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1.  Assessment of abdominal fat compartments using DXA in premenopausal women from anorexia nervosa to morbid obesity 
Obesity (Silver Spring, Md.)  2013;21(12):10.1002/oby.20424.
Objective
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.
Results
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.
Conclusions
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.
doi:10.1002/oby.20424
PMCID: PMC3690161  PMID: 23512706
2.  Increased FDG uptake in Association with Reduced Extremity Fat in HIV Patients 
Antiviral therapy  2012;18(2):243-248.
Background/Objective
HIV lipodystrophy - characterized by peripheral lipoatrophy, with or without central fat accumulation - confers increased metabolic risk. However, the functional activity of HIV lipodystrophic tissue in relation to metabolic risk has yet to be fully explored in vivo through the use of non-invasive imaging techniques. This study assesses the relationship between FDG uptake in various fat depots and metabolic/immune parameters among subjects with HIV lipodystrophy.
Design/Methods
Lipodystrophic men on anti-retroviral therapy (ART) underwent whole-body 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) scans and detailed metabolic/immune phenotyping.
Results
FDG uptake in the subcutaneous adipose tissue (SAT) of the extremities (mean standardized uptake value, or SUV, of the arm and leg SAT) was found to correlate with the degree of peripheral lipoatrophy (r = 0.7, p = 0.01). Extremity SAT FDG uptake was positively associated with HOMA-IR (r = 0.6, p = 0.02) and fasting hyperinsulinemia (r = 0.7, p 0.01), while fat percentage of extremities was not. Further, extremity SAT FDG uptake was significantly associated with CD4 count (r = 0.6, p = 0.05). In multivariate modeling for HOMA-IR, extremity SAT FDG uptake remained significant after controlling for BMI and TNF-α (R2 for model = 0.71, p = 0.02; SUV in the extremity SAT β-estimate 12.3, p = 0.009).
Conclusions
In HIV lipodystrophic patients, extremity SAT FDG uptake is increased in association with reduced extremity fat and may contribute to insulin resistance. Noninvasive assessments of in situ inflammation using FDG-PET may usefully complement histological and gene expression analyses of metabolic dysregulation in peripheral fat among HIV+ patients.
doi:10.3851/IMP2420
PMCID: PMC3670757  PMID: 23041595
HIV; lipodystrophy; FDG-PET/CT; insulin resistance
4.  Effects of Lifestyle Modification and Metformin on Atherosclerotic Indices among HIV-Infected Patients with the Metabolic Syndrome 
AIDS (London, England)  2012;26(5):587-597.
Objective
Metabolic abnormalities including diabetes, dyslipidemia, hypertension, and abdominal obesity occur commonly in HIV patients, are associated with increased coronary artery calcification (CAC), and contribute to increased cardiovascular disease (CVD) in this population. We hypothesized that lifestyle modification (LSM) and metformin would improve CVD indices in HIV patients with metabolic syndrome.
Design
A randomized, placebo controlled trial to investigate LSM and metformin, alone and in combination, over one year, among 50 HIV-infected patients with metabolic syndrome.
Methods
We assessed CAC, cardiovascular and metabolic indices.
Results
Among the participants, duration of HIV-infection was 14±1 yr and duration of antiretroviral therapy was 6±1 yr. Metformin-treated subjects demonstrated significantly less progression of CAC (−1±2 vs. 33±17, P=0.004, metformin vs. placebo) whereas the effect of LSM on CAC progression was not significant (8±6 vs. 21±14, P=0.82, LSM vs. no LSM). Metformin had a significantly greater effect on CAC than LSM (P=0.01). Metformin-treated subjects also demonstrated less progression in calcified plaque volume (−0.4±1.9 vs. 27.6±13.8 mm3, P=0.008) and improved HOMA-IR (P=0.05) compared to placebo. Subjects randomized to LSM vs. no LSM showed significant improvement in HDL (P=0.03), hsCRP (P=0.05), and cardiorespiratory fitness. Changes in CAC among the 4 groups: 1) no LSM, placebo (43±30); 2) LSM, placebo (19±7); 3) no LSM, metformin (1±1); and 4) LSM, metformin (−4±6) were different (P=0.03 for ANOVA and linear trend across groups), the majority of this effect was mediated by metformin. Results are mean ± SEM.
Conclusion
Metformin prevents plaque progression in HIV-infected patients with the metabolic syndrome.
doi:10.1097/QAD.0b013e32834f33cc
PMCID: PMC3675446  PMID: 22112605
Lifestyle modification; metformin; HIV; atherosclerosis
5.  Modular MR-compatible lower leg exercise device for whole-body scanners 
Skeletal radiology  2011;40(10):1349-1354.
Purpose
To develop a modular MR-compatible lower leg exercise device for muscle testing using a clinical 3 T MR scanner.
Materials and methods
An exercise device to provide isotonic resistance to plantar- or dorsiflexion was constructed from nonferrous materials and designed for easy setup and use in a clinical environment. Validation tests were performed during dynamic MR acquisitions. For this purpose, the device was tested on the posterior lower leg musculature of five subjects during 3 min of exercise at 30% of maximum voluntary plantarflexion during 31-phosphorus MR spectroscopy (31P-MRS). Measures of muscle phosphocreatine (PCr), inorganic phosphate (Pi), and pH were obtained before, during, and after the exercise protocol.
Results
At the end of exercise regimen, muscle PCr showed a 28% decrease from resting levels (to 21.8±3.9 from 30.4±3.0 mM) and the average PCr recovery rate was 35.3±8.3 s. Muscle Pi concentrations increased 123% (to 14.6±4.7 from 6.5±3.3 mM) and pH decreased 1.5% (to 7.06±0.14 from 7.17±0.07) from resting levels.
Conclusion
The described MR-compatible lower leg exercise was an effective tool for data acquisition during dynamic MR acquisitions of the calf muscles. The modular design allows for adaptation to other whole-body MR scanners and incorporation of custom-built mechanical or electronic interfaces and can be used for any MR protocol requiring dynamic evaluation of calf muscles.
doi:10.1007/s00256-011-1098-2
PMCID: PMC3667703  PMID: 21271342
Exercise; Ergometer; MR-compatible
6.  Comparison of 3.0 T Proton Magnetic Resonance Spectroscopy Short and Long Echo-Time Measures of Intramyocellular Lipids in Obese and Normal-Weight Women 
Purpose
To compare correlations of intramyocellular lipids (IMCL) measured by short and long echo-time proton magnetic resonance spectroscopy (1H-MRS) with indices of body composition and insulin resistance in obese and normal-weight women.
Materials and Methods
We quantified IMCL of tibialis anterior (TA) and soleus (SOL) muscles in 52 premenopausal women (37 obese and 15 normal weight) using single-voxel 1H-MRS PRESS at 3.0 T with short (30 msec) and long (144 msec) echo times. Statistical analyses were performed to determine correlations of IMCL with body composition as determined by computed tomography (CT) and insulin resistance indices and to compare correlation coefficients from short and long echo-time data. Signal-to-noise ratio (SNR), linewidth, and coefficients of variation (CV) of short and long echo-time spectra were calculated.
Results
Short and long echo-time IMCL from TA and SOL significantly correlated with body mass index (BMI) and abdominal fat depots (r = 0.32 to 0.70, P = <0.05), liver density (r = −0.39 to −0.50, P < 0.05), and glucose area under the curve as a measure of insulin resistance (r = 0.47 to 0.49, P < 0.05). There was no significant difference between correlation coefficients of short and long echo-time spectra (P > 0.5). Short echo-time IMCL in both muscles showed significantly higher SNR (P < 0.0001) and lower CVs when compared to long echo-time acquisitions. Linewidth measures were not significantly different between groups.
Conclusion
IMCL quantification using short and long echo-time 1H-MRS at 3.0 T is useful to detect differences in muscle lipid content in obese and normal-weight subjects. In addition, IMCL correlates with body composition and markers of insulin resistance in this population with no significant difference in correlations between short and long echo-times. Short echo-time IMCL quantification of TA and SOL muscles at 3.0 T was superior to long echo-time due to better SNR and better reproducibility.
doi:10.1002/jmri.22226
PMCID: PMC3662051  PMID: 20677267
IMCL; 1H-MR spectroscopy; echo-time; obesity
7.  Effects of growth hormone in women with abdominal adiposity: a 6-month randomized, double-blind, placebo-controlled trial 
Objective
Abdominal adiposity is associated with increased cardiovascular risk and decreased growth hormone (GH) secretion. The objective of our study was to determine the effects of GH in abdominally obese women on body composition and cardiovascular risk markers.
Materials and Methods
In this randomized, double-blind, placebo-controlled study, 79 obese premenopausal women received GH vs. placebo for six months. Primary endpoints were: 1) total abdominal (TAT) fat by CT (body composition) and 2) high-sensitivity C-reactive protein (hsCRP) (cardiovascular risk marker). Body composition was assessed by CT, DXA and proton MR spectroscopy. Serum cardiovascular risk markers, carotid intima-media thickness and endothelial function were measured.
Results
Mean 6-month GH dose was 1.7±0.1 mg/day, resulting in a mean IGF-1 SDS increase from −1.7±0.08 to −0.1±0.3 in the GH group. GH administration decreased TAT and hsCRP compared with placebo. In addition, it increased thigh muscle mass and lean body mass, and decreased subcutaneous abdominal and trunk fat, tPA, apoB, and apoB/LDL compared with placebo. Visceral adipose tissue decreased and IMCL increased within the GH group. Six-month change in IGF-1 levels was negatively associated with 6-month decrease in TAT and VAT. One subject had a 2-hour glucose >200 mg/mL at 3 months; four subjects, three of whom were randomized to GH, had 2-hour glucose levels >200 mg/mL at study end.
Conclusion
GH administration in abdominally obese premenopausal women exerts beneficial effects on body composition and cardiovascular risk markers, but is associated with a decrease in glucose tolerance in a minority of women.
doi:10.1530/EJE-11-1068
PMCID: PMC3651853  PMID: 22275471
growth hormone; visceral obesity; body composition; cardiovascular risk
8.  Adiponectin Is Inversely Associated With Intramyocellular and Intrahepatic Lipids in Obese Premenopausal Women 
Obesity (Silver Spring, Md.)  2010;19(5):911-916.
Adiponectin, an adipokine secreted by adipocytes, exerts beneficial effects on glucose and lipid metabolism and has been found to improve insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. Adiponectin is found in several isoforms and the high-molecular weight (HMW) form has been linked most strongly to the insulin-sensitizing effects. Fat content in skeletal muscle (intramyocellular lipids, IMCL) and liver (intrahepatic lipids, IHL) can be quantified noninvasively using proton magnetic resonance spectroscopy (1H-MRS). The purpose of our study was to assess the relationship between HMW adiponectin and measures of glucose homeostasis, IMCL and IHL, and to determine predictors of adiponectin levels. We studied 66 premenopausal women (mean BMI 31.0 ± 6.6 kg/m2) who underwent 1H-MRS of calf muscles and liver for IMCL and IHL, computed tomography (CT) of the abdomen for abdominal fat depots, dual-energy X-ray absorptiometry (DXA) for fat and lean mass assessments, HMW and total adiponectin, fasting lipid profile and an oral glucose tolerance test (homeostasis model assessment of insulin resistance (HOMAIR), glucose and insulin area under the curve). There were strong inverse associations between HMW adiponectin and measures of insulin resistance, IMCL and IHL, independent of visceral adipose tissue (VAT) and total body fat. IHL was the strongest predictor of adiponectin and adiponectin was a predictor of HOMAIR. Our study showed that in premenopausal obese women HMW adiponectin is inversely associated with IMCL and IHL content. This suggests that adiponectin exerts positive effects on insulin sensitivity in obesity by decreasing intracellular triglyceride content in skeletal muscle and liver; it is also possible that our results reflect effects of insulin on adiponectin.
doi:10.1038/oby.2010.296
PMCID: PMC3607306  PMID: 21151017
9.  Comparison of DXA and CT in the Assessment of Body Composition in Premenopausal Women With Obesity and Anorexia Nervosa 
Obesity (Silver Spring, Md.)  2010;18(11):2227-2233.
Accurate methods for assessing body composition in subjects with obesity and anorexia nervosa (AN) are important for determination of metabolic and cardiovascular risk factors and to monitor therapeutic interventions. The purpose of our study was to assess the accuracy of dual-energy X-ray absorptiometry (DXA) for measuring abdominal and thigh fat, and thigh muscle mass in premenopausal women with obesity, AN, and normal weight compared to computed tomography (CT). In addition, we wanted to assess the impact of hydration on DXA-derived measures of body composition by using bioelectrical impedance analysis (BIA). We studied a total of 91 premenopausal women (34 obese, 39 with AN, and 18 lean controls). Our results demonstrate strong correlations between DXA- and CT-derived body composition measurements in AN, obese, and lean controls (r = 0.77–0.95, P < 0.0001). After controlling for total body water (TBW), the correlation coefficients were comparable. DXA trunk fat correlated with CT visceral fat (r = 0.51–0.70, P < 0.0001). DXA underestimated trunk and thigh fat and overestimated thigh muscle mass and this error increased with increasing weight. Our study showed that DXA is a useful method for assessing body composition in premenopausal women within the phenotypic spectrum ranging from obesity to AN. However, it is important to recognize that DXA may not accurately assess body composition in markedly obese women. The level of hydration does not significantly affect most DXA body composition measurements, with the exceptions of thigh fat.
doi:10.1038/oby.2010.5
PMCID: PMC3607308  PMID: 20111013
10.  Vertebral Bone Marrow Fat Is Positively Associated With Visceral Fat and Inversely Associated With IGF-1 in Obese Women 
Obesity (Silver Spring, Md.)  2010;19(1):49-53.
Recent studies have demonstrated an important physiologic link between bone and fat. Bone and fat cells arise from the same mesenchymal precursor cell within bone marrow, capable of differentiation into adipocytes or osteoblasts. Increased BMI appears to protect against osteoporosis. However, recent studies have suggested detrimental effects of visceral fat on bone health. Increased visceral fat may also be associated with decreased growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels which are important for maintenance of bone homeostasis. The purpose of our study was to assess the relationship between vertebral bone marrow fat and trabecular bone mineral density (BMD), abdominal fat depots, GH and IGF-1 in premenopausal women with obesity. We studied 47 premenopausal women of various BMI (range: 18–41 kg/m2, mean 30 ± 7 kg/m2) who underwent vertebral bone marrow fat measurement with proton magnetic resonance spectroscopy (1H-MRS), body composition, and trabecular BMD measurement with computed tomography (CT), and GH and IGF-1 levels. Women with high visceral fat had higher bone marrow fat than women with low visceral fat. There was a positive correlation between bone marrow fat and visceral fat, independent of BMD. There was an inverse association between vertebral bone marrow fat and trabecular BMD. Vertebral bone marrow fat was also inversely associated with IGF-1, independent of visceral fat. Our study showed that vertebral bone marrow fat is positively associated with visceral fat and inversely associated with IGF-1 and BMD. This suggests that the detrimental effect of visceral fat on bone health may be mediated in part by IGF-1 as an important regulator of the fat and bone lineage.
doi:10.1038/oby.2010.106
PMCID: PMC3593350  PMID: 20467419
11.  Determinants of bone mineral density in obese premenopausal women 
Bone  2010;48(4):748-754.
Despite being a risk factor for cardiovascular disease and diabetes mellitus, obesity has been thought to protect against osteoporosis. However, recent studies have demonstrated a differential impact of specific fat compartments on bone mineral density (BMD) with visceral adipose tissue (VAT) having potential detrimental effects on BMD. Visceral obesity is also associated with dysregulation of the GH/IGF-1 axis, an important regulator of bone homeostasis. The purpose of our study was to evaluate the differential effects of abdominal fat depots and muscle, vitamin D, and hormonal determinants, including insulin-like growth factor-1 (IGF-1), testosterone, and estradiol, on trabecular BMD of the lumbar spine. We studied 68 healthy obese premenopausal women (mean BMI: 36.7 ± 4.2 kg/m2). Quantitative computed tomography (QCT) was used to assess body composition and lumbar trabecular BMD. There was an inverse association between BMD and VAT, independent of age and BMI (p= 0.003). IGF-1 correlated positively with BMD and negatively with VAT and, in stepwise multivariate regression modeling, was the strongest predictor of BMD and procollagen type 1 amino-terminal propeptide (P1NP). Thigh muscle cross sectional area (CSA), and thigh muscle density were also associated with BMD (p<0.05), but 25-hydroxyvitamin D [25(OH)D], testosterone, free testosterone and estradiol levels were not. 25(OH)D was associated inversely with BMI, total and subcutaneous abdominal adipose tissue (p< 0.05). These findings support the hypothesis that VAT exerts detrimental effects, whereas muscle mass exerts positive effects on BMD in premenopausal obese women. Moreover, our findings suggest that IGF-1 may be a mediator of the deleterious effects of VAT on bone health through effects on bone formation.
doi:10.1016/j.bone.2010.12.011
PMCID: PMC3073669  PMID: 21195217
bone mineral density; obesity; visceral adipose tissue; IGF -1; P1NP; quantitative computed tomography (QCT)
12.  Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults 
Mitochondrial dysfunction may contribute to the development of insulin resistance and type 2 diabetes. Nucleoside reverse transcriptase inhibitors (NRTIs), specifically stavudine, are known to alter mitochondrial function in human immunodeficiency virus (HIV)-infected individuals, but the effects of stavudine on glucose disposal and mitochondrial function in muscle have not been prospectively evaluated. In this study, we investigated short-term stavudine administration among healthy control subjects to determine effects on insulin sensitivity. A secondary aim was to determine the effects of stavudine on mitochondrial DNA (mtDNA) and function. Sixteen participants without personal or family history of diabetes were enrolled. Subjects were randomized to receive stavudine, 30 – 40 mg, twice a day, or placebo for 1 mo. Insulin sensitivity determined by glucose infusion rate during the hyperinsulinemic euglycemic clamp was significantly reduced after 1-mo exposure in the stavudine-treated subjects compared with placebo (−0.8 ± 0.5 vs. +0.7 ± 0.3 mg· kg−1 · min−1, P = 0.04, stavudine vs. placebo). In addition, muscle biopsy specimens in the stavudine-treated group showed significant reduction in mtDNA/nuclear DNA (−52%, P = 0.005), with no change in placebo-treated subjects (+8%, P = 0.9). 31P magnetic resonance spectroscopy (MRS) studies of mitochondrial function correlated with insulin sensitivity measures (r2 = 0.5, P = 0.008). These findings demonstrate that stavudine administration has potent effects on insulin sensitivity among healthy subjects. Further studies are necessary to determine whether changes in mtDNA resulting from stavudine contribute to effects on insulin sensitivity.
doi:10.1152/ajpendo.00550.2006
PMCID: PMC3206591  PMID: 17284576
human immunodeficiency virus; insulin resistance; magnetic resonance spectroscopy
13.  Increased intramyocellular lipid accumulation in HIV-infected women with fat redistribution 
The human immunodeficiency virus (HIV)-lipodystrophy syndrome is associated with fat redistribution and metabolic abnormalities, including insulin resistance. Increased intramyocellular lipid (IMCL) concentrations are thought to contribute to insulin resistance, being linked to metabolic and body composition variables. We examined 46 women: HIV infected with fat redistribution (n = 25), and age- and body mass index-matched HIV-negative controls (n = 21). IMCL was measured by 1H-magnetic resonance spectroscopy, and body composition was assessed with computed tomography, dual-energy X-ray absorptiometry (DEXA), and magnetic resonance imaging. Plasma lipid profile and markers of glucose homeostasis were obtained. IMCL was significantly increased in tibialis anterior [135.0 ± 11.5 vs. 85.1 ± 13.2 institutional units (IU); P = 0.007] and soleus [643.7 ± 61.0 vs. 443.6 ± 47.2 IU, P = 0.017] of HIV-infected subjects compared with controls. Among HIV-infected subjects, calf subcutaneous fat area (17.8 ± 2.3 vs. 35.0 ± 2.5 cm2, P < 0.0001) and extremity fat by DEXA (11.8 ± 1.1 vs. 15.6 ± 1.2 kg, P = 0.024) were reduced, whereas visceral abdominal fat (125.2 ± 11.3 vs. 74.4 ± 12.3 cm2, P = 0.004), triglycerides (131.1 ± 11.0 vs. 66.3 ± 12.3 mg/dl, P = 0.0003), and fasting insulin (10.8 ± 0.9 vs. 7.0 ± 0.9 μIU/ml, P = 0.004) were increased compared with control subjects. Triglycerides (r = 0.39, P = 0.05) and extremity fat as percentage of whole body fat by DEXA (r = −0.51, P = 0.01) correlated significantly with IMCL in the HIV but not the control group. Extremity fat (β = −633.53, P = 0.03) remained significantly associated with IMCL among HIV-infected patients, controlling for visceral abdominal fat, abdominal subcutaneous fat, and antiretroviral medications in a regression model. These data demonstrate increased IMCL in HIV-infected women with a mixed lipodystrophy pattern, being most significantly associated with reduced extremity fat. Further studies are necessary to determine the relationship between extremity fat loss and increased IMCL in HIV-infected women.
doi:10.1152/japplphysiol.00797.2005
PMCID: PMC3205444  PMID: 16223978
magnetic resonance spectroscopy; insulin resistance; protease inhibitor; acquired immunodeficiency syndrome
14.  Improved Triglycerides and Insulin Sensitivity with 3 Months of Acipimox in Human Immunodeficiency Virus-infected Patients with Hypertriglyceridemia 
Context
Metabolic abnormalities such as hypertriglyceridemia remain a challenge for optimizing long-term health in HIV-infected patients.
Objective
Elevation of free fatty acids (FFAs) may contribute to hyperlipidemia and insulin resistance in HIV. We evaluated the efficacy and safety of chronic inhibition of lipolysis in HIV-infected men and women with hypertrigyceridemia. We hypothesized that acipimox would lead to significant reductions in triglycerides and improved insulin sensitivity, compared with placebo.
Design
A 3-month, randomized, double-blind, controlled trial of acipimox (250 mg thrice daily) vs. placebo was conducted in 23 HIV-infected men and women with hypertriglyceridemia (>150 mg/dl), abnormal fat distribution, and no current lipid-lowering therapy. The primary outcome variable was triglyceride concentration, and insulin sensitivity measured by hyperinsulinemic euglycemic clamp was a secondary outcome.
Setting
The study was conducted at an academic medical center.
Results
Acipimox resulted in significant reductions in FFAs [mean change −0.38 (0.06) vs. 0.08 (0.06) mEq/liter with placebo, −68 vs. +17% change from mean baseline, P < 0.0001], decreased rates of lipolysis (P < 0.0001), and a median triglyceride decrease from 238 mg/dl at baseline to 190 mg/dl, compared with an increase from 290 to 348 mg/dl in the placebo group (P = 0.01). Acipimox improved insulin sensitivity [acipimox +2.31 (0.74) vs. placebo −0.21 (0.90) mg glucose per kilogram lean body mass per minute, or +31 vs. −2% change from mean baseline values, P = 0.04]. Improvements in insulin sensitivity were significantly correlated with reductions in FFAs (r = −0.62, P = 0.003) and lipolysis (r = −0.59, P = 0.005).
Conclusions
Acipimox resulted in significant sustained reductions in lipolysis, improved glucose homeostasis, and significant but modest reductions in triglycerides in HIV-infected individuals with abnormal fat distribution and hypertriglyceridemia. Improvement in overall metabolic profile with acipimox suggests a potential clinical utility for this agent that requires further investigation.
doi:10.1210/jc.2006-1174
PMCID: PMC3196527  PMID: 16940448
15.  Effects of TNF-α neutralization on adipocytokines and skeletal muscle adiposity in the metabolic syndrome 
In a prior study, we have shown that tumor necrosis factor (TNF)-α neutralization improves inflammatory markers and total adiponectin in patients with the metabolic syndrome, without improving insulin sensitivity. In this study, we sought to extend our understanding of the effects of TNF-α neutralization in this human model of obesity by investigating the responses of high-molecular-weight (HMW) adiponectin, resistin, leptin, and muscle adiposity to etanercept in patients with the metabolic syndrome. Fifty-six men and women with the metabolic syndrome enrolled in a double-blind randomized placebo-controlled trial. Circulating concentrations of total and HMW adiponectin, resistin, and leptin were determined at baseline and after 4 wk of treatment with etanercept. Muscle adiposity was measured by computed tomography (CT). Although etanercept increased total adiponectin concentration, the HMW form, which is thought to mediate insulin sensitivity, was unchanged. Thus the ratio of HMW to total adiponectin decreased following etanercept treatment compared with placebo (−0.03 ± 0.03 vs. 0.06 ± 0.03, P = 0.02). Resistin tended to decrease in the etanercept-treated group compared with placebo (−0.6 ± 0.7 vs. 1.2 ± 0.7 ng/ml, P = 0.06), whereas leptin was not altered. Etanercept decreased muscle attenuation on CT [−0.61 ± 0.64 Hounsfield units (HU) vs. 1.54 ± 0.77 HU in placebo, P = 0.04], suggesting an increase in muscle adiposity. Together, these results demonstrate that neutralization of TNF-α in obese humans results in differential effects on critical adipokines and body composition indexes. These findings may help to explain the lack of effect on insulin sensitivity and extend our knowledge of the biological effects of TNF-α neutralization in obesity.
doi:10.1152/ajpendo.00089.2007
PMCID: PMC3196534  PMID: 17374698
tumor necrosis factor-α; adiponectin; resistin; muscle adiposity; metabolic syndrome
16.  Breath-hold 1H-MR spectroscopy for intrahepatic lipid quantification at 3 Tesla 
Objective
To compare breath-hold 1H-MRS to respiratory-gated 1H-MRS and CT for quantification of hepatic lipid content.
Methods
Twenty-three premenopausal women underwent breath-hold point-resolved single voxel (PRESS) 1H-MRS of the liver followed by respiratory-gated 1H-MRS at 3Tesla and CT slice through the liver. Interscan variability for 1H-MRS was assessed in six volunteers. Pearson correlation coefficients, Bland-Altman 95% limit of agreement, and concordance correlation coefficients were calculated.
Results
There was a strong correlation between breath-hold and respiratory-gated 1H-MRS (r=0.94, p<0.0001, concordance correlation coefficient:0.75). Using Bland-Altman analysis, all but two data points were within the limits of agreement. Both 1H-MRS techniques had low inter-scan variability. There was an inverse correlation of both 1H-MRS techniques with CT attenuation values of the liver.
Conclusions
Breath-hold 1H-MRS is a reliable method to measure hepatic lipid content at 3Tesla. Breath-hold 1H-MRS of the liver provides data that closely correlates with that obtained from longer duration respiratory-gated technique.
doi:10.1097/RCT.0b013e3181cefb89
PMCID: PMC2877282  PMID: 20498538
MR spectroscopy; liver; lipids
17.  INTRAMYOCELLULAR LIPID QUANTIFICATION: COMPARISON BETWEEN 3.0- AND 1.5-TESLA 1H MR SPECTROSCOPY 
Magnetic resonance imaging  2007;25(7):1105-1111.
OBJECTIVE
To prospectively compare measurement precision of calf intramyocellular lipid (IMCL) quantification at 3.0T and 1.5T using 1H magnetic resonance spectroscopy (1H-MRS).
MATERIALS AND METHODS
We examined the soleus and tibialis anterior (TA) muscles of 15 male adults [21–48 years of age, body mass index (BMI)=21.9–38.0 kg/m2]. Each subject underwent 3.0T and 1.5T single-voxel short-echo-time point-resolved 1H-MRS both at baseline and 31-day follow-up. The IMCL-methylene peak (1.3 ppm) was scaled to unsuppressed water peak (4.7 ppm) using the LCModel routine. Full width at half maximum (FWHM) and signal-to-noise ratios (SNR) of unsuppressed water peak were measured using jMRUI software. Measurement precision was tested by comparing interexamination coefficients of variation (CV) between different field strengths using Wilcoxon matched pairs rank test in all subjects. Overweight subjects (BMI>25 kg/m2) were analyzed separately to examine benefits of 3.0T acquisitions in subjects with increased adiposity.
RESULTS
No significant difference between 3.0T and 1.5T was noted in CVs for IMCL of soleus (P=0.5). CVs of TA were significantly higher at 3.0T (P=0.02). SNR was significantly increased at 3.0T for soleus (64%, P<0.001) and TA (62%, P<0.001), however lower than the expected improvement of 100%. FWHM at 3.0T was significantly increased for soleus (19%, P<0.001) and TA (7%, P<0.01). Separate analysis of overweight subjects showed no significant difference between 3.0T and 1.5T CVs for IMCL of soleus (P=0.8) and TA (P=0.4).
CONCLUSION
Using current technology, 1H-MRS for IMCL at 3.0T did not improve measurement precision compared to 1.5T.
doi:10.1016/j.mri.2006.12.003
PMCID: PMC2034287  PMID: 17707173
Proton magnetic resonance spectroscopy; Muscle; Lipids; 3.0-Tesla
18.  Use of FDG-PET in differentiating benign from malignant compression fractures 
Skeletal Radiology  2008;37(5):405-413.
Objective
The objective was to evaluate the use of fluorodeoxyglucose positron emission tomography (FDG-PET) in differentiating benign from malignant compression fractures.
Patients and methods
In a retrospective analysis, we identified 33 patients with 43 compression fractures who underwent FDG-PET. On FDG-PET the uptake pattern was recorded qualitatively and semiquantitatively and fractures were categorized as benign or malignant. Standardized uptake values (SUV) were obtained. MRI, CT, and biopsy results as well as clinical follow-up for 1–3 years served as standards of reference. The Student’s t test was used to determine whether there was a statistically significant difference between the SUV for benign and malignant compression fractures.
Results
There were 14 malignant and 29 benign compression fractures, including 5 acute benign fractures. On FDG-PET, 5 benign fractures were falsely classified as malignant (false-positive). Three of these patients underwent prior treatment with bone marrow-stimulating agents. There were two false-negative results. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG-PET in differentiating benign from malignant compression fractures were 86%, 83%, 84%, 71%, and 92% respectively. The difference between SUV values of benign and malignant fractures was statistically significant (1.9 ± 0.97 for benign and 3.9 ± 1.52 for malignant fractures, p < 0.001). SUV of benign acute and chronic fractures were not statistically significant.
Conclusion
Fluorodeoxyglucose positron emission tomography is useful in differentiating benign from malignant compression fractures. Therapy with bone marrow-stimulating agents can mimic malignant involvement.
doi:10.1007/s00256-008-0452-5
PMCID: PMC2271083  PMID: 18278491
Spine; Compression fractures; Malignant; Benign; FDG-PET

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