VAT, whereas low leg SAT is associated with low CVD risk in controls.
PMCID: PMC3249238  PMID: 21767228
HIV; fat redistribution; lipoatrophy; visceral fat; cardiovascular risk
10.  Higher Insulin, Triglycerides, and Blood Pressure With Greater Trunk Fat in Tanner 1 Chinese 
Obesity (Silver Spring, Md.)  2007;15(4):1004-1011.
The aims of this study were to investigate the body fat distribution pattern in prepubertal Chinese children and to investigate the relationship between central fat distribution and specific biomarkers of cardiovascular disease.
Research Methods and Procedures
The study was conducted in an urban Mainland Chinese (Jinan, Shandong) sample of children using a cross-sectional design. Pubertal status was determined by Tanner criteria. Measurements included weight, height, waist circumference, DXA measures of total body fat and trunk fat; fasting serum measures of glucose, insulin, triglyceride, cholesterol, high-density lipoprotein-cholesterol; and systolic and diastolic blood pressure. Multiple regression models were developed with the biomarkers of cardiovascular risk factor as the dependent variables, and adjustments were made for significant covariates, including sex, age, height, weight, waist circumference, total body fat, trunk fat, and interactions.
A total of 247 healthy prepubertal subjects were studied. After co-varying for age, weight, height, and extremity fat (the sum of arm fat and leg fat), girls had greater trunk fat than boys (p < 0.0001, R2 for model = 0.95). Insulin and triglyceride were positively related to central fat measured by DXA-trunk fat (p < 0.05) but not related to the waist circumference. In the blood pressure model, waist circumference was a significant predictor of both systolic blood pressure and diastolic blood pressure, while DXA-trunk fat was associated with diastolic blood pressure only. Significant interactions between sex and trunk fat, and sex and total fat, were found in relation to diastolic blood pressure.
In prepubertal Chinese children, greater trunk fat was significantly associated with higher insulin and triglyceride in boys and girls and was associated with higher diastolic blood pressure in boys only.
PMCID: PMC2726721  PMID: 17426336
fat distribution; cardiovascular risk factors; prepubertal; Chinese
11.  Waist to hip ratio and trunk to extremity fat (DXA) are better surrogates for IMCL and for visceral fat respectively than for subcutaneous fat in adolescent girls 
Increased visceral adipose tissue (VAT) and intramyocellular lipids (IMCL) are associated with increased metabolic risk. Clinical and DXA body composition measures that are associated with VAT are generally even more strongly associated with subcutaneous adipose tissue (SAT) reflecting general adiposity, and thus are not specific for VAT. Measures more strongly associated with VAT than SAT (thus more specific for VAT), and predictors of IMCL have not been reported.
We studied 30 girls 12-18 years; 15 obese, 15 normal-weight. The following were assessed: (1) anthropometric measures: waist circumference at the umbilicus and iliac crest (WC-UC and WC-IC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), (2) DXA measures: total fat, percent body fat (PBF), percent trunk fat (PTF), trunk-to-extremity fat ratio (TEFR), (3) MRI and 1H-MRS: VAT and SAT (L4-L5), soleus-IMCL.
Group as a whole: WC, trunk fat and PBF were more strongly associated with SAT than VAT; none were specific for VAT. In contrast, PTF and TEFR were more significantly associated with VAT (r = 0.83 and 0.81 respectively, p <0.0001 for both) than SAT (r = 0.77 and 0.75, p < 0.0001 for both). Strongest associations of S-IMCL were with WHR (r = 0.66, p = 0.0004). Subgroup analysis: In obese girls, WHR and WHtR were more strongly correlated with VAT (r = 0.62 and 0.82, p = 0.04 and 0.001) than SAT (r = 0.41 and 0.73, p not significant and 0.007), and for DXA measures, PTF and TEFR were more significantly associated with VAT (r = 0.70 and 0.72, p = 0.007 and 0.006) than SAT (r = 0.52 and 0.53, p = 0.07 and 0.06). In controls, PTF and TEFR were more strongly correlated with VAT (r = 0.79, p = 0.0004 for both) than SAT (r = 0.71 and 0.72, p = 0.003 for both). WHR was associated with IMCL in obese girls (r = 0.78, p = 0.008), but not controls.
Overall, WHR (anthropometry), and PTF and TEFR (DXA) are good surrogates for IMCL and for visceral fat respectively in adolescent girls.
PMCID: PMC3018385  PMID: 21143876
12.  Validation of Dual Energy X-Ray Absorptiometry Measures of Abdominal Fat by Comparison with Magnetic Resonance Imaging in an Indian Population 
PLoS ONE  2012;7(12):e51042.
Abdominal adiposity is an important risk factor for diabetes and cardiovascular disease in Indians. Dual energy X-ray absorptiometry (DXA) can be used to determine abdominal fat depots, being more accessible and less costly than gold standard measures such as magnetic resonance imaging (MRI). DXA has not been fully validated for use in South Asians. Here, we determined the accuracy of DXA for measurement of abdominal fat in an Indian population by comparison with MRI.
146 males and females (age range 18–74, BMI range 15–46 kg/m2) from Hyderabad, India underwent whole body DXA scans on a Hologic Discovery A scanner, from which fat mass in two abdominal regions was calculated, from the L1 to L4 vertebrae (L1L4) and from the L2 to L4 vertebrae (L2L4). Abdominal MRI scans (axial T1-weighted spin echo images) were taken, from which adipose tissue volumes were calculated for the same regions.
Intra-class correlation coefficients between DXA and MRI measures of abdominal fat were high (0.98 for both regions). Although at the level of the individual, differences between DXA and MRI could be large (95% of DXA measures were between 0.8 and 1.4 times MRI measures), at the sample level, DXA only slightly overestimated MRI measures of abdominal fat mass (mean difference in L1L4 region: 2% (95% CI:0%, 5%), mean difference in L2L4 region:4% (95% CI: 1%, 7%)). There was evidence of a proportional bias in the association between DXA and MRI (correlation between difference and mean −0.3), with overestimation by DXA greater in individuals with less abdominal fat (mean bias in leaner half of sample was 6% for L1L4 (95%CI: 2, 11%) and 7% for L2L4 (95% CI:3,12%).
DXA measures of abdominal fat are suitable for use in Indian populations and provide a good indication of abdominal adiposity at the population level.
PMCID: PMC3522679  PMID: 23272086
13.  Serum concentrations of phthalate metabolites are related to abdominal fat distribution two years later in elderly women 
Environmental Health  2012;11:21.
Phthalates, commonly used to soften plastic goods, are known PPAR-agonists affecting lipid metabolism and adipocytes in the experimental setting. We evaluated if circulating concentrations of phthalates were related to different indices of obesity using data from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Data from both dual-energy X-ray absorptiometry (DXA) and abdominal magnetic resonance imaging (MRI) were used.
1,016 subjects aged 70 years were investigated in the PIVUS study. Four phthalate metabolites were detected in the serum of almost all subjects (> 96%) by an API 4000 liquid chromatograph/tandem mass spectrometer. Abdominal MRI was performed in a representative subsample of 287 subjects (28%), and a dual-energy X-ray absorptiometry (DXA)-scan was obtained in 890 (88%) of the subjects two year following the phthalate measurements.
In women, circulating concentrations of mono-isobutyl phthalate (MiBP) were positively related to waist circumference, total fat mass and trunk fat mass by DXA, as well as to subcutaneous adipose tissue by MRI following adjustment for serum cholesterol and triglycerides, education, smoking and exercise habits (all p < 0.008). Mono-methyl phthalate (MMP) concentrations were related to trunk fat mass and the trunk/leg-ratio by DXA, but less powerful than MiBP. However, no such statistically significant relationships were seen in men.
The present evaluation shows that especially the phthalate metabolite MiBP was related to increased fat amount in the subcutaneous abdominal region in women measured by DXA and MRI two years later.
PMCID: PMC3379932  PMID: 22472124
Phthalates; Obesity; Mono-isobutyl phthalate; DXA; Abdominal MRI; PIVUS; Fat distribution; PPAR agonist
14.  Association Between Hepatitis C Virus Coinfection and Regional Adipose Tissue Volume in HIV-Infected Men and Women 
Coinfection with hepatitis C virus (HCV) is reported to be associated with a higher prevalence of lipodystrophy than HIV infection alone. We examine the association between HCV and adipose tissue volume in HIV-infected men and women.
Cross-sectional analysis of HIV-infected subjects from the study of Fat Redistribution and Metabolic Change in HIV Infection. MRI measured regional adipose tissue volume. Detectable HCV RNA defined HCV infection.
Twenty percent of 792 men and 26% of 329 women were HIV/HCV-coinfected. HIV/HCV-coinfected and HIV-monoinfected women had similar amounts of subcutaneous adipose tissue (SAT) in the leg, lower trunk, upper trunk, and arm and similar amounts of visceral adipose tissue (VAT). Similar findings were seen in men, except in the leg and VAT. After adjustment, HCV infection remained associated with more leg fat in men (12.2%, 95% confidence interval [CI]: 0.3 to 25.3; P = 0.043). Among those on stavudine, HIV-monoinfected men had less leg fat (−7% effect per year of stavudine use, 95% CI: −9 to −5; P < 0.001); a weaker association was seen in HIV/HCV-coinfected men (−2% effect, 95% CI: −7 to 3; P = 0.45). Indinavir was associated with less leg fat (−4% in HIV-monoinfected men, 95% CI: −6 to −1; P = 0.002; −5% in HIV/HCV-coinfected men, 95% CI: −11 to 2; P = 0.14).
Our findings suggest that HIV/HCV coinfection is not associated with less SAT in men and women. HCV infection seems to mitigate the loss of leg fat seen in HIV-infected men on stavudine.
PMCID: PMC3164885  PMID: 17356466
adipose tissue volume; fat distribution; hepatitis C virus; HIV; lipodystrophy
15.  Gender and Genetic Effects on Upper and Lower Body Fat and Associations with Diabetes in Multigenerational Families of African Heritage 
Very few studies have comprehensively defined the genetic and environmental influences on body fat storage in the arms and legs and their association with diabetes, especially in families of African heritage.
We analyzed body fat distribution by dual-energy X-ray absorptiometry (DXA; percent total fat, percent trunk fat, percent arm fat, and percent leg fat), and fasting serum glucose in 471 individuals (mean age 43 yrs) from 8 multigenerational Afro-Caribbean families (mean family size=51; 3535 relative pairs).
Diabetes was inversely associated with percent leg fat (P=0.009) and to some extent positively associated with percent arm fat, independent of age, gender, and body size (P=0.08), but not with anthropometric or DXA measures of total and central adiposity. Furthermore, percent leg fat was inversely, whereas percent arm fat was positively associated with BMI, waist circumference and serum glucose (p<0.01). Residual heritability (h2r) for arm and leg fat was significant (P<0.01) and high: 62% (for percent arm fat) and 40% (for percent leg fat). Moreover, gender-specific h2r for leg fat was considerably higher (P=0.02) in women than in men (h2r values 58% vs. 17%, respectively). Genetic correlation (ρg) between arm and leg fat was −0.61 (p<0.01), suggesting that only 37% of the co-variation between these two adipose tissue depots may be due to shared genetic influences.
This study provides new evidence for a strong genetic and gender contribution to upper and lower body fat, with relatively little co-variation between these traits due to shared genes. Our findings also suggest that in this population leg fat is associated with diabetes independent of overall adiposity.
PMCID: PMC2474724  PMID: 18502265
Body Fat; African; DXA; Heritability; Family Study; Diabetes
16.  Bone mass, body composition and vitamin D status of ARV-naïve, urban, black South African women with HIV infection, stratified by CD4 count 
Osteoporosis International  2013;24(11):2855-2861.
This is the first report examining vitamin D status and bone mass in African women with HIV infection using dual-energy X-ray absorptiometry (DXA) with an appropriate HIV-negative control group. Unlike previous publications, it demonstrates no difference in bone mineral density (BMD) or vitamin D status in HIV-positive patients, at different disease stages, vs. HIV-negative subjects.
Low bone mass and poor vitamin D status have been reported among HIV-positive patients; suggesting HIV or its treatment may increase the risk of osteoporosis, a particular concern for women in countries with high HIV prevalence such as South Africa. We describe bone mass and vitamin D status in urban premenopausal South African women, who were HIV positive but not on antiretroviral therapy (ARV).
This study is a cross-sectional measurement of BMD and body composition by DXA and vitamin D status by serum 25-hydroxyvitamin D (25(OH)D) concentration. Subjects were recruited into three groups: HIV negative (n = 98) and HIV positive with preserved CD4 cell count (non-ARV; n = 74) or low CD4 cell counts prior to ARV initiation (pre-ARV; n = 75).
The mean (standard deviation (SD)) age of women was 32.1 (7.2) years. Mean CD4 (SD) counts (×106/l) were 412 (91) and 161 (69) in non-ARV and pre-ARV groups (p < 0.0001). Pre-ARV women were significantly lighter and had lower mean BMI than the other two groups (p < 0.002). The pre-ARV group also had significantly less fat and lean mass compared with non-ARV and HIV-negative subjects (p ≤ 0.05). After full adjustment, there were no significant differences in BMD at any site (p > 0.05) between the groups, nor was vitamin D status significantly different between groups (p > 0.05); the mean (SD) cohort 25(OH)D being 60 (18) nmol/l.
Contrary to previous studies, these HIV-positive women did not have lower BMD or 25(OH)D concentrations than HIV-negative controls, despite the pre-ARV group being lighter with lower BMI.
Electronic supplementary material
The online version of this article (doi:10.1007/s00198-013-2373-y) contains supplementary material, which is available to authorized users.
PMCID: PMC3841578  PMID: 23719859
Body composition; Bone mineral density; Dual energy X-ray absorptiometry; HIV infection; Vitamin D
17.  Multiple frequency bioimpedance is an adequate tool to assess total and regional fat mass in HIV-positive patients but not to diagnose HIV-associated lipoatrophy: a pilot study 
HIV-associated lipodystrophy syndrome causes systemic metabolic alterations and psychological distress that worsen the quality of life of these patients. An early detection should be considered to efficiently treat it. Objective criteria or reference indices are needed for an early diagnosis. Bioelectrical Impedance Analysis (BIA) is an operator-independent, repeatable and non-invasive method of body composition evaluation that is less expensive than dual-energy X-ray absorptiometry (DXA) and/or CT scans. The aims of this pilot study were to validate the data obtained by BIA to measure fat mass in HIV-positive patients with/without lipoatrophy and to determine if BIA correctly diagnoses lipoatrophy in HIV-positive patients.
Thirty-nine participants were included in this preliminary study. Fourteen were HIV-negative (eight men) whereas 25 were HIV-positive patients (17 men). Eleven of the HIV-positive patients were classified as lipoatrophic according to subjective evaluation by the physicians. Total and regional body composition was measured in basal conditions by DXA and by BIA. To obtain abdominal CT scan fat values, transverse slices with 6-mm thickness were acquired at the L4-L5 intervertebral space.
BIA measurements of total and regional body fat were significantly correlated with those obtained by DXA (p < 0.05 to <0.01) in HIV-positive patients. However, agreement between methods was poor as not very high ICC (intraclass correlation coefficient) values were observed. BIA and DXA showed higher ICC values in lipoatrophic patients. The visceral index obtained by BIA was correlated with total and visceral fat in L4 measured by CT scan (r = 0.607 and r = 0.617, respectively, p < 0.01) in HIV-positive patients. The Fat Mass Ratio (FMR) calculated by BIA did not correlate or agree with DXA values.
Multi-frequency BIA could be an effective method to evaluate the evolution of total and regional fat composition in HIV-positive patients with/without lipoatrophy. The correlations between BIA and DXA improved in lipoatrophic patients and in men, suggesting that its efficacy depends on fat mass, gender and probably other factors. The visceral index obtained by BIA seems to be a reliable indicator of abdominal obesity. However, BIA did not fulfil the need for easy quantitative diagnostic tools for lipoatrophy, and it did not provide sufficient diagnostic cut-off values for this syndrome.
PMCID: PMC3875389  PMID: 24378223
HIV-associated lipoatrophy; fat mass; bioimpedance; dual-energy X-ray absorptiometry (DXA); computed tomography (CT scan); diagnostic cut-off values
18.  Assessment of abdominal fat compartments using DXA in premenopausal women from anorexia nervosa to morbid obesity 
Obesity (Silver Spring, Md.)  2013;21(12):2458-2464.
The purpose of this study was to test a newly developed DXA method for abdominal fat depot quantification in subjects with AN, normal weight, and obesity using CT as a gold standard.
Design and Methods
135 premenopausal women (overweight/obese: n=89, normal-weight: n=27, AN: n=19); abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and total adipose tissue (TAT) areas determined on CT and DXA.
There were strong correlations between DXA and CT measurements of abdominal fat compartments in all groups with the strongest correlation coefficients in the normal-weight and overweight/obese groups. Correlations of DXA and CT VAT measurements were strongest in the obese group and weakest in the AN group. DXA abdominal fat depots were higher in all groups compared to CT, with the largest % mean difference in the AN group and smallest in the obese group.
A new DXA technique is able to assess abdominal fat compartments including VAT in premenopausal women across a large weight spectrum However, DXA measurements of abdominal fat were higher than CT, and this percent bias was most pronounced in the AN subjects and decreased with increasing weight, suggesting that this technique may be more useful in obese individuals.
PMCID: PMC3690161  PMID: 23512706
19.  Changes in fat and skeletal muscle with exercise training in obese adolescents: comparison of whole-body MRI and dual energy X-ray absorptiometry 
Obesity (Silver Spring, Md.)  2013;21(10):2063-2071.
We examined skeletal muscle (SM) and fat distribution using whole-body MRI in response to aerobic (AE) versus resistance exercise (RE) training in obese adolescents and whether DXA provides similar estimates of fat and SM change as MRI.
Design and Methods
Thirty-nine obese boys (12–18 yr) were randomly assigned to one of three 3-month interventions: AE (n=14), RE (n=14) or a control (n=11).
At baseline, MRI-measured total fat was significantly greater than DXA-measured total fat [Δ=3.1 kg (95% CI: −0.4 to 7.4 kg, P<0.05)], wherein underestimation by DXA was greatest in those with the highest total fat. Overall, the changes in total fat were not significantly different between MRI and DXA [Δ= −0.4 kg (95% CI: −3.5 to 2.6 kg, P>0.05)], but DXA tended to overestimate MRI fat losses in those with larger fat losses. MRI-measured SM and DXA-measured LBM (lean body mass) were significantly correlated, but as expected the absolute values were different at baseline [Δ= −28.4 kg (95% CI: −35.4 to −21.3 kg, P<0.05)]. Further, DXA overestimated MRI gains in SM in those with larger SM gains.
Although DXA and MRI-measured total and regional measures tended to be correlated at baseline and changes with exercise, there were substantial differences in the absolute values derived using DXA versus MRI. Further, there were systemic biases in the estimation between the methods wherein DXA tended to overestimate fat losses and SM gains compared to MRI. Thus, the changes in body composition observed are influenced by the method employed.
PMCID: PMC3726562  PMID: 23512818
skeletal muscle; lean body mass; fat; adolescents; DXA; exercise training
20.  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
21.  Carotid intima media thickness is associated with body fat abnormalities in HIV-infected patients 
BMC Infectious Diseases  2014;14:348.
HIV-infected patients may be at increased risk of cardiovascular (CV) events, and lipodystrophy is generally associated with proatherogenic metabolic disturbances. Carotid intima-media thickness (cIMT) has been used as a surrogate marker for atherosclerosis and it has been shown to be an independent risk factor for CV disease. Our objective was to evaluate cIMT in HIV-infected patients on combined anti-retroviral therapy (cART) with and without lipodystrophy defined by fat mass ratio (L-FMR), and to determine the association of lipodystrophy and visceral obesity [(visceral (VAT), subcutaneous adipose tissue (SAT) volume and VAT/SAT ratio, objectively evaluated by CT scan] with cIMT.
Cross-sectional study of 199 HIV-infected patients. Body composition by DXA and abdominal CT, lipids, blood pressure, inflammatory markers, and cIMT by ultrasonography were performed. L-FMR was defined as the ratio of the percentage of trunk fat mass to the percentage of lower limb fat mass by DXA. Categorical variables were compared using the chi-square or Fisher’s exact test. Spearman correlation coefficients were estimated to study the association between cIMT and clinical and metabolic characteristics. Means of cIMT, adjusted for age, were calculated, using generalized linear models.
L-FMR was present in 41.2% of patients and cIMT was higher in these patients [0.81 (0.24) vs. 0.76 (0.25); p = 0.037)]. Lipodystrophic patients had higher VAT and VAT/SAT ratio and lower SAT. cIMT was associated with lipodystrophy evaluated by FMR, trunk fat, total abdominal fat, VAT and VAT/SAT ratio. No association was observed between cIMT and leg fat mass. Using generalized linear models, cIMT means were adjusted for age and no significant differences remained after this adjustment. The adjusted mean of cIMT was 0.787 (95% CI: 0.751-0.823) in patients without lipodystrophy, and 0.775 (95% CI: 0.732-0.817) in those with lipodystrophy (p = 0.671).
HIV-infected patients on cART with lipodystrophy defined by FMR, had a significantly higher cIMT. Carotid IMT was also associated with classical cardiovascular risk factors. In these patients, visceral adipose tissue had a significant impact on cIMT, although age was the strongest associated factor.
PMCID: PMC4087129  PMID: 24958511
Lipodystrophy; HIV; Carotid intima media thickness; Fat mass ratio; Body composition
22.  Commonality versus specificity among adiposity traits in normal-weight and moderately overweight adults 
Many adiposity traits have been related to health complications and premature death. These adiposity traits are intercorrelated but their underlying structure has not been extensively investigated. We report on the degree of commonality and specificity among multiple adiposity traits in normal-weight and moderately overweight adult males and females (mean body mass index (BMI) = 22.9 kg m−2, s.d. = 2.4).
A total of 75 healthy participants were assessed for a panel of adiposity traits including leg, arm, trunk, total fat masses and visceral adipose tissue (VAT) derived from dual energy X-ray absorptiometry (DXA), hepatic and muscle lipids from proton magnetic resonance spectroscopy, fat cell volume from an abdominal subcutaneous adipose tissue biopsy (n = 36) and conventional anthropometry (BMI and waist girth). Spearman’s correlations were calculated and were subjected to factor analysis.
Arm, leg, trunk and total fat masses correlated positively (r = 0.78–0.95) with each other. VAT correlated weakly with fat mass indicators (r = 0.24–0.31). Intrahepatic lipids (IHL) correlated weakly with all fat mass traits (r = 0.09–0.34), whereas correlations between DXA depots and intramyocellular lipids (IMCL) were inconsequential. The four DXA fat mass measures, VAT, IHL and IMCL depots segregated as four independent factors that accounted for 96% of the overall adiposity variance. BMI and waist girth were moderately correlated with the arm, leg, trunk and total fat and weakly with VAT, IHL and IMCL.
Adiposity traits share a substantial degree of commonality, but there is considerable specificity across the adiposity variance space. For instance, VAT, IHL and IMCL are typically poorly correlated with each other and are poorly to weakly associated with the other adiposity traits. The same is true for BMI and waist girth, commonly used anthropometric indicators of adiposity. These results do not support the view that it will be possible to identify adequate anthropometric indicators of visceral, hepatic and muscle lipid content in normal-weight and moderately overweight individuals.
PMCID: PMC4086512  PMID: 23949614
adiposity; hepatic fat; myocellular fat; visceral adipose tissue; common variants
23.  Assessment of EchoMRI-AH™ vs. Dual-energy X-ray Absorptiometry (DXA) to Measure Human Body Composition 
The sensitivity to detect small changes in body composition (fat mass and fat-free mass) largely depends on the instrument's precision. We compared EchoMRI-AH™ and DXA (Hologic QDR-4500A) for estimating fat mass in 301 volunteers.
Body composition was evaluated in 136 males and 165 females with a large range of body mass index (19–49 kg/m2) and age (19–91 y old) using DXA and EchoMRI-AH™. In a subsample of 13 lean (BMI=19–25 kg/m2) and 21 overweight/obese (BMI>25 kg/m2) individuals, within-subject precision was evaluated from repeated measurements taken within one hour (n=3) and one-week apart (mean of three measurements taken on each day).
Using Bland-Altman analysis, we compared the mean of the fat mass measurements vs. the difference in fat mass measured by both instruments. We found that EchoMRI-AH™ quantified larger amount of fat vs. DXA in non-obese (BMI<30 kg/m2; [1.1, CI95:-3.7 – 6.0 kg]) and obese (BMI≥30 kg/m2; [4.2, CI95:-1.4 – 9.8 kg]) participants. Within-subject precision (coefficient of variation %) in fat mass measured within one hour was remarkably better when measured by EchoMRI-AH™ than DXA (<0.5% vs. <1.5%, respectively; p<0.001). However, one-week apart within-subject variability showed similar values for both instruments (<2.2%; p=0.15).
EchoMRI-AH™ yielded greater fat mass values when compared with DXA (Hologic QDR-4500A), particularly in fatter subjects. EchoMRI-AH™ and DXA showed similar one-week apart precision when fat mass was measured both in lean and overweight/obese individuals.
PMCID: PMC3145037  PMID: 21224826
Obesity; Nuclear magnetic resonance; Fat mass; Lean mass; Body mass index
24.  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
25.  DXA estimates of fat in abdominal, trunk and hip regions varies by ethnicity in men 
Nutrition & Diabetes  2013;3(3):e64-.
The aim of this study was to determine whether the quantity of fat is different across the central (that is, android, trunk) and peripheral (that is, arm, leg and gynoid) regions among young African-American (AA), Asian (AS), Hispanic (HI) and non-Hispanic White (NHW) men.
Subjects and Methods:
A cohort of 852 men (18–30 years; mean total body fat percent (TBF%)=18.8±7.9, range=3.7–45.4) were assessed for body composition in five body regions via dual-emission X-ray absorptiometry (DXA).
HI men (21.8±8.3) had higher TBF% than AA (17.0±10.0), NHW (17.9±7.2) and AS (18.9±8.0) groups (P-values <0.0001). AS had a lower BMI (23.9±3.4) than all other groups, and NHW (24.7±3.2) had a lower BMI than HI (25.7±3.9) and AA (26.5±4.7; P-values<0.0001). A linear mixed model (LMM) revealed a significant ethnicity by region fat% interaction (P<0.0001). HI men had a greater fat% than NHW for every region (adjusted means (%); android: 29.6 vs 23.3; arm: 13.3 vs 10.6; gynoid: 27.2 vs 23.8; leg: 21.2 vs 18.3; trunk: 25.5 vs 20.6) and a greater fat% than AA for every region except the arm. In addition, in the android and trunk regions, HI had a greater fat% than AS, and AS had a higher fat% than AA. Finally, the android fat% for AS was higher than that of NHW. When comparing the region fat% within ethnicities, the android region was greater than the gynoid region for AS and HI, but did not differ for AA and NHW, and the arm region had the least fat% in all ethnicities.
Fat deposition and body fat patterning varies by ethnicity.
PMCID: PMC3608895  PMID: 23507968
ethnicity; DXA; android fat; body fat distribution; gynoid fat

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