Genetic studies may help explain abnormalities of fat distribution in HIV-infected patients treated with antiretroviral therapy (ARV).
Subcutaneous adipose tissue (SAT) volume measured by magnetic resonance imaging (MRI) in leg, lower trunk, upper trunk, and arm was examined in 192 HIV-infected Caucasian men, ARV-treated from the Fat Redistribution and Metabolic Change in HIV infection (FRAM) study. Single nucleotide polymorphisms (SNPs) were assayed using the Illumina HumanCNV370-quad beadchip. Multivariate and univariate genome wide association analyses of the four SAT depots were implemented in PLINK software adjusted for age and ARV duration. Functional annotation analysis (FAA) using Ingenuity Systems Pathway Analysis tool (IPA) was carried out for markers with P<10-3 near known genes identified by multivariate analysis.
Loci (rs10504906, rs13267998, rs921231) in or near the anion exchanger solute carrier family 26, member 7 isoform a (SLC26A7) were strongly associated with upper trunk and arm SAT (9.8*10-7≤P<7.8*10-6). Loci (rs193139, rs7523050, rs1761621) in and near a gene rich region including G-protein-signaling modulator 2 (GPSM2) and syntaxin binding protein 3 (STXBP3) were significantly associated with lower body SAT depots (9.9*10-7≤P<9.5*10-6). GPSM2 is associated with cell division and cancer while STXBP3 is associated with glucose metabolism in adipoctyes. IPA identified atherosclerosis, mitochondrial function and T-Cell mediated apoptosis as processes related to SAT volume in HIV-infected individuals (P<5*10-3).
Our results are limited by the small sample size and replication is needed, however this genomic scan uncovered new genes associated with metabolism and inflammatory pathways that may affect SAT volume in ARV-treated HIV-infected patients.
HIV; HAART; GWAS; Subcutaneous Fat; SAT
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.
buffalo hump; fat distribution; insulin resistance; lipodystrophy; visceral obesity
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.
adipose tissue volume; fat distribution; hepatitis C virus; HIV; lipodystrophy
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.
Body Fat; African; DXA; Heritability; Family Study; Diabetes
Studies in persons without HIV infection have compared percentage body fat (%BF) and waist circumference as markers of risk for the complications of excess adiposity, but only limited study has been conducted in HIV-infected subjects.
We compared anthropometric and magnetic resonance imaging (MRI)–based adiposity measures as correlates of metabolic complications of adiposity in HIV-infected and control subjects.
The study was a cross-sectional analysis of 666 HIV-positive and 242 control subjects in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study assessing body mass index (BMI), waist (WC) and hip (HC) circumferences, waist-to-hip ratio (WHR), %BF, and MRI-measured regional adipose tissue. Study outcomes were 3 metabolic risk variables [homeostatic model assessment (HOMA), triglycerides, and HDL cholesterol]. Analyses were stratified by sex and HIV status and adjusted for demographic, lifestyle, and HIV-related factors.
In HIV-infected and control subjects, univariate associations with HOMA, triglycerides, and HDL were strongest for WC, MRI-measured visceral adipose tissue, and WHR; in all cases, differences in correlation between the strongest measures for each outcome were small (r ≤ 0.07). Multivariate adjustment found no significant difference for optimally fitting models between the use of anthropometric and MRI measures, and the magnitudes of differences were small (adjusted R2 ≤ 0.06). For HOMA and HDL, WC appeared to be the best anthropometric correlate of metabolic complications, whereas, for triglycerides, the best was WHR.
Relations of simple anthropometric measures with HOMA, triglycerides, and HDL cholesterol are approximately as strong as MRI-measured whole-body adipose tissue depots in both HIV-infected and control subjects.
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.
HIV; lipodystrophy; lipoatrophy; lipohypertrophy; visceral obesity; fat redistribution; body composition
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.
In 2008 the National Center for Health Statistics released a dual energy x-ray absorptiometry (DXA) whole body dataset from the NHANES population-based sample acquired with modern fan beam scanners in 15 counties across the United States from 1999 through 2004. The NHANES dataset was partitioned by gender and ethnicity and DXA whole body measures of %fat, fat mass/height2, lean mass/height2, appendicular lean mass/height2, %fat trunk/%fat legs ratio, trunk/limb fat mass ratio of fat, bone mineral content (BMC) and bone mineral density (BMD) were analyzed to provide reference values for subjects 8 to 85 years old. DXA reference values for adults were normalized to age; reference values for children included total and sub-total whole body results and were normalized to age, height, or lean mass. We developed an obesity classification scheme by using estabbody mass index (BMI) classification thresholds and prevalences in young adults to generate matching classification thresholds for Fat Mass Index (FMI; fat mass/height2). These reference values should be helpful in the evaluation of a variety of adult and childhood abnormalities involving fat, lean, and bone, for establishing entry criteria into clinical trials, and for other medical, research, and epidemiological uses.
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.
DXA; cross-calibration; densitometry; body composition; pencil beam; fan beam; iDXA
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.
HIV infection; lipodystrophy; lipoatrophy; lipohypertrophy; visceral obesity; fat redistribution; body composition
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.
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.
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.
Alterations in regional fat are often reported in HIV infection. Prior studies have not distinguished between normal changes in regional fat related to sexual maturation and those due to HIV. The study aim was to compare changes in regional fat distribution in HIV-infected (HIV+) and healthy (HIV−) children and adolescents living in the United States.
Serial dual energy X-ray absorptiometry was performed at baseline and two annual follow-up visits in 64 HIV+ and 147 HIV− participants aged 6–16 years. Total, leg, arm, and trunk fat masses (kg) and regional fat distribution as the percentage of total body fat (%) were compared.
HIV+ and HIV− participants did not differ in total fat mass, but the HIV+ group had significantly lower leg and greater arm fat and trunk fat percentage at all time points. Over time, decreases in leg fat percentage and increases in arm fat percentage were more marked among the HIV+ group. Differences between HIV+ and HIV− groups in arm and leg fat percentage remained significant when age, sex, race, height, and pubertal stage were accounted for by mixed effect modeling. Apart from prior treatment with stavudine, no differences in fat distribution were observed according to treatment or degree of immunodeficiency or viremia.
Although no single pattern of change in regional fat distribution was uniquely associated with HIV, perinatally HIV-infected youth manifest significantly decreased leg fat and increased arm and trunk fat. These differences increase over time and may contribute to cardiovascular disease risk.
adolescent HIV infection; dual X-ray absorptiometry; lipoatrophy; lipodystrophy; pediatric HIV infection; regional fat
The purpose of this study was to test the associations between cognitive and psychological eating behavior traits and detailed measures of adiposity and body fat distribution using imaging-based methods in a cross-sectional study. Eating behavior traits (compensatory and routine restraint, external eating, and emotional eating) were assessed using the validated Weight-Related Eating Questionnaire, and measures of adiposity using anthropometry, dual energy X-ray absorptiometry (DXA), and magnetic resonance imaging (MRI). Each adiposity outcome of interest (total fat, ratio of trunk fat to periphery fat, visceral and subcutaneous fat as % of abdominal area, and % liver fat) was regressed on the four eating behaviors while adjusting for age and race/ethnicity. This study included a total of 60 postmenopausal Japanese American (n=30) and white (n=30) women (age: 60-65y, BMI: 18.8-39.6 kg/m2). Weight-related eating behavior traits did not differ by ethnicity. Higher external eating scores were associated with measures of total adiposity, including higher BMI (β = 0.36, p = 0.02) and DXA total fat mass (β = 0.41, p = 0.001), and with MRI abdominal subcutaneous fat (β = 0.55, p = 0.001). Higher routine restraint scores were associated with visceral adiposity (β = 0.42, p = 0.04). Our findings suggest that different weight-related eating behavior traits might increase not only total adiposity but also abdominal and visceral fat deposition associated with higher metabolic risks. Future research, preferably in a prospective study of men and women and including biomarkers related to psychological stress, will be needed to explore potential underlying biological mechanisms.
Eating Behaviors; Body Fat Distribution; Central Obesity; Liver Fat; Subcutaneous Adipose Tissue; Visceral Fat
Method: Height squared indices were derived for fat mass (FMI), fat free mass (FFMI), and bone mineral content (BMCI) of the arm, leg, and trunk by DXA in 51 patients and 18 age/sex matched healthy subjects.
Results: The arm and leg FFMI in patients were less than in healthy controls (p<0.05); the deficit was leg>arm>trunk (-18.19%, -14.86%, +0.09%, p<0.02) and was related to severity of lung disease. Patients with a normal BMI and low total FFM (hidden loss) had a lower arm, leg and trunk FFMI than those with a normal BMI and total FFM (p<0.05). The BMCI for all body segments was lower in patients than in controls (p<0.001). The BMCI was lower in the leg and trunk (p<0.01) in patients with severe disease than in those with mild lung disease. In those with hidden FFM loss the BMCI was lower (p<0.05 in leg and trunk). There was no difference in the BMCI deficit between body segments. Fat mass in patients was not reduced.
Conclusion: Preferential loss of FFM is related to severity of lung disease and occurs in patients with a normal BMI. A similar loss of BMC occurs while FM is preserved. A hierarchical pattern of FFM loss of legs>arms>trunk was shown; BMC loss was evenly distributed.
Familial partial lipodystrophies (FPLD) are clinically heterogeneous disorders characterized by selective loss of adipose tissue, insulin resistance and metabolic complications. Until genetic studies become available for clinical practice, clinical suspicion and pattern of fat loss are the only parameters leading clinicians to consider the diagnosis. The objective of this study was to compare body composition by dual energy X-ray absorptiometry (DXA) in patients with FPLD and control subjects, aiming to find objective variables for evaluation of FPLD.
Eighteen female patients with partial lipodystrophy phenotype and 16 healthy controls, matched for body mass index, sex and age were studied. All participants had body fat distribution evaluated by DXA measures. Fasting blood samples were obtained for evaluation of plasma leptin, lipid profile and inflammatory markers. Genetic studies were carried out on the 18 patients selected that were included for statistical analysis. Thirteen women confirmed diagnosis of Dunnigan-type FPLD (FPLD2).
DXA revealed a marked decrease in truncal fat and 3 folds decrease in limbs fat percentage in FPLD2 patients (p <0.001). Comparative analysis showed that ratio between trunk and lower limbs fat mass, characterized as Fat Mass Ratio (FMR), had a greater value in FLPD2 group (1.86 ± 0.43 vs controls 0.93 ± 0.10; p <0.001) and a improved accuracy for evaluating FPLD2 with a cut-off point of 1.2. Furthermore, affected women showed hypoleptinemia (FLPD2 4.9 ± 2.0 vs controls 18.2 ± 6.8; p <0.001), insulin resistance and a more aggressive lipid profile.
In this study, assessment of body fat distribution by DXA permitted an objective characterization of FLPD2. A consistent pattern with marked fat reduction of lower body was observed in affected patients. To our knowledge this is the first time that cut-off values of objective variables were proposed for evaluation of FPLD2.
Body composition; Dual-Energy X-ray Absorptiometry (DXA); Lipodystrophy
The association between regional fat mass distribution and cardiometabolic risk factors has been inconsistent in the literature, and data for ethnic minority groups, such as non-Hispanic blacks and Hispanics, are lacking. We aimed to examine this association among 8802 US residents who participated in the 1999-2004 US National Health and Nutrition Examination Survey (NHANES). Body composition was measured using dual-energy X-ray absorptiometry (DXA). Leg fat indices included leg fat mass (FM), leg fat mass percent (FM%), leg to whole body FM ratio (leg/whole) and leg to trunk FM ratio (leg/trunk). We evaluated the correlation between leg fat indices and adiposity-related risk factors, as well as the association of these indices with metabolic syndrome (MetS). After adjusting for covariates including age, gender, and trunk FM or trunk FM%, higher leg FM and leg FM% were, in general, correlated favorably with adiposity-related risk factors and associated with lower odds of MetS in all ethnicities, including non-Hispanic whites and blacks and Hispanic groups. In addition, in all multivariate-adjusted models, leg/whole and leg/trunk ratios were strongly associated with lower levels of most risk factors and decreased odds of MetS in these ethnicities (all odds ratios comparing extreme quintiles < 0.1). Our results show that leg fat accumulation is inversely associated with adiposity-related biological factors and risk of MetS in both whites and ethnic groups, suggesting that regional fat distribution plays an important role in the etiology of adiposity-related diseases in these populations.
—Femoral-gluteal adipose tissue (AT) may be cardioprotective through fatty acids uptake. Femoral-gluteal AT has previously been defined as leg fat measured by dual energy x-ray absorptiometry (DXA); however, subcutaneous adipose tissue (SAT) and intermuscular adipose tissue (IMAT) are inseparable using DXA. This study investigated the independent relationships between femoral-gluteal SAT, femoral-gluteal IMAT, and cardiovascular disease (CVD) risk factors [fasting serum measures of glucose, total cholesterol (TC), high density lipoprotein cholesterol (HDLC), triglycerides (TG) and insulin] and whether race differences exist in femoral-gluteal AT distribution. Adult Caucasians (56 men and 104 women), African-Americans (37 men and 76 women), and Asians (11 men and 35 women) had total AT (TAT) including femoral-gluteal AT (upper leg SAT and IMAT) and visceral AT (VAT) by magnetic resonance imaging (MRI). General linear models identified the independent effects of femoral-gluteal SAT and femoral-gluteal IMAT on each risk factor after covarying for TAT, VAT, age, race, sex, and two-way interactions. Femoral-gluteal IMAT and glucose (P < 0.05) were positively associated independent of VAT. There were also significant inverse associations between femoral-gluteal SAT and insulin (P < 0.01) and TG (P < 0.05), although the addition of VAT rendered these effects nonsignificant, possibly due to collinearity. Asian women had less femoral-gluteal SAT and greater VAT than Caucasians and African-Americans (P < 0.05) and Asian and African-American men had greater femoral-gluteal IMAT than Caucasians, adjusted for age and TAT (P < 0.05 for both). Femoral-gluteal SAT and femoral-gluteal IMAT distribution varies by sex and race, and these two components have independent and opposing relationships with CVD risk factors.
leg fat; body composition; health risk
The purpose of this study was to assess the agreement of the Lunar DPX-L with the newer Prodigy dual-energy X-ray absorptiometer (DXA) for determining total-body and regional (arms, legs, trunk) bone mineral density (BMD), bone mineral content (BMC), fat mass (FM), lean tissue mass (LTM), total body mass (BM) and percent fat. A total of 106 apparently healthy males (n=34) and females (n=72) between the ages of 8–72 years were scanned consecutively on the DPX-L (software version 1.35) and Prodigy DXA (enCORE v. 3.6 software). Paired t-tests indicated significantly higher measures by Prodigy for BM (percent difference= 1.1%) and total-body BMD (2.2%), BMC (2.9%), FM (3.5%), and percent fat (2.8%; P<0.001), but not LTM (−0.2%). Regional estimates of FM and bone tended to be overestimated by Prodigy relative to DPX-L. The percent difference was most pronounced for FM in the arms (14.2%) and trunk (8.5%), BMD in the legs (4.9%), LTM in arms (5.6%), and BMC in the trunk (5.9%); but all total-body and regional measures were strongly and significantly correlated (P<0.001). The method of Bland and Altman indicated that the Prodigy overestimated DPX-L for BM (r=0.343; P<0.001), and total-body measures of BMD (r=0.460; P<0.001), and BMC (r=0.321; P<0.001) at higher values, as indicated by the significant, positive association between difference (Prodigy−DPX-L) versus mean ((Prodigy+DPX-L)/2). Regionally, Prodigy overestimated DPX-L for BMD in the legs, BMC in the legs and trunk, and FM in the arms at higher values (P<0.001). In contrast, FM in the legs was underestimated by Prodigy relative to DPX-L at higher values (P<0.001), and no regional bias was observed for LTM. In conclusion, we recommend that correction equations be used for comparing BM, total-body BMD and BMC, and regionally for BMD in the legs, BMC in the legs and trunk, and FM in the arms and legs. The use of correction equations for other estimates is not required for making direct comparisons.
Lunar; DPX-L; Prodigy; DXA; validation; fat mass; lean mass; bone
Among postmenopausal women, declining estrogen may facilitate fat partitioning from the periphery to the intra-abdominal space. Furthermore, it has been suggested that excess androgens contribute to a central fat distribution pattern in women. The objective of this longitudinal study was to identify independent associations of the hormone milieu with fat distribution in postmenopausal women. 53 healthy postmenopausal women, either using or not using hormone replacement therapy (HRT), were evaluated at baseline and 2 years. The main outcomes were intra-abdominal adipose tissue (IAAT), subcutaneous abdominal adipose tissue (SAAT), and total thigh fat analyzed by computed tomography (CT) scanning and leg fat and total body fat mass measured by dual energy X-ray absorptiometry (DXA). Serum estradiol, estrone, estrone sulfate, total testosterone, free testosterone, androstenedione, DHEA-S, SHBG, and cortisol were assessed. On average in all women combined, IAAT increased by 10% (10.5 cm2) over two years (P<0.05). Among HRT users, estradiol was inversely associated with, and estrone was positively associated with, 2-yr gain in IAAT. Among HRT non-users, free testosterone was inversely associated with, and SHBG was positively associated with, 2-yr gain in IAAT. These results suggest that in postmenopausal women using HRT, greater circulating estradiol may play an integral role in limiting lipid deposition to the intra-abdominal cavity, a depot associated with metabolically detrimental attributes. However, a high proportion of weak estrogens may promote fat partitioning to the intra-abdominal cavity over time. Further, among postmenopausal women not using HRT, greater circulating free testosterone may limit IAAT accrual.
Despite the positive association between body mass index (BMI) and bone mineral density (BMD) and content (BMC), the role of fat distribution in BMD/BMC remains unclear. We examined relationships between BMD/BMC and various measurements of fat distribution and studied the role of BMI, insulin, and adiponectin in these relations. Using a cross-sectional investigation of 2631 participants from the Erasmus Rucphen Family study, we studied associations between BMD (using dual-energy X-ray absorptiometry (DXA]) at the hip, lumbar spine, total body (BMD and BMC), and fat distribution by the waist-to-hip ratio (WHR), waist-to-thigh ratio (WTR), and DXA-based trunk-to-leg fat ratio and android-to-gynoid fat ratio. Analyses were stratified by gender and median age (48.0 years in women and 49.2 years in men) and were performed with and without adjustment for BMI, fasting insulin, and adiponectin. Using linear regression (adjusting for age, height, smoking, and use of alcohol), most relationships between fat distribution and BMD and BMC were positive, except for WTR. After BMI adjustment, most correlations were negative except for trunk-to-leg fat ratio in both genders. No consistent influence of age or menopausal status was found. Insulin and adiponectin levels did not explain either positive or negative associations. In conclusion, positive associations between android fat distribution and BMD/BMC are explained by higher BMI but not by higher insulin and/or lower adiponectin levels. Inverse associations after adjustment for BMI suggest that android fat deposition as measured by the WHR, WTR, and DXA-based android-to-gynoid fat ratio is not beneficial and possibly even deleterious for bone.
Fat distribution; Bone mineral density; Body composition; Android-to-gynoid fat ratio; Waist-to-hip ratio; Insulin; Adiponectin
Excess accumulation of visceral fat is a prominent risk factor for cardiovascular and metabolic morbidity. While computed tomography (CT) is the gold standard to measure visceral adiposity, this is often not possible for large studies - thus valid, but less expensive and intrusive proxy measures of visceral fat are required such as dual-energy X-ray absorptiometry (DXA). Study aims were to a) identify a valid DXA-based measure of visceral adipose tissue (VAT), b) estimate VAT heritability and c) assess visceral fat association with morbidity in relation to body fat distribution.
A validation sample of 54 females measured for detailed body fat composition - assessed using CT, DXA and anthropometry – was used to evaluate previously published predictive models of CT-measured visceral fat. Based upon a validated model, we realised an out-of-sample estimate of abdominal VAT area for a study sample of 3457 female volunteer twins and estimated VAT area heritability using a classical twin study design. Regression and residuals analyses were used to assess the relationship between adiposity and morbidity.
Published models applied to the validation sample explained >80% of the variance in CT-measured visceral fat. While CT visceral fat was best estimated using a linear regression for waist circumference, CT body cavity area and total abdominal fat (R2 = 0.91), anthropometric measures alone predicted VAT almost equally well (CT body cavity area and waist circumference, R2 = 0.86). Narrow sense VAT area heritability for the study sample was estimated to be 58% (95% CI: 51-66%) with a shared familial component of 24% (17-30%). VAT area is strongly associated with type 2 diabetes (T2D), hypertension (HT), subclinical atherosclerosis and liver function tests. In particular, VAT area is associated with T2D, HT and liver function (alanine transaminase) independent of DXA total abdominal fat and body mass index (BMI).
DXA and anthropometric measures can be utilised to derive estimates of visceral fat as a reliable alternative to CT. Visceral fat is heritable and appears to mediate the association between body adiposity and morbidity. This observation is consistent with hypotheses that suggest excess visceral adiposity is causally related to cardiovascular and metabolic disease.
Visceral fat; Adiposity; DXA; Type 2 diabetes; Hypertension; Subclinical atherosclerosis; Liver function
Central (truncal) adiposity is associated strongly with insulin resistance and diabetes. There are very few reports comparing methods of trunk fat measurement in their ability to predict glycaemia and insulin resistance. We report a comparative analysis of different trunk fat measurements in predicting glycaemia and insulin resistance in middle aged Indian men.
Materials and Methods
Trunk fat measurements were performed using anthropometry, magnetic resonance imaging (MRI), dual-energy X-ray absorptiometry (DXA) and computed tomography (CT) on 128 men. Additional measurements were taken to characterise insulin resistance (Matsuda index) and beta cell function (Insulinogenic Index), glycaemia (fasting and 120 min glucose concentrations). Using residual approach we compared the ability of different trunk fat measurement techniques to predict insulin resistance, beta cell function and glycaemia.
There was a strong association between trunk fat measures from each technique with glycaemia and insulin resistance indices but not with the Insulinogenic Index. Insulin resistance and glycaemia, were best predicted using anthropometric measurements, notably by waist circumference and subscapular skinfold thickness. Neither MRI measures of trunk or visceral fat nor DXA trunk fat added significantly. CT liver density contributed to some extent to predict insulin resistance and 120 min glucose after anthropometric measurements.
Our results suggest that, in Indian men, anthropometric measurements are good predictors of glycaemia and insulin resistance. Other complex measurements such as MRI, DXA and CT make only a small addition to the prediction. This finding supports the application of anthropometry for determining trunk fat in clinical and epidemiological settings.
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.
ethnicity; DXA; android fat; body fat distribution; gynoid fat