BackgroundExcess muscle fat is observed in obesity and associated with greater burden of cardiovascular risk factors and higher risk of mortality. Liraglutide reduces total body weight and visceral fat but its effect on muscle fat and adverse muscle composition is unknown.MethodsThis is a pre-specified secondary analysis of a randomized, double-blind, placebo-controlled trial that examined the effects of liraglutide plus a lifestyle intervention on visceral adipose tissue and ectopic fat among adults without diabetes with body mass index >= 30 kg/m2 or >= 27 kg/m2 and metabolic syndrome. Participants were randomly assigned to a once-daily subcutaneous injection of liraglutide (target dose 3.0 mg) or matching placebo for 40 weeks. Body fat distribution and muscle composition was assessed by magnetic resonance imaging at baseline and 40-week follow-up. Muscle composition was described by the combination of thigh muscle fat and muscle volume. Treatment difference (95% confidence intervals [CI]) was calculated by least-square means adjusted for baseline thigh muscle fat. The association between changes in thigh muscle fat and changes in body weight were assessed using Spearman correlation coefficients. The effect of liraglutide versus placebo on adverse muscle composition, denoted by high thigh muscle fat and low thigh muscle volume, was explored.ResultsAmong the 128 participants with follow-up imaging (92.2% women, 36.7% Black), median muscle fat at baseline was 7.8%. The mean percent change in thigh muscle fat over median follow-up of 36 weeks was -2.87% among participants randomized to liraglutide (n = 73) and 0.05% in the placebo group (absolute change: -0.23% vs. 0.01%). The estimated treatment difference adjusted for baseline thigh muscle fat was -0.24% (95% CI, -0.41 to -0.06, P-value 0.009). Longitudinal change in thigh muscle fat was significantly associated with change in body weight in the placebo group but not the liraglutide group. The proportion of participants with adverse muscle composition decreased from 11.0% to 8.2% over follow-up with liraglutide, but there was no change with placebo.ConclusionsIn a cohort of predominantly women with overweight or obesity in the absence of diabetes, once-daily subcutaneous liraglutide was associated with a reduction in thigh muscle fat and adverse muscle composition compared with placebo. The contribution of muscle fat improvement to the cardiometabolic benefits of liraglutide requires further study.

AimsTo describe the overall fat distribution patterns independent of body mass index (BMI) in participants with type 2 diabetes (T2D) in the SURPASS-3 MRI substudy by comparison with sex- and BMI-matched virtual control groups (VCGs) derived from the UK Biobank imaging study at baseline and Week 52. MethodsFor each study participant at baseline and Week 52 (N = 296), a VCG of >= 150 participants with the same sex and similar BMI was identified from the UK Biobank imaging study (N = 40 172). Average visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT) and liver fat (LF) levels and the observed standard deviations (SDs; standardized normal z-scores: z-VAT, z-aSAT and z-LF) were calculated based on the matched VCGs. Differences in z-scores between baseline and Week 52 were calculated to describe potential shifts in fat distribution pattern independent of weight change. ResultsBaseline fat distribution patterns were similar across pooled tirzepatide (5, 10 and 15 mg) and insulin degludec (IDeg) arms. Compared with matched VCGs, SURPASS-3 participants had higher baseline VAT (mean [SD] z-VAT +0.42 [1.23]; p < 0.001) and LF (z-LF +1.24 [0.92]; p < 0.001) but similar aSAT (z-aSAT -0.13 [1.11]; p = 0.083). Tirzepatide-treated participants had significant decreases in z-VAT (-0.18 [0.58]; p < 0.001) and z-LF (-0.54 [0.84]; p < 0.001) but increased z-aSAT (+0.11 [0.50]; p = 0.012). Participants treated with IDeg had a significant change in z-LF only (-0.46 [0.90]; p = 0.001), while no significant changes were observed for z-VAT (+0.13 [0.52]; p = 0.096) and z-aSAT (+0.09 [0.61]; p = 0.303). ConclusionIn this exploratory analysis, treatment with tirzepatide in people with T2D resulted in a significant reduction of z-VAT and z-LF, while z-aSAT was increased from an initially negative value, suggesting a possible treatment-related shift towards a more balanced fat distribution pattern with prominent VAT and LF loss.

Background & Aims: Adverse muscle composition (MC) (i.e., low muscle volume and high muscle fat) has previously been linked to poor functional performance and comorbidities in non-alcoholic fatty liver disease (NAFLD). In this study we aimed to investigate associations of all-cause mortality with liver fat, NAFLD, and MC in the UK Biobank imaging study.Methods: Magnetic resonance images of 40,174 participants were analyzed for liver proton density fat fraction (PDFF), thigh fat-free muscle volume (FFMV) z-score, and muscle fat infiltration (MFI) using the AMRA (R) Researcher. Participants with NAFLD were sex-, age-, and BMI-matched to participants without NAFLD with low alcohol consumption. Adverse MC was identified using previously published cut-offs. All-cause mortality was investigated using Cox regression. Models within NAFLD were crude and subsequently adjusted for sex, age, BMI (M1), hand grip strength, physical activity, smoking, alcohol (M2), and previous cancer, coronary heart disease, type 2 diabetes (M3).Results: A total of 5,069 participants had NAFLD. During a mean (+/- SD) follow-up of 3.9 (+/- 1.4) years, 150 out of the 10,138 participants (53% men, age 64.4 [+/- 7.6] years, BMI 29.7 [+/- 4.4] kg/m2) died. In the matched dataset, neither NAFLD nor liver PDFF were associated with all-cause mortality, while all MC variables achieved significance. Within NAFLD, adverse MC, MFI and FFMV z-score were significantly associated with all-cause mortality and remained so in M1 and M2 (crude hazard ratios [HRs] 2.84, 95% CI 1.70-4.75, p <0.001; 1.15, 95% CI 1.07-1.24, p <0.001; 0.70, 95% CI 0.55-0.88, p <0.001). In M3, the rela-tionship was attenuated for adverse MC and FFMV z-score (adjusted HRs 1.72, 95% CI 1.00-2.98, p = 0.051; 0.77, 95% CI 0.58-1.02, p = 0.069) but remained significant for MFI (adjusted HR 1.13, 95% CI 1.01-1.26, p = 0.026).Conclusions: Neither NAFLD nor liver PDFF was predictive of all-cause mortality. Adverse MC was a strong predictor of all -cause mortality in individuals with NAFLD.Impact and implications: Individuals with fatty liver disease and poor muscle health more often suffer from poor functional performance and comorbidities. This study shows that they are also at a higher risk of dying. The study results indicate that measuring muscle health (the patients muscle volume and how much fat they have in their muscles) could help in the early detection of high-risk patients and enable targeted preventative care.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background:Optimal fluid status is an important issue in hemodialysis. Clinical evaluation of volume status and different diagnostic tools are used to determine hydration status in these patients. However, there is still no accurate method for this assessment. Purpose:To propose and evaluate relative lean water signal (LWSrel) as a water-fat MRI-based tissue hydration measurement. Study Type:Prospective. Population:A total of 16 healthy subjects (56 & PLUSMN; 6 years, 0 male) and 11 dialysis patients (60.3 +/- 12.3 years, 9 male; dialysis time per week 15 +/- 3.5 hours, dialysis duration 31.4 +/- 27.9 months). Field Strength/Sequence:A 3 T; 3D spoiled gradient echo. Assessment:LWSrel, a measurement of the water concentration of tissue, was estimated from fat-referenced MR images. Segmentations of total adipose tissue as well as thigh and calf muscles were used to measure LWSrel and tissue volumes. LWSrel was compared between healthy subjects and dialysis patients, the latter before and after dialysis. Bioimpedance-based body composition monitor over hydration (BCM OH) was also measured. Statistical Tests:T-tests were used to compare differences between the healthy subjects and dialysis patients, as well as changes between before and after dialysis. Pearson correlation was calculated between MRI and non-MRI biomarkers. A P value < 0.05 was considered statistically significant. Results:The LWSrel in adipose tissue was significantly higher in the dialysis cohort compared with the healthy cohort (246.8% +/- 60.0% vs. 100.0% +/- 10.8%) and decreased significantly after dialysis (246.8 +/- 60.0% vs. 233.8 +/- 63.4%). Thigh and calf muscle volumes also significantly decreased by 3.78% +/- 1.73% and 2.02% +/- 2.50% after dialysis. There was a significant correlation between changes in adipose tissue LWSrel and ultrafiltration volume (r = 87), as well as with BCM OH (r = 0.66). Data Conclusion:MRI-based LWSrel and tissue volume measurements are sensitive to tissue hydration changes occurring during dialysis.

Introduction: Cardiovascular disease (CVD) risk amongst those with type 2 diabetes (T2D) is heterogenous. The role of imaging-based cardiometabolic biomarkers (e.g., coronary artery calcium [CAC] score, and hepatic triglyceride content [HTC]) in CVD risk stratification in T2D is unclear. To better understand this, we sought to evaluate the individual and joint associations between CAC and hepatic steatosis (HS) with clinical atherosclerotic CVD (ASCVD) in Dallas Heart Study (DHS) participants with and without T2D. Methods: We examined participants in the DHS, a multi-ethnic cohort study, without self-reported ASCVD. CAC scoring was performed via computed tomography with the mean of two consecutive scores used. HTC was measured using magnetic resonance spectroscopy, and HS was defined as HTC >5.5% The primary outcome was incident ASCVD, defined as coronary heart disease (CHD; myocardial infarction, percutaneous coronary intervention, or coronary artery bypass graft surgery), ischemic stroke, transient ischemic attack, or CVD death. Cox regression analyses, and interaction testing was performed to evaluate the individual and joint associations between CAC and HS with ASCVD. The association between HS and coronary heart disease was validated in the UK Biobank (UKB).Results: A total of 1252 DHS participants were included with mean age 44.8 & PLUSMN; 9.3 years, mean body mass index 28.7 & PLUSMN; 5.9 kg/m2, 55% female, and 59% black with an overall prevalence of T2D of 9.7%. CAC scores were significantly higher (p < 0.01) and HS was significantly more prevalent in those with T2D (p < 0.01). Over a median of 12.3 years, 8.3% of participants experienced ASCVD events. The ASCVD event rate was significantly higher in participants with T2D (20.5% vs 7.0%, p < 0.01). Continuous CAC was associated with ASCVD events in the overall cohort regardless of T2D status with a significant interaction present between CAC and T2D status on ASCVD, Pinteraction = 0.02. HTC was not associated with ASCVD risk in participants without T2D but was inversely associated with risk in participants with T2D (HR 0.91, 95% CI 0.83-0.99 per 1% increase in HTC, p = 0.02), Pinteraction = 0.02. Amongst 37,266 UKB participants, 4.5% had T2D. CHD events occurred in 2.2% of participants, with 10.2% of events occurring amongst those with T2D. An inverse relationship between HTC and CHD was also found amongst those with T2D in UKB with a significant interaction between T2D status and HTC on CHD (HR per 1% increase in HTC 0.95, 95% CI 0.91-0.99, p = 0.01, Pinteraction = 0.02).Conclusions: In the DHS, we found that CAC was associated with ASCVD risk independent of T2D status. We did not observe an association between HTC and ASCVD in participants without T2D, but there was an inverse association between HTC and ASCVD in those with T2D that was replicated in the UKB cohort. Further investigation is warranted to understand the possible protective association of HS in participants with T2D.& COPY; 2023 Elsevier Inc. All rights reserved.

BackgroundSymptomatic spinal stenosis is a prevalent complication in adults with achondroplasia. Increased muscle fat infiltration (MFI) and reduced thigh muscle volumes have also been reported, but the pathophysiology is poorly understood. We explored whether the increased MFI and reduced thigh muscle volumes were associated with the presence of symptomatic spinal stenosis and physical functioning.MethodsMFI and thigh muscle volumes were assessed by MRI in 40 adults with achondroplasia, and compared to 80 average-statured controls, matched for BMI, gender, and age. In achondroplasia participants, the six-minute walk-test (6MWT), the 30-s sit-to-stand test (30sSTS), and a questionnaire (the IPAQ) assessed physical functioning.ResultsSymptomatic spinal stenosis was present in 25 of the participants (the stenosis group), while 15 did not have stenosis (the non-stenosis group). In the stenosis group, 84% (21/25) had undergone at least one spinal decompression surgery. The stenosis group had significantly higher MFI than the non-stenosis group, with an age-, gender and BMI-adjusted difference in total MFI of 3.3 percentage points (pp) (95% confidence interval [CI] 0.04 to 6.3 pp; p = 0.03). Compared to matched controls, the mean age-adjusted difference was 3.3 pp (95% CI 1.7 to 4.9 pp; p < 0.01). The non-stenosis group had MFI similar to controls (age-adjusted difference - 0.9 pp, 95% CI - 3.4 to 1.8 pp; p = 0.51). MFI was strongly correlated with the 6MWT (r = - 0.81, - 0.83, and - 0.86; all p-values < 0.01), and moderately correlated with the 30sSTS (r = - 0.56, - 0.57, and - 0.59; all p-values < 0.01). There were no significant differences in muscle volumes or physical activity level between the stenosis group and the non-stenosis group.ConclusionIncreased MFI in the thigh muscles was associated with the presence of symptomatic spinal stenosis, reduced functional walking capacity, and reduced lower limb muscle strength. The causality between spinal stenosis, accumulation of thigh MFI, and surgical outcomes need further study. We have demonstrated that MRI might serve as an objective muscle biomarker in future achondroplasia studies, in addition to functional outcome measures. The method could potentially aid in optimizing the timing of spinal decompression surgery and in planning of post-surgery rehabilitation.

Background: The underlying pathophysiological mechanisms of chronic Whiplash Associated Disorders (WAD) are not fully understood. More knowledge of morphology is needed to better understand the disorder, improve diagnostics and treatments. The aim was to investigate dorsal neck muscle volume (MV) and muscle fat infiltration (MFI) in relation to self-reported neck disability among 30 participants with chronic WAD grade II-III compared to 30 matched healthy controls.

Methods: MV and MFI at spinal segments C4 through C7 in both sexes with mild- to moderate chronic WAD (n = 20), severe chronic WAD (n = 10), and age- and sex matched healthy controls (n = 30) was compared. Muscles: trapezius, splenius, semispinalis capitis and semispinalis cervicis were segmented by a blinded assessor and analyzed.

Results: Higher MFI was found in right trapezius (p = 0.007, Cohen’s d = 0.9) among participants with severe chronic WAD compared to healthy controls. No other significant difference was found for MFI (p = 0.22–0.95) or MV (p = 0.20–0.76).

Conclusions: There are quantifiable changes in muscle composition of right trapezius on the side of dominant pain and/or symptoms, among participants with severe chronic WAD. No other statistically significant differences were shown for MFI or MV. These findings add knowledge of the association between MFI, muscle size and self-reported neck disability in chronic WAD.

Aims/hypothesis South Asians have a two- to fivefold higher risk of developing type 2 diabetes than those of white European descent. Greater central adiposity and storage of fat in deeper or ectopic depots are potential contributing mechanisms. We collated existing and new data on the amount of subcutaneous (SAT), visceral (VAT) and liver fat in adults of South Asian and white European descent to provide a robust assessment of potential ethnic differences in these factors. Methods We performed a systematic review of the Embase and PubMed databases from inception to August 2021. Unpublished imaging data were also included. The weighted standardised mean difference (SMD) for each adiposity measure was estimated using random-effects models. The quality of the studies was assessed using the ROBINS-E tool for risk of bias and overall certainty of the evidence was assessed using the GRADE approach. The study was pre-registered with the OSF Registries (https://osf. io/w5bf9). Results We summarised imaging data on SAT, VAT and liver fat from eight published and three previously unpublished datasets, including a total of 1156 South Asian and 2891 white European men, and 697 South Asian and 2271 white European women. Despite South Asian men having a mean BMI approximately 0.5-0.7 kg/m(2) lower than white European men (depending on the comparison), nine studies showed 0.34 SMD (95% CI 0.12, 0.55; I-2 =83%) more SAT and seven studies showed 0.56 SMD (95% CI 0.14, 0.98; I-2 =93%) more liver fat, but nine studies had similar VAT (-0.03 SMD; 95% CI -0.24, 0.19;1 2 =85%) compared with their white European counterparts. South Asian women had an approximately 0.9 kg/m(2) lower BMI but 0.31 SMD (95% CI 0.14, 0.48; I-2=53%) more liver fat than their white European counterparts in five studies. Subcutaneous fat levels (0.03 SMD; 95% CI -0.17, 0.23; I-2 =72%) and VAT levels (0.04 SMD; 95% CI -0.16, 0.24; I-2 =71%) did not differ significantly between ethnic groups in eight studies of women. Conclusions/interpretation South Asian men and women appear to store more ectopic fat in the liver compared with their white European counterparts with similar BMI levels. Given the emerging understanding of the importance of liver fat in diabetes pathogenesis, these findings help explain the greater diabetes risks in South Asians.

There is an intimate body-brain connection in ageing, and obesity is a key risk factor for poor cardiometabolic health and neurodegenerative conditions. Although research has demonstrated deleterious effects of obesity on brain structure and function, the majority of studies have used conventional measures such as waist-to-hip ratio, waist circumference, and body mass index. While sensitive to gross features of body composition, such global anthropometric features fail to describe regional differences in body fat distribution and composition. The sample consisted of baseline brain magnetic resonance imaging (MRI) acquired from 790 healthy participants aged 18-94 years (mean +/- standard deviation (SD) at baseline: 46.8 +/- 16.3), and follow-up brain MRI collected from 272 of those individuals (two time-points with 19.7 months interval, on average (min = 9.8, max = 35.6). Of the 790 included participants, cross-sectional body MRI data was available from a subgroup of 286 participants, with age range 19-86 (mean = 57.6, SD = 15.6). Adopting a mixed cross-sectional and longitudinal design, we investigated cross-sectional body magnetic resonance imaging measures of adipose tissue distribution in relation to longitudinal brain structure using MRI-based morphometry (T1) and diffusion tensor imaging (DTI). We estimated tissue-specific brain age at two time points and performed Bayesian multilevel modelling to investigate the associations between adipose measures at follow-up and brain age gap (BAG) - the difference between actual age and the prediction of the brains biological age - at baseline and follow-up. We also tested for interactions between BAG and both time and age on each adipose measure. The results showed credible associations between T1-based BAG and liver fat, muscle fat infiltration (MFI), and weight-to-muscle ratio (WMR), indicating older-appearing brains in people with higher measures of adipose tissue. Longitudinal evidence supported interaction effects between time and MFI and WMR on T1-based BAG, indicating accelerated ageing over the course of the study period in people with higher measures of adipose tissue. The results show that specific measures of fat distribution are associated with brain ageing and that different compartments of adipose tissue may be differentially linked with increased brain ageing, with potential to identify key processes involved in age-related transdiagnostic disease processes.

Objectives: We examined the longitudinal and cross- sectional relationship between automated MRI-analysis and single-slice axial CT imaging for determining muscle size and muscle fat infiltration (MFI) of the anterior thigh.

Methods: Twenty-two patients completing sex-hormone treatment expected to result in muscle hypertrophy (n = 12) and atrophy (n = 10) underwent MRI scans using 2-point Dixon fat/water-separated sequences and CT scans using a system operating at 120 kV and a fixed flux of 100 mA. At baseline and 12 months after, auto- mated volumetric MRI analysis of the anterior thigh was performed bilaterally, and fat-free muscle volume and MFI were computed. In addition, cross-sectional area (CSA) and radiological attenuation (RA) (as a marker of fat infiltration) were calculated from single slice axial CT-images using threshold-assisted planimetry. Linear regression models were used to convert units.

Results: There was a strong correlation between MRI- derived fat-free muscle volume and CT-derived CSA (R = 0.91), and between MRI-derived MFI and CT-derived RA (R = −0.81). The 95% limits of agreement were ±0.32 L for muscle volume and ±1.3% units for %MFI. The longi- tudinal change in muscle size and MFI was comparable across imaging modalities.

Conclusions: Both automated MRI and single-slice CT-imaging can be used to reliably quantify anterior thigh muscle size and MFI.

Advances in knowledge: This is the first study examining the intermodal agreement between automated MRI anal- ysis and CT-image assessment of muscle size and MFI in the anterior thigh muscles. Our results support that both CT- and MRI-derived measures of muscle size and MFI can be used in clinical settings.