MRI assessment of lean and adipose tissue distribution in female patients with Cushing's disease.

OBJECTIVE: Chronic hypercortisolemia due to Cushing's disease (CD) results in abnormal adipose tissue (AT) distribution. Whole-body magnetic resonance imaging (MRI) was used to examine lean and AT distribution in female patients with CD to further understand the role of glucocorticoid excess in the development of abnormal AT distribution and obesity. DESIGN: Cross-sectional and case-control study. PATIENTS: Fifteen women with CD and 12 healthy controls. MEASUREMENTS: Mass of skeletal muscle (SM) and AT in the visceral (VAT), subcutaneous (SAT), and intermuscular (IMAT) compartments from whole-body MRI and serum levels of insulin, glucose, and leptin were measured. RESULTS: CD patients had leptin values that correlated to total AT (TAT) and SAT (P < 0.05) but not to VAT. CD patients had higher VAT/TAT ratios (P < 0.01) and lower SAT/TAT ratios (P < 0.05) compared to controls. TAT, VAT, and trunk SAT (TrSAT) were greater in CD patients (P < 0.01). SM was less in CD (P < 0.001) but IMAT was not different. CONCLUSIONS: TAT, VAT, trSAT, and the proportion of AT in the visceral depot were greater in CD although the proportion in the subcutaneous depot was less. SM was less but IMAT was not different. These findings have implications for understanding the role of cortisol in the abnormal AT distribution and metabolic risk seen in patients exposed to chronic excess glucocorticoids.

Trends in nonalcoholic fatty liver disease-related hospitalizations in US children, adolescents, and young adults.

OBJECTIVE: To investigate temporal trends of nonalcoholic fatty liver disease (NAFLD) and obesity among hospitalized US children, adolescents, and young adults over the past 2 decades and to examine potential sex disparities in NAFLD hospitalizations. METHODS: Hospitalization discharges with NAFLD or obesity were identified among children and young adults (6-25 years, weighted n = 91,687,413) from the 1986 to 2006 National Hospital Discharge Survey data. Age- and sex-specific rates and trends in hospitalizations with NAFLD and obesity were estimated. Rates were standardized to age distribution of the 2000 US Census population. Sex disparities were examined for the most recent period 2004 to 2006 (weighted n = 12,969,532). RESULTS: Between 1986 to 1988 and 2004 to 2006, hospitalizations with NAFLD diagnosis increased from 0.9 to 4.3/100,000 population (P < 0.001). During the same time, hospitalizations with a diagnosis of obesity increased from 35.5 to 114.7/100,000 population (P < 0.001). During 2004 to 2006, hospitalization rates with a diagnosis of NAFLD were higher among females than among males (5.9 vs 2.7/100,000 population, P < 0.001), as were hospitalizations with a diagnosis of obesity (140.8 vs 61.5/100,000 population, P < 0.001). Obesity and diabetes were reported in 43.3% and 31.9%, respectively, of discharges with NAFLD. CONCLUSION: The prevalence of NAFLD among young hospitalized patients increased in the past 2 decades, paralleling obesity-related hospitalizations. This could be a consequence of the obesity epidemic or of increased screening for liver disease.

Body composition in premature adrenarche by structural MRI, 1H MRS and DXA.

BACKGROUND: Premature adrenarche (PA) is recognized to be a possible precursor of polycystic ovarian syndrome, type 2 diabetes mellitus and cardiovascular disease. Visceral adiposity and increased intramyocellular lipid (IMCL) are associated with insulin resistance and increased risk of cardiovascular disease. AIM: To determine whether prepubertal girls with PA have altered visceral adiposity and/or increased muscle lipid content compared to prepubertal girls without PA using proton magnetic resonance imaging (MRI) and spectroscopy (1H MRS). PATIENTS AND METHODS: We performed total body dual energy X-ray absorptiometry (DXA) scans, MRI of the trunk, and MRS of the tibialis anterior muscle in the right calf on six girls with PA and eight prepubertal controls. RESULTS: Amount of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT), and VAT to SAT ratio did not differ significantly between the PA and control girls. Those with PA, however, had significantly greater IMCL than controls (p = 0.004). CONCLUSIONS: This study adds further evidence that PA is not a benign condition, and future studies investigating early intervention with dietary and exercise counseling may help diminish potential risk for diabetes mellitus and/or cardiovascular disease.

Dual-energy X-ray absorptiometry is a valid tool for assessing skeletal muscle mass in older women.

Assessing skeletal muscle mass (SMM) is critical in studying and detecting sarcopenia. Direct measurements by MRI or computerized tomography are expensive or high in radiation exposure. Dual-energy X-ray absorptiometry (DXA) is promising for body composition assessments, but the validity of DXA for predicting SMM in the elderly is still under investigation. The objective of this study was to assess the relationship between DXA-derived measurements of lean soft tissue mass (LSTM) and SMM in older women. Study participants were postmenopausal women (n = 101) recruited in southern Arizona. Total and regional body composition was measured using MRI and DXA (QDR4500w). The participants' mean age was 70.7 +/- 6.4 y and their mean BMI was 27.4 +/- 5.1 kg/m2. DXA-derived LSTM was highly correlated with MRI-derived SMM for the whole body (r = 0.94; P < 0.001) and leg region (r = 0.91; P < 0.001). In multivariate models, adjusting for age and DXA-derived percent fat slightly increased the amount of variance in SMM that can be explained by the DXA-derived LSTM assessments for the leg region but not for the total body. In conclusion, although the relationships between DXA measures and MRI-derived SMM vary by region of interest, the overall prediction of SMM by DXA is excellent. We conclude that DXA is a reliable method for cross-sectional assessments of SMM in older women.

Insulin Resistance and Inflammation in Hypogonadotropic Hypogonadism and Their Reduction After Testosterone Replacement in Men With Type 2 Diabetes.

OBJECTIVE: One-third of men with type 2 diabetes have hypogonadotropic hypogonadism (HH). We conducted a randomized placebo-controlled trial to evaluate the effect of testosterone replacement on insulin resistance in men with type 2 diabetes and HH. RESEARCH DESIGN AND METHODS: A total of 94 men with type 2 diabetes were recruited into the study; 50 men were eugonadal, while 44 men had HH. Insulin sensitivity was calculated from the glucose infusion rate (GIR) during hyperinsulinemic-euglycemic clamp. Lean body mass and fat mass were measured by DEXA and MRI. Subcutaneous fat samples were taken to assess insulin signaling genes. Men with HH were randomized to receive intramuscular testosterone (250 mg) or placebo (1 mL saline) every 2 weeks for 24 weeks. RESULTS: Men with HH had higher subcutaneous and visceral fat mass than eugonadal men. GIR was 36% lower in men with HH. GIR increased by 32% after 24 weeks of testosterone therapy but did not change after placebo (P = 0.03 for comparison). There was a decrease in subcutaneous fat mass (-3.3 kg) and increase in lean mass (3.4 kg) after testosterone treatment (P < 0.01) compared with placebo. Visceral and hepatic fat did not change. The expression of insulin signaling genes (IR-ß, IRS-1, AKT-2, and GLUT4) in adipose tissue was significantly lower in men with HH and was upregulated after testosterone treatment. Testosterone treatment also caused a significant fall in circulating concentrations of free fatty acids, C-reactive protein, interleukin-1ß, tumor necrosis factor-α, and leptin (P < 0.05 for all). CONCLUSIONS: Testosterone treatment in men with type 2 diabetes and HH increases insulin sensitivity, increases lean mass, and decreases subcutaneous fat.

Visceral adipose tissue: relations between single-slice areas and total volume.

BACKGROUND: Visceral adipose tissue (VAT), which is linked with the metabolic consequences of obesity, is usually characterized by measuring VAT area at the L4-L5 vertebral interspace. However, the location of the slice with the strongest relation to VAT volume is not established. OBJECTIVE: We sought to investigate the relations between cross-sectional VAT areas at different anatomic locations and VAT volume in a large, diverse sample of healthy subjects. DESIGN: VAT volume was derived from slice areas taken at 5-cm intervals from magnetic resonance images in 121 healthy men [x +/- SD age: 41.9 +/- 15.8 y; body mass index (BMI; in kg/m(2)): 26.0 +/- 3.2; VAT: 2.7 +/- 1.8 L] and 198 healthy women (age: 48.1 +/- 18.7 y; BMI: 27.0 +/- 5.4; VAT: 1.7 +/- 1.2 L). Regression models were developed to identify the best single slice for estimating VAT volume. RESULTS: The VAT area 10 cm above L4-L5 (A(+10)) in men (R(2) = 0.932, P < 0.001) and 5 cm above L4-L5 (A(+5)) in women (R(2) = 0.945, P < 0.001) had the highest correlation with abdominal VAT. R(2) increased by only 3.8% in men and 0.5% in women with adjustment for age, race, scanning position, BMI, and waist circumference. Studies using A(+10) in men and A(+5) in women will require 14% and 9% fewer subjects, respectively, than those using slices at L4-L5 and will have equivalent power. CONCLUSION: Measurement of slice areas at A(+10) in men and A(+5) in women provides greater power for the detection of VAT volume differences than does measurement at L4-L5.

Total body skeletal muscle and adipose tissue volumes: estimation from a single abdominal cross-sectional image.

A single abdominal cross-sectional computerized axial tomography and magnetic resonance image is often obtained in studies examining adipose tissue (AT) distribution. An abdominal image might also provide additional useful information on total body skeletal muscle (SM) and AT volumes with related physiological insights. We therefore investigated the relationships between abdominal SM and AT areas from single images and total body component volumes in a large and diverse sample of healthy adult subjects. Total body SM and AT volumes were derived by whole body multislice magnetic resonance imaging in 123 men [age (mean +/- SD) of 41.6 +/- 15.8 yr; body mass index of 25.9 +/- 3.4 kg/m(2)] and 205 women (age of 47.8 +/- 18.7 yr; body mass index of 26.7 +/- 5.6 kg/m(2)). Single abdominal SM and AT slice areas were highly correlated with total body SM (r = 0.71-0.92; r = 0.90 at L(4)-L(5) intervertebral space) and AT (r = 0.84-0.96; r = 0.94 at L(4)-L(5) intervertebral space) volumes, respectively. R(2) increased by only 5.7-6.1% for SM and 2.7-4.4% for AT with the inclusion of subject sex, age, ethnicity, scanning position, body mass index, and waist circumference in the model. The developed SM and AT models were validated in an additional 49 subjects. To achieve equivalent power to a study measuring total body SM or AT volumes, a study using a single abdominal image would require 17-24% more subjects for SM and 6-12% more subjects for AT. Measurement of a single abdominal image can thus provide estimates of total body SM and AT for group studies of healthy adults.

Assessment of abdominal fat compartments using DXA in premenopausal women from anorexia nervosa to morbid obesity.

OBJECTIVE: To test a newly developed dual energy X-ray absorptiometry (DXA) method for abdominal fat depot quantification in subjects with anorexia nervosa (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. CONCLUSION: 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.

Dual-energy X-ray performs as well as clinical computed tomography for the measurement of visceral fat.

Visceral adipose tissue (VAT) is associated with adverse health effects including cardiovascular disease and type 2 diabetes. We developed a dual-energy X-ray absorptiometry (DXA) measurement of visceral adipose tissue (DXA-VAT) as a low cost and low radiation alternative to computed tomography (CT). DXA-VAT was compared to VAT assessed using CT by an expert reader (E-VAT). In addition, the same CT slice was also read by a clinical radiographer (C-VAT) and a best-fit anthropomorphic and demographic VAT model (A-VAT) was developed. Whole body DXA, CT at L4-L5, and anthropometry were measured on 272 black and white South African women (age 29 ± 8 years, BMI 28 ± 7 kg/m(2), waist circumference (WC) 89 ± 16 cm). Approximately one-half of the dataset (n = 141) was randomly selected and used as a training set for the development of DXA-VAT and A-VAT, which were then used to estimate VAT on the remaining 131 women in a blinded fashion. DXA-VAT (r = 0.93, standard error of the estimate (SEE) = 16 cm(2)) and C-VAT (r = 0.93, SEE = 16 cm(2)) were strongly correlated to E-VAT. These correlations with E-VAT were significantly stronger (P < 0.001) than the correlations of individual anthropometry measurements and the A-VAT model (WC + age, r = 0.79, SEE = 27 cm(2)). The inclusion of anthropometric and demographic measurements did not substantially improve the correlation between DXA-VAT and E-VAT. DXA-VAT performed as well as a clinical read of VAT from a CT scan and better than anthropomorphic and demographic models.

A single MRI slice does not accurately predict visceral and subcutaneous adipose tissue changes during weight loss.

Earlier cross-sectional studies found that a single magnetic resonance imaging (MRI) slice predicts total visceral and subcutaneous adipose tissue (VAT and SAT) volumes well. We sought to investigate the accuracy of trunk single slice imaging in estimating changes of total VAT and SAT volume in 123 overweight and obese subjects who were enrolled in a 24-week CB-1R inverse agonist clinical trial (weight change, -7.7 ± 5.3 kg; SAT change, -5.4 ± 4.9 l, VAT change, -0.8 ± 1.0 l). VAT and SAT volumes at baseline and 24 weeks were derived from whole-body MRI images. The VAT area 5-10 cm above L(4)-L(5) (A(+5-10)) (R(2) = 0.59-0.70, P < 0.001) best predicted changes in VAT volume but the strength of these correlations was significantly lower than those at baseline (R(2) = 0.85-0.90, P < 0.001). Furthermore, the L(4)-L(5) slice poorly predicted VAT volume changes (R(2) = 0.24-0.29, P < 0.001). Studies will require 44-69% more subjects if (A(+5-10)) is used and 243-320% more subjects if the L(4)-L(5) slice is used for equivalent power of multislice total volume measurements of VAT changes. Similarly, single slice imaging predicts SAT loss less well than cross-sectional SAT (R(2) = 0.31-0.49 vs. R(2) = 0.52-0.68, P < 0.05). Results were the same when examined in men and women separately. A single MRI slice 5-10 cm above L(4)-L(5) is more powerful than the traditionally used L(4)-L(5) slice in detecting VAT changes, but in general single slice imaging poorly predicts VAT and SAT changes during weight loss. For certain study designs, multislice imaging may be more cost-effective than single slice imaging in detecting changes for VAT and SAT.

Relationship between MRI-measured bone marrow adipose tissue and hip and spine bone mineral density in African-American and Caucasian participants: the CARDIA study.

CONTEXT: An increasing number of studies suggest that bone marrow adipose tissue (BMAT) might play a role in the pathogenesis of osteoporosis. Our previous study of Caucasian women demonstrated that there is an inverse relationship between BMAT and whole-body bone mineral density (BMD). It is unknown whether visceral adipose tissue (VAT), sc adipose tissue (SAT), and skeletal muscle had an effect on the relationship between BMAT and BMD. OBJECTIVE: In the present study we investigated the relationship between pelvic, hip, and lumbar spine BMAT with hip and lumbar spine BMD in the population-based Coronary Artery Risk Development in Young Adults (CARDIA) sample with adjustment for whole-body magnetic resonance imaging (MRI)-measured VAT, SAT, and skeletal muscle. DESIGN: T1-weighted MRI was acquired for 210 healthy African-American and Caucasian men and women (age 38-52 yr). Hip and lumbar spine BMD were measured by dual-energy x-ray absorptiometry. RESULTS: Pelvic, hip, and lumbar spine BMAT had negative correlations with hip and lumbar spine BMD (r = -0.399 to -0.550, P < 0.001). The inverse associations between BMAT and BMD remained strong after adjusting for demographics, weight, skeletal muscle, SAT, VAT, total adipose tissue (TAT), menopausal status, lifestyle factors, and inflammatory markers (standardized regression coefficients = -0. 296 to -0.549, P < 0.001). Among body composition measures, skeletal muscle was the strongest correlate of BMD after adjusting for BMAT (standardized regression coefficients = 0.268-0.614, P < 0.05), with little additional contribution from weight, SAT, VAT, or total adipose tissue. CONCLUSION: In this middle-aged population, a negative relationship existed between MRI-measured BMAT and hip and lumbar spine BMD independent of demographics and body composition. These observations support the growing evidence linking BMAT with low bone density.

Ectopic lipid accumulation and reduced glucose tolerance in elderly adults are accompanied by altered skeletal muscle mitochondrial activity.

CONTEXT: Aging is associated with insulin resistance and unfavorable changes in body composition including increased fat accumulation, particularly in visceral and ectopic depots. Recent studies suggest that skeletal muscle mitochondrial activity may underlie some age-associated metabolic abnormalities. OBJECTIVE: Our objective was to measure mitochondrial capacity and coupling of the vastus lateralis muscle in elderly and young adults using novel in vivo approaches and relate mitochondrial activity to metabolic characteristics. DESIGN: This was a cross-sectional study. PARTICIPANTS AND INTERVENTION: Fourteen sedentary young (seven males and seven females, 20-34 yr of age) and 15 sedentary elderly (seven males and eight females, 70-84 yr of age) nonobese subjects selected for similar body weight underwent measures of body composition by magnetic resonance imaging and dual-energy x-ray absorptiometry, oral glucose tolerance, and in vivo mitochondrial activity by (31)P magnetic resonance and optical spectroscopy. Muscle biopsy was carried out in the same muscle to measure mitochondrial content, antioxidant activity, fiber type, and markers of mitochondrial biogenesis. RESULTS: Elderly volunteers had reduced mitochondrial capacity (P = 0.05) and a trend for decreased coupling efficiency (P = 0.08) despite similar mitochondrial content and fiber type distribution. This was accompanied by greater whole-body oxidative stress (P = 0.007), less skeletal muscle mass (P < 0.001), more adipose tissue in all depots (P ≤ 0.002) except intramyocellular (P = 0.72), and lower glucose tolerance (P = 0.07). CONCLUSIONS: Elderly adults show evidence of altered mitochondrial activity along with increased adiposity, oxidative stress, and reduced glucose tolerance, independent of obesity. We propose that mild uncoupling may be induced secondary to age-associated oxidative stress as a mechanism to dissipate the proton-motive force and protect against further reactive oxygen species production and damage.

Prospective cohort study of spinal muscular atrophy types 2 and 3.

OBJECTIVE: To characterize the natural history of spinal muscular atrophy type 2 and type 3 (SMA 2/3) beyond 1 year and to report data on clinical and biological outcomes for use in trial planning. METHODS: We conducted a prospective observational cohort study of 79 children and young adults with SMA 2/3 who participated in evaluations for up to 48 months. Clinically, we evaluated motor and pulmonary function, quality of life, and muscle strength. We also measured SMN2 copy number, hematologic and biochemical profiles, muscle mass by dual x-ray absorptiometry (DXA), and the compound motor action potential (CMAP) in a hand muscle. Data were analyzed for associations between clinical and biological/laboratory characteristics cross-sectionally, and for change over time in outcomes using all available data. RESULTS: In cross-sectional analyses, certain biological measures (specifically, CMAP, DXA fat-free mass index, and SMN2 copy number) and muscle strength measures were associated with motor function. Motor and pulmonary function declined over time, particularly at time points beyond 12 months of follow-up. CONCLUSION: The intermediate and mild phenotypes of SMA show slow functional declines when observation periods exceed 1 year. Whole body muscle mass, hand muscle compound motor action potentials, and muscle strength are associated with clinical measures of motor function. The data from this study will be useful for clinical trial planning and suggest that CMAP and DXA warrant further evaluation as potential biomarkers.

Between-slice intervals in quantification of adipose tissue and muscle in children.

Magnetic Resonance Imaging (MRI) is increasingly being used in children to quantify adipose tissue (AT) and skeletal muscle (SM) in vivo. It is unclear whether the every 5 cm whole body MRI protocol used in adults is appropriate when applied in children. Whole body MRI continuous 1 cm thick slices were acquired in 73, aged 5-17-year-old healthy children. Images were segmented into subcutaneous (SAT), visceral (VAT), intermuscular AT (IMAT), and SM. The percentage difference between volumes measured by the continuous protocol and volumes estimated with protocols of different between-slice intervals (i.e., interval = 2, 3, 4 and 5 cm) was larger with an increase in interval size, depot size, weight and body mass index percentile. For group comparisons, studies will require less than 5.4% more subjects if an every 5 cm protocol is used for equivalent power as the every 1 cm protocol. For individual subject comparisons, interval protocols can be used to reliably distinguish between subjects who differ in SM or SAT volume by 0.14 to 0.64 L (i.e., 1 to 5% of SM or SAT volume) or more, or in VAT or IMAT volume by 0.06 to 0.21 L (i.e., 10 to 30% of VAT or IMAT volume) or more. The every 5 cm image acquisition protocol can be considered as accurate as the contiguous protocol for group comparisons in children, as well as for comparison of SM and SAT among individual children. However, a smaller slice interval protocol would be more accurate for comparison of VAT or IMAT among individual children.

Muscle volume estimation by magnetic resonance imaging in spinal muscular atrophy.

Thigh muscle volume was assessed using magnetic resonance imaging in 16 subjects with spinal muscular atrophy. Scans were successful for 14 of 16 subjects (1 type 1, 6 type 2, and 7 type 3) as young as 5.7 years. Muscle volume with normal and abnormal signal was measured using blinded, semiautomated analysis of reconstructed data. Results were compared with segmental lean mass estimated by dual-energy X-ray absorptiometry and correlated with clinical and electrophysiological measures of disease severity. Muscle volume was reduced with abnormal signal quality. Test-retest reliability (r = .99) and correlation with dual-energy X-ray absorptiometry (r = .91) were excellent. Type 2 subjects had lower volume (3.5 ± 1.6 vs 6.3 ± 2.8 mL/cm height; P = .06) and higher percentage of muscle with abnormal signal (68% ± 20% vs 47% ± 27%; P = .14) than type 3. Reproducibility, tolerability, and strong correlation with clinical measures make magnetic resonance imaging a candidate biomarker for clinical research.

Intermuscular adipose tissue and metabolic associations in HIV infection.

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.

Ethnic differences in pancreatic fat accumulation and its relationship with other fat depots and inflammatory markers.

OBJECTIVE: Visceral adipose tissue (VAT) and hepatic fat are associated with insulin resistance and vary by sex and ethnicity. Recently, pancreatic fat fraction (PFF) has also been linked with increasing obesity. Our aim was to assess ethnic and sex differences in PFF and its relationship to other fat depots, circulating free fatty acids (FFA), insulin secretion and sensitivity, and inflammation in obese adolescents and young adults. RESEARCH DESIGN AND METHODS: We examined 138 (40 males, 98 females) obese Hispanics and African Americans (13-25 years). Subcutaneous adipose tissue and VAT volumes, hepatic fat fraction (HFF), and PFF were determined by magnetic resonance imaging. Insulin sensitivity and ß-cell function were assessed during an intravenous glucose tolerance test. RESULTS: Hispanics had higher PFF than African Americans (7.3 ± 3.8 vs. 6.2 ± 2.6%, P = 0.03); this ethnic difference was higher in young adults compared with children and adolescents (ethnicity × age: P = 0.01). Males had higher PFF than females (P < 0.0001). PFF was positively correlated with VAT (r = 0.45, P < 0.0001), HFF (r = 0.29, P < 0.0001), and FFA (r = 0.32, P = 0.001). PFF positively correlated with inflammatory markers but lost significance when adjusted for VAT. In multiple stepwise regression analysis, VAT and FFA were the best predictors of PFF (adjusted R(2) = 0.40). There were no significant correlations between PFF and markers of insulin sensitivity or ß-cell function. CONCLUSIONS: PFF is higher in Hispanics than African Americans, and this difference increases with age. In young obese individuals, PFF is related to VAT, HFF, and circulating FFA, thus possibly contributing to their increased risk for type 2 diabetes and related metabolic disorders.

Thigh muscle volume measured by magnetic resonance imaging is stable over a 6-month interval in spinal muscular atrophy.

Changes in thigh muscle volume over 6 months were assessed using magnetic resonance imaging in 11 subjects aged 6 to 47 years with spinal muscular atrophy (4 type 2 and 7 type 3; 4 ambulatory and 3 nonambulatory). Muscle volume with normal and abnormal signal was measured using blinded, semiautomated analysis of reconstructed data. Volumes at baseline and 6 months were correlated with clinical function at each epoch. There was minimal increase in normal (0.3 ± 1.4 mL/cm) and total (0.1 ± 1.3 mL/cm) muscle. Muscle volume correlated closely with clinical function. Minimal interval change in muscle volume is consistent with the established clinical history of minimal disease progression over intervals shorter than 1 year. Relative constancy of muscle volume estimation and correlation with established functional measures suggest a role for segmental magnetic resonance imaging as a biomarker of treatment effect in future therapeutic trials.

Bioelectrical impedance analysis can be a useful screen for excess adiposity in spinal muscular atrophy.

Accurate, noninvasive measures of body composition are needed for management of patients with spinal muscular atrophy. Fat mass index (fat mass/height(2) in kg/m(2)) was measured in 16 subjects with spinal muscular atrophy using 5 bioelectrical impedance analysis equations and compared with a reference method, dual-energy x-ray absorptiometry. The machine default equation, validated by Cordain, was the primary analysis. Fat mass index calculated by impedance measures differed by between -2.5 kg/m(2) and 1.7 kg/m(2) from the reference mean (8.3 ± 5.0 kg/m(2)). The Cordain equation provided the smallest difference (-0.4 ± 2.0 kg/m(2)), with correlation coefficient of 0.92. The Cordain equation showed high sensitivity (85.7%) and specificity (100%) for prediction of ''at risk for overweight'' (fat mass index > 85th percentile for age and gender). Although insufficiently accurate for use as a research tool, bioelectrical impedance can have application as a well-tolerated, noninvasive, easily used screening tool for excess adiposity in patients with spinal muscular atrophy.

Adiposity is increased among high-functioning, non-ambulatory patients with spinal muscular atrophy.

The relationship between body composition and function in spinal muscular atrophy (SMA) is poorly understood. 53 subjects with SMA were stratified by type and Hammersmith functional motor scale, expanded score into three cohorts: low-functioning non-ambulatory (type 2 with Hammersmith score < 12, n=19), high-functioning non-ambulatory (type 2 with Hammersmith score > or = 12 or non-ambulatory type 3, n=17), and Ambulatory (n=17). Lean and fat mass was estimated using dual-energy X-ray absorptiometry. Anthropometric data was incorporated to measure fat-free (lean mass in kg/stature in m(2)) and fat (fat mass in kg/stature in m(2)) mass indices, the latter compared to published age and sex norms. Feeding dysfunction among type 2 subjects was assessed by questionnaire. Fat mass index was increased in the high-functioning non-ambulatory cohort (10.4+/-4.5) compared with both the ambulatory (7.2+/-2.1, P=0.013) and low-functioning non-ambulatory (7.6+/-3.1, P=0.040) cohorts. 12 of 17 subjects (71%) in the high-functioning non-ambulatory cohort had fat mass index > 85th percentile for age and gender (connoting "at risk of overweight") versus 9 of 19 subjects (47%) in the low-functioning non-ambulatory cohort and 8 of 17 ambulatory subjects (47%). Despite differences in clinical function, a similar proportion of low functioning (7/18, 39%) and high functioning (2/7, 29%) type 2 subjects reported swallowing or feeding dysfunction. Non-ambulatory patients with relatively high clinical function may be at particular risk of excess adiposity, perhaps reflecting access to excess calories despite relative immobility, emphasizing the importance of individualized nutritional management in SMA.