The impact of anorexia nervosa and BMI polygenic risk on childhood growth: A 20-year longitudinal population-based study.

Growth deviating from the norm during childhood has been associated with anorexia nervosa (AN) and obesity later in life. In this study, we examined whether polygenic scores (PGSs) for AN and BMI are associated with growth trajectories spanning the first two decades of life. AN PGSs and BMI PGSs were calculated for participants of the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 8,654). Using generalized (mixed) linear models, we associated PGSs with trajectories of weight, height, body mass index (BMI), fat mass index (FMI), lean mass index (LMI), and bone mineral density (BMD). Female participants with AN PGSs one standard deviation (SD) higher had, on average, 0.004% slower growth in BMI between the ages 6.5 and 24 years and a 0.4% slower gain in BMD between the ages 10 and 24 years. Higher BMI PGSs were associated with faster growth for BMI, FMI, LMI, BMD, and weight trajectories in both sexes throughout childhood. Female participants with both a high AN PGS and a low BMI PGS showed slower growth compared to those with both a low AN PGS and a low BMI PGS. We conclude that AN PGSs and BMI PGSs have detectable sex-specific effects on growth trajectories. Female participants with a high AN PGS and low BMI PGS likely constitute a high-risk group for AN, as their growth was slower compared to their peers with high PGSs on both traits. Further research is needed to better understand how the AN PGS and the BMI PGS co-influence growth during childhood and whether a high BMI PGS can mitigate the effects of a high AN PGS.

Body composition parameters in systemic sclerosis-a systematic review and meta-analysis.

BACKGROUND: The aim of this systematic review and meta-analysis was to summarize current evidence regarding body composition (BC) in SSc in order to gain new insights and improve clinical care in the context of the nutritional status of SSc patients. METHODS: The databases Web of Science, PubMed, Scopus and Cochrane Library were searched on 4 January 2023. Studies were included if they provided data regarding BC obtained by dual-energy X-ray absorptiometry (DXA) or bioelectrical impedance analysis (BIA) in patients with SSc and healthy controls (HC). The study design criteria for inclusion were cohort and observational studies. The risk of bias assessment was performed using the Newcastle-Ottawa scale. For meta-analysis, mean difference with a 95% confidence interval was obtained and all results were depicted as forest plots. RESULTS: The number of retrieved publications was 593, of which nine were included in a random-effects meta-analysis totalling 489 SSc patients and 404 HC. Overall, significantly lower body mass index, lean mass (LM), fat mass (FM) and phase angle values were found in SSc patients when compared with HC. Furthermore, FM and LM were significantly lower in SSc patients when the DXA method was applied, whereas the same parameters were comparable between two groups of participants when BIA was applied. CONCLUSION: Altered BC is characteristic of SSc patients indicating the need for regular nutritional status assessment in order to improve the quality of life and clinical care of patients with SSc.

Among people on osteoporosis medication, loss of appendicular or total body lean mass is an independent risk factor for hip and major osteoporotic fractures.

People with prior lean mass loss had a ~ 10% higher risk of MOF and ~ 22-26% higher risk of hip fracture, and the results were similar in people on anti-osteoporosis medications. Loss of lean mass is associated with increased fracture risk. Patients should be encouraged to pursue strategies to prevent loss of lean mass. BACKGROUND: Sarcopenia increases fracture risk. If the risk persists after starting osteoporosis medication, patients may need to be encouraged to pursue strategies to prevent loss of lean mass. OBJECTIVE: To estimate the effects of loss in appendicular lean mass (ALM) or total body lean mass (TBLM) on subsequent fracture risk and effect modification with anti-osteoporosis medication use. METHODS: We conducted a registry-based cohort study linked to population-based data. We identified individuals ≥ 40 years of age with two DXA assessments ≥ 1 year apart and minimum 0.5 years of observation. ALM and TBLM were estimated from weight, sex, and percent fat from DXA (R2 = 0.91 and 0.84 vs total body DXA, respectively). We report hazard ratios (HR) from Cox regression models estimating time to first incident major osteoporotic fracture (MOF) and hip fracture, adjusted for fracture risk; osteoporosis medication was included as an interaction term and used to stratify analyses. RESULTS: We included 21,249 individuals (mean 67 [SD 10] years, 95% female, 37% on osteoporosis medication). The mean follow-up was 7 years (SD 4). A total of 1868 and 548 people had incident MOF and hip fracture, respectively. People with prior ALM loss (HR per SD 1.09, 95% CI 1.04-1.15) or TBLM loss (HR per SD 1.09, 95% CI 1.42-1.14) had a higher risk of MOF. Hip fracture risk was greater in people with prior ALM loss (HR per SD 1.22, 95% CI 1.12-1.33) and TBLM loss (HR per SD 1.26, 95% CI 1.16-1.38). There were no interactions with anti-osteoporosis medication use (all p > 0.3). When restricted to people on anti-osteoporosis medication, each SD in ALM or TBLM loss was associated with 8-9% increased MOF risk and 18-23% increased hip fracture risk. CONCLUSIONS: Loss of lean mass is associated with increased fracture risk among individuals on anti-osteoporosis medication. Patients should be encouraged to pursue strategies to prevent sarcopenia.

Appendicular lean mass index and motor function in ambulatory patients with Duchenne muscular dystrophy.

INTRODUCTION/AIMS: Appendicular lean mass index (ALMI) has been linked to motor function in patients with Duchenne muscular dystrophy (DMD). However, quantification of the relationship between ALMI and disease-specific clinical outcome assessment trajectories is needed. The purpose of this study was to determine associations between dual-energy x-ray absorptiometry (DXA) derived estimates of ALMI and motor function in ambulatory patients with DMD. METHODS: A retrospective analysis of longitudinal clinical visit data from 137 glucocorticoid-treated patients with DMD collected via structured motor assessment protocol evaluated associations between ALMI and motor function indexed by the North Star Ambulatory Assessment (NSAA) and 10 Meter Walk/run Test (10MWT). Body composition was assessed using DXA. ALMI was calculated by dividing arm and leg lean mass by height in m2; fat mass index (FMI) was calculated by dividing whole body fat mass by height in m2. Linear mixed-effects models were used to estimate associations between ALMI and motor function, controlling for age and FMI. RESULTS: The full prediction model (age, age,2 ALMI, and FMI) explained 57% of the variance in NSAA scores and 63% of the variance in 10MWT speed. A 1 kg/m2 higher ALMI value predicted a 5.4-point higher NSAA score (p < .001) and 0.45 m/s faster 10MWT speed (p < .001). A 1 kg/m2 higher FMI value predicted a 1.5-point lower NSAA score (p < .001) and 0.14 meters/second slower 10MWT speed (p < .001). DISCUSSION: DXA-derived estimates of ALMI and FMI are associated with motor function in DMD and may explain variation in DMD disease progression.

Thyroid Hormone Clearance in the Paraventricular Nucleus of Male Mice Regulates Lean Mass and Physical Activity.

INTRODUCTION: The actions of thyroid hormones (THs) in the central nervous system are relevant to food intake and energy expenditure. TH receptors exhibit high expression in brain areas modulating energy balance, including the arcuate, paraventricular (PVN), supraoptic, and ventromedial (VMH) hypothalamic nuclei. METHODS: To examine the role of THs in the regulation of energy balance via action in specific hypothalamic nuclei of the adult mouse, we performed experiments of conditional inactivation of DIO3, the enzyme responsible for the clearance of THs, in the lateral hypothalamus (LH), and VMH and PVN hypothalamic nuclei. We accomplished DIO3 genetic inactivation via stereotaxic injection of the AAV-cre vector into adult mice homozygous for a "floxed" Dio3 allele. RESULTS: Dio3 inactivation in the LH and VMH of males or females did not result in significant changes in body weight 8 weeks after injection. However, inactivation of Dio3 in the PVN resulted in increased body weight (both fat mass and lean mass) and locomotor activity, and decreased hypothalamic Mc4r expression in male, but not female mice. However, PNV-specific Dio3 KO did not cause hyperphagia. CONCLUSION: These results suggest local TH action influences MC4R signaling and possibly other PVN-associated circuitries, with consequences for body composition and energy balance endpoints, but not for orexigenic pathways. They also support a regulatory role for PVN Dio3 in the central regulation of energy homeostasis in adult life.

Updated reference values for BMD and lean mass measured by DXA in Thai children.

INTRODUCTION: This study established normative references for total body less head (TBLH) BMD, lumbar spine (L1-L4) BMD, and both total and appendicular lean mass (LM) in Thai children and adolescents (aged 5-18 years) using DXA. This work expands upon 2014 normative data for Thai children, which included L2-L4 BMD, total body BMD (head included), and total LM. MATERIALS AND METHODS: We reanalyzed total body and lumbar spine DXA scans (Lunar Prodigy Pro, GE Healthcare; enCORE version 7.53) from 174 boys and 193 girls, using upgraded software (enCORE version 17SP2) for TBLH BMD, L1-L4 BMD, and LM analysis. The "enhanced" mode was applied for TBLH BMD and LM. Adjustments for total and appendicular LM were made relative to squared height (m2) to account for body size variability. RESULTS: Normative data stratified by sex and Tanner stage were generated for TBLH BMD, L1-L4 BMD, and LM indices. Weight and Tanner stage significantly determined BMD and LM. Adolescent girls exhibited higher LSBMD values due to earlier pubertal onset. Boys showed higher LM indices with more rapid gains during growth spurts. CONCLUSION: This study provides updated normative reference values for BMD (TBLH and L1-L4) and LM (total and appendicular) in Thai children and adolescents, measured via DXA. These references will enhance the assessment of low bone mass and LM deficits in Thai pediatric populations, particularly in those with chronic illnesses.

High starch intake favours body weight control in neutered and spayed cats living in homes fed ad libitum.

Different starch-to-protein ratios were compared among neutered and spayed domiciled cats. Male and female obese and non-obese cats were fed kibble diets ad libitum for 4 months high in starch (HS (38 % crude protein (CP)): starch 32 %, protein 38 %; DM basis) or high in protein (HP (55 % CP): starch 19 %, protein 55 %) but similar in energy and fat in a crossover design. Physical activity was evaluated using an accelerometer, and body composition (BC), energy expenditure (EE) and water turnover (WT) using the doubly labelled water method. Results were compared in a 2 diet × 2 sex × 2 body condition factorial arrangement. Cats fed the HS (38 % CP) diet maintained a constant body weight, but lean mass (LM) tended to be reduced in female obese but to be increased in male non-obese (P < 0·08) and increased in female non-obese cats (P = 0·01). The HP (55 % CP) diet induced an increase in cat body weight and LM (P < 0·05) without altering BC proportion. EE tended to be higher in males (351 (se 8) kJ/kg0·67/d) than females (330 (se 8) kJ/kg0·67/d; P = 0·06), was unaffected by diet or BC, decreased as age increased (R 2 0·44; P < 0·01) and increased as physical activity increased (R 2 0·58; P < 0·01). WT was higher for the HP (55 % CP) diet (P < 0·01) and increased with EE (R 2 0·65; P < 0·01). The HS (38 % CP) diet favoured body weight control during 4 months of ad libitum feeding. Caution is necessary to balance protein in diets of female obese cats over 5 years, as they may have low energy and food intake, with LM loss.

A sex-specific association of leukocyte telomere length with thigh muscle mass.

OBJECTIVES: Telomeres are DNA-protein complexes at the ends of linear chromosomes that protect against DNA degradation. Telomeres shorten during normal cell divisions and therefore, telomere length is an indicator of mitotic-cell age. In humans, telomere shortening is a potential biomarker for disease risk, progression and premature death. Physical activity has been associated with longer leukocyte telomere length (LTL) in some studies. In the current study the relationship between LTL, thigh muscle mass and adipose tissue distribution was explored. METHODS: We performed anthropometric measurements and magnetic resonance imaging (MRI) measurements of the thigh in 149 healthy subjects (77 male, 72 female). LTL was measured using qPCR. Additionally, the subjects answered a questionnaire concerning their training behaviour. RESULTS: In male subjects, LTL was significantly associated with thigh muscle mass, independent of age and body mass index (p=0.006). In addition, a slight association of LTL with weekly endurance units in the male group was found. These relations could not be observed in females. CONCLUSIONS: In conclusion, we observed a sex-specific association of LTL and thigh muscle mass in healthy males. The reason of this sex-specific association is currently unclear, but could be related to different training effects and/or hormonal pathways in men and women.

Association between predicted fat mass, predicted lean mass, predicted percent fat and type 2 diabetes mellitus in Japanese adults: a retrospective study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is known to have obesity as a risk factor. Body mass index cannot distinguish between lean mass and fat mass. We aimed to examine the association between predicted fat mass, predicted lean mass, predicted percent fat and risk of T2DM in Japanese adults. We also explored whether these three new parameters could predict T2DM better than other obesity markers. METHODS: This present study is a secondary data analysis. The study enrolled 20,944 Japanese individuals who participated in the NAGALA medical assessment program between 2004 and 2015. 15,453 participants who are eligible and have complete information were included to our analysis. Through the use of Kaplan-Meier curve, restricted cubic spline and univariate and multivariate Cox regression analysis, the relationship between predicted fat mass, predicted lean mass, predicted percent fat and T2DM risk was examined. The area under the curve method was used to assess the differences between these markers of obesity. RESULTS: A total of 373 cases of T2DM occurred over a median time of 5.4 years. In the male group, we found a U-shaped connection between predicted fat mass, predicted lean mass, and T2DM onset (p value, non-linearity < 0.05). A linear relationship was found between predicted percent fat and T2DM onset. The linear relationship was also found in the female group for predicted fat mass, and predicted percent fat. And for women, predicted lean mass was not an independent predictor. The area under the curve (AUC) for predicted fat mass, predicted lean mass, predicted percent fat in men was 0.673 (95%CI: 0.639 ~ 0.707), 0.598 (95%CI: 0.561 ~ 0.635), 0.715 (95%CI: 0.684 ~ 0.745), respectively. In males, WHtR was the strongest predictor (AUC 0.7151, 95%CI: 0.684 ~ 0.746), followed by predicted percent fat (AUC 0.7150, 95%CI: 0.684 ~ 0.745). In the females, WHtR was also the strongest predictor (AUC 0.758, 95%CI: 0.703 ~ 0.813), followed by body mass index (AUC 0.757, 95%CI: 0.704 ~ 0.811) and predicted percent fat (AUC 0.742, 95%CI: 0.687 ~ 0.798). CONCLUSION: Predicted fat mass, predicted lean mass, predicted percent fat were strongly connected with an increased risk for developing T2DM in Japanese, particularly in males. WHtR and predicted percent fat had a slightly better discrimination than other common obesity indicators in males. In the females, predicted fat mass and predicted percent fat were associated with T2DM risk, WHtR and body mass index had the slightly higher predictive power.

Risk and determinants of sarcopenia in people with diabetes: a case-control study from Qatar Biobank cohort.

BACKGROUND: Diabetes is associated with impairments in muscle mass and quality increasing the risk of sarcopenia. Thus, this study aimed to investigate the odds of sarcopenia and its associated risk factors among Qatari adults (> 18 years), while exploring the modulating effects of health and lifestyle factors. METHODS: Using a case-control design, data from 767 participants (481 cases with diabetes and 286 controls without diabetes) was collected from Qatar Biobank (QBB). Sociodemographic, lifestyle factors including dietary intake, anthropometric and biochemical measures were analyzed. Handgrip strength, Dual X-ray absorptiometry (DXA), and Bio-impedance were used to assess muscle strength, muscle mass and muscle quality, respectively. The risk of sarcopenia was estimated using the European consensus on definition and diagnosis of sarcopenia. RESULTS: Cases with diabetes were older (55 vs. 36 years; P < 0.001), had higher BMI (31.6 vs. 28.3 kg/m2; P < 0.001), lower cardiorespiratory fitness (50.0% "Moderate" fitness for cases, 62.9% "High" fitness for controls), and consumed less total (59.0 vs. 64.0; P = 0.004) and animal protein (39.0 vs. 42.0; P = 0.001), compared to controls based on a computed score. Participants with diabetes also had lower appendicular lean mass/BMI, handgrip strength, and higher probability of sarcopenia/probable sarcopenia (P < 0.005). Adjusted multiple logistic regression revealed that elevated cardiorespiratory fitness (ß = 0.299, 95%CI:0.12-0.74) and blood triglycerides (ß = 1.475, 95% CI: 1.024-2.124), as well as being a female (ß = 0.086, 95%CI: 0.026-0.288) and having higher BMI (ß = 0.908, 95%CI: 0.852-0.967) and ALM/BMI (ß = 0.000, 95% CI: 0.000-0.007) are independent predictors (p < 0.05) of sarcopenia risk. CONCLUSIONS: This study highlights the intricate relationship between diabetes and sarcopenia, revealing modifiable risk factors. Individuals with diabetes were found to have a higher likelihood of sarcopenia, which was associated with lower fitness levels and higher blood triglycerides. Protective factors against sarcopenia included being female and having higher BMI and ALM/BMI ratios.

A causal relationship between appendicular lean mass and atrial fibrillation: A two sample Mendelian randomization study.

BACKGROUND AND AIM: The relationship between appendicular lean mass (ALM) and most cardiovascular events has been established, but the direct association between ALM and atrial fibrillation (AF) remains uncertain. METHODS AND RESULTS: Herein, we identified 494 single-nucleotide polymorphisms (SNPs) strongly associated with ALM as instrumental variables (P < 5E-8) based on a genome-wide association study (GWAS) with 450,243 European participants. Then, we employed five Mendelian randomization (MR) analysis methods to investigate the causal relationship between ALM and AF. All results indicated a causal relationship between ALM and AF, among Inverse variance weighted (P = 8.44E-15, odds ratio [OR]: 1.16, 95 % confidence interval [CI]: 1.114-1.198). Furthermore, we performed a sensitivity analysis, which revealed no evidence of pleiotropy (egger_intercept = 0.000089, P = 0.965) or heterogeneity (MR Egger, Q Value = 0.980; Inverse variance weighted, Q Value = 0.927). The leave-one-out method demonstrates that individual SNPs have no driven impact on the whole causal relationship. Multivariable MR analysis indicates that, after excluding the influence of hypertension and coronary heart disease, a causal relationship between ALM and AF still exists (P = 7.74E-40, OR 95 %CI: 1.389 (1.323-1.458)). Importantly, the Radial MR framework analysis and Robust Adjusted Profile Score (RAPS) further exhibit the robustness of this causal relationship. CONCLUSION: A strong association between ALM and AF was confirmed, and high ALM is a risk factor for AF.

Bone health and body composition in transgender adults before gender-affirming hormonal therapy: data from the COMET study.

PURPOSE: Preliminary data suggested that bone mineral density (BMD) in transgender adults before initiating gender-affirming hormone therapy (GAHT) is lower when compared to cisgender controls. In this study, we analyzed bone metabolism in a sample of transgender adults before GAHT, and its possible correlation with biochemical profile, body composition and lifestyle habits (i.e., tobacco smoke and physical activity). METHODS: Medical data, smoking habits, phospho-calcic and hormonal blood tests and densitometric parameters were collected in a sample of 125 transgender adults, 78 Assigned Females At Birth (AFAB) and 47 Assigned Males At Birth (AMAB) before GAHT initiation and 146 cisgender controls (57 females and 89 males) matched by sex assigned at birth and age. 55 transgender and 46 cisgender controls also underwent a complete body composition evaluation and assessment of physical activity using the International Physical Activity Questionnaire (IPAQ). RESULTS: 14.3% of transgender and 6.2% of cisgender sample, respectively, had z-score values < -2 (p = 0.04). We observed only lower vitamin D values in transgender sample regarding biochemical/hormonal profile. AFAB transgender people had more total fat mass, while AMAB transgender individuals had reduced total lean mass as compared to cisgender people (53.94 ± 7.74 vs 58.38 ± 6.91, p < 0.05). AFAB transgender adults were more likely to be active smokers and tend to spend more time indoor. Fat Mass Index (FMI) was correlated with lumbar and femur BMD both in transgender individuals, while no correlations were found between lean mass parameters and BMD in AMAB transgender people. CONCLUSIONS: Body composition and lifestyle factors could contribute to low BMD in transgender adults before GAHT.

Correlation between body composition and bone mineral density differs by sex and skeletal site in overweight and obese Chinese subjects.

Previous studies have yielded inconsistent results regarding the relationship between obesity and bone mineral density (BMD). The aim of this study was to determine the influence of body composition on BMD and the serum sclerostin level in overweight and obese adults. The study had a cross-sectional design and included 90 men and 118 women with a body mass index ≥25. Fat mass, lean mass, and spinal and pelvic BMD were measured using dual-emission X-ray absorptiometry. Subcutaneous fat, visceral fat, and lean mass were measured between L2 and L3 by 16-slice spiral computed tomography. The serum sclerostin level was determined by enzyme-linked immunosorbent assay. Pearson analysis showed that fat mass and appendicular lean mass were positively correlated with spinal BMD in both sexes. A positive association of both fat mass and lean mass with pelvic BMD, which was stronger in women, was also found. Partial correlation analysis showed the positive association between fat mass and BMD was significantly attenuated but the positive association between lean mass and pelvic BMD remained after adjustment for age and body weight. A negative correlation was observed between visceral fat and spinal and pelvic BMD only in women, and the positive association between lean mass with pelvic BMD was more obvious in women than in men, indicating body composition seemed to have a greater impact on the BMD in women. The serum sclerostin level was positively associated with BMD but not with body composition. These findings suggest that the correlation between body composition and BMD is influenced by sex and skeletal site.

Frailty in Midlife as a Predictor of Changes in Body Composition from Midlife into Old Age: A Longitudinal Birth Cohort Study.

INTRODUCTION: Few studies have investigated the association between frailty and subsequent body composition. METHODS: We performed separate linear mixed model analyses to study the associations between changes in the participant frailty status assessed by a frailty index (FI) and subsequent body mass index (BMI), lean mass index (LMI), fat mass index (FMI), and FMI to LMI ratio values assessed on three occasions over 17 years. The analyses were carried out among 996 participants spanning from age 57 to 84 years. RESULTS: With advancing age, LMI and BMI decreased, whereas FMI and FMI to LMI ratio increased. Participants with "stable frailty," followed by those with "increasing frailty" experienced faster decreases in LMI and faster increases in FMI and FMI to LMI ratio values from midlife into old age relative to those in the group "stable not frail." Contrastingly, those in the highest third of absolute annual increase in FMI and FMI to LMI ratio became more frail faster from midlife into old age relative to those in the lowest third. CONCLUSIONS: We found evidence of an adverse health outcome of frailty where lean indices declined faster and fat indices and fat-to-lean ratios increased faster from midlife into old age. The changes resembled those that occurred with aging, but at a faster pace. The relationship between body composition and frailty is likely bidirectional, where high or increasing levels of fat are associated with the risk of becoming more frail earlier, but where a longer duration of frailty may increase the risk of faster age-related changes to body composition.

The association between non­high­density lipoprotein cholesterol to high­density lipoprotein cholesterol ratio (NHHR) and low muscle mass in adults aged 20-59: a population-based study in the United States.

BACKGROUND: The ratio between non-high-density lipoprotein cholesterol and high-density lipoprotein cholesterol (NHHR) is a reliable marker for assessing the risk linked to lipid metabolism disorders. Sarcopenia, characterized by age-related loss of muscle mass and strength/function, includes the assessment of muscle mass, muscle strength, and muscle-specific strength. However, research into NHHR's relationship with low muscle mass risk remains unexplored. METHODS: Our study utilized a cross-sectional approach, examining data derived from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Through multivariable linear and logistic regression, we investigated the relationships of the NHHR with muscle mass and low muscle mass. We visualized the results using smoothing curves and assessed threshold effects. We also performed various subgroup and sensitivity analyses. RESULTS: This research encompassed 9,012 participants and demonstrated significant nonlinear associations between NHHR and ALMBMI or low muscle mass risk in a generalized additive model (GAM), pinpointing critical NHHR values (3.328 and 3.367) where changes in NHHR significantly impacted ALMBMI and low muscle mass risk. CONCLUSIONS: The NHHR demonstrates a significant association with an increased risk of low muscle mass among middle-aged Americans. This ratio has potential as a predictive marker for low muscle mass. Further exploration of NHHR is expected to aid in advancing preventive and therapeutic measures for this condition.

Appendicular lean mass and the risk of stroke and Alzheimer's disease: a mendelian randomization study.

BACKGROUND: Appendicular lean mass (ALM) is a good predictive biomarker for sarcopenia. And previous studies have reported the association between ALM and stroke or Alzheimer's disease (AD), however, the causal relationship is still unclear, The purpose of this study was to evaluate whether genetically predicted ALM is causally associated with the risk of stroke and AD by performing Mendelian randomization (MR) analyses. METHODS: A two-sample MR study was designed. Genetic variants associated with the ALM were obtained from a large genome-wide association study (GWAS) and utilized as instrumental variables (IVs). Summary-level data for stroke and AD were generated from the corresponding GWASs. We used random-effect inverse-variance weighted (IVW) as the main method for estimating causal effects, complemented by several sensitivity analyses, including the weighted median, MR-Egger, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods. Multivariable analysis was further conducted to adjust for confounding factors, including body mass index (BMI), type 2 diabetes mellitus (T2DM), low density lipoprotein-C (LDL-C), and atrial fibrillation (AF). RESULTS: The present MR study indicated significant inverse associations of genetically predicted ALM with any ischemic stroke ([AIS], odds ratio [OR], 0.93; 95% confidence interval [CI], 0.89-0.97; P = 0.002) and AD (OR, 090; 95% CI 0.85-0.96; P = 0.001). Regarding the subtypes of AIS, genetically predicted ALM was related to the risk of large artery stroke ([LAS], OR, 0.86; 95% CI 0.77-0.95; P = 0.005) and small vessel stroke ([SVS], OR, 0.80; 95% CI 0.73-0.89; P < 0.001). Regarding multivariable MR analysis, ALM retained the stable effect on AIS when adjusting for BMI, LDL-C, and AF, while a suggestive association was observed after adjusting for T2DM. And the estimated effect of ALM on LAS was significant after adjustment for BMI and AF, while a suggestive association was found after adjusting for T2DM and LDL-C. Besides, the estimated effects of ALM were still significant on SVS and AD after adjustment for BMI, T2DM, LDL-C, and AF. CONCLUSIONS: The two-sample MR analysis indicated that genetically predicted ALM was negatively related to AIS and AD. And the subgroup analysis of AIS revealed a negative causal effect of genetically predicted ALM on LAS or SVS. Future studies are required to further investigate the underlying mechanisms.

The causal relationship of human blood metabolites with the components of Sarcopenia: a two-sample Mendelian randomization analysis.

BACKGROUND: Sarcopenia is a progressive loss of muscle mass and function. Since skeletal muscle plays a critical role in metabolic homeostasis, identifying the relationship of blood metabolites with sarcopenia components would help understand the etiology of sarcopenia. METHODS: A two-sample Mendelian randomization study was conducted to examine the causal relationship of blood metabolites with the components of sarcopenia. Summary genetic association data for 309 known metabolites were obtained from the Twins UK cohort and KORA F4 study (7824 participants). The summary statistics for sarcopenia components [hand grip strength (HGS), walking pace (WP), and appendicular lean mass (ALM)] were obtained from the IEU Open GWAS project (461,089 participants). The inverse variance weighted method was used, and the MR-Egger, weighted median, and MR-PRESSO were used for the sensitivity analyses. Metabolic pathways analysis was further performed. RESULTS: Fifty-four metabolites associated with sarcopenia components were selected from 275 known metabolites pool. Metabolites that are causally linked to the sarcopenia components were mainly enriched in amino sugar and nucleotide sugar metabolism, galactose metabolism, fructose and mannose metabolism, carnitine synthesis, and biotin metabolism. The associations of pentadecanoate (15:0) with ALM, and 3-dehydrocarnitine and isovalerylcarnitine with HGS were significant after Bonferroni correction with a threshold of P < 1.82 × 10- 4 (0.05/275). Meanwhile, the association of hyodeoxycholate and glycine with the right HGS, and androsterone sulfate with ALM were significant in the sensitivity analyses. CONCLUSION: Blood metabolites from different metabolism pathways were causally related to the components of sarcopenia. These findings might benefit the understanding of the biological mechanisms of sarcopenia and targeted drugs development for muscle health.

DXA-based appendicular composition measures in healthy aging Caucasian Greek women: a cross-sectional study.

As the global population of older persons increases, age-related medical conditions will have a greater impact on public health. DXA-derived bone and soft tissue metrics are associated with adverse clinical events in aging persons. This study aims to investigate the regional body composition of the appendices by whole-body DXA scans, and the age-related relationships between measures of bone and soft tissue in healthy Caucasian females of a Greek origin residing in the Mediterranean area. Body composition of the legs and the arms was analyzed, and lean mass (LM) and fat mass (FM) metrics were calculated in 330 women aged 20-85 years, using DXA. Peak bone mineral density (BMD) of the legs and arms was achieved between ages 20-30 and 41-50 years, respectively. The overall BMD reduction with age was for the legs 43% and the arms 32.2% (p < 0.001). Peak %LM of the legs and the arms was achieved between ages 20-30. The overall reduction of %LM with age was for the legs 22.5% (p < 0.001) and arms 6.6% (p < 0.05). Peak %FM of the legs and arms was attained between ages 31-40 and 61-70, respectively. The overall %FM reduction with age was for the legs and arms 7.5% and 1.9% (p > 0.05). In appendicular sites, Greek women reach peak values of bone mass in the legs first, in early adulthood. Bone loss predominates in the legs as women age. Also, with advancing age Greek women show preferential significant decreases of %LM and %FM in the legs as opposed to the arms. Although variation in appendicular bone and soft tissue metrics is present, the implications of variable biological crosstalks among the tissue components as women age may ultimately lay the foundation for future clinical trials aimed at healthy aging.

Age-related variations in trunk composition and patterns of regional bone and soft tissue changes in adult Caucasian women by DXA.

We explored the regional variations in body composition with advancing age in healthy Caucasian females living in the Mediterranean area. The objectives of this study were to establish body composition values for the trunk in healthy women of a Greek origin and to evaluate the effects of aging on the distribution of truncal bone mass, fat mass (FM) and lean mass (LM). Body composition of the trunk and detailed analysis of its anatomical components-the ribs, the thoracic spine, the lumbar spine and the pelvis, and FM and LM ratios--were calculated in 330 women aged 20-85 years, using DXA. Peak bone mineral density (BMD) of the trunk was attained between ages 30 and 33. The overall truncal BMD reduction with age was 20.7% (p < 0.001). Peak %LM of the trunk was achieved at age 20. The overall reduction of %LM with age for the trunk was 9.8% (p < 0.001). Peak %FM of the trunk was attained between ages 68 and 73, and the overall %FM reduction with age was 2.8% (p > 0.05). Multiple comparative analyses showed that the 51-60 years age group was the landmark age for significant changes of truncal bone mass measures across all age groups (p = 0). For truncal LM and FM metrics, multigroup comparative analysis showed the turning point of significant changes in soft tissue was the 41-50 age bracket (p = 0 and p = 0, respectively). In Greek women, truncal %LM exceeded by far %FM across all ages (p = 0). Our results suggest that aging affects body composition of the trunk in ambulatory healthy women of a Greek origin differently, leading to menopausal loss of bone mass, senior adulthood loss of lean mass, and middle-age storage of fat mass. In adult women, these age-related associations between bone and soft tissue metrics on DXA exams carry implications for the attainment of optimal peak values and shifts in body composition overtime, impacting lifelong skeletal health.

Association of body composition with ambulatory blood pressure among Chinese youths.

BACKGROUND: For youths, abnormalities in ambulatory blood pressure (ABP) patterns are known to be associated with increased cardiovascular disease risk and potential target organ damage. Body composition, including indicators such as lean mass index (LMI), fat mass index (FMI), and visceral fat level (VFL), plays a significant role in blood pressure (BP) regulation. However, little is known about the association between these body composition indicators and ABP. Therefore, the present study examined the association between these body composition indicators and BP among Chinese youths. METHODS: A total of 477 college students aged 17 to 28 years old (mean ± Standard deviation = 18.96 ± 1.21) from a university in Changsha, Hunan Province, China, were included in this study. Body composition indicators were measured with a bioelectrical impedance body composition analyzer, and 24-hour ambulatory blood pressure monitoring (ABPM) was conducted. Multivariable logistic regression was performed to assess the relationship between body composition indicators and abnormal ABP. RESULTS: The prevalence of abnormal BP, including 24-hour BP, daytime BP, nighttime BP, and clinic BP, were 4.8%, 4.2%, 8.6%, and 10.9%, respectively. After adjusting for potential covariates, LMI [abnormal 24-hour BP (OR = 1.85, 95%CI:1.31, 2.62), abnormal daytime BP (OR = 1.76, 95%CI:1.21, 2.58), abnormal nighttime BP (OR = 1.64, 95%CI:1.25, 2.14), abnormal clinic BP (OR = 1.84, 95%CI:1.38, 2.45)], FMI [abnormal 24-hour BP (OR = 1.20, 95%CI:1.02, 1.41), abnormal daytime BP (OR = 1.30, 95%CI:1.07, 1.57), abnormal nighttime BP (OR = 1.24, 95%CI:1.10, 1.39), abnormal clinic BP (OR = 1.42, 95%CI:1.22, 1.65)], and VFL [abnormal 24-hour BP (OR = 1.22, 95%CI:1.06, 1.39), abnormal daytime BP (OR = 1.29, 95%CI:1.10, 1.51), abnormal nighttime BP (OR = 1.24, 95%CI:1.12, 1.39), abnormal clinic BP (OR = 1.38, 95%CI:1.21, 1.57)] are positively linked to abnormal BP. Additionally, there were significant sex differences in the association between body composition and abnormal BP. CONCLUSIONS: Our findings suggested maintaining an individual's appropriate muscle mass and fat mass and focusing on the different relations of males' and females' body composition is crucial for the achievement of appropriate BP profiles.