Low skeletal muscle mass as an early sign in children with fabry disease.

BACKGROUND & AIMS: Fabry disease (FD) is a rare X-linked metabolic storage disorder due to the deficiency of lysosomal α-galactosidase A which causes the accumulation of glycosphingolipids throughout the body. Underweight and low BMI have been occasionally reported in FD patients previously. Whether underweight is common in the early stage of FD and body composition analysis to determine the cause have not been reported. METHODS: Children who were diagnosed with FD in the Children's Hospital of Zhejiang University School of Medicine from July 2014 to December 2022 were enrolled. Clinical data were obtained from medical records. Whole body dual energy X-ray absorptiometry scans (DXA) were used to assess body composition (fat mass, FM; fat free mass, FFM and bone mass) according to the International Society of Clinical Densitometry's standard operating method. Whole body muscle mass was calculated as fat-free mass minus bone mass. Appendicular skeletal muscle mass (ASM) was calculated as the sum of the arm and the leg muscle mass. The FM, FFM, ULSM and LLSM indices were calculated by dividing the total FM, FFM, and upper and lower limb skeletal muscle mass (ULSM and LLSM) by the height squared. RESULTS: A total of eighteen children (14 boys and 4 girls) were enrolled. Thirteen boys had the classical phenotype, and five children (1 boy with the N215S mutation and 4 girls) had the late-onset phenotype. Seven children with the classical phenotype (53.8%) and two of the five children (40%) with the late-onset phenotype had abnormal BMIs. Sixteen of the eighteen children (88.9%) had a height in the normal range, suggesting that low BMI was mainly due to underweight. By DXA body composition analysis, the FMI was abnormal in 3 children (2 boys and 1 girl), and the FFMI was abnormal in 12 children (9 boys and 3 girls). For the classical phenotype, 2 of the 13 children (15.4%) had abnormal FMI values, while 10 (76.9%) had abnormal FFMI values. Eight patients (61.5%) with the classical phenotype had a significant reduction in muscle mass index, ASM index and LLSM index values compared with age- and sex- matched Chinese controls. Late-onset patients also had mild low skeletal muscle mass compared to controls. The results suggested that low skeletal muscle mass is common in early FD. CONCLUSIONS: This is the first study to examine body composition and muscle mass in early Fabry disease patients. Low skeletal muscle mass is a common early symptom in children with Fabry disease, suggesting that skeletal muscle is significantly affected in the early stages of FD.

Altered White Matter Connectivity in Young Acutely Underweight Patients With Anorexia Nervosa.

OBJECTIVE: Reductions of gray matter volume and cortical thickness in anorexia nervosa (AN) are well documented. However, findings regarding the integrity of white matter (WM) as studied via diffusion weighted imaging (DWI) are remarkably heterogeneous, and WM connectivity has been examined only in small samples using a limited number of regions of interest. The present study investigated whole-brain WM connectivity for the first time in a large sample of acutely underweight patients with AN. METHOD: DWI data from predominantly adolescent patients with acute AN (n = 96, mean age = 16.3 years) and age-matched healthy control participants (n = 96, mean age = 17.2 years) were analyzed. WM connectivity networks were generated from fiber-tractography-derived streamlines connecting 233 cortical/subcortical regions. To identify group differences, network-based statistic was used while taking head motion, WM, and ventricular volume into account. RESULTS: Patients with AN were characterized by 6 WM subnetworks with abnormal architecture, as indicated by increased fractional anisotropy located primarily in parietal-occipital regions and accompanied by reduced radial diffusivity. Group differences based on number of streamlines reached only nominal significance. CONCLUSION: Our study reveals pronounced alterations in the WM connectome in young patients with AN. In contrast to known reductions in gray matter in the acutely underweight state of AN, this pattern does not necessarily indicate a deterioration of the WM network. Future studies using advanced MRI sequences will have to clarify interrelations with axonal packing or myelination, and whether the changes should be considered a consequence of undernutrition or a vulnerability for developing or maintaining AN.

Characterization of endogenous bile acid composition in individuals with cold-activated brown adipose tissue.

INTRODUCTION: Bile acid signaling has been suggested to promote BAT activity in various experimental models. However, little is known if and how physiologic bile acid metabolism is linked to BAT function in humans. Here we investigated the association between BAT activity and circulating bile acid concentrations in lean and obese individuals. METHODS: BAT 18F-fluorodeoxyglucose uptake was measured after a standardized cooling protocol by positron emission tomography/computed tomography. Cold-induced thermogenesis was assessed by indirect calorimetry. Fasting bile acid concentrations were determined by high performance liquid chromatography-high-resolution mass spectrometry. RESULTS: In a cohort of 24 BAT-negative and 20 BAT-positive individuals matched by age, sex, and body mass index, circulating bile acid levels were similar between groups except for higher ursodeoxycholic acid and a trend towards a lower 12α-OH/non-12α-OH bile acid ratio in lean participants with active BAT compared to those without. Moreover, the 12α-OH/non-12α-OH ratio, a marker of CYP8B1 activity, correlated negatively with BAT volume and activity. CONCLUSION: Fasting concentrations of major bile acids are not associated with cold-induced BAT activity in humans. However, the inverse association between BAT activity and 12α-OH/non-12α-OH ratio may suggest CYP8B1 as a potential new target in BAT function and warrants additional investigation.

3D free-hand ultrasound to register anatomical landmarks at the pelvis and localize the hip joint center in lean and obese individuals.

3D free-hand ultrasound (3DFUS) is becoming increasingly popular to assist clinical gait analysis because it is cost- and time-efficient and does not expose participants to radiation. The aim of this study was to evaluate its reliability in localizing the anterior superior iliac spine (ASIS) at the pelvis and the hip joint centers (HJC). Additionally, we evaluated its accuracy to get a rough estimation of the potential to use of 3DFUS to segment bony surface. This could offer potential to register medical images to motion capture data in future. To evaluate reliability, a test-retest study was conducted in 16 lean and 19 obese individuals. The locations of the ASIS were determined by manual marker placement (MMP), an instrumented pointer technique (IPT), and with 3DFUS. The HJC location was also determined with 3DFUS. To quantify reliability, intraclass correlation coefficients (ICCs), the standard error of measurement (SEm), among other statistical parameters, were calculated for the identified locations between the test and retest. To assess accuracy, the surface of a human plastic pelvic phantom was segmented with 3DFUS in a distilled water bath in 27 trials and compared to a 3D laser scan of the pelvis. Regarding reliability, the MMP, but especially the IPT showed high reliability in lean (SEm: 2-3 mm) and reduced reliability in obese individuals (SEm: 6-15 mm). Compared to MMP and IPT, 3DFUS presented lower reliability in the lean group (SEm: 2-4 mm vs. 2-8 mm, respectively) but slightly better values in the obese group (SEm: 7-11 mm vs. 6-16 mm, respectively). Correlations between test-retest reliability and torso body fat mass (% of body mass) indicated a moderate to strong relationship for MMP and IPT but only a weak correlation for the 3DFUS approach. The water-bath experiments indicated an acceptable level of 3.5 (1.7) mm of accuracy for 3DFUS in segmenting bone surface. Despite some difficulties with single trials, our data give further rise to the idea that 3DFUS could serve as a promising tool in future to inform marker placement and hip joint center location, especially in groups with higher amount of body fat.

Implications of Abdominal Adipose Tissue Distribution on Nonalcoholic Fatty Liver Disease and Metabolic Syndrome: A Chinese General Population Study.

INTRODUCTION: Visceral adipose tissue (VAT) has been found to play a critical role in the development of metabolic syndrome and nonalcoholic fatty liver disease (NAFLD) independent of generalized obesity. METHODS: In this secondary study of prospectively acquired data, 625 participants underwent magnetic resonance spectroscopy and chemical shift fat-water separation MRI (2-point Dixon) of the liver and whole abdomen, respectively, in a 3 Tesla magnet. Whole abdominal VAT and subcutaneous adipose tissue (SAT) were extracted from the 2-point Dixon image series using an automated method. Clinical/anthropometric/blood biochemistry parameters were measured. Using region-specific body mass index, participants were classified into 3 paired subgroups (lean, overweight, and obese) and presence of NAFLD (liver fat content ≥ 5.5%). RESULTS: All relevant clinical/anthropometric/blood biochemistry characteristics and liver enzymes were statistically significant between groups (P < 0.001). NAFLD was found in 12.1%, 43.8%, and 68.3% and metabolic syndrome in 51.1%, 61.9%, and 65% of the lean, overweight, and obese, respectively. Odds ratio for metabolic syndrome and NAFLD was increased by 2.73 (95% confidence interval [CI] 2.18-3.40) and 2.53 (95% CI 2.04-3.12), respectively, for 1SD increase in VAT volume while prevalence of metabolic syndrome was increased by 2.26 (95% CI 1.83-2.79) for 1SD increase in liver fat content (%). VAT/SAT ratio in the lean with fatty liver showed the highest ratio (0.54) among all the subgroups, without a significant difference between the lean and obese with NAFLD (P = 0.127). DISCUSSION: Increased VAT volume/disproportional distribution of VAT/SAT may be vital drivers to the development of metabolic syndrome and NAFLD irrespective of body mass index category.

Heterogeneity in insulin-stimulated glucose uptake among different muscle groups in healthy lean people and people with obesity.

AIMS/HYPOTHESIS: It has been proposed that muscle fibre type composition and perfusion are key determinants of insulin-stimulated muscle glucose uptake, and alterations in muscle fibre type composition and perfusion contribute to muscle, and consequently whole-body, insulin resistance in people with obesity. The goal of the study was to evaluate the relationships among muscle fibre type composition, perfusion and insulin-stimulated glucose uptake rates in healthy, lean people and people with obesity. METHODS: We measured insulin-stimulated whole-body glucose disposal and glucose uptake and perfusion rates in five major muscle groups (erector spinae, obliques, rectus abdominis, hamstrings, quadriceps) in 15 healthy lean people and 37 people with obesity by using the hyperinsulinaemic-euglycaemic clamp procedure in conjunction with [2H]glucose tracer infusion (to assess whole-body glucose disposal) and positron emission tomography after injections of [15O]H2O (to assess muscle perfusion) and [18F]fluorodeoxyglucose (to assess muscle glucose uptake). A biopsy from the vastus lateralis was obtained to assess fibre type composition. RESULTS: We found: (1) a twofold difference in glucose uptake rates among muscles in both the lean and obese groups (rectus abdominis: 67 [51, 78] and 32 [21, 55] µmol kg-1 min-1 in the lean and obese groups, respectively; erector spinae: 134 [103, 160] and 66 [24, 129] µmol kg-1 min-1, respectively; median [IQR]) that was unrelated to perfusion or fibre type composition (assessed in the vastus only); (2) the impairment in insulin action in the obese compared with the lean group was not different among muscle groups; and (3) insulin-stimulated whole-body glucose disposal expressed per kg fat-free mass was linearly related with muscle glucose uptake rate (r2 = 0.65, p < 0.05). CONCLUSIONS/INTERPRETATION: Obesity-associated insulin resistance is generalised across all major muscles, and is not caused by alterations in muscle fibre type composition or perfusion. In addition, insulin-stimulated whole-body glucose disposal relative to fat-free mass provides a reliable index of muscle glucose uptake rate.

White matter microstructural differences in underweight adolescents with anorexia nervosa and a preliminary longitudinal investigation of change following short-term weight restoration.

PURPOSE: Anorexia nervosa (AN) affects approximately 2.9% of females and has the highest mortality rate among all psychiatric disorders. Despite several advances, the neurobiology of this disorder is still not well understood. Several studies have reported abnormalities in the white matter, but it is not know if these are disease-related or secondary to undernutrition. This study aimed to further our understanding of white matter pathology using diffusion-weighted imaging in underweight adolescents with AN, and to examine changes occurring after short-term weight restoration. METHODS: Analyses were conducted on diffusion-weighted imaging from 24 female adolescents with AN and 17 age- and gender-matched healthy controls (HC), aged 14-19 years. Groups were compared on fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) using tract-based spatial statistics analysis and DTI measures were correlated with eating disorder examination questionnaire (EDE-Q) subscales and body mass index (BMI). Preliminary repeated-measure analyses were also conducted on eight participants after short-term weight restoration (median 41 days). RESULTS: Widespread increases in MD of up to 9% were found in underweight AN relative to HC, particularly in the corpus callosum. This was associated with both increased AD and RD, suggestive of dys- or de-myelination. There were no significant group differences in FA, and no significant correlations between DTI measures, BMI or EDE-Q subscale score. Weight restoration therapy significantly reduced MD, to levels significantly lower than HC, but did not consistently alter FA across individuals. CONCLUSIONS: White matter microstructure is significantly altered in female adolescents with AN, with preliminary longitudinal data suggesting that it may be reversible with short-term weight restoration. LEVEL OF EVIDENCE: Level III: evidence obtained from well-designed cohort or case-control analytic studies.

Patterns of Regional Cerebral Blood Flow as a Function of Obesity in Adults.

BACKGROUND: While obesity has been shown to be a risk factor for Alzheimer's disease, the potential mechanisms underlying this risk may be clarified with better understanding of underlying physiology in obese persons. OBJECTIVE: To identify patterns of cerebral perfusion abnormality in adults as a function of body mass index (BMI) defined weight categories, including overweight or obese status. METHODS: A large psychiatric cohort of 35,442 brain scans across 17,721 adults (mean age 40.8±16.2 years, range 18-94 years) were imaged with SPECT during baseline and concentration scans, the latter done after each participant completed the Connors Continuous Performance Test II. ANOVA was done to identify patterns of perfusion abnormality in this cohort across BMI designations of underweight (BMI < 18.5), normal weight (BMI = 18.5 to 24.9), overweight (BMI 24.9 to 29.9), obesity (BMI≥30), and morbid obesity (BMI≥40). This analysis was done for 128 brain regions quantifying SPECT perfusion using the automated anatomical labeling (AAL) atlas. RESULTS: Across adulthood, higher BMI correlated with decreased perfusion on both resting and concentration brain SPECT scans. These are seen in virtually all brain regions, including those influenced by AD pathology such as the hippocampus. CONCLUSION: Greater BMI is associated with cerebral perfusion decreases in both resting and concentration SPECT scans across adulthood.

The influence of obesity on cerebral blood flow in young adults using arterial spin labeling MRI.

Obesity causes damage to several organs, including the brain. Recent studies have been focusing on understanding the mechanisms through which obesity affects brain structure and function using neuroimaging techniques. A functional biomarker, such as cerebral blood flow (CBF), is a powerful tool that can be used to explore neural dysfunction. However, there is currently limited information regarding the association between CBF and obesity. The study was conducted to investigate the potential effect of obesity on brain perfusion in a young cohort aged 20-30 years. A total of 21 obese (body mass index (BMI) > 26 kg/m2 ) and 21 lean (BMI < 24 kg/m2 ) right-handed volunteers were included in this study. CBF was acquired using the 2D single post-labeling delay (PLD) arterial spin labeling (ASL) technique on a 3 T MRI scanner. A multiple regression analysis was performed to examine the difference in global and regional gray matter (GM) CBF between the groups. CBF value was assigned as the dependent variable, whereas age, sex, and group (obese or lean) were considered as the independent variables. Results showed that group-related differences in CBF were homogeneous across brain regions, as obese subjects had significantly lower global GM CBF than lean subjects (P < 0.05). In the voxelwise analysis, obese individuals had significantly lower CBF in the left pulvinar of the thalamus and visual association areas, including Brodmann area (BA) 7, BA18, and BA19, than lean subjects. Although the signal-to-noise ratio was slightly compromised for 2D sequences and subject-specific arterial transit time was not estimated due to a single PLD sequence, this study demonstrated alterations in CBF in obese subjects, particularly in regions of the pulvinar of the thalamus and its synchronously related areas such as visual association areas. These results suggest that ASL provides a potential platform for further obesity-related research.

Relating anthropometric indicators to brain structure in 2-month-old Bangladeshi infants growing up in poverty: A pilot study.

Anthropometric indicators, including stunting, underweight, and wasting, have previously been associated with poor neurocognitive outcomes. This link may exist because malnutrition and infection, which are known to affect height and weight, also impact brain structure according to animal models. However, a relationship between anthropometric indicators and brain structural measures has not been tested yet, perhaps because stunting, underweight, and wasting are uncommon in higher-resource settings. Further, with diminished anthropometric growth prevalent in low-resource settings, where biological and psychosocial hazards are most severe, one might expect additional links between measures of poverty, anthropometry, and brain structure. To begin to examine these relationships, we conducted an MRI study in 2-3-month-old infants growing up in the extremely impoverished urban setting of Dhaka, Bangladesh. The sample size was relatively small because the challenges of investigating infant brain structure in a low-resource setting needed to be realized and resolved before introducing a larger cohort. Initially, fifty-four infants underwent T1 sequences using 3T MRI, and resulting structural images were segmented into gray and white matter maps, which were carefully evaluated for accurate tissue labeling by a pediatric neuroradiologist. Gray and white matter volumes from 29 infants (79 â€‹± â€‹10 days-of-age; F/M â€‹= â€‹12/17), whose segmentations were of relatively high quality, were submitted to semi-partial correlation analyses with stunting, underweight, and wasting, which were measured using height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) scores. Positive semi-partial correlations (after adjusting for chronological age and sex and correcting for multiple comparisons) were observed between white matter volume and HAZ and WAZ; however, WHZ was not correlated with any measure of brain volume. No associations were observed between income-to-needs or maternal education and brain volumetric measures, suggesting that measures of poverty were not associated with total brain tissue volume in this sample. Overall, these results provide the first link between diminished anthropometric growth and white matter volume in infancy. Challenges of conducting a developmental neuroimaging study in a low-resource country are also described.

Aortic CT angiography using the double region of interest timing bolus technique: feasibility of 80 kVp scanning in lean patients.

To investigate the feasibility of aortic computed tomography angiography (CTA) performed at 80 kVp in lean patients using the double region of interest timing bolus (DRTB) technique compared to 100 kVp scanning. This study was approved by the institutional ethics committee, and all patients provided written informed consent. We prospectively included 165 patients from July 2018 to February 2019. We used an 80 kVp protocol when the maximal tube current did not exceed the limit using automatic exposure control; otherwise, 100 kVp was selected. The scan parameters for aortic CTA were determined from the test scan data. Enhancement at six points of the aortoiliac arteries and noise at the bifurcation level were measured. We compared the enhancement and signal to noise ratio (SNR) using Student's t-test. The tube voltage was 80 kVp in 87 patients (53%). The enhancement of the aortoiliac arteries was significantly higher (449.3 ± 77.8 vs 378.7 ± 53.1 HU, p < 0.0001) and the SNR was similar (42.4 ± 11.1 vs 40.0 ± 10.6, p = 0.17), and the amount of contrast medium was lower (33.0 ± 2.5 vs 41.8 ± 3.3 ml, p < 0.001) in the 80 kVp group compared to the 100 kVp group. Reducing the tube current to 80 kVp could decrease the amount of contrast medium used compared to the 100 kVp protocol, while maintaining image quality, for aortic CTA using the DRTB technique.

Lean non-alcoholic fatty liver disease and development of diabetes: a cohort study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD), a condition associated with multiple metabolic abnormalities, is frequently observed in normal weight individuals (lean NAFLD). The metabolic consequences of lean NAFLD, however, are not well characterized. Thus, this study aimed to evaluate the risk of incident diabetes in lean NAFLD. METHODS: This is a cohort study of 51,463 adults without diabetes, history of liver disease or cancer at baseline who participated in a regular health screening exam. Fatty liver was diagnosed by ultrasonography. The study outcome was the development of diabetes during follow-up. RESULTS: During 236,446.6 person-years of follow-up (median follow-up of 4.0 years), 5370 participants developed diabetes. In fully adjusted models, the hazard ratios (HRs) for incident diabetes comparing lean participants with NAFLD, overweight/obese participants without NAFLD and overweight/obese participants with NAFLD to lean participants without NAFLD, were 1.18 (95% CI: 1.03-1.35), 1.06 (0.98-1.14) and 1.45 (1.34-1.57), respectively. The fully adjusted HR for incident diabetes for lean NAFLD participants with low NAFLD fibrosis score (NFS) (<-1.455) and with intermediate-to-high NFS (≥-1.455) compared to lean participants without NAFLD were 1.32 (1.14-1.53) and 2.73 (2.10-3.55), respectively. CONCLUSIONS: In this large cohort study, the presence and severity of NAFLD in normal weight adults was associated with an increased incidence of diabetes independently of established risk factors. Indeed, isolated lean NAFLD was a stronger risk factor for incident diabetes than the presence of overweight/obesity without NAFLD. Subjects with lean NAFLD require careful monitoring for the development of metabolic abnormalities.

Dynamic changes in white matter microstructure in anorexia nervosa: findings from a longitudinal study.

BACKGROUND: Gray matter (GM) 'pseudoatrophy' is well-documented in patients with anorexia nervosa (AN), but changes in white matter (WM) are less well understood. Here we investigated the dynamics of microstructural WM brain changes in AN patients during short-term weight restoration in a combined longitudinal and cross-sectional study design. METHODS: Diffusion-weighted images were acquired in young AN patients before (acAN-Tp1, n = 56) and after (acAN-Tp2, n = 44) short-term weight restoration as well as in age-matched healthy controls (HC, n = 60). Images were processed using Tract-Based-Spatial-Statistics to compare fractional anisotropy (FA) across groups and timepoints. RESULTS: In the cross-sectional comparison, FA was significantly reduced in the callosal body in acAN-Tp1 compared with HC, while no differences were found between acAN-Tp2 and HC. In the longitudinal arm, FA increased with weight gain in acAN-Tp2 relative to acAN-Tp1 in large parts of the callosal body and the fornix, while it decreased in the right corticospinal tract. CONCLUSIONS: Our findings reveal that dynamic, bidirectional changes in WM microstructure in young underweight patients with AN can be reversed with brief weight restoration therapy. These results parallel those previously observed in GM and suggest that alterations in WM in non-chronic AN are also state-dependent and rapidly reversible with successful intervention.

Bone mineral density comparison of adolescents with constitutional thinness and anorexia nervosa.

BACKGROUND: The negative impact of anorexia nervosa (AN) on bone health is well defined. However, there are very few studies evaluating the effect of constitutional thinness on bone health, especially in the adolescent period and in the male gender. The aim of this study is to compare the bone mineral density (BMD) measurements of adolescents with AN and with constitutional thinness. METHODS: Between April 2013 and March 2014, 40 adolescents with AN and 36 adolescents with constitutional thinness participated in the study. The femoral neck and lumbar spine BMD were measured by dual energy X-ray absorptiometry (DXA). RESULTS: Mean lumbar z and BMD scores of adolescents with constitutional thinness were significantly lower than in adolescents with AN, whereas the mean femoral z and BMD scores were not significantly different. When males were compared separately, lumbar z and BMD values of the constitutionally thin group were found to be significantly lower than in the AN group. This difference was not significant for females. CONCLUSIONS: The difference between the male and female results of our study suggested two hypotheses. The significantly lower BMD values in constitutionally thin boys are attributed to their longer duration of low body mass index (BMI). Although the duration of low BMI is also longer for constitutionally thin girls, similar BMD values of AN and constitutionally thin female groups are attributed to the additional negative impact of estrogen deficiency on the bone health of girls with AN.

Comparison between invasive and noninvasive techniques of evaluation of microvascular structural alterations.

BACKGROUND: The evaluation of the morphological characteristics of small resistance arteries in humans is challenging. The gold standard method is generally considered to be the measurement by wire or pressure micromyography of the media-to-lumen ratio of subcutaneous small vessels obtained by local biopsies. However, noninvasive techniques for the evaluation of retinal arterioles were recently proposed; in particular, two approaches, scanning laser Doppler flowmetry (SLDF) and adaptive optics, seem to provide useful information; both of them provide an estimation of the wall-to-lumen ratio (WLR) of retinal arterioles. Moreover, a noninvasive measurement of basal and total capillary density may be obtained by videomicroscopy/capillaroscopy. No direct comparison of these three noninvasive techniques in the same population was previously performed; in particular, adaptive optics was never validated against micromyography. METHODS: In the current study, we enrolled 41 controls and patients: 12 normotensive lean controls, 12 essential hypertensive lean patients, nine normotensive obese patients and eight hypertensive obese patients undergoing elective surgery. All patients underwent a biopsy of subcutaneous fat during surgery. Subcutaneous small resistance artery structure was assessed by wire micromyography and the media-to-lumen ratio was calculated. WLR of retinal arterioles was obtained by SLDF and adaptive optics. Functional (basal) and structural (total) microvascular density was evaluated by capillaroscopy before and after venous congestion. RESULTS AND CONCLUSION: Our data suggest that adaptive optics has a substantial advantage over SLDF in terms of evaluation of microvascular morphology, as WLR measured with adaptive optics is more closely correlated with the M/L of subcutaneous small arteries (r = 0.84, P < 0.001 vs. r = 0.52, P < 0.05, slopes of the relations: P < 0.01 adaptive optics vs. SLDF). In addition, the reproducibility of the evaluation of the WLR with adaptive optics is far better, as compared with SLDF, as intraobserver and interobserver variation coefficients are clearly smaller. This may be important in terms of clinical evaluation of microvascular morphology in a clinical setting, as micromyography has substantial limitations in its clinical application due to the local invasiveness of the procedure.

A requiem for BMI in the clinical setting.

PURPOSE OF REVIEW: Quetelet reported in the nineteenth century that body weight varies across adults with the square of height. Quetelet's index, now known as BMI, is accepted by most health organizations as a first-level measure of body fat and as a screening tool for diagnosing excess adiposity. Modern imaging methods now, however, indicate that BMI has limited predictive value for estimating body fat and lean mass at the individual level. The use of BMI as a measure of body composition in the clinical setting should therefore be challenged. RECENT FINDINGS: Recent studies enrolling cancer and surgical patients reported discrepant outcomes when BMI was used as a body composition surrogate. Sarcopenia, loss of muscle mass and function, which affects the elderly and those with chronic and acute diseases, is not accurately diagnosed with BMI. The distribution of adipose tissue is not characterized by BMI, specific measures of which have greater predictive value for metabolic impairments and clinical outcomes. SUMMARY: BMI, as the traditional tool for assessing malnutrition and obesity, is not appropriate to accurately differentiate between important body weight components and therefore should not be used for making clinically important decisions at the individual patient level.

Factors Associated with Bone Health in Malaysian Middle-Aged and Elderly Women Assessed via Quantitative Ultrasound.

Risk factors for osteoporosis may vary according to different populations. We aimed to investigate the relationship between risk factors of osteoporosis and bone health indices determined via calcaneal quantitative ultrasound (QUS) in a group of Malaysian women aged 50 years or above. A cross-sectional study was performed on 344 Malaysian women recruited from a tertiary medical centre in Kuala Lumpur, Malaysia. They answered a self-administered questionnaire on their social-demographic details, medical history, lifestyle, and physical activity status. Their height was measured using a stadiometer, and their body composition estimated using a bioelectrical impedance device. Their bone health status was determined using a water-based calcaneal QUS device that generated three indices, namely speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index (SI). A T-score was computed from SI values using a reference database from a mainland Chinese population. Women with three or more lifetime pregnancies, who were underweight and not drinking coffee had a significantly lower BUA. Stepwise multiple linear regression showed that SOS was predicted by age alone, BUA and SI by years since menopause, body mass index (BMI), and number of lifetime pregnancies, and T-score by years since menopause and percentage of body fat. As a conclusion, suboptimal bone health in middle-aged and elderly Malaysian women as indicated by QUS is associated with old age, being underweight, having a high body fat percentage, and a high number of lifetime pregnancies. Women having several risk factors should be monitored more closely to protect their bones against accelerated bone loss.

Lean Mass and Fat Mass as Mediators of the Relationship Between Physical Activity and Bone Mineral Density in Postmenopausal Women.

BACKGROUND: The relationship between physical activity (PA) and bone health is well known, but the role of lean mass (LM) and fat mass (FM) in this relationship remains uncertain. Therefore, the aim of this study was to examine the mediating effect of LM and FM on the relationship between PA and bone mineral density (BMD) in postmenopausal women. MATERIALS AND METHODS: This cross-sectional study involved 282 postmenopausal women aged between 50 and 65 year, who were randomly selected from Hongqi community of Harbin City in China. PA was measured using an International PA Questionnaire. Body composition, BMD of the lumbar spine, hip, and total body were measured using dual-energy X-ray absorptiometry. Mediation analysis was performed to investigate the mediating effect of LM and FM on the relationship between PA and BMD. RESULTS: In partial correlation analysis, PA, LM, and FM were positively related to BMD. Positive correlation was found between PA and LM. There were significant differences in BMD between different categories of PA, but the differences disappeared after adjusting for LM. Mediation analysis showed that LM and FM played a mediating role in the relationship between PA and BMD. LM appeared to mediate the effect of BMD in the spine, hip, and total body by 26.91%, 19.55% and 47.98%, respectively; and FM was 22.23%, 27.97%, and 33.02%, respectively. CONCLUSION: LM and FM affected the relationship between PA and BMD as mediator. Postmenopausal women with high LM and FM had more BMD.

Impact of tissue photon attenuation in small animal cardiac PET imaging.

OBJECTIVES: Tissue photon attenuation is one of the essential artifacts requiring correction in clinical cardiac positron emission tomography (PET) imaging. However, due to small body size its impact on diagnostic accuracy in small rodents is considered to be limited or even ignorable. The present cardiac PET study compares lean and obese rats to determine the influence of tissue attenuation on quantitative assessment as well as regional tracer distribution. METHODS: A dedicated small animal PET system equipped with a 57Co rotating source for transmission was used. To assess the impact of tissue attenuation in rats with different body sizes, cardiac 18F-FDG -PET studies for Zucker diabetic fatty rats (obese rats) and Zucker lean rats (lean rats) were performed. The radiotracer activity reduction by attenuation was compared between the two groups. Regional tracer distribution calculated with and without attenuation correction was also assessed. RESULTS: The chest diameter was significantly longer in obese than in lean rats (5.6±0.3cm in obese and 4.5±0.2cm in lean rats, p<0.0001). Whereas the activity reduction by attenuation was significantly greater in obese than in lean rats (44.1±2.5% and 5.1±3.1%, p<0.0001), the regional variation of tissue attenuation among the ventricular walls was minimal in both lean (p=0.73) and obese rats (p=0.65). CONCLUSION: Attenuation correction is indispensable for accurate comparison of cardiac tracer activity between animals with different body size, whereas it can be omitted for evaluation of regional tracer distribution.

Vertebral Volumetric Bone Density and Strength Are Impaired in Women With Low-Weight and Atypical Anorexia Nervosa.

Context: Areal bone mineral density (BMD) is lower, particularly at the spine, in low-weight women with anorexia nervosa (AN). However, little is known about vertebral integral volumetric BMD (Int.vBMD) or vertebral strength across the AN weight spectrum, including "atypical" AN [body mass index (BMI) ≥18.5 kg/m2]. Objective: To investigate Int.vBMD and vertebral strength, and their determinants, across the AN weight spectrum. Design: Cross-sectional observational study. Setting: Clinical research center. Participants: 153 women (age 18 to 45): 64 with low-weight AN (BMI <18.5 kg/m2; 58% amenorrheic), 44 with atypical AN (18.5≤BMI<23 kg/m2; 30% amenorrheic), 45 eumenorrheic controls (19.2≤BMI<25 kg/m2). Measures: Int.vBMD and cross-sectional area (CSA) by quantitative computed tomography of L4; estimated vertebral strength (derived from Int.vBMD and CSA). Results: Int.vBMD and estimated vertebral strength were lowest in low-weight AN, intermediate in atypical AN, and highest in controls. CSA did not differ between groups; thus, vertebral strength (calculated using Int.vBMD and CSA) was driven by Int.vBMD. In AN, Int.vBMD and vertebral strength were associated positively with current BMI and nadir lifetime BMI (independent of current BMI). Int.vBMD and vertebral strength were lower in AN with current amenorrhea and longer lifetime amenorrhea duration. Among amenorrheic AN, Int.vBMD and vertebral strength were associated positively with testosterone. Conclusions: Int.vBMD and estimated vertebral strength (driven by Int.vBMD) are impaired across the AN weight spectrum and are associated with low BMI and endocrine dysfunction, both current and previous. Women with atypical AN experience diminished vertebral strength, partially due to prior low-weight and/or amenorrhea. Lack of current low-weight or amenorrhea in atypical AN does not preclude compromise of vertebral strength.